Breast atypia, a lighter follow-up

Translation and synthesis by Cancer Rose, February 10, 2024

Journal article on atypia and new recommendations

Free opinion, Dr C.Bour, radiologist

Related article on 'in situ'

Atypia detected at breast cancer screening and subsequent development of cancer: observational analysis of the prospective Sloane atypia cohort in England.

BMJ 2024; 384 doi: https://doi.org/10.1136/bmj-2023-077039 (Published February 01, 2024) https://doi.org/10.1136/bmj-2023-077039

Karoline Freeman, senior research fellow (Warwick Screening, Division of Health Sciences, Warwick Medical School, University of Warwick, Coventry, UK) ; David Jenkinson, senior research fellow (Screening Quality Assurance Service, NHS England, Birmingham, UK),Karen Clements, breast cancer research manager (Screening Quality Assurance Service, NHS England, Birmingham, UK),  Matthew G Wallis, consultant radiologist,  Sarah E Pinder, professor of breast pathology,   Elena Provenzano, lead consultant breast pathologist,  Hilary Stobart, patient representative, Nigel Stallard, professor of medical statistics,  Olive Kearins, national lead breast screeningNisha Sharma, consultant breast radiologist Abeer Shaaban, consultant pathologist, Cliona Clare Kirwan, consultant oncoplastic breast surgeonBridget Hilton, national audit project senior QA officerAlastair M Thompson, section chief breast surgerySian Taylor-Phillips, professor of population health on behalf of the Sloane Project Steering Group.

WHAT IS AN ATYPIA?

This term covers what are also known as "borderline lesions", which are on the increase as a result of screening and the multiplication of breast biopsies.

They constitute a fringe of breast abnormalities between strictly benign and strictly malignant lesions, and the boundaries between the two are often blurred, frequently leading the pathologist to "upgrade" his report for fear of undertreatment. These lesions are a major source of the problem of over-treatment generated by systematic breast cancer screening.

Frontier lesions are varied, bearing different names depending on their characterization under the microscope, and are classified in the table below, according to the risk of breast cancer attributed to them. The second table lists the therapeutic proposals currently in place.

ISSUES AND BACKGROUND

These borderline lesions raise a number of problems.

First of all, for the pathologist, their diagnostic identification requires a high level of experience, an infallible technique, and a solid knowledge of the classification criteria to ensure that the result of the histological analysis is reproducible and identical if read by another pathologist, which is not always guaranteed....

Then, for the patient, treatment is based on what has been identified in the guided biopsy specimen. But the different entities found in a sample are sometimes intertwined, and the boundaries unclear; in a focal point of atypia, there may be a micro-focal of in situ, making classification decisions very difficult and leading to more extensive treatment. And very often, most of these lesions, which were thought to lead de facto to breast cancer, are surgically excised, as illustrated in figure 1 of the article on the study we're about to discuss (Click on the image).

This is a study of a cohort of 3,238 women diagnosed with epithelial atypia, known as the English 'Sloane' cohort. This cohort is linked to the English Cancer Registry and the Mortality and Birth Information System, to obtain information on subsequent breast cancers and mortality.

The aim of the study was to compare the number and type of breast cancers developed after atypia screening with the 11.3 cancers estimated to be found subsequently by screening per 1000 women over a three-year screening cycle, in the UK.
More specifically: The aim is to find out whether women with atypia have an increased risk of developing more cancers, and if so, which atypia are more predisposing to cancer.
To this end, data from this cohort were collected on radiology, histopathology, surgery and radiotherapy forms, in order to provide robust and generalizable evidence on atypia behavior.
The occurrence of subsequent cancers was compared by comparing women in the 'Sloane Atypia' project database with data from the National Cancer Registry, and mortality information was added. The main follow-up criteria are the number and type of invasive breast cancers detected one, three and six years after the diagnosis of atypia, by type of atypia, age and year of diagnosis.

CURRENT FINDINGS ON ATYPIA

The authors first observe:
“There was a fourfold increase in detection of atypia after the introduction of digital mammography between 2010 (n=119) and 2015 (n=502).”

This can be seen very clearly in the detailed graphs below, compiled in figure 3 of the article. (Click on the image)

Overall, this surge in over-detections was easily observed when we switched to digital mammography around 2010, which is much more sensitive to the detection of microcalcifications in particular. Microcalcifications are one of the three main radiological signs that we look for on mammograms, which may indicate the presence of cancer including : masses, architectural distortions and microcalcifications, which the digital process detects particularly well.

The explanations put forward for the excess detection of these lesions are as follows:
“We propose that the gradual introduction of digital mammography in England since 2010, which identifies more microcalcifications could explain a large proportion of the increase in atypia from 2012 and might be the reason why lower rates of subsequent invasive cancers were detected in women with atypia from 2012 onwards.
The remaining increase in atypia incidence might be because of a shift in atypia definitions and pathologists refining their diagnostic criteria, particularly the diagnosis and terminology of columnar cell lesions.”

“Another factor possibly relating to the increase in atypia could be the increased size of the biopsy needle that might have been used in recent years, increasing the probability of finding atypia and decreasing the probability of misclassifying atypia as DCIS.”

STUDY RESULTS

The analysis focused on the following key questions:

1.         How many women develop cancer after a diagnosis of atypia, and when?
2.         What type of cancer occurs?
3.         How many cancers are not detected when atypia is diagnosed?
4.         Does the risk of developing cancer depend on the type of atypia?
5.         How does this compare with women screened without the diagnosis of atypia?

The results are as follows:

"-The number of cancers after diagnosis of atypia (at 3 and 6 years) was low, and these cancers were similar to those in the general screening population, with similar homolateral and contralateral risk.
-Few cancers were missed when atypia was diagnosed, and VAE (minimally invasive vacuum-assisted excision) did not result in more missed cancers than surgical management.
-The number of cancers did not differ significantly by type of atypia, breast density or age, after adjustment for year of diagnosis.
-The number of cancers after 3.5 years following diagnosis of atypia was equal to the number of cancers in the general screening population.
-Cancer risk in recent years has been lower than historical risk, probably due to the introduction of digital mammography which identifies more microcalcifications, a change in atypia nomenclature and refinement of diagnostic criteria by pathologists, as well as an increase in biopsy needle size.

To summarize: "Women with more recently detected atypia had lower rates of subsequent cancers detected within three years" and "the grade, size and lymph node involvement of subsequent invasive cancers were similar to those of cancers detected in the general screening population, with equal numbers of homolateral and contralateral cancers."

The analyses confirmed that, in the short term, many atypical lesions may represent risk factors rather than true precursors to invasive cancer, and concluded that annual mammography for 5 years after the diagnosis of atypia may not benefit women under the current English NHS breastcancer screening program. In addition, recent changes to mammography and biopsy techniques appear to identify cases of atypia that are more likely to represent overdiagnosis."

CONCLUSION

The authors conclude as follows:

"It appears that few cancers were unrecognized at the time of diagnosis of atypia, and that non-surgical management proved as safe as surgical excision of atypia in this cohort."
The characteristics of cancers detected after atypia were similar to cancers detected in the general screening population and no subgroup was identified that was at increased risk of developing invasive cancer. Therefore, the reporting of atypia at screening could contribute to the problem of overdiagnosis in breast cancer screening.”

And so they suggest:

Many epithelial atypia diagnoses might represent risk factors rather than precursor lesions for invasive cancer “
"Annual mammography in the short term after atypia diagnosis might not be beneficial and should be reviewed."

IMPLICATIONS FOR CLINICAL PRACTICE

Recommendations for the follow-up of these lesions are likely to require substantial change.
The authors write:

"The results suggest that an additional annual mammogram for the first three years following a diagnosis of epithelial atypia may not be necessary in addition to the standard UK screening practice offered to all women (i.e. once every three years).
The number of women diagnosed with atypia who developed cancer in the first three years was low."

Guidelines in the UK, Europe and America generally recommend excision of atypia by biopsy or surgical biopsy-exeresis, followed by close imaging surveillance.
Based on what this study adds in terms of knowledge about these lesions, the authors, in a second publication which we shall see, suggest a modification of the recommendations.

The additional insights that the Sloane cohort study provides are:
"- Breast cancer diagnosis within three years of atypia was low, particularly in more recent years (since 2012), and may contribute to increased overdiagnosis in breast cancer screening.
- More frequent mammography for five years after the diagnosis of atypia may not be beneficial in quality-assured breast cancer screening programs that include universal use of digital mammography and vacuum-assisted excision of indeterminate lesions; these surveillance protocols should be reviewed.
- Surgical removal of atypia has not been shown to be necessary to avoid missed cancers; suction-assisted excision appears to be as safe as surgical excision in the management of atypia."

Recommendations based on these new data should be considered.

Evidence-informed recommendations on managing breast screening atypia: perspectives from an expert panel consensus meeting reviewing results from the Sloane atypia project

British Journal of Radiology, Volume 97, Issue 1154, February 2024, Pages 324–330, https://doi.org/10.1093/bjr/tqad053

Karoline Freeman, PhD,  Alice Mansbridge, BSc,  Hilary Stobart, MSc,  Karen Clements, BSc, Matthew G Wallis, MBChB,  Sarah E Pinder, MBChB,  Olive Kearins, MSc, Abeer M Shaaban, MBBCh, MSc, PhD,  Cliona C Kirwan, MBBS, BSc, PhD, Louise S Wilkinson, BMBCh,  Sharon Webb, MPH,  Emma O’Sullivan, BSc, Jacquie Jenkins, MSc,  Suzanne Wright, PhD,  Kathryn Taylor, DCR, MSc, Claire Bailey, BNurs,  Chris Holcombe, MD,  Lynda Wyld, BMedSci, MBChB, PhD, Kim Edwards, MBBCh, DMRD,  David J Jenkinson, PhD,  Nisha Sharma, MRCP, Elena Provenzano, MB BS, PhD,  Bridget Hilton, BSc,  Nigel Stallard, PhD, Alastair M Thompson, BSc, MBChB, MD, Sian Taylor-Phillips, PhD on behalf of the Sloane Project Steering Group

A half-day consensus meeting was held, attended by 11 clinical experts, a representative of the Independent Cancer Patients Voice, six NHS England representatives, and two researchers, to discuss the results of the Sloane Atypia analysis, mentioned above, and to re-consider existing guidelines and actions.

Until now, explain the authors, “The guidelines were based around existing evidence on upgrade rates to cancer on excision and long-term cancer risk. However, no evidence on the effectiveness of short-term regular surveillance mammography was available and the guidelines included a comment that this should be amended as “more data and national guidance become available.”

Which is now the case.

REVISED RECOMMENDATIONS FOR WOMEN IN THE UNITED KINGDOM

The group decided by a majority of 17/19 (89.5%, one person left the group) on the current evidence, that annual surveillance mammography for the first five years is not beneficial for women with atypia, regardless of the type of atypia or the woman's age.

The group recommended that women with screen detected atypia should be offered routine 3-yearly screening (as is done for the population of women aged 50-70 in the UK), with a clear message that thorough investigation has shown that they do not have cancer and therefore management should be the same as for those without cancer.

SITUATION IN FRANCE

We very much hope that French recommendations will also wisely evolve towards de-escalation of follow-up.

For the time being, this is what is recommended by the Institut National du Cancer and the Haute Autorité de Santé:

In addition to reducing the annual mammography follow-up scheduled for 10 years in France (up to now, only 5 years in the UK), and the associated risks (radiation, over-diagnosis), it would also reduce the anxiety associated with this excessive follow-up, and free these women from the "high-risk woman" label.
The 2019 HAS recommendations concerning "specific screening modalities for high-risk women" are based on the 2014 recommendation, with the bibliography including a framework note dating back to 2011; we can't say that the sources are very recent.

It's high time to modernize all this, and, of course, to provide women with clear information on the escalating overdiagnosis and overtreatment that occur as a result of screening itself, as requested by the 2016 citizens' consultation, which has so far gone carefully ignored.

Reflexion of a radiologist

February 11, 2024, Dr Cécile Bour, Radiologist

After reading recent publications on carcinomas in situ and so-called "borderline" lesions of the breast, representing a useless over-detection of screening because they have no impact on women's lives, I'd like to make a few personal observations. They are based on my own practice and the findings I've been able to accumulate, having followed this screening closely from its genesis and generalization in 2004 as a young radiologist, all the way to the present day, at an age when my career is coming to an end.

It's important to remember, over and over again, that the main aim of screening is not to find as many lesions as possible, or to find as many things as possible, but to achieve three types of benefit:
- to reduce mortality from the disease,
- to reduce the number of advanced forms of breast cancer,
- to ease the burden of treatment, by reducing the need for total mastectomies and other major treatments.

The effect on breast cancer mortality is unproven (according to various hypotheses and meta-analyses, it would be necessary, broadly speaking, to monitor 700 to 2,500 women for fourteen to 20 years to find a single death avoided). In parallel:
- Excess diagnoses, called overdiagnoses, according to the most pessimistic assessments reach 30 to 50%.
- Interval cancers, despite all efforts at early detection, which are the most harmful and aggressive, still account for a third of all cancer cases.
-aggressive treatments are on the increase. (Approximately 30 to 35% more chemotherapy and radiotherapy. Surgical procedures are not decreasing at all, on the contrary).

From the 1990s onwards, as screening became more widespread, there was a surge in the number of ductal cancers in situ.
This spectacular increase in the number of in situ cancers diagnosed was reported as early as 1996 by Virginia Ernster, an epidemiologist at the University of California, San Francisco (Ernster VL, Barclay J et al. Incidence of and treatment for ductal carcinoma in situ of the breast. JAMA. 1996 Mar 27;275(12):913-8. )

Atypical lesions and borderline lesions were already highlighted by Nielsen in a meta-analysis of autopsy studies, based on 13 studies from 10 different countries, over 6 decades (1948 to 2010), including 2363 autopsies with 99 cases of so-called "incidentalomas" ("incidental findings"), precancerous lesions, cancers in situ and atypical hyperplasia, but few invasive cancers.

Two studies also shed light on these lesions and the fact that their presence in the breast is frequent, without impacting women's lives: the Nashville, Tennessee study (Page Dl, Dupont WD et al. Continued local recurrence of carcinoma 15-25 years after a diagnosis of low grade ductal carcinoma in situ of the breast treated only by biopsy. Cancer. 1995 Oct 1;76(7):1197-200. ), and the Bologna study in Italy (Eusebi V, Feudale E, Foschini MP et al. Long-term follow-up of in situ carcinoma of the breast. Seminars in Diagnostic Pathology. 1989;6(2):165-173. )
They report cases of women for whom the diagnosis of carcinoma in situ was made ten to twenty years late. When the biopsies were first read, in the 1950s for one study and in 1960 for the other, the lesions were classified as benign.
The women had therefore not been treated.
But after a more recent re-reading of these same biopsies, it turned out that these women were in fact carriers of in situ cancer.
How did these cancers, which had escaped the vigilance of doctors, evolve? Ten years later, 25% of the Tennessee women who were still alive had invasive cancer, and twenty years later, 11% of the Italian women had invasive cancer. In other words, 75% and 89% respectively of these women with carcinoma in situ had NOT developed invasive cancer.

Of course, you could argue that it's a pity for the majority of women with in situ cancer to be treated unnecessarily to save the small minority with DCIS who will develop invasive cancer. But it's an acceptable harm all in all.
If this were indeed the case and if the treatment of DCIS were beneficial, we would see a reduction in the most serious forms of cancer among women screened, and a drastic drop in breast cancer mortality. But this is not happening.
A very recent study shows that screening does not prolong life.
The Toronto study shows that treating ductal cancer in situ does not reduce breast cancer mortality, and preventing recurrence by radiotherapy or mastectomy does not reduce breast cancer mortality either.

The diagnosis of in situ cancer by screening has a profound impact on the quality of life of women who, uninformed of the potential dangers to which screening exposes them, continue to undergo aggressive treatment and the profound fear of disease without any proven benefit.

Where are we now?

We're trying to "catch up". We've gone wrong, we've promised women the impossible, and since this Titanic of screening can't go backwards, we're trying to throw it a few lifelines by attempting, as best we can, to limit the damage and advocate therapeutic de-escalation.
But we are cynical enough to do this "in agreement with the patient", giving her the opportunity to make her "own decision".

So, yes, it's all very well and very modern to make a shared decision, and we're all in favor of it, who could be against ?
But in the end, after decades of terrorizing women that they might get breast cancer if we relaxed the pressure even a little, after telling them that every minute counts, that we mustn't leave even the smallest degraded cell in a breast, now we're putting the brakes on to reduce our abusive treatments. And we're putting all the weight of the decision, which women will always feel is fraught with consequences, on their shoulders. The questions "Did I do the right thing?" will hang over her like a sword of Damocles for the rest of her life, from exam to exam.

The therapeutic de-escalation we're calling for, will do nothing to relieve women of mortal anguish. We've just loosely shifted the burden of responsibility from the doctor to the woman. Instead of having the courage, all of us, to tell women that screening campaigns were introduced too quickly, too early, without sufficient proof, that we were on the wrong track, that we screwed up, that there's no real loss of chance in not going for screening, that we can do without it, that in the end, the further we go, the more we tinker, the more we change our "therapeutic cuisine" without getting to the end of the killer cancer, the only one we needed to curb, which screening has completely failed to do.

I believe it is incredibly cynical to place all of the responsibility on the shoulders of women.

Related article: Changing the narrative on ductal carcinoma in situ and breast cancer risk

We've often talked about the particular case of carcinoma in situ (DCIS), considered a non-cancer, or "stage 0" cancer, to the extent that it is not counted in the figures for new cases of breast cancer in the statistics of institutes monitoring disease epidemiology, nor by the French National Cancer Institute.

Some scientists think it should be " renamed ", and no longer referred to as " carcinoma ". It is currently considered more as a non-obligatory risk factor for subsequent breast cancer.
We need to change the narrative on this particular entity, and re-consider the risk it exposes women to of invasive cancer, and thereby also change follow-up attitudes and therapeutic recommendations.
In short, we need to take the same steps as for atypia, in any case to move towards a de-escalation of treatment, and a less frightening vision for women of their " disease " condition.

This is what emerges from this October 2023 publication, which we translate below, and which gives the results of a research project, called PRECISION. The aim of this research project is to find out how low-risk DCIS differs from higher-risk DCIS, to help women better adapt treatments and avoid over-treatment.

The article:

Article written by Bethan Warman, with thanks to Esther Lips, Marjanka Schmidt, Jelle Wesseling and Hilary Stobart for their input.

In 2015, Cancer Grand Challenges set the Lethal versus Non-lethal Cancers challenge with the aim of finding ways to distinguish between lethal cancers that need treating and non-lethal cancers that don’t. Since 2017, the PRECISION team, led by Professor Jelle Wesseling of The Netherlands Cancer Institute (NKI), has been addressing this challenge in ductal carcinoma in situ (DCIS).

DCIS is the presence of abnormal cells within the breast milk ducts. By definition, these abnormal cells are non-invasive, but in a small number of cases they can develop into ipsilateral (same breast) invasive breast cancer. 
Despite the chances of progression to breast cancer being low, DCIS is often referred to as early breast cancer and therefore treated as such. Part of PRECISION’s efforts has been to refine this narrative. 

In a new multinational study of over 47,000 women with DCIS from the Netherlands, UK and US, published in the British Medical Journal, the team reported that the 10-year cumulative incidence of ipsilateral invasive breast cancer after DCIS was 3.2%. 
“I think our most important finding is that invasive ipsilateral cancer after DCIS is really a rare event and so it's even more important that we find out who are the women that are at risk. DCIS itself is not life threatening, and we don't want to treat all women intensively, unnecessarily,” says Professor Marjanka Schmidt of the NKI, co-investigator in PRECISION and lead author of the paper.

The finding was part of a study that set out to determine the association of DCIS size and margin status with the risk of developing ipsilateral invasive breast cancer. These two clinical factors are often used in the clinic to stratify the risk of DCIS lesions and determine the course of treatment. 
Currently, treatment is generally recommended for all women with DCIS and may include surgery, radiation and hormone therapy. Doctors may use the grade of DCIS to help decide on the best treatment approach. 
But in most cases, women will have undergone treatment for DCIS that would have not progressed to cancer. To reduce the burden of overtreatment, there is an urgent need to find ways to distinguish the cases of DCIS that are at high risk of developing into invasive breast cancer from those that are at low risk. 

The team combined data from four patient cohorts – one from the Netherlands, one from the UK and two from the US – comprising 47,695 women diagnosed with DCIS between 1999 and 2017 who had received either breast conserving surgery or mastectomy, often followed by radiotherapy or hormone treatment, or both.

They found only a weak association between DCIS size and margin status and the risk of subsequent invasive breast cancer in the same breast, concluding that clinical features such as these were limited in discriminating between low- and high-risk DCIS.
“We concluded that these associations are not large enough to, in clinical practice, drive the decisions around who we should treat and who we should not treat,” says Marjanka. 

The study is the largest of its kind to date to explore the value of prognostic risk factors after DCIS, made possible by the international collaborations established between the research groups in PRECISION and the large-scale funding of the Cancer Grand Challenges initiative. 
“By combining and comparing the multiple patient cohorts, we saw that the risk of subsequent invasive breast cancer in the same breast is very similar for the UK, US and the Netherlands, and other clinical variables are actually very comparable too. Although the cohorts have been collected in a different way and the treatments are somewhat different between countries, the actual risks amongst women are very similar,” adds Dr Esther Lips of the NKI, PRECISION co-investigator and senior author on the paper.

Emphasising the need for the Lethal versus Non-lethal Cancers challenge

The vision for the Lethal versus Non-lethal Cancers challenge was to be able to identify changes that distinguish a non-lethal from a potentially lethal tumour and then determining how these changes can be detected accurately. 
This work from the PRECISION team really emphasises the need of solving this challenge in DCIS, and raises important considerations for the clinical management of DCIS.
“Everything we knew about DCIS in daily practice prior to PRECISION was largely based on relatively small, often biased series that could not yield the impact to inform guidelines in the clinic,” says Jelle.
“While we want to preserve the excellent treatment outcomes for women with high-risk DCIS, we need to know exactly which women are at high risk. And I think this paper shows that some key clinically used factors, such as size and margin status, are in fact not really indicative of the risk. Even though it makes a slight difference, it doesn't have clinical utility.”

Alongside the team’s research, the collaborative work of the PRECISION team has sparked important conversations across national borders amongst researchers, patient advocates and clinicians around defining DCIS and raising awareness about breast cancer risk. 
Understanding the risk is particularly important for women with DCIS who face the decision of whether or not to pursue treatment. “Women need much more information about their individual future risks before they make treatment decisions, but the dilemma is that clinicians and scientists still can’t safely distinguish which DCIS will progress and which will not,” says Hilary Stobart, a patient advocate on the team. 
“The international PRECISION team is working hard to resolve this dilemma by working together to find a combination of biomarkers which will safely distinguish those women who have DCIS which needs treating and those who do not. This large ‘real-world’ international study is an important step towards that goal, so that women and their clinicians will be able to make informed treatment decisions and potentially avoid overtreatment. It has been a great privilege to be a patient advocate working with the PRECISION team.”

The findings underline the need for new prognostic markers, and PRECISION has been exploring several avenues with the aim of finding biological markers that can be used as tools to assess breast cancer risk following a DCIS diagnosis.
The PRECISION team is funded by Cancer Research UK and the KWF Dutch Cancer Society. 
“In a multidisciplinary team, PRECISION tries to identify risk factors to predict whether a woman with DCIS needs treatment or not. Being able to tailor treatments to an individual’s risk, with the aim to prevent overtreatment, fits very well with KWF’s main goals to stimulate better treatment for every type of cancer and to aim for a better quality of life for patients,” says Carla van Gils, director of the KWF Dutch Cancer Society.

Read the full paper in the British Medical Journal.

Cancer Rose est un collectif de professionnels de la santé, rassemblés en association. Cancer Rose fonctionne sans publicité, sans conflit d’intérêt, sans subvention. Merci de soutenir notre action sur HelloAsso.


Cancer Rose is a French non-profit organization of health care professionals. Cancer Rose performs its activity without advertising, conflict of interest, subsidies. Thank you to support our activity on HelloAsso.

Reflections of a radiologist

February 11, 2024, Dr Cécile Bour, Radiologist

After reading recent publications on carcinomas in situ and so-called "borderline" lesions of the breast, representing a useless over-detection of screening because they have no impact on women's lives, I'd like to make a few personal observations. They are based on my own practice and the findings I've been able to accumulate, having followed this screening closely from its genesis and generalization in 2004 as a young radiologist, all the way to the present day, at an age when my career is coming to an end.

It's important to remember, over and over again, that the main aim of screening is not to find as many lesions as possible, or to find as many things as possible, but to achieve three types of benefit:
- to reduce mortality from the disease,
- to reduce the number of advanced forms of breast cancer,
- to ease the burden of treatment, by reducing the need for total mastectomies and other major treatments.

The effect on breast cancer mortality is unproven (according to various hypotheses and meta-analyses, it would be necessary, broadly speaking, to monitor 700 to 2,500 women for fourteen to 20 years to find a single death avoided). In parallel:
- Excess diagnoses, called overdiagnoses, according to the most pessimistic assessments reach 30 to 50%.
- Interval cancers, despite all efforts at early detection, which are the most harmful and aggressive, still account for a third of all cancer cases.
-Aggressive treatments are on the increase. (Approximately 30 to 35% more chemotherapy and radiotherapy. Surgical procedures are not decreasing at all, on the contrary).

From the 1990s onwards, as screening became more widespread, there was a surge in the number of ductal cancers in situ.
This spectacular increase in the number of in situ cancers diagnosed was reported as early as 1996 by Virginia Ernster, an epidemiologist at the University of California, San Francisco (Ernster VL, Barclay J et al. Incidence of and treatment for ductal carcinoma in situ of the breast. JAMA. 1996 Mar 27;275(12):913-8. )

Atypical lesions and borderline lesions were already highlighted by Nielsen in a meta-analysis of autopsy studies, based on 13 studies from 10 different countries, over 6 decades (1948 to 2010), including 2363 autopsies with 99 cases of so-called "incidentalomas" ("incidental findings"), precancerous lesions, cancers in situ and atypical hyperplasia, but few invasive cancers.

Two studies also shed light on these lesions and the fact that their presence in the breast is frequent, without impacting women's lives: the Nashville, Tennessee study (Page Dl, Dupont WD et al. Continued local recurrence of carcinoma 15-25 years after a diagnosis of low grade ductal carcinoma in situ of the breast treated only by biopsy. Cancer. 1995 Oct 1;76(7):1197-200. ), and the Bologna study in Italy (Eusebi V, Feudale E, Foschini MP et al. Long-term follow-up of in situ carcinoma of the breast. Seminars in Diagnostic Pathology. 1989;6(2):165-173. )
They report cases of women for whom the diagnosis of carcinoma in situ was made ten to twenty years late. When the biopsies were first read, in the 1950s for one study and in 1960 for the other, the lesions were classified as benign.
The women had therefore not been treated.
But after a more recent re-reading of these same biopsies, it turned out that these women were in fact carriers of in situ cancer.
How did these cancers, which had escaped the vigilance of doctors, evolve? Ten years later, 25% of the Tennessee women who were still alive had invasive cancer, and twenty years later, 11% of the Italian women had invasive cancer. In other words, 75% and 89% respectively of these women with carcinoma in situ had NOT developed invasive cancer.

Of course, you could argue that it's a pity for the majority of women with in situ cancer to be treated unnecessarily to save the small minority with DCIS who will develop invasive cancer. But it's an acceptable harm all in all.
If this were indeed the case and if the treatment of DCIS were beneficial, we would see a reduction in the most serious forms of cancer among women screened, and a drastic drop in breast cancer mortality. But this is not happening.
A very recent study shows that screening does not prolong life.
The Toronto study shows that treating ductal cancer in situ does not reduce breast cancer mortality, and preventing recurrence by radiotherapy or mastectomy does not reduce breast cancer mortality either.

The diagnosis of in situ cancer by screening has a profound impact on the quality of life of women who, uninformed of the potential dangers to which screening exposes them, continue to undergo aggressive treatment and the profound fear of disease without any proven benefit.

Where are we now?

We're trying to "catch up". We've gone wrong, we've promised women the impossible, and since this Titanic of screening can't go backwards, we're trying to throw it a few lifelines by attempting, as best we can, to limit the damage and advocate therapeutic de-escalation.
But we are cynical enough to do this "in agreement with the patient", giving her the opportunity to make her "own decision".

So, yes, it's all very well and very modern to make a shared decision, and we're all in favor of it, who could be against ?
But in the end, after decades of terrorizing women that they might get breast cancer if we relaxed the pressure even a little, after telling them that every minute counts, that we mustn't leave even the smallest degraded cell in a breast, now we're putting the brakes on to reduce our abusive treatments. And we're putting all the weight of the decision, which women will always feel is fraught with consequences, on their shoulders. The questions "Did I do the right thing?" will hang over her like a sword of Damocles for the rest of her life, from exam to exam.

The therapeutic de-escalation we're calling for, will do nothing to relieve women of mortal anguish. We've just loosely shifted the burden of responsibility from the doctor to the woman. Instead of having the courage, all of us, to tell women that screening campaigns were introduced too quickly, too early, without sufficient proof, that we were on the wrong track, that we screwed up, that there's no real loss of chance in not going for screening, that we can do without it, that in the end, the further we go, the more we tinker, the more we change our "therapeutic cuisine" without getting to the end of the killer cancer, the only one we needed to curb, which screening has completely failed to do.

I believe it is incredibly cynical to place all of the responsibility on the shoulders of women.

Cancer Rose est un collectif de professionnels de la santé, rassemblés en association. Cancer Rose fonctionne sans publicité, sans conflit d’intérêt, sans subvention. Merci de soutenir notre action sur HelloAsso.


Cancer Rose is a French non-profit organization of health care professionals. Cancer Rose performs its activity without advertising, conflict of interest, subsidies. Thank you to support our activity on HelloAsso.

Reduced mortality attributable to screening? We talk about it again

January 18, 2024 by Cancer Rose

Publication JAMA
Caswell-Jin JL, Sun LP, Munoz D, et al. Analysis of Breast Cancer Mortality in the US—1975 to 2019. JAMA. 2024;331(3):233–241. doi:10.1001/jama.2023.25881

Synthesis by Cancer Rose, 18/01/2024

Question

What are the relative associations of breast cancer screening, treatment of stage I to III breast cancer, and treatment of metastatic breast cancer with improved breast cancer mortality in the US between 1975 and 2019?

Results

Improvements in treatment and screening after 1975 were associated with a 58% reduction in breast cancer mortality in 2019, from an estimated 64 deaths without intervention to 27 per 100 000 women (age adjusted). Approximately 29% of this reduction was associated with treating metastatic breast cancer, 25% with screening, and 47% with treating stage I to III breast cancer.

Significance and conclusion

Based on 4 simulation models, breast cancer screening, treatment of stage I to III breast cancer, and treatment of metastatic breast cancer were each associated with reduced breast cancer mortality between 1975 and 2019 in the US.

Limitations and criticisms

According to the authors:

This study has several limitations.

Firstly, the accuracy of the model depends on the assumptions made, for which exact data were not always available.
Secondly, the models did not take into account potential disparities, for example, by age, race and ethnicity, in the spread or effectiveness of screening and treatment. Disparities in breast cancer screening, as well as the promptness and quality of treatment, may contribute to differential breast cancer mortality rates.
Thirdly, treatment costs and their links with outcomes were not included in the models.

Critical review of Cancer Rose, by Dr V.Robert, statistician

Above all, there is at least one major problem: the estimated reductions in mortality are made in relation to the mortality without intervention (in the absence of screening and chemotherapy) estimated by the models.
To obtain this mortality without intervention in 2019, one applies the lethality of 1975 (before screening and chemotherapy, i.e. without intervention) to the cancers of 2019 (the process is a little more complex, but it basically equals to this).
Since the incidence of cancers has risen as a result of screening, this leads to a theoretical increase in mortality, from 48 deaths / 100,000 (actual mortality without intervention) in 1975 to 65 deaths / 100,000 (mortality without intervention estimated by the model) in 2019.
The problem is that the increase in cancer incidence is essentially due to screening, and therefore largely to over-diagnosis, whose lethality is zero. The lethality modelled for 1975 is therefore meaningless for cancers in 2019, which include over-diagnosis.

A recently published meta-analysis showed no gain in lifespan through screening, raising more disturbing questions about the relevance of maintaining and especially promoting screening without informing the population-.

Read here: https://cancer-rose.fr/en/2023/09/08/screenings-dont-extend-lifespan/

Cancer Rose est un collectif de professionnels de la santé, rassemblés en association. Cancer Rose fonctionne sans publicité, sans conflit d’intérêt, sans subvention. Merci de soutenir notre action sur HelloAsso.


Cancer Rose is a French non-profit organization of health care professionals. Cancer Rose performs its activity without advertising, conflict of interest, subsidies. Thank you to support our activity on HelloAsso.

Interview with researcher K.J.Jorgensen

26/10/2023

[Oncoinfo – Istantanee di Oncologia: seguici su http://oncoinfo.it]

Do we have an overdiagnosis problem in mammography screening programmes for early detection of breast cancer in asymptomatic women? The question is more urgent than ever now that the U.S. Preventive Services Task Force changed its recommendation for the starting age for mammography screening from 50 to 40 years. We've met Karsten Juhl Jørgensen (Department of Clinical Research - Københavns Universitet, Cochrane Denmark) a the meeting Medicine & the Media in Florence.

TRANSCRIPTION

Do we have an overdiagnosis problem in mammography screening programmes for early detection of breast cancer screening in asymptomatic women?
(Editor's note, read here : overdiagnosis)

Yes, so overdiagnosis is a really an unavoidable problem with basically all types of screening.
And it has to do with the fact that people die from all sorts of causes apart from the disease that we're screening for. So if you detect that disease early, there is a risk that people will die from something else before this disease that you screen for would develop into something serious.

Another reason is that when you screen for a disease, you often detect a different type of disease than what you do when you detect symptoms in patients and then make a diagnosis.
So we know that many diseases including breast cancer, is not just a single entity. We're dealing with diseases that span a spectrum, various degrees of severity.
(Editor's note, read here : cancer development)

And that, if we screen, because the least  aggressive cancers takes the longest time to develop, those are predominantly the ones that we are going to find with screening.
This simply because there is more time to detect them.
All the aggressive tumors, those that most often kill people develop quickly.
So they fall through the mesh of our screen and are not detected by screening but pops up between screening rounds.

So those are one of some of the well-known limitations of cancer screening. So this is called length bias, the longer you have to detect the cancer, the more you'll detect.
And it contributes to overdiagnosis because the slowest least aggressive cancers are predominantly the ones that are overdiagnosed, but they're still cancers
So they're still treated and people still become cancer patients with all the implications that this has for their well-being. So we know that breast screening and many other types of screening they have harms, just like any other medical intervention has harms.

That's really the only thing we can be sure about any intervention. Any treatment it always has harms so the question is then if these harms are outweighed by the benefit. And that's one question if we're talking about patients that comes to us as doctors seeking treatment.
They’re seeking help with the problem that they feel that they have .
Then we have a responsibility to do our best to help these patients, even if we might not have a complete understanding a complete knowledge about the effects of the interventions that we could use.  
But if as a society we choose to go out and offer a screening program to a healthy population, there's a completely different obligation on us to know what we're doing for sure.

So we have been worrying about new recommendations to expand breast cancer screening for age groups where the evidence is really uncertain.
There's uncertainty about the effects of breast screening for all age groups, but they're particularly large for women in their 40s and for women over 70 years of age.
That's why we haven't screened those age groups for many decades in many countries.

But recently, new recommendations came out from the US preventive Services Task Force recommending breast screening for women in their 40s, and we were worried about that because really the foundations  for that recommendation were different from what we're used to see from the US preventive Services Task Force.
(Editor's note, read here: lowering the age of screening?)
They have usually been a flagship for evidence-based medicine methods and has been a really trusted organization but in this particular instance, rather than trusting the evidence that we do have from randomized trials and which we've known about for years they have chosen to do model calculations and base their recommendations on those.

 And that's really deviating from some of the fundamental principles of evidence-based medicine and we find that worrying because if you base your recommendation on models  you're more likely to make mistakes.
All models are based on assumptions, not knowledge, it's like the weather forecast and models cannot always be trusted. So that's a worry, it's a worry both because we might make a wrong decision and harm people through screening, but also because it deviates resources from things we really know works.

 And if we look at breast cancer mortality in women over 40, we are really seeing a very  positive development where the risk of dying from breast cancer for woman in her 40s has been cut in half over the past 30 years without screening.
(Editor's note, read here: risk of death)

So we've become much better at treating women, young women with breast cancer which of course is an incredible success story, that we should really be proud of as a profession.
And we should praise the oncologists through a responsible for this very positive development.
But at the same time it also means  that there has never been less reason to start screening women in their 40s because we are already doing much better than we ever have before in history, really towards this disease.

 So there is no crisis in a breast cancer in women in their 40s, we're doing very well and in my opinion we need to be certain that if we're going to do more and invite these women to screening, we don't end up doing more harm than good.

Cancer Rose est un collectif de professionnels de la santé, rassemblés en association. Cancer Rose fonctionne sans publicité, sans conflit d’intérêt, sans subvention. Merci de soutenir notre action sur HelloAsso.


Cancer Rose is a French non-profit organization of health care professionals. Cancer Rose performs its activity without advertising, conflict of interest, subsidies. Thank you to support our activity on HelloAsso.

Mammogram: YES or NO?

22/10/2023

Mammogram: YES or NO?
“Should I get Screened ?”
By Dr. Cécile Bour, Radiologist

Since the Nordic Cochrane Collaboration alert in the 2000s questioning the effectiveness of mammography screening and pointing to its risks, new studies have emerged in 2023, evaluating the overdiagnosis caused by screening on the rise.
Meanwhile, a recently published systematic review suggests that life expectancy gains from mammography screening are uncertain and unlikely.

Unfortunately, women are deliberately left outside the loop of this new knowledge and are still subjected to the promotion of screening without being informed of its risks and harms.
It's time for this knowledge to finally progress and become accessible to all women in all countries.

The book "Mammogram: Yes or No ", first published in French in a paper version in 2021, is now available in English in ebook format for a wider, English-speaking audience.
This is a practical book for all women who have questions about breast cancer screening.

A handbook for women

Based on patients' questions heard during consultations, the author, a Radiologist practicing in France, provides the information needed to help every woman better understand the implications of screening and to be aware of its drawbacks.

As closely as possible to scientific data, she strives to answer such questions as..:

"You're sure you'll see everything if you get a mammogram, an ultrasound, or an MRI, right?"

"There are ten women at my workplace. We all have screening mammograms because one of us will get it. I've heard it's one in every eight! Is that correct?"

"I read that the cure rate for breast cancer is 90%. Is this true?”

"The Radiologist informed me that it was a very small cancer. Isn't it true that the earlier it's discovered, the better?"

"Shouldn't mammograms be done earlier, before the age of 50?"

"What is overdiagnosis?"

 "Is it really so bad to detect harmless cancers?"

Why?

Because they've never been presented with the data in a balanced way, some readers are only now likely to discover that the appropriateness of breast cancer screening is scientifically debatable.

Women will find clarifications to the fundamental questions that every woman asks herself without necessarily finding answers on the official sites. They can discuss with their doctor and make their choice, following the principle of an informed decision, whether they live in a French-speaking country or beyond our borders.

Press release

Cancer Rose est un collectif de professionnels de la santé, rassemblés en association. Cancer Rose fonctionne sans publicité, sans conflit d’intérêt, sans subvention. Merci de soutenir notre action sur HelloAsso.


Cancer Rose is a French non-profit organization of health care professionals. Cancer Rose performs its activity without advertising, conflict of interest, subsidies. Thank you to support our activity on HelloAsso.

An interactive decision-support tool, for you!

October the 1st

Cancer Rose - Press Release

October 1st, 2023

The French Association Cancer Rose proposes an interactive decision-support tool in three languages (French, English, German) on breast cancer screening to help each woman assess her own benefits/harms balance.

This tool can easily be used alone or with the help of a practitioner during a medical consultation. https://oad.cancer-rose.fr/

The tool presents two versions for the balance of benefits and harms:  

  • A benefits/harms balance based on unfavorable hypotheses to screening.
  • A benefits/harms balance based on favorable hypotheses to screening.

It is possible to enter the age for the start and the end of participation in screening to obtain a personalized estimate of expected benefits (avoided deaths) and harms (overdiagnosis and false alarms) associated with screening.

PRESS RELEASE

Access to the decision tool possible too from the home page

Cancer Rose est un collectif de professionnels de la santé, rassemblés en association. Cancer Rose fonctionne sans publicité, sans conflit d’intérêt, sans subvention. Merci de soutenir notre action sur HelloAsso.


Cancer Rose is a French non-profit organization of health care professionals. Cancer Rose performs its activity without advertising, conflict of interest, subsidies. Thank you to support our activity on HelloAsso.

Lowering the age of screening? A Pandora’s Box

Comments by Cancer Rose, 17/09/2023

The New USPSTF Mammography Recommendations — A Dissenting View

  • Steven Woloshin, M.D., 
  • Karsten Juhl Jørgensen, M.D., D.Med.Sci., 
  • Shelley Hwang, M.D., M.P.H., 
  • and H. Gilbert Welch, M.D., M.P.H.

De : Dartmouth Institute and Dartmouth Cancer Center, Lebanon, NH (S.W.); the Lisa Schwartz Foundation for Truth in Medicine, Norwich, VT (S.W., K.J.J., S.H., H.G.W.); Cochrane Denmark and the Center for Evidence-Based Medicine Odense, Department of Clinical Research, University of Southern Denmark, Odense (K.J.J.); the Department of Surgery, Duke University, Durham, NC (S.H.); and the Center for Surgery and Public Health, Department of Surgery, Brigham and Women’s Hospital, Boston (H.G.W.).

https://www.nejm.org/doi/full/10.1056/NEJMp2307229

September 16, 2023

The US Public Health Task Force (USPSTF) issued new recommendations for mammography screening in May 2023, advocating the start of routine mammography at age 40.
This represents a 10-year shift in the recommendations for screening, compared with the previous guidelines, which recommended breast cancer screening starting at age 50 due to the increased risks for younger populations and the limited benefits.

The decision was motivated by two arguments:
-an increase in breast cancers in younger women and
-an increase in the most aggressive cancers in black women.

We have summarized this announcement and the reactions it generated here: https://cancer-rose.fr/en/2023/05/16/lowering-the-age-for-starting-screening-but-at-what-cost/

This change in age recommendations has been widely disputed, particularly on the grounds that it will improve 'equal' treatment for the poorest social classes.
This recommendation is by no means trivial, and the price to be paid by women is likely to be very high, which is why the authors issued a warning yesterday.

Why should this concern us?

Firstly, several recent studies from this year clearly call into question the effectiveness of mammographic screening itself.
No, it doesn't 'save lives' - that myth has long been debunked - and there's no evidence that screenings in general extend lifespan.
No, mammographic screening is not responsible for a reduction in breast cancer mortality; the risk of death from breast cancer is decreasing, whether screening or not.
Breast cancer treatments are improving dramatically, so the value of primary detection is declining, which should make screening obsolete in the future.
No, mammographic screening is not harmless, the harms outweigh the benefits, and overdiagnosis is worse in current assessments.

Secondly, the American recommendations, which are highly advantageous to providers in the women's imaging sector, risk serving as an example and opening a Pandora's box that will then be impossible to close again; voices are already being raised here and there calling even for annual mammography screening...
There's nothing 'conspiracy' about this argument, In fact, breast cancer care is, it must be said publicly, a vast and profitable business, fueled by women's fear of the disease.
This cancer business is what journalist John Horgan explains at length in this article.

Thirdly, a European trial called MyPEBS, has just completed the integration of women allocated to the various study groups. 
This study, which is supposed to evaluate individualized screening based on each woman's risk of developing cancer, is clearly calibrated to encourage more and at younger age screening, as it recruits women as young as 40, and includes flagrant biases which we denounced in an open letter along with other health watchdog groups.

Women will not have to choose between screening or no screening but between a standard screening and ... more screening if they are designated “at risk”. 
However, the 'low-risk' sub-group will include very few women, and all the others will be assigned to higher-risk sub-groups very quickly, since the software, which has not been scientifically validated, admits very generous risk criteria, and women will be screened more frequently by mammography.
For example, having had a breast biopsy for even a benign lesion is a risk factor, and the number of biopsy procedures in young women for benign lesions such as fibro-adenomas has risen considerably in recent years, making many women de facto "at risk".

In short,

at a time when mammographic screening is struggling to demonstrate any relevance whatsoever, and evidence of its harmfulness is mounting, we are moving both across the Atlantic and in Europe towards more screening, in more young women, with no regard for the risks to which the population is exposed, and of course without informing them.
No one should know....

A Dissenting View

The authors state (excerpts) :

Recently, the U.S. Preventive Services Task Force (USPSTF) changed its recommendation for the starting age for mammography screening from 50 to 40 years.1
Previously, the Task Force deemed screening in 40-to-50-year-old women a personal choice. Because USPSTF recommendations are so influential, mammography screening for women in their 40s will probably become a health care performance measure; if so, it will effectively become a public health imperative with which primary care practitioners must comply. Such a change will affect more than 20 million U.S. women, and it raises some important questions.

First, is there new evidence that mortality from breast cancer is increasing? To the contrary, there has been a steady decrease in breast-cancer mortality in the United States — a major success story of modern medicine.
...
Similar patterns (of mortality reduction) are seen in other high-income countries, including both those where screening of women in their 40s is very rare (Denmark and the United Kingdom) and those where screening is rare in all age groups (Switzerland) — which suggests that the decline has resulted largely from improved treatment, not screening (see graphs).

Second, is there new evidence that the benefit of mammography is increasing? Since the previous USPSTF recommendation was made, there have been no new randomized trials of screening mammography for women in their 40s. Eight randomized trials for this age group, including the most recent (the U.K. Age trial), revealed no significant effect.2
.....
Fast-growing cancers are more likely to be missed by screening, often appearing in the interval between exams......
The USPSTF’s increasing reliance on complex statistical modeling is problematic. Estimated effects can be extremely sensitive to modeling assumptions, which often reflect the conventional wisdom at the time.
.......
So does the balance of benefits and harms support a new public health imperative? Relative risk reductions can be misleading since they contain no information about absolute risk, which is already low and steadily decreasing for this age group. To clarify the potential effects of the updated guideline in absolute terms, the table summarizes the benefits and harms.

.....
In other words, with screening, the likelihood of not dying from breast cancer in the next 10 years increases from 99.7% to 99.8%.
This effect is small, particularly in light of the potential harms and what seem to be overly optimistic assumptions of benefits. By far the most common outcomes are false alarms: the USPSTF model estimates that 36% of women 40 to 49 years of age will have at least one in a 10-year course of biennial screening.......
And some will experience fear: about a third of women describe the experience as “very scary” or “the scariest time of my life.”4....
The harms will be more frequent if screening occurs annually rather than biennially, as is the current practice for most U.S. women.
.....
Given the steadily decreasing mortality over the past 30 years attributable to improved treatments, it’s likely that fewer and fewer women will benefit from screening over time, while more screening will increase the harms.
The Task Force also argues that the new recommendation is an important first step in reducing the disparity between Black and White women in mortality from breast cancer.
....
But it’s hard to imagine how recommending the same intervention to both groups would reduce the disparity, particularly given that screening rates are already similarly high for Black and White women in their 40s......
Nor would earlier screening address the problems facing poor women, who tend to be disproportionately Black, such as the lower quality of medical services available, delayed follow-up on abnormal scans, delays to treatment, and less use of adjuvant therapy. Indeed, lowering the screening age could actually exacerbate the problems contributing to the disparity — by diverting resources toward expanded screening. We need to do more of what really works: ensure that high-quality treatment is more readily accessible to poor women with breast cancer.
.....

It would be better to allow women to make their own decisions based on their own assessment of the data and their values — and to redirect resources to ensuring that all women with breast cancer receive the best and most equitable treatment possible.

References

  1. Preventive Services Task Force. Draft recommendation statement — breast cancer: screening. May 9, 2023 (https://www.uspreventiveservicestaskforce.org/uspstf/draft-recommendation/breast-cancer-screening-adults. opens in new tab).

2. Gøtzsche PC, Jørgensen KJ. Screening for breast cancer with mammography. Cochrane Database Syst Rev 2013;2013(6):CD001877-CD001877.

3. Kramer BS, Elmore JG. Projecting the benefits and harms of mammography using statistical models: proof or proofiness? J Natl Cancer Inst 2015;107(7):djv145-djv145.

4. Schwartz LM, Woloshin S, Fowler FJ Jr, Welch HG. Enthusiasm for cancer screening in the United States. JAMA 2004;291:71-78.

5. Hayse B, Hooley RJ, Killelea BK, Horowitz NR, Chagpar AB, Lannin DR. Breast cancer biology varies by method of detection and may contribute to overdiagnosis. Surgery 2016;160:454-462.

Cancer Rose est un collectif de professionnels de la santé, rassemblés en association. Cancer Rose fonctionne sans publicité, sans conflit d’intérêt, sans subvention. Merci de soutenir notre action sur HelloAsso.


Cancer Rose is a French non-profit organization of health care professionals. Cancer Rose performs its activity without advertising, conflict of interest, subsidies. Thank you to support our activity on HelloAsso.

Screenings don’t extend lifespan

28/08/2023

Estimated Lifetime Gained With Cancer Screening Tests

A Meta-Analysis of Randomized Clinical Trials

https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2808648?guestAccessKey=c7d91084-054d-49f3-97be-9b302f883c9c&utm_source=twitter&utm_medium=social_jamaim&utm_term=11181634494&utm_campaign=article_alert&linkId=232083149

Michael Bretthauer, MD, PhD; Paulina Wieszczy, MSc, PhD; Magnus Løberg, MD, PhDet alMichal F. Kaminski, MD, PhD; Tarjei Fiskergård Werner, MSc; Lise M. Helsingen, MD, PhD; Yuichi Mori, MD, PhD; Øyvind Holme, MD, PhD; Hans-Olov Adami, MD, PhD; Mette Kalager, MD, PhD
 
JAMA Intern Med. Published online August 28, 2023. doi:10.1001/jamainternmed.2023.3798

This is a systematic review and meta-analysis published by authors from the Institute of Health and Society at the University of Oslo (Norway), examining 18 long-term randomized clinical trials, seeking to estimate the length of life 'gained' through cancer screening.

Several screening tests are analyzed: mammography screening for breast cancer; colonoscopy, sigmoidoscopy, fecal occult blood testing(FOBT) for colorectal cancer; CT screening for lung cancer in current and former smokers; prostate-specific antigen (PSA) testing for prostate cancer.

The study involves 2.1 million people, more precisely 721,718 men for PSA screening, 614,431 men and women for sigmoidoscopy screening, 598,934 men and women for fecal blood testing every two years, 84,585 men and women for colonoscopy screening and 73,634 women for mammography screening ; a smaller sample size for annual fecal blood screening (30,964 men and women) and lung cancer CT screening (20,505 men and women).

The review covers trials with more than 9 years of follow-up (10 to 15 years of follow-up on average) reporting all-cause mortality and estimated acquired life expectancy for 6 commonly used cancer screening tests, comparing 'screening' with 'no screening'.

The endpoint was the duration of life in the 'screening' groups compared with the 'non-screening' groups, based on reported data for all-cause mortality and cancer-specific mortality.

In other words, the years of life "gained" by screening were calculated as the difference in observed lifespan (in person-years) between the "screening" and "non-screening" groups.
The analysis focused on the general population.

MEDLINE and Cochrane Library databases were used as the basis for this search.
Observational and modelling studies were not included due to multiple potential biases.

Key points and main results :

Question: Cancer screening tests are promoted to save lives, but to what extent is life actually prolonged by commonly used cancer screening tests?

Answer: The results of this meta-analysis suggest that colorectal cancer screening by sigmoidoscopy can prolong life by around 3 months; the gain in life span for other screening tests seems unlikely or uncertain.

In this figure, horizontal arrows illustrate four people who underwent screening.
Arrows pointing to the right: 2 people who benefited from screening live longer thanks to early cancer detection and cure.
Arrows pointing to the left: 2 people who suffered screening-related harm and died earlier than those who were not screened.
The blue circle shows the effect of screening on population longevity, calculated as the sum of all individual benefits minus all individual harms.

We can see that, overall, there is no net gain in life expectancy, which is what screening promised when the national campaigns were launched.

Lifetime gains

The authors write: “Based on the observed relative risks for all-cause mortality and the reported follow-up time in the trials, the only screening test that significantly increased longevity was sigmoidoscopy, by 110 days (95% CI, 0-274 days) (Table 2..).
We found no statistically significant outcomes for longevity with mammography screening (0 days; 95% CI, −190 to 237 days) and FOBT screening with yearly or biennial screening (0 days; 95% CI, −70.7 to 70.7 days).
Colonoscopy screening (37 days; 95% CI, −146 to 146 days) and PSA screening (37 days; 95% CI, −37 to 73 days) may have an association with longevity of about 5 weeks, and lung cancer screening among smokers or former smokers of about 3 months (107 days; 95% CI, −286 to 430 days), but these estimates are uncertain (Table 2..)“

Right: life "gained"; left: life "lost".

Diamond dots indicate point estimates of days of life gained or lost for each screening test. Left and right arrows indicate the 95% confidence interval.
CT stands for computed tomography for lung cancer, FOBT for faecal occult blood test, and PSA for prostate-specific antigen.

Discussion

The authors elaborate on their findings.
“Our study quantifies whether use of 6 commonly used cancer screening tests is associated with length of life. One test (sigmoidoscopy) significantly prolonged life and longevity by 110 days, although the lower bound of the 95% CI extended to 0. Fecal testing and mammography screening did not appear to prolong life in the trials, while estimates for prostate cancer screening and lung cancer screening are uncertain.

In recent decades, organized cancer screening programs have been established in Europe, Canada, the Pacific Islands, and in many countries in Asia. In the US, cancer screening is offered by many institutions and encouraged and reimbursed by most health care payers. Several studies have investigated the association between screening and all-cause mortality.6,28 Few have translated their results to practical and easy-to-grasp estimates for health care professionals and individuals on how much cancer screening may increase life expectancy. Our study provides these estimates."

“Even if we did not observe longer lives in general with 5 of the 6 screening tests, some individuals prolong their life due to these screening tests. Cancer is prevented or detected in an early stage, and the individuals survive screening and subsequent treatment without harms or complications. Without screening, these patients may have died of cancer because it would have been detected at a later, incurable stage. Thus, these patients experience a gain in lifetime. “

"However, other individuals experience a lifetime loss due to screening.35,36 This loss is caused by harms associated with screening or with treatment of screening-detected cancers, for example, due to colon perforation during colonoscopy or myocardial infarction following radical prostatectomy.37,38
For 5 of the 6 screening tests investigated herein, the findings suggest that most individuals will not have any gain in longevity.
For those who have their longevity altered with screening, the cumulative loss for those who are harmed must be outweighed in duration by the cumulative gain experienced by those who benefit to show unchanged lifetime in individuals who undergo screening compared with those who do not”.
......
“Our study may provide easy-to-understand estimates for prolongation of life attributable to screening that may be used in shared decision-making with individuals who consider undergoing a screening test. Our estimates may also serve to prioritize public health initiatives in comparison with other preventive measures, such as obesity treatment or prevention of cardiovascular disease.28
The lack of increased longevity with screening may also occur due to competing causes of death. Many of the cancers we are screening for share risk factors with more prevalent causes of death, such as cardiovascular and metabolic diseases. A lack of a significant increase in longevity due to cancer screening may therefore be due to death from competing causes at the same time a patient would have died of cancer without screening. A mortality shift from cancer to other causes of death without increased length of life is thus plausible."

“Due to the stigma and the psychological burden, a cancer diagnosis may also cause extra noncancer-specific deaths from suicide, cardiovascular disease, and accidents.41,42 Also, increased surveillance after cancer screening may increase the risk of other incidental disease, which would not have been detected without screening.43

Adherence to more than 1 screening test may potentially increase longevity. The one study that was available28 does not suggest that there is an additive effect of screening for more than 1 cancer. Although such outcomes are possible, the competing risk of other disease might also outweigh the influence of screening for 2 or more cancer sites on length of life...."

Another concern addressed by the authors is quality of life after cancer:
« In addition to lifetime gained or lost with screening, quality of life is important. Quality-adjusted life-years (QALYs) are difficult to measure and interpret, but recent analyses of QALYs for mammography screening estimates in Norway suggest that net QALY in modern mammography screening in Norway may be negative.29 »

Conclusions and relevance of the study:

The results of this meta-analysis suggest that current evidence does not support the claim that cancer screening tests save lives by extending lifespan, with the possible exception of sigmoidoscopy screening for colorectal cancer.

References

1.

Vanchieri  C.  National Cancer Act: a look back and forward.   J Natl Cancer Inst. 2007;99(5):342-345. doi:10.1093/jnci/djk119PubMedGoogle ScholarCrossref

2.

Bretthauer  M, Kalager  M.  Principles, effectiveness and caveats in screening for cancer.   Br J Surg. 2013;100(1):55-65. doi:10.1002/bjs.8995PubMedGoogle ScholarCrossref

3.

Woloshin  S, Schwartz  LM, Black  WC, Kramer  BS.  Cancer screening campaigns—getting past uninformative persuasion.   N Engl J Med. 2012;367(18):1677-1679. doi:10.1056/NEJMp1209407PubMedGoogle ScholarCrossref

4.

Seffrin  JR. We know cancer screening saves lives. American Cancer Society Cancer Action Network, October 23, 2009. Accessed May 3, 2020. https://www.fightcancer.org/news/we-know-cancer-screening-saves-lives

5.

Schwartz  LM, Woloshin  S, Fowler  FJ  Jr, Welch  HG.  Enthusiasm for cancer screening in the United States.   JAMA. 2004;291(1):71-78. doi:10.1001/jama.291.1.71
ArticlePubMedGoogle ScholarCrossref

6.

Knudsen  AB, Zauber  AG, Rutter  CM,  et al.  Estimation of benefits, burden, and harms of colorectal cancer screening strategies: modeling study for the US Preventive Services Task Force.   JAMA. 2016;315(23):2595-2609. doi:10.1001/jama.2016.6828
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Schröder  FH, Hugosson  J, Roobol  MJ,  et al; ERSPC Investigators.  Screening and prostate cancer mortality: results of the European Randomised Study of Screening for Prostate Cancer (ERSPC) at 13 years of follow-up.   Lancet. 2014;384(9959):2027-2035. doi:10.1016/S0140-6736(14)60525-0PubMedGoogle ScholarCrossref

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Lundgren  PO, Kjellman  A, Norming  U, Gustafsson  O.  Long-term outcome of a single intervention population based prostate cancer screening study.   J Urol. 2018;200(1):82-88. doi:10.1016/j.juro.2018.01.080PubMedGoogle ScholarCrossref

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Andriole  GL, Crawford  ED, Grubb  RL  III,  et al; PLCO Project Team.  Prostate cancer screening in the randomized Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial: mortality results after 13 years of follow-up.   J Natl Cancer Inst. 2012;104(2):125-132. doi:10.1093/jnci/djr500PubMedGoogle ScholarCrossref

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de Koning  HJ, van der Aalst  CM, de Jong  PA,  et al.  Reduced lung-cancer mortality with volume CT screening in a randomized trial.   N Engl J Med. 2020;382(6):503-513. doi:10.1056/NEJMoa1911793PubMedGoogle ScholarCrossref

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Wille  MM, Dirksen  A, Ashraf  H,  et al.  Results of the randomized Danish Lung Cancer Screening Trial with focus on high-risk profiling.   Am J Respir Crit Care Med. 2016;193(5):542-551. doi:10.1164/rccm.201505-1040OCPubMedGoogle ScholarCrossref

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Pinsky  PF, Miller  EA, Zhu  CS, Prorok  PC.  Overall mortality in men and women in the randomized Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.   J Med Screen. 2019;26(3):127-134. doi:10.1177/0969141319839097PubMedGoogle ScholarCrossref

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Cancer Rose est un collectif de professionnels de la santé, rassemblés en association. Cancer Rose fonctionne sans publicité, sans conflit d’intérêt, sans subvention. Merci de soutenir notre action sur HelloAsso.


Cancer Rose is a French non-profit organization of health care professionals. Cancer Rose performs its activity without advertising, conflict of interest, subsidies. Thank you to support our activity on HelloAsso.

The risk of death from breast cancer is declining, with screening or not

Breast cancer mortality in 500 000 women with early invasive breast cancer in England, 1993-2015: population based observational cohort study

BMJ 2023; 381 doi: https://doi.org/10.1136/bmj-2022-074684 (Published 13 June 2023)

Cite this as: BMJ 2023;381:e074684

Carolyn Taylor, professor of oncology and honorary clinical oncologist2,  
Paul McGale, statistician
1,  
Jake Probert, statistician
1,  
John Broggio, cancer analytical lead
3,  
Jackie Charman, senior cancer analyst
3,  
Sarah C Darby, professor of medical statistics
1,  
Amanda J Kerr, systematic reviewer
1,  
Timothy Whelan, radiation oncologist
4,  
David J Cutter, senior clinical research fellow and clinical oncologist
2,  
Gurdeep Mannu, lecturer in general surgery
1,  
David Dodwell, senior clinical research fellow and clinical oncologist
2

1Nuffield Department of Population Health, University of Oxford, Oxford, UK
2Oxford University Hospitals, Oxford, UK
3National Disease Registration Service (NDRS), NHS England, Birmingham, UK
4Department of Oncology, McMaster University and Juravinski Cancer Centre, Hamilton, ON Canada

June the 16th, 2023

Aim of the study

This is an observational cohort study (a group of subjects followed for the duration of the study) involving 512,447 women.

There are two objectives:

1°- Assessment of annual breast cancer mortality rates and cumulative risks by time since diagnosis for women diagnosed during each of the following calendar periods: 1993-99, 2000-04, 2005-09, and 2010-15.

2°- Examination of variations in these mortality rates according to several criteria: according to the calendar period of diagnosis, according to the time elapsed since diagnosis, according to whether or not the cancer was detected by screening, and according to the characteristics of the patients and the tumours they presented.

Overall, almost half the cancers in women in the age groups eligible for screening were detected by screening.

Main results:

Crude risks of breast cancer mortality decreased with increasing calendar period.

In other words, women in calendar periods closer to our contemporary period are more likely to survive long after a cancer diagnosis than women diagnosed in calendar periods further back in time, with a significant magnitude.

The cumulative five-year mortality risk from breast cancer was :

- 14.4% for women diagnosed between 1993 and 1999, and
- 4.9% for women diagnosed between 2010 and 2015.

These results correspond to the entire cohort of 512,447 women aged 18-89, including :
-women eligible for screening, with cancer detected as part of organized screening: 128,240 women (i.e., around a quarter of the cohort)
-women eligible for screening but not screened, with cancer detected outside screening: 133,427 women (i.e., around a quarter of the cohort)
-women not eligible for organized screening: 250,780 women (around half the cohort).

The composition of groups is shown in Table 1, extracted below:

Adjusted annual breast cancer mortality rates also decreased similarly with the advancing calendar period in almost all patient groups, by a factor of around three for estrogen receptor-positive cancers, which correspond to forms of cancer with a better prognosis, and by around two for estrogen receptor-negative cancers, which correspond to more pejorative forms of cancer. The mortality risk improves with the advancement of the calendar periods studied towards more recent years than earlier years.

The study's main aim was to use five-year breast cancer mortality risks for newly diagnosed patients. Indeed, say the authors, these mortality rates, which are now known, can be used to estimate breast cancer mortality risks for today's patients.

The study aims to inform patients and clinicians of the likely absolute mortality risks for patients treated for breast cancer today, considering, among other things, the characteristics of their tumor.

The study shows that, for women diagnosed with early breast cancer, the risk of dying within five years fell considerably between the 1990s and 2010-2015. For most newly diagnosed women, the risk of dying from breast cancer within five years was 3% or less. This is helpful information for women living today.

The authors conclude, "It should be noted, however, that the improvements in breast cancer mortality observed in women whose cancer was detected by screening were paralleled in women whose cancer was not detected by screening."

Detailed conclusions:

The prognosis for women with early invasive breast cancer has improved considerably since the 1990s. Most can expect to survive cancer in the long term, although the risk remains appreciable for a few.

Since the 1990s, the five-year cumulative risk of death from breast cancer has fallen from 14.4% to 4.9% overall, with reductions observed in almost all patient groups.
Indeed, the five-year cumulative mortality risk was 14.4% (95% confidence interval 14.2% to 14.6%) for women diagnosed between 1993 and 1999 and gradually decreased with increasing calendar period to 4.9% (from 4.8% to 5.0%) for women diagnosed later, between 2010 and 2015.
This shows that breast cancer mortality rates decreased with the calendar period of diagnosis over the study period.

But although decreases occurred in almost all patient groups, the magnitude of the mortality rate decreased, and the 5-year risk of cancer death varied considerably between women with different characteristics:
- the risk of mortality was less than 3% for 62.8% of women,
- but 20% or more for 4.6%, corresponding to particularly aggressive forms of cancer that are difficult to cure.

In our data," explain the authors, "the lack of mortality reduction in women aged 80 to 89 with estrogen receptor-negative breast cancer may be explained by the fact that these women generally do not receive systematic adjuvant treatment (treatment that complements the main treatment to prevent the risk of local recurrence or metastases, e.g., hormone therapy or immunotherapy), or radiotherapy, so any improvement in these treatments per se would not have affected mortality in this group of patients. ), or those who do not receive radiotherapy, so any improvement in these treatments per se would not affect mortality in this group of patients.
Patients under 40 years of age at diagnosis had a higher risk of breast cancer mortality than those diagnosed at 40, which is explained by the fact that breast cancers in younger women are inherently more aggressive than those in older women.

The authors found that breast cancer mortality always decreased as a function of the calendar period of diagnosis, irrespective of differences in tumour characteristics, and even the improvements in breast cancer mortality observed in women whose cancer was detected by screening were accompanied by improvements also in those whose cancer was not detected by screening.

This is summarized in the illustration below, which presents the results for all women (a quarter of whom are eligible and screened, a quarter are cancer cases in eligible but unscreened women, and half are women not eligible for screening):

It can be argued that screening has enabled the detection of smaller and smaller tumors over the years with significant technological improvements in mammography equipment, with tumors found of ever lower grades, but, say the authors, this decline in mortality cannot be attributed to changes in tumor size, number of positive nodes or tumor grade alone, as breast cancer mortality continued to decline according to the calendar period of diagnosis, even after adjusting for these factors.

Furthermore, screening and more sensitive breast imaging techniques are likely to have led only to earlier diagnosis and longer survival without altering the clinical course of the disease. Survival, it should be remembered, corresponds to the duration of life after cancer diagnosis and increases with improved treatment and overdiagnosis. The earlier in a person's life cancers are detected that were not destined to kill their host anyway, that are very low-grade and will remain so, the more survival data are artificially improved, without affecting life expectancy.

Relationship with screening

For patients diagnosed with screened or unscreened cancer, annual breast cancer mortality rates and cumulative breast cancer mortality risks showed similar downward trends to those for all women, depending on the calendar period of diagnosis.

The study shows that the improvements in breast cancer mortality observed in women whose cancer was detected by screening were also paralleled by improvements in those whose cancer was not detected by screening.
The increase in screening does not, therefore, explain the improvements in mortality.

The contribution of the study

Other studies have already shown the very marginal role of screening in the decline in breast cancer mortality since the 1990s.
We already know that the risk of breast cancer mortality following early invasive breast cancer diagnosis has decreased over the last few decades.

Bleyer and Miller's impact study concluded that the link between screening mammography and the degree of reduction in breast cancer mortality observed in recent years was increasingly controversial. Their comparison of eight countries in Europe and North America showed no correlation between the intensity of national screening and the timing or even the extent of reduction in breast cancer mortality.

The evidence from the three different approaches (temporal approach, magnitude approach, and comparative approach with other non-screened pathologies) and other additional observations did not support the hypothesis that mammography screening was the main reason for the reduction in breast cancer mortality observed in Europe and North America.

Similarly, P.Autier's study of the three pairs of countries compared suggested that screening had not played a direct role in reducing breast cancer mortality, given the contrast between the temporal differences in the implementation of mammographic screening and the similarity in mortality reductions between the pairs of countries.
In other words, countries that introduced screening earlier than other countries that introduced it later experienced a similar reduction in breast cancer mortality. In contrast, there should have been an amplifying phenomenon in mortality reduction due to the earlier introduction of campaigns. There is, therefore, no link between screening activity and reduced mortality.

And invasive metastatic cancer remains at the same level, as screening is unable to detect this aggressive form of cancer because of its intrinsic biologically aggressive characteristics and often because of its high velocity.

To conclude, we quote this study: Søren R Christiansen, Philippe Autier, Henrik Støvring, Change in effectiveness of mammography screening with decreasing breast cancer mortality: a population-based study.
Summarized here.

According to the authors, improvements in cancer therapies over the past 30 years have reduced mortality, which could erode the benefit-disadvantage balance of mammography screening.
Furthermore, future improvements in managing breast cancer patients will increasingly reduce the benefit-harm ratio of screening.
The benefit of mammography in terms of mortality reduction is diminishing, while the harms, such as overdiagnosis, are constant.
Screening leads to both over-diagnosis and over-treatment, at both human and economic costs,

What the study here provides is an estimate of the extent of the decline in breast cancer mortality rates observed since the 90s, and this is not linked to screening or any other factor related to the tumor or the woman carrying cancer since there is no difference in variations in mortality rates whatever these factors may be, whether the cancer is found by screening or not.
The reason for this is most likely to be found in the therapeutic improvements of recent decades.

Illustration: annual mortality rates and cumulative mortality risks

Cumulative risk is the sum of the various annual risks, present over 5 years. The mortality risk function describes the evolution as a function of time and cumulative factors of the instantaneous risk of death.

Summary by Cancer Rose

This is a descriptive epidemiological study. It aims to quantify the reduction in mortality observed since the 90s. This reduction is not a scoop, but it was interesting to quantify it globally and by sub-group.
It ranges from 14.4% to 4.9% at 5 years between the two periods examined, for all women, with a similar reduction depending on the group (screened or not).

Studies of the impact of screening (see our article) have already demonstrated this reduction in breast cancer mortality since the 90s. Still, the impact of screening is very marginal, or even non-existent, since this reduction is not synchronized with the introduction of screening campaigns.

In essence, the authors conclude that recent data show an improvement in breast cancer mortality risk compared with older data, which is confirmed by their results. They make several points: "... Therefore, increases in screening cannot solely explain the decreases in breast cancer mortality that we observed” and a little further on: " this observational study cannot determine the specific causes of these reductions in mortality.
And yet again, probably the most important: "... Notably, however, the improvements in breast cancer mortality seen in women with screen-detected cancers were paralleled by improvements in those whose cancers were not screen-detected.”

This study confirms (and, above all, quantifies) the downward trend in breast cancer mortality, but it does not conclude (nor does it enable us to conclude) the cause(s) of this decline.

What's important to understand is that in this study, we're not talking about the mortality rate but the cumulative RISK of mortality over 5, 10, or 15 years. These cumulative mortality risks depend on the time T0 chosen. Here, T0 is the date of cancer diagnosis. Therefore, the mortality risks presented in the study are influenced by the lead time (since T0 will be earlier for screened cancers than for unscreened cancers). They will give an apparent better success rate in the screened groups.
Lead-time bias is a well-known inherent bias in screening, giving the illusion of better cancer survival when we've just anticipated its 'date of onset'.

The prognosis for breast cancers is improving, but it is impossible to say how much of this is due to screening, therapeutic advances, and confounding factors such as early diagnosis bias, overdiagnosis in particular, and social and economic factors.

According to the studies already available (see article), the role of screening is probably marginal, and apparent success in screened groups is influenced by lead time.

Rapid responses in BMJ

Dr Vincent Robert is our statistician.

Per-Henrik Zahl is researcher on the Norwegian Institute of Public Health

https://www.bmj.com/content/381/bmj-2022-074684/rapid-responses

Opinion

Risk of breast cancer death after a diagnosis of early invasive breast cancer

BMJ 2023; 381 doi: https://doi.org/10.1136/bmj.p1355 (Published 13 June 2023)Cite this as: BMJ 2023;381:p1355

Mairead MacKenzie, patient advocate1,  
Hilary Stobart, patient advocate1,  
David Dodwell, senior clinical research fellow and clinical oncologist23,  
Carolyn Taylor, professor of oncology and honorary clinical oncologist23

  1. 1Independent Cancer Patients’ Voice
  2. 2.     2Nuffield Department of Population Health, University of Oxford
  3. 3.     3Oxford University Hospitals, Oxford, UK

Two patient advocates reflect on how they helped to shape a research study into breast cancer

Mairead MacKenzie and Hilary Stobart were diagnosed with breast cancer some years ago. They’re just two of the half a million women who contributed their data to our study of women diagnosed with early breast cancer in England. As patient advocates, they also helped to shape the study.

Hilary and Mairead both feel that up-to-date information is needed on outcomes after a diagnosis of early breast cancer. They used their expertise as patients to highlight how data from women diagnosed with breast cancer in the past could help in the clinic today. Moreover, the study also gave them a chance to reflect on all that has changed since they were diagnosed with cancer.

“You don't have much grasp of having cancer until you've had it,” explains Hilary. “You suddenly join a club that you don't want to be part of, and you find you have an awful lot in common with the other people in the club. You have a different perspective on what's important.”

Our study was informed by that perspective.

The study provides risk estimates for individual patients. Both Hilary and Mairead stress that doctors need to help patients understand that breast cancer is “not all one thing.” Prognosis varies widely according to risk factors such as tumour size, lymph node involvement and whether the tumour was detected by screening.

“When I was diagnosed 20 years ago, I was not given a prognosis other than the fact that this is serious and we need to treat you quickly,” says Mairead. “But I think good, clear communication about prognosis can make a vast difference to a patient's quality of life, and how they can cope with things.”

“When people are diagnosed with breast cancer they may already know somebody who has died from breast cancer,” adds Hilary. “They might assume that their risk is the same, but many of them might only have less than 1% risk of dying from breast cancer at five years.”

“For the majority of women, the prognosis is good,” agrees Mairead. “This study backs that up and gives reassurance—because, initially, everybody thinks they're going to die.”

The study shows that, for women diagnosed with early breast cancer, the risk of dying from it within five years reduced substantially between the 1990s and 2010-15. For most women diagnosed recently their five year risk of breast cancer death was 3% or less.

Breast cancer patients have contributed to that improvement.

“I’ve yet to meet a cancer patient who isn’t happy for their data to be used for research,” says Mairead. “If there's a chance of doing something that might make it easier for those coming after, patients nearly always say yes.”

“And if people hadn't said yes, we wouldn't be where we are now, would we?” agrees Hilary “We know our treatment now is good because of all the work that was done earlier …the large numbers of trials and the thousands of women who were prepared to go into them.”

Our results are part of that legacy. They quantify decades of improvements and lay the foundation for more to come. Meanwhile, they can inform how doctors talk with patients about their prognosis today.

“It’s good news,” concludes Hilary. “It shows what we’ve done, and that we need to go on doing it. More studies like this one will be needed in the future. Breast cancer is still with us. There’s a lot more to do.”

Cancer Rose est un collectif de professionnels de la santé, rassemblés en association. Cancer Rose fonctionne sans publicité, sans conflit d’intérêt, sans subvention. Merci de soutenir notre action sur HelloAsso.


Cancer Rose is a French non-profit organization of health care professionals. Cancer Rose performs its activity without advertising, conflict of interest, subsidies. Thank you to support our activity on HelloAsso.

Screening for…cytoliosis!

The impact of influences in a medical screening programme invitation: a randomized controlled trial

May 7, 2023, BY CANCER ROSE

Christian Patrick Jauernik 1,2,  Or Joseph Rahbek 1,2,  Thomas Ploug 3,  Volkert Siersma 1, John Brandt Brodersen 1,2
1  Department of Public Health, The Research Unit for General Practice and Section of General Practice, University of Copenhagen, Copenhagen, Denmark
2  The Primary Health Care Research Unit, Zealand Region, Sorø, Denmark
3  Centre for Applied Ethics and Philosophy of Science, Department of Communication and Psychology, Aalborg University Copenhagen, Copenhagen, Denmark
European Journal of Public Health, ckad067, https://doi.org/10.1093/eurpub/ckad067

The authors of this publication had the idea of screening for a fictitious disease, "cytoliosis," non-transmissible and potentially fatal, and sent out invitations for screening using pamphlets, which were also fictional.
This trial is randomized with seven arms, i.e., seven groups of people in a total of 600 people studied. Each group received a pamphlet with messages that differed to a greater or lesser extent in their incentive to participate in screening.

The objectives of the study were:
1) to assess whether the different methods of influence had a significant effect on the intention to participate in a screening program, and
2) to assess whether participants were aware of these influences and whether there was a relationship between intention to participate and awareness.

Introduction and background

According to the authors:

"Screening programs for different cancers are implemented in many developed countries. They have intended benefits, including a reduction in mortality and morbidity plus less radical treatments.1"
However, cancer screening programmes come with many unintended harms such as false-positive results, overdiagnosis and overtreatment, possibly leading to physical, psychological or social harms.2 The quality of screening programmes is sometimes evaluated by a considerable participation rate.3–5"

From the perspective of health authorities, it is assumed that a cancer screening program is more beneficial than harmful, and that a high participation rate would maximize the expected benefits of the screening program. In addition, citizens with lower socioeconomic status are found to have a higher incidence of cancer diseases (except breast cancer) but are less likely to participate in screening programs.

“This creates another incentive for health authorities to make screening participation barrier-free and simple to promote equality in health. The healthcare authorities can systematically influence citizens in subtle ways that may increase participation rates without making the choice to participate adequately informed.”

« Not all citizens will share the same assessment of the benefits/harms as the health authorities. And even if they agree with the health authorities that the benefits outweigh the harms on a population level, they may still not wish to participate because they on an individual level might receive more harm than benefit—current evidence suggests that the more informed citizens are less likely to participate in cancer screening.10,11 »

The authors refer to a study published in 2019 on the methods of influence health authorities use to push populations to participate in various screening programs. These methods range from anxiety-provoking messages to minimizing the risks and harms of screening.
Our French National Cancer Institute (INCa) was cited in this study in the categories of 1) Misrepresentation of statistics and 2) Unbalanced representation of harm versus benefit.

It is amusing, by the way, that said INCa is very keen to classify the screening controversy as fake news on a page titled "enlightenment" while itself being caught at fault for manipulating the public with its biased and misleading documentation. The author of this 2019 study on public manipulation is a co-author of this current study; in 2019, he distinguished in his publication 5 categories of people's influences:
1.      Tendentious presentation of statistics Biased presentation of statistics,
2.     Omission of harmful effects and emphasis on benefits,
3.     Recommendations of participation,
4.     Opt-out systems -This consists of assigning citizens a pre-determined appointment at the time of the invitation. If the person does not wish to participate, the person must actively opt-out. The patient's non-refusal is considered de facto acceptance to participate.
5.     Fear appeals.

These types of influences significantly affect individual participation by circumventing or thwarting reflection and may be incompatible with informed decision-making.

Cytoliosis

This disease created for the study, supposedly deadly, was invented to avoid a bias due to preconceived ideas and fears related to cancer.

“The pamphlet for screening for cytoliosis (i.e. 'the neutral') was partially based on the Danish colorectal cancer (CRC) screening pamphlet, and cytoliosis shared the same incidence and mortality as CRC.17 The screening programme for cytoliosis shared the same benefits (e.g., mortality reduction) and harms (e.g., false positives, physical harm, and overtreatment) as CRC screening for a 50–60-year-old male. The harms of the fictitious screening programme were increased compared with CRC screening to better balance the benefits and harms of participation.”

Seven different brochures were distributed, one for each of the seven groups in this randomized study:
A- The "neutral" pamphlet
B- A pamphlet with relative risk reductions to accentuate the reduction in mortality.
( Similar to the INCa process for breast cancer, giving percentages of mortality reduction that correspond to comparison rates between populations, but not at all to the real, absolute data.
This technique of misleading in the presentation of mortality reduction is constantly used by INCa, even though the citizens criticized it during the citizens consultation on breast cancer screening in 2016; nothing has changed in the communication of INCa, and we can still read in the documents a "20% mortality reduction", which corresponds in real life to a single woman whose life is prolonged by screening on women 2000 screened and on 10 years of screening, which is no longer the same thing ....)
C- The third pamphlet misrepresented the harms versus the benefits, omitting the harmful effects and emphasizing the benefits, again very similar to INCa's methods with deliberate omission of the most important risks,(read https://cancer-rose.fr/en/2021/10/23/inca-still-outrageously-dishonest-and-unethical-2/)
D- The fourth pamphlet was based on pre-booked appointments (opt-out system, see above)
E- The fifth pamphlet contained an explicit recommendation to participate
F- The sixth pamphlet appealed to fear
G- And finally, a last pamphlet contained all the influence systems at the same time.

All the types of influence studied were inspired by real examples of cancer screening programs (pamphlets 2 and 4 for our French institute)

All the pamphlets can be found in the PDF appendix

The results

A- Main result: a measure of intention to participate

"The lowest proportion of people intending to participate (31.8%) was observed in the group that received the neutral pamphlet (A), while the proportion of people with the intention to participate ranged from 39.2% to 80.0% when the other, non-neutral pamphlets were distributed.."

See Table 2

Intention to participate (without adjustment for socio-demographic status) increased statistically significantly in groups that received brochures containing relative risk reductions (B), misrepresentation of harms versus benefits (C), an explicit recommendation to participate (E), fear appeals (F), and all influences combined(G)

B- Secondary outcome: awareness of influences and effect of awareness of influences on intention to participate

Were participants aware of the influences they were subject to participate more, and was there a relationship between intention to participate and this awareness of the influences experienced?
"A majority ranging from 60.0% to 78.3% of participants," the authors say, "reported no awareness that their choice was attempting to be influenced (pamphlets B through G).
There was no clear difference between responses to the neutral brochure (A) and the pamphlets containing a deliberate attempt to influence participants' choice."
"Participants who received a pamphlet  with influence (B-G) and did not indicate awareness that their choice was influenced had a higher intention to participate than those who felt the pamphlet was trying to influence their choice and then correctly located an influence."

The authors also say that participants with an influential pamphlet who were unaware of this had more intention to participate than those who felt the pamphlet was trying to direct their choice but failed to locate the influence correctly.

Nevertheless, the authors warn that "Secondary outcomes should be interpreted cautiously. Because secondary outcomes are measured after participants have indicated their intention to participate, this may affect their response about whether the pamphlet was trying to guide their choice. We hypothesize that participants who intended to participate may be more reluctant to admit they were potentially influenced."

In any case, it is certain and demonstrated that the five categories of influence increase intention to participate when used in materials sent to screening targets.
Less than half of the participants recognized these influences, and not knowing about them was de facto associated with an increase in intention to participate.

Author's conclusion

"These results call for reflection and discussion on using different types of influence to increase participation rates in cancer screening programs. The potential risks of participation in cancer screening programs can be serious and substantial, and the intended effect of increasing participation rates through the use of influences must be carefully weighed against the unintended effect of potentially circumventing participants' informed choice.

Thus, there is a need to find alternative ways to evaluate cancer screening programs besides participation rates.
One such alternative could be the rate of informed decisions made by potential screening participants."

This is even though, as the authors speculate, citizens might feel helpless upon learning about the multiple risks of screenings.

Other aspects in a person's decision-making to participate or not are also to be considered:
"Information material is not the only aspect of decision making, and this study does not examine external reasons for participants' choices, e.g., society's (health) culture, society's own and general attitudes toward health interventions, sense of duty, behavior, and opinions of significant others, barriers to intention and actual behavior, financial incentives of health professionals to increase screening uptake, etc. ...Research on external reasons can quantify the importance of decision making on information materials."
"The considerable effect of influences that are further reinforced by unawareness (of these influences) suggests that the application of these influences should be carefully considered for interventions where informed participation is intended."

The editors of this publication suggest that further research into the potential negative effects of these influences be considered, as the negative effects of these influence techniques on the population result in a weakening of trust in health authorities.

APPENDIX-PAMPHLETS

Cancer Rose Commentary

This publication, along with Rahbek's from 2019, is another reminder of the disastrous effects on people's health of the harmful influences that misleading and unbalanced information materials can cause.

It should always be kept in mind that materials for screenings are sent to populations that are doing well and have, a priori, no clinical complaints. The influence used to get them into potentially harmful screening processes is akin to imposing a potentially harmful health device without informing and deceiving people. This is ethically indefensible, yet done by health authorities.

The French INCa is cited in this 2019 study, as can be seen in a summary table of the study (https://cancer-rose.fr/wp-content/uploads/2021/04/nouveau-tableau.pdf; see highlighted parts); rather than devoting resources to pointing the finger at a growing controversy about the relevance of breast cancer screening, the institute would do well to devote time and resources to correcting its serious communication flaws that mislead French citizens on breast cancer screening.

Concerning breast cancer screening, we can put this study in relation to another one, a French one, published in 2016, showing that when women are given a little more objective information about breast cancer screening by mammography, they participate less.(https://cancer-rose.fr/en/2021/01/24/objective-information-and-less-acceptance-of-screening-by-women/ )

This study went relatively unnoticed, and for a good reason, since for the health authorities, only one criterion counts, that is the uptake, the misleading of women is a fully assumed scientific theme. (https://cancer-rose.fr/en/2020/12/17/manipulation-of-information/)

References of the study

Références

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4          The Danish Health Agency. Screening for cervical cancer – recommendations. [Danish] 2012. Available at: http://www.sst.dk/~/media/B1211EAFEDFB47C5822E883205F99B79.ashx (15 January 2020, date last accessed).

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