Breast cancer mortality in neighbouring European countries, with different levels of screening but similar access to treatment: trend analysis of WHO mortality database
Pr. Philippe Autier research director (International Prevention Research Institute), Mathieu Boniol senior statistician (Northern Ireland Cancer Registry, Belfast, Northern Ireland, UK; Department of Public Health, Norwegian University of Science and Technology, Trondheim, Norway) BMJ 2011;343:d4411 doi: 10.1136/bmj.d4411
Breast cancer mortality is compared (non-randomized comparative study) by matching countries in pairs, with the second country having introduced screening ten years later.
Northern Ireland (United Kingdom) 1990 / Republic of Ireland 2000 Sweden 1986 / Norway 1996 The Netherlands 1989 /Belgium and Flanders (Belgian region south of the Netherlands) 2001
The study concludes that breast cancer mortality declines similarly despite a significant difference in the year of introduction and participation in screening. Therefore, there is no link between screening activity and decreased mortality. Metastatic invasive cancer remains at the same rates. One of the best proofs that this screening is not effective.
Between 1989 and 2006, deaths from breast cancer decreased by 29% in Northern Ireland and by 26% in the Republic of Ireland; by 25% in the Netherlands and by 20% in Belgium and by 25% in Flanders; by 16% in Sweden and by 24% in Norway. The time trend and year of the downward inflexion was similar between Northern Ireland and the Republic of Ireland and between the Netherlands and Flanders. In Sweden, mortality rates have decreased steadily since 1972, with no downward inflexion until 2006. Countries of each pair had similar health care services and prevalence of risk factors for breast cancer mortality, but different implementation of mammography screening, with a gap of about 10-15 years.
Conclusion of the authors
The contrast between the time differences in implementation of mammography screening and the similarity in reductions in mortality between the country pairs suggest that screening did not play a direct part in the reductions in breast cancer mortality.
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.
Miller's study, published in 2014, is a randomized controlled trial, which corresponds to the highest quality criteria for population-based studies. Data are analyzed from groups whose subjects are randomly selected and then compared.
Here, the study involves 90,000 women, 45,000 with screening, 45,000 without screening. In fact the trials (NBSS 1 and 2 , National Breast screening studys ) were conducted in Canada in the 1980s with women screened annually for 5 years with annual mammography and clinical examination, and then followed up for 10 years. Here Miller proposes a re-evaluation after 25 years of follow-up for these two groups.
What are the conclusions?
1°-No difference in mortality between the two groups (mortality = number of deaths in relation to the total number of people screened).
2° Survival rates are identical, regardless of tumor stage(survival = number of deaths in relation to the number of cancers diagnosed)
3° 22% over-diagnosis
4° No difference between the two groups in the rate of fatal cancers.
More precisely, Miller finds 22% overdiagnosis, or 1 overdiagnosis (and thus overtreatment) for every 424 women who received mammography screening, for a zero benefit regarding the reduction of mortality from breast cancer.
The criticisms that have been made against Miller have been varied. First, it was argued that there could have been contamination of both groups because of the length of follow-up. In fact, some of the follow-ups stop after 7 to 10 years, which limits two drawbacks: some women in the non-screening group could still have had a mammogram one year or the other, while some women in the screening group could have "missed" a year of mammography. Waiting another 20 years would dilute or blur the results.
-First, the effect of non-compliance in the screening group and contamination in the non-screening group will rather lead to an underestimation of over-diagnosis.
-Secondly, the detractors of these studies argued that it would take a very long time to see the effectiveness of screening, as it would only be over a very long period of time that the danger of undetected cancers in the non-screened group would be seen. But here, even after 25 years, we still do not see this famous " dormant cancer " finally appearing, and no excess mortality of women who are not screened, perhaps because dormant cancer does not exist...
Miller was also criticized for not being representative of the French system, which screens every two years and begins at age 50 (whereas the Canadian trials targeted women aged 40-59). However, in the United States there was a debate about starting screening at 40 years of age.
It is clear that mammography was prematurely marketed to us as the ideal way to reduce the danger of cancer, particularly the killer one.
Ref : Miller AB, Wall C, Baines CJ, Sun P, To T, Narod SA. Twenty five years follow-up for breast cancer incidence and mortality of the Canadian National Breast Screening Study: randomised screening trial. The BMJ. 2014 Feb 11;348:g366
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.
Our collective has conducted a study (see news release) to verify the assertion of defenders of systematic screening that, after implementation of generalized screening, there would be a decrease of surgical practices. As this postulate has not been verified in France, we are relying on the PMSI (program for the medicalization of information systems) which records hospital stays in an exhaustive manner. The findings of the article to be published in the October issue of the journal Médecine, and in open access by following this link, show that the de-escalating of surgical procedures has not occurred:
Following the feedback and questions received from readers, we provide below some explanations to clarify the most frequently asked questions.
_____________
WHAT DOES THE STUDY SAY?
First of all, contrary to what our opponents say, the PMSI (program for the medicalization of information systems) is completely reliable. The rating errors that could occur here and there are not significant, in fact the quotation of mastectomy procedures does not change, the surgeons know them very well. If there were errors, they would be made in both directions. It should be noted in this regard that the figures put forward in studies other than ours on surgical procedures come from the same data source that surgeons use to report their data. In France, there is no other data base for epidemiological and statistical analyses due to the lack of a national cancer registry, an information system that exists in other countries. Any "cheating" on the quotations is highly visible, leads to severe sanctions by the national insurance fund against fraudsters, and is not credible, as the figures for total mastectomy procedures, which are more remunerative, would then be at the expense of those for partial mastectomies, but this is not the case, as all procedures are on the increase. Over the last four years, an average of 19,966 total mastectomies have been performed annually, compared with 18,351 annually in the four years preceding the generalization of organized screening (2000-2003), an increase of 8.8%.
Indeed, at the same time, the number of breast cancers diagnosed each year has increased. But, even in relation to this figure, the numbers don't add up.
In 2012, there are still practiced 4 total mastectomy procedures for 10 new cancers, as in the year 2000. And there are 15 partial mastectomy procedures for 10 new cancers compared to less than 13 in 2000.
In other words, the number of partial mastectomies is increasing faster than the incidence of invasive cancers. And the number of total mastectomies is increasing in parallel with the number of invasive breast cancers.
Under these circumstances, we should speak of a therapeutic escalation, not of a de-escalation.
-------------------------------------
Role of individual screening
Indeed, some patients have recourse to individual screening; the changes in breast cancer surgery that we have noted cannot be explained by the screening coverage that has remained stable (organized and individual screening added) in recent years.
On the other hand, while the lack of decrease in screening coverage may explain the lack of decrease in total mastectomies, it does not exonerate screening from any responsibility for the significant increase in the number of lumpectomies and partial mastectomies. This increase in the number of surgery procedures depends less on the number of women screened than on the sensitivity and specificity of the screening. With technical progress, double reading of mammograms, the switch to numerical mammography, and an improvement in the skills of radiologists, the sensitivity of mammography is steadily improving.
Therefore, it is rather the performance of screening in detecting increasingly small tumors that is responsible for the increase in the number of surgery procedures, as it leads to an increase in over-diagnosis, and consequently over-treatment.
Once again, the truth is that an unfulfilled promise was made to women, by announcing that the generalization of organized screening would result in "lighter" treatments.
_______
On the issue of total mastectomies
Click to enlarge
Some are satisfied with the decrease in the ratio of total mastectomies to partial mastectomies, or the ratio of total mastectomies to "total procedures". This apparent improvement is only due to the fact that partial mastectomies are increasing significantly compared to total mastectomies, which are also increasing, but to a lesser extent. However, this is not a good indicator of a de-escalating treatment. It would only be gratifying if the number of total mastectomies were reduced. Unfortunately, this is not the case.
The annual number of total mastectomies is not decreasing, neither the number of total mastectomies relative to the incidence of invasive cancers. How can these results be explained?
- The recommendations requesting that conservative surgery be favored whenever possible are perhaps not followed, in such a way that the intended benefit of screening is cancelled out.
- Or total mastectomies are performed for non-invasive tumors (notably CIS). These procedures represent an over-treatment associated with over-diagnosis. They would make lose the benefit of a general trend towards more conservative surgery for invasive cancers.
When the progression is considered without even considering the time scale, the general picture is one of an increasing trend, almost linear with a fairly high random variability.
We do not note any definite break in this linear trend and it would be impossible to locate the year when screening under invitation became generalized if the years on the x-axis were not indicated (2004). (This can be confirmed by a Davies test). Therefore, the trend in the annual number of total mastectomies has not been modified by the generalization of organized screening. No reduction in this rate can be claimed.
concerning total mastectomies
In the statistics of cancer incidence presented by INCA (French National institute of Cancer) site, only the figures concerning invasive cancers are reported, since cancers in situ (CIS) correspond to a separate entity, wrongly referred to as 'cancer' and not considered as 'real' cancer, and they are not taken into account.
It has been shown that surgery does not improve the prognosis of in situ cancers. This is why we have studied the ratio of the number of mastectomies to the incidence of invasive cancers and not invasive + cancers in situ.
The number of mastectomies (of all types) is greater than the number of new cancers. It therefore seems that in situ cancers are surgically operated on "in doubt", not only by partial mastectomy, but also sometimes by total mastectomy.
QUANTIFIED APPROACH :
Our observation is as follows: for every 1,000 invasive cancers, 213 more surgical operations were performed in 2012 compared to 2000 (a).
This is an excess of 10,387 interventions compared to what the incidence of invasive cancers indicates (b).
Another method of calculation can be used: in 2012 there are 71,916 interventions compared to 53,876 in 2000. There are therefore 18,040 additional interventions in 2012 (c). Of these 18,040 additional interventions, 7,663 can be explained by a rise in the incidence of invasive cancers (d).
The remaining 18,040-7,663 = 10,377 interventions cannot be explained by the rise in invasive cancers. To the nearest rounding errors, the 10,387 given by the other method of calculation are included.
Re-interventions have a limited part to play, since they account for just 3% of mastectomies. Our hypothesis is therefore that, for the most part, these 10,377 additional procedures are attributable to over-diagnosis leading to over-treatment.
a) (ratio of total acts in 2012 year x 1000) – (ratio of total acts in 2000 year x 1000) = (1.475 x 1000) - (1.262 x 1000) = 213
b) 213 x 2012 year incidence = 213 x 48,763 = 10,387
c) 71.916 - 53.876 = 18.040
d) 2012 year incidence x ratio acts/incidence year 2000 = number of acts related to the increase in incidence between year 2000 and year 2012 = (48,763 x 1.262) - 53,876 = 7,663
THE PART OF TOTAL MASTECTOMIES
Chart
There is a statistically significant decrease in the proportion of total mastectomies (p < 0.00001 in Spearman's rank correlation test). However, this decrease in the proportion of total mastectomies is not synonymous with a lighter surgical procedure. Indeed, as shown in the graph below, the decrease in the part of total mastectomies is not due to a decrease in total mastectomies but to a greater increase in partial mastectomies than in total mastectomies.
click on the image to enlarge :
CONCERNING THE AGING OF THE POPULATION
The increase in total mastectomies could be attributed to the increase and aging of the female population.
To test whether this hypothesis stands true, the annual number of mastectomies can be related to the annual number of new cases of breast cancer.
A mastectomy is performed because there is cancer and not because of being a woman.
In summary, two arguments allow us to claim that screening has not lead to a de-escalating in surgical procedure of breast cancer.
1. The trend towards an increase in the annual number of total mastectomies has not changed as a result of the generalization of the screening under invitation.
2. The number of total mastectomies per 1,000 new invasive breast cancers has not been decreased due to the generalization of screening under invitation.
Thanks to Dr Vincent Robert for all these analyses.
_____________
Our study was presented at the congress of the French Society of Breast Senology and Pathology, November 2017 in Lille.
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.
Autors : Steven A. Narod, MD, FRCPC1,2; Javaid Iqbal, MD1; Vasily Giannakeas, MPH1,2; Victoria Sopik, MSc1; Ping Sun, PhD1 JAMA Oncol. Published online August 20, 2015. doi:10.1001/jamaoncol.2015.2510
Treating ductal carcinoma in situ does not reduce breast cancer mortality, according to a recent observational study conducted by scientists at Women's College Hospital in Toronto and the University of Toronto, published in the journal "JAMA Oncology" in August, 2015.
Their conclusions are based on the largest recorded data ever analyzed, based on 18 U.S. registries including 100,000 women followed for 20 years with a diagnosis of ductal carcinoma in situ (DCIS).
It should be reminded that this is not a cancer, contrary to what its denomination might seem to indicate. It is a precancerous/adenomatous lesion that remains inside the mammary canal without invading the surrounding tissues. It is a lesion with a good prognosis, it corresponds to stage 0 of breast cancer. This type of precancerous lesion is diagnosed much more frequently since the widespread use of mammography. Some of these lesions are thought to be precursors of breast cancer. There is a risk for patients of local recurrence into either DCIS or infiltrating ductal carcinoma, which is potentially metastasizing and therefore life-threatening.
However, it is not yet known how to determine which DCIS will progress to infiltrating cancer and which will not. The patient usually is treated by a partial or total mastectomy, depending on the extent, and in any case a total mastectomy upon recurrence, followed by radiation therapy. Until now, this treatment was considered to have a preventive effect on the development of invasive cancer and was therefore beneficial for the patient's survival.
It now would seem that the treatment does not make a difference on survival and women with this condition and even heavily treated (sometimes by bilateral mastectomy) have the same probability of dying from breast cancer compared to women in the general population.
Prevention of recurrence with either radiotherapy or mastectomy did not prevent death from breast cancer.
Therefore, the treatment of precancerous lesions (DCIS) seems excessive in breast pathology. Moreover, in colonic pathology, precancerous lesions are never treated by radiotherapy.
According to Philippe Autier from the International Prevention Research Institute (IPRI), the situation is impossible to solve from a legal and practical point of view, especially since the diagnosis of DCIS can never be 100% certain until the surgical specimen is examined under the microscope. The problem, according to him, is inherent to mammography, especially digital mammography, which is too performant regarding the detection of small calcifications which are the most frequent radiological signs of these forms of precancerous lesions.
He believes that the problem of over-diagnosis, i.e. the detection of in situ or invasive cancers that would not have manifested themselves and would not have threatened patient's life, will not be eliminated as long as screening is based on this method.
This reasoning can be taken one step further: it seems quite pointless that current technology tends to invent increasingly sensitive detection methods that will serve for detecting precancerous lesions, of which many will never develop into cancer...
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.
Archie Bleyer, MD is Chair of the Institutional Review Board for the St. Charles Health System in Central Oregon and author/co-author of over 100_original_reports on clinical research that required CISR approval. He is also a clinical research professor.
Archie Bleyer, Professor of Clinical Research at the Oregon University of Science and Health published together with G.Welch, American cancer researcher in 2012 in the NEJM, an update on the effects of three decades of screening on breast cancer incidence from 1978 to 2008. The finding of the study was that the small reduction observed in advanced cancers was not proportional to the impressive increase (doubling) in the early stage cancers.
This year Archie Bleyer and Tony Miller, Professor Emeritus at the University of Toronto, who conducted a 25-year follow-up study of women from Canadian trials*, are studying the extent to which reduced breast cancer mortality is attributable to screening mammography. The authors examine the impact of screening mammography along three dimensions:
1) A chronology study, to see if the decline in breast cancer mortality would be correlated with the introduction of screening campaigns.
2) A magnitude study to examine whether the decline in mortality would be proportional to the rate of screening mammography.
3) And then, an analogy study, by studying the mortality reduction model for other forms of cancer, for which population screening is not conducted.
Regarding the first two axes of study, using data from eight European and North American countries, the authors find no correlation between the penetration of national screening and either the chronology or magnitude of national breast cancer mortality reduction.
(Indeed, since the 1990s, cancer mortality has been decreasing, but the reasons highlighted by other studies (Autier, Jorgensen, Kalager) are essentially therapeutic progress, and perhaps the effects of real prevention campaigns against risk factors are also being seen)
The magnitude of the mortality decline is even greater in the unscreened, younger women than in the screened population, as observed in the United States.
There is no correlation between the extent of screening and the magnitude of the decrease in cancer mortality in recent years.
Finally, the comparative study of 14 other types of cancers shows a similar decline in mortality rates for these cancers, even though these other cancers are not subject to screening campaigns.
*Twenty five year follow-up for breast cancer incidence and mortality of the Canadian National Breast Screening Study: randomised screening trial.
BMJ 2014; 348 doi: http://dx.doi.org/10.1136/bmj.g366 (Published 11 February 2014)
The authors conclude that the degree to which observed reductions in breast cancer mortality is attributable to screening mammography has become increasingly controversial.
A comparison of eight countries in Europe and North America shows no correlation between national screening penetration and either the chronology or magnitude of national breast cancer mortality reduction.
Evidence from the three different approaches and other additional observations do not support the hypothesis that mammography screening is a primary reason for breast cancer mortality reduction in Europe and North America.
Pr P. Autier conclusions: The contrast between the timing of breast cancer screening being implemented and the similarity in mortality reduction between the country pairs do not suggest that a large proportion of the mortality reduction can be attributed to mammography screening.
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.
Several international researchers complain about the fact that by making estimates of specific breast cancer mortality, the deaths resulting from heavy treatment that women undergo after cancer detection are largely underestimated. Assessing overall mortality would also allow the inclusion of deaths due to treatment.
In a synthesis, Gotsche, a former Cochrane Collaboration Investigator, an independent collective of Nordic researchers, writes :
I believe that if screening had been a drug, it would have been withdrawn from the market long ago. Many drugs are withdrawn although they benefit many patients, when serious harms are reported in rather few patients. The situation with mammography screening is the opposite: Very few, if any, will benefit, whereas many will be harmed. I therefore believe it is appropriate that a nationally appointed body in Switzerland has now recommended that mammography screening should be stopped because it is harmful.
Harms from breast cancer screening outweigh benefits if death caused by treatment is included
Over the past 30 years, the percentage of patients undergoing chemotherapy has increased from 20% to about 80% [1]. It is obvious that chemotherapy will expose the patient to effects on her survival, her comfort of life, expose her to other morbid effects [2] [3].
Anti-hormonal treatments (anti-aromatases or Tamoxifen) can cause thromboembolic complications and myocardial infarction. A risk of secondary endometrial cancer with Tamoxifen has been noted. [4] [5] Women may experience earlier signs of menopause, arthralgia, neuropathies and cognitive dysfunction, weight gain....
Radiotherapy can cause heart and lung complications. The risk of radiogenic coronaritis increases by 7.4% per gray received by the heart and is the cause of sometimes major cardiac problems and poor prognosis. [6] [7]
But also more serious diseases such as haemopathies [8] and radiation-induced lung or oesophageal cancers. [9]
For all these reasons, Michael Baum, Professor Emeritus of Surgery, a British oncologist specialized in the treatment of breast cancer, concludes: « harms from breast cancer screening outweigh benefits if death caused by treatment is included »
Authors' CONCLUSIONS - Adjuvant radiotherapy after simple mastectomy for early breast cancer results in a slight excess of late mortality due to other cancers and heart disease. The risk must be weighed against the higher risk of local recurrence in the absence of immediate postoperative radiotherapy. The balance must be assessed for each patient ....
The direct association between higher breast cancer mortality and the proportion of women who use the private health sector (and use screening more often) is in line with studies on the subject published in Brazil. This counter-intuitive conclusion of increased access to health care leading to increased mortality can be explained by "over-diagnosis", but the authors also point out that wealthier women are more exposed to potential carcinogens.
According to the authors, mammography screening did not have a positive effect: rather, it was associated with an increase in breast cancer mortality.
Treatment of breast cancer has many side effects that can result from surgical complications, radiation therapy, chemotherapy and anti-estrogen therapy. The authors note that the absence of a decrease in all-cause mortality between screened and unscreened populations has been attributed to the additional risks of treatment, which are more common in screened women. The increased risks of cardiovascular disease due to cardiac toxicity from anthracycline and trastuzumab treatment and radiation therapy are well documented, and the authors also cite radiation-induced cancer due to radiation from mammography and radiation therapy.
Jorgensen k. J. Breast cancer mortality in organised mammography screening in Denmark: comparative study. BMJ. 2010;340:c1241.
The study by Karsten Jorgensen (of the Nordic Cochrane Centre) identified all cases of breast cancer deaths in Denmark from 1971 to 2006 by year, region and five-year age groups (correlated with the total female population). Breast cancers occurring in women excluded from screening (women aged 35-54 and 75 and over) were included. Mortality was observed during the ten years where screening may have had an effect.
The result is surprising because the reduction in mortality appears to be greater in unscreened areas.
Breast cancer mortality in women aged 55-74 was reduced:
- by 1% in areas where screening was available,
- by 2% in areas where it did not exist,
- of 5% in women aged 35-54 years where screening was available,
- by 6% in the same age group in areas where it did not exist.
- No change in mortality was observed in women over 75 years of age.
The reduction in mortality recorded in Denmark is therefore not related to screening, and is even more pronounced in areas where screening is not practiced.
(Indeed, in many countries where screening has been introduced, there has been some reduction in mortality since the 1990s, i.e. before the introduction of screening programs and national campaigns. Therapeutic advances are one explanation for this state of affairs, perhaps also the real prevention campaigns (move more, eat less...), the elimination of hormonal substitutes treatments).
5° A meta-analysis: Positive and negative effects on long-term survival of radiotherapy for early breast cancer: an overview of randomized trials
Published May 20, 2000 DOI: https://doi.org/10.1016/S0140-6736(00)02263-7
The long-term effects of radiation therapy on mortality from breast cancer and other causes remain uncertain.
The methods
This is a meta-analysis of the 10- and 20-year outcomes of 40 "unconfounded" randomized trials* of radiotherapy for early breast cancer. It is a review of individual patient data on recurrence and cause specific mortality in 20,000 women, half of whom were node-positive.
The areas of radiotherapy generally included not only the chest wall but also the axillary, superclavicular and internal mammary lymph nodes.
* "Unconfounded randomised trials of radiotherapy": Only trials in which comparisons are "unfounded" are included. By definition, in unconfirmed clinical trials, a group differs from the others only in the treatment of interest.
Results
A reduction of about two-thirds in the local recurrence rate was observed in all trials, largely independent of patient type or type of radiation therapy. Therefore, to assess the effects on breast cancer mortality, the results of all trials were combined.
Breast cancer mortality was reduced but mortality from other causes, particularly cardiovascular, was increased. There was little effect on early deaths, but analyses of later deaths indicate that, on average after the second year, radiotherapy reduced annual breast cancer mortality rates by 13.2% but increased those from other causes by 21.2%. Nodal status, age and decade of follow-up strongly influenced the ratio of breast cancer mortality to other mortality.
Interpretation
Radiotherapyregimen capable of producing a two-thirds reduction in the local recurrence observed in these trials, but without long-term hazard, are likely to result in an absolute increase in survival at 20 years of about 2 to 4% (except for women at particularly low risk of local recurrence).
The average risk observed in these trials, however, would reduce this 20-year survival benefit in young women and would reverse the benefit in older women.
Bibliography
[1] Spielman, Khalil, Kinetics of tumor proliferation and efficacy of adjuvant chemotherapy. Study of mitotic activity. In: Breast cancer. Proceedings of the postgraduate French-language course in oncology. pp. 455-46
[2] Morgan g, WarD r, Barton m. The contribution of cytotoxic chemotherapy to 5-year survival in adult malignancies. Clinical Oncology. 2004 Dec;16(8):549- 60. Review.
[3]Cancer Drugs Approved on the Basis of a Surrogate End Point and Subsequent Overall SurvivalAn Analysis of 5 Years of US Food and Drug Administration Approvals
[4] Matthews A , Stanway S Long term adjuvant endocrine therapy and risk of cardiovascular disease in female breast cancer survivors: systematic review. BMJ. 2018 Oct 8;363:k3845.
[5] Fleming CA , Heneghan HM et al. Meta-analysis of the cumulative risk of endometrial malignancy and systematic review of endometrial surveillance in extended tamoxifen therapy. British Journal of Surgery. 2018 Aug;105(9):1098-1106.
[7]Sarah C. Darby, Ph.D., Marianne Ewertz et al. Risk of Ischemic Heart Disease in Women after Radiotherapy for Breast Cancer. The New England Journal of Medicine. 2013;368:987-998.
[8] Martin MG , JS Welch et al. Therapy related acute myeloid leukemia in breast cancer survivors, a population-based study. Breast Cancer Research and Treatment. 2009 Dec;118(3):593-8.
[9] Bois ME , Vogel V et al. Second malignant neoplasms: assessment and strategies for risk reduction. Journal of Clinical Oncology. 2012 Oct 20;30(30):3734-45.
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.
Authors : Harding C, Pompei F., Burmistrov D., et al. JAMA Intern Med. Published online July 06, 2015. doi:10.1001/jamainternmed.2015.3043
Objective
The objective of this study is to try to measure the benefits and harms of breast cancer screening during the year 2000 with a 10-year follow-up, as is carried out in the USA (women over 40 years of age), by comparing data from different counties regarding screening intensity, breast cancer diagnoses, breast cancer mortality, mastectomies. It was carried out on 16 million women and 53207 patients diagnosed with breast cancer.
Results
In counties where screening is more intensive, it is found:
- an increase in the number of breast cancer diagnoses (+16% for a 10% increase in participation in screening), mainly by tumours smaller than 2 cm.
- no reduction in breast cancer mortality
- no reduction in the number of advanced breast cancers
- no reduction in mastectomies.
(Click to enlarge)
These data are difficult to link with effective mammography screening, where the increase in small breast cancers must be accompanied by a decrease in advanced cancers and breast cancer mortality.
The most likely explanation is that the numerous small cancers detected by systematic mammography are essentially over-diagnoses, i.e. tumors that are not or are very slowly progressive, or spontaneously regressive, whose diagnosis is useless and harmful, whereas screening would not (or rarely) allow a better prognosis for progressive cancers.
This is a study whose level of evidence is limited by its nature (individual data are not known), but supported by its large size (16 million women), as well as by the additional analyses carried out by the authors.
The trials on which the organized screening of breast cancer by mammography is based are old, and their conclusions (fragile, moreover, because of certain biases and inconsistencies that have since been revealed [1]) cannot be applied to the current situation.
Conclusion
In conclusion, the study confirms the lack of effectiveness of breast cancer screening as found in other studies, including in Europe. [2], [3], [4],[5],[6],[7]
[2] Autier P., Boniol M., Gavin A., Vatten L. J. « Breast cancer mortality in neighbouring European countries with different levels of screening but similar access to treatment: trend analysis of WHO mortality database » BMJ 2011;343:d4411 http://www.bmj.com/content/343/bmj.d4411
[3] Autier P., Boniol M., Middleton R., et al. « Advanced breast cancer incidence following poupulation-based mammographic screening » Annals of Oncology 22 : 1726-1735, 2011 http://annonc.oxfordjournals.org/content/22/8/1726.long
[4] Jørgensen K. J., Zahl P.-H., Gøtzsche P. C. «Breast cancer mortality in organised mammography screening in Denmark: comparative study » BMJ 2010;340:c1241 http://www.bmj.com/content/340/bmj.c1241
[5] Jørgensen K. J., Gøtzsche P. C. « Overdiagnosis in publicly organised mammography screening programmes: systematic review of incidence trends » BMJ 2009;339:b2587 http://www.bmj.com/content/339/bmj.b2587
[6] Junod B., Zahl P.-H., Kaplan R. M., et al. « An investigation of the apparent breast cancer epidemic in France: screening and incidence trends in birth cohorts » BMC Cancer 2011, 11:401 doi:10.1186/1471-2407-11-401, adaptation en français sur http://www.formindep.org/Investigation-de-l-epidemie,487.html
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.
Yet another study, other than that of Prof. Autier, recently published in the BMJ* (see at the bottom of the article) reinforces the fear that among the women treated after detection of a cancerous lesion through screening, and therefore in absence of symptoms, a certain number (one out of two in the Autier study from the Netherlands) would never have suffered from it during their lifetime; the removal of a breast, unnecessary radiotherapy or tiring chemotherapy could have been avoided for these women.
Authors :
Elizabeth T. Thomas1 , Chris Del Mar 2 , Paul Glasziou 2 , Gordon Wright 1 , Alexandra Barratt 3 and Katy J. L. Bell 2,3
1 Faculty of Health Sciences and Medicine, Bond University, Robina, QLD 4229, Australia.
2 Centre for Research in Evidence-based Practice, Faculty of Health Sciences and Medicine, Bond University, Robina, QLD 4229, Australia.
3 Sydney School of Public Health, Sydney Medical School, Edward Ford Building (A27), University of Sydney, Fisher Road, Sydney, NSW 2006, Australia
Background
Autopsy studies have demonstrated the frequency of occult cancers in the population, but the evaluations performed by these primary studies involved a small number of deceased patients each time.
Results
The authors included 13 studies from 10 different countries, over 6 decades (from 1948 to 2010), comprising 2363 autopsies with 99 cases of so-called "incidentalomas" (cancers of incidental finding), or precancerous lesions.
When the histological examination was more comprehensive (on more than 20 histological sections), there were more incidentalomas detected, mostly in situ cancers and atypical hyperplasias, but few invasive cancers.
This means that the more histological research is carried out on deceased persons, the more latent cancers are found, with an average frequency of this "accidental" cancer of around 19.5% (0.85% invasive cancer + 8.9% in situ cancer + 9.8% atypical hyperplasia).
Therefore, the more we seek and the more we find, which raises questions about the development of more and more efficient investigative techniques that are going to discover more and more of these lesions abusively. The consequences of the resulting over-treatments are to be considered even more seriously in older women because of the increased susceptibility to adverse effects of treatments in this population.
Conclusion
Systematic review in ten countries over more than six decades has found that incidental discovery of occult, in situ cancers or precancerous lesions is very common in women, in whom breast disease was not known during their lifetime.
It appears that cancerous or pre-cancerous lesions are discovered incidentally in 2 out of 10 women during these autopsies. The authors estimate that 40% of invasive cancers detected by systematic mammography and 24% of all invasive cancers would be over-diagnosed.
This high frequency of undetected cancers, in situ and atypical hyperplasias in these autopsy studies, suggests that screening programs should be more cautious in promoting detection methods with increased sensitivity, thus increasing these unnecessary diagnoses.
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.
How women perceive the data from screening, influenced by optimistic slogans and presentations, versus reality:
When the authors of the report of the Swiss Medical Board (a Swiss medical commission independent from government authorities) evaluated the relevance of the mammographic screening program for breast cancer (see article), (PDF Article) they looked at one data that had been studied in several countries (4), namely how women perceive the benefits of screening according to what has been communicated about it and the information they have received, and that have made their beliefs on the subject. The authors have presented a comparative table, with data gathered from the perception survey of American women in Part A, and real, objective data from the most probable scenarios, observed from the most convincing and among the most reliable studies in Part B (1-3) The authors were astonished by the significant discrepancy between women's beliefs about the benefits of screening and reality.
The projected number of women in their fifties who would survive, develop breast cancer and die from other causes while doing regularly screening over 10 years, was compared to the expected number of women who would survive, develop breast cancer or die from other causes, and not doing screening.
71.5% of these interviewed American women estimated that screening mammography reduced by half the risk of dying from breast cancer, and 72.1% believed that at least 80 deaths would be prevented for every 1,000 women invited for screening. The presentation of mortality risk reduction as a percentage embellishes the data. A 20% reduction in mortality (a figure found on public institution websites, women committees websites and in the information brochures distributed to women) does not mean that 20 out of every 100 women will die of breast cancer, but that only one less woman will die of it in the best case (and without considering the other, more numerous women screened, who will at the same time suffer from overdiagnosis and false alarms). The relative risk reduction of 20% corresponds to a comparison between the screened and unscreened groups. If, for example, 5 out of 1000 unscreened women die and 4 out of 1000 screened women die of breast cancer, the relative risk reduction resulting from the comparison of these two groups corresponds to this 20% ((5-4)/5=0.2 ), but in absolute terms it is only one woman who is saved. The data that the authors have collected for the Swiss population show also these optimistic expectations in a similar way.
The authors legitimately ask the question, how can women make an informed decision if the benefits of the screening program are overestimated? We asked ourselves the same question…and tried to answer it (see the brochure on the home page).
REFERENCES
1-Gotzsche PC, Jorgensen KJ. Screening for breast cancer with mammography. Cochrane Database Syst Rev 2013;6:CD001877-CD001877 Medline
2-Independent UK Panel on Breast Cancer ScreeningThe benefits and harms of breast cancer screening: an independent review. Lancet 2012;380:1778-1786 Medline
3-Miller AB, Wall C, Baines CJ, Sun P, To T, Narod SA. Twenty five year follow-up for breast cancer incidence and mortality of the Canadian National Breast Screening Study: randomised screening trial. BMJ 2014;348:g366-g366 Medline
4-Domenighetti G, D'Avanzo B, Egger M, et al. Women's perception of the benefits of mammography screening: population-based survey in four countries. Int J Epidemiol2003;32:816-821 Medline
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.
1. Section of Medical Oncology and hematology, University of Manitoba, Winnipeg, Manitoba, Canada
2. Research Institute of Oncology and Hematology, CancerCare Manitoba, Winnipeg, Manitoba, Canada
3. Cancer Screening program, CancerCare Manitoba, Winnipeg, Manitoba, Canada
4. Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Manitoba, Canada
5. Department of Community Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
Study objectives
« Evaluate the differences and similarities in characteristics and outcomes of breast cancers detected by mammographic screening compared to those detected between screening mammograms (interval cancers) in women participating in a population-based screening program »
Results of study
« In this cohort study of 69 025 women, interval breast cancers accounted for one-fourth of breast cancers in routinely screened women, were 6 times more likely to be grade III, and had 3.5 times increased hazards of breast cancer death compared with screen-detected cancers. »
Meaning
« Heterogeneity in breast cancer defies assumptions necessary for screening mammography in its current form to be maximally effective; strategies beyond routine screening mammography are needed to prevent, detect, and avert deaths from the more lethal interval breast cancers. »
Explanation :
Breast cancer does not follow the linear and mechanistic pattern assumed.
Natural history of cancer
The theory that cancer can be treated because it has been diagnosed when very small, seems to be intuitive, flattering, yet contrary to observation (clinical cases, autopsy studies). In the case of breast cancer screening, we also have to deal with the true belief which is underpinned by frequently repeated mantra such as "cancer can knock on every door," "the smaller the better," "prevention is cure." Is it true?
These clichés are based on a linear and mechanistic theory of natural history of cancer. Cancer is believed to evolve in an ineluctable way, according to a set pattern. A cancer cell, then a nodule, then a large nodule, then a local invasion, followed by metastases and inevitable death.
But reality is a lot more complex than that.
Small does not mean caught on time, it can simply be a silent cancer, little or never progressive, even regressive, that would have been diagnosed during screening but would never have been killing the woman.
Or, on the contrary, at the time of diagnosis it may already be metastatic, while small or sometimes even occult.
Large does not mean being caught too late, but simply the case of a rapidly growing cancer that, due to its fast development, would be large at the time of diagnosis. In general, it is true that these lesions are on average more aggressive, but this is not absolute. In older women who give up to consult, large cancers may have significant local consequences, such as skin erosions or severe retractions, but without having spread to the distance.
We see these cases in consultation every day, which we consider "paradoxical".
Not all the cancers evolve and most of them do not become metastatic, they can stagnate, regress, grow so slowly that the patient will die of something else before.
The authors come here to this conclusion: due to intrinsically slow growth, many of the small tumors detected excessively by screening have a very good prognosis, which means that they are not expected to become large tumors and are inherently favorable. They are the ones that cause overdiagnosis, which results directly from the activity of screening. They will not develop enough to become dangerous.
In contrast, large tumors, responsible for deaths and most often with immediate poor prognosis, escape unfortunately to mammographic detection, due to too rapid kinetic growth.
A previous similar study:
Sarauj Niraula et al. cohort research remembers us a very important and comprehensive study of Pr. Autier. Mammographic screening: a major issue in medicine
One chapter in this major analysis deals with the specificity of cancers found through mammographic screening, which are less severe and with better prognosis cancers; they are those "selected" through screening, half of which would be overdiagnostics, meaning needless diagnostics that would never have killed the woman.
Mammography indicates for example a high sensitivity for ductal carcinoma in situ cancers, and a relatively low sensitivity for certain aggressive cancers such as 'triple negative' breast cancer.
Mammography basically does not detect lobular carcinoma in situ or invasive cancers that represent 8-14% of all breast cancers. Lobular carcinomas penetrate the tissues without forming masses, making it impossible to identify them by mammography.
Invasive cancers detected by mammography have the clinical and pathological characteristics of less aggressive tumors compared to interval cancers, i.e. those that progress rapidly between two mammograms, escape detection and have aggressive characteristics.
In addition, after analyzing the characteristics of these tumors and the expansion of the disease at the time of diagnosis, the risk of dying from a screened breast cancer is lower than the risk of dying from an interval cancer.
The authors of this study also reported that the interval cancers were similar to breast cancers diagnosed in the absence of screening.
So, if interval cancers are similar to cancers diagnosed in the absence of any screening, and if cancers screened have on average a better prognosis than interval cancers, it logically follows that a proportion of cancers screened are non-lethal cancers that would never have been symptomatic during a woman's lifetime.
These lesions have the microscopic morphological characteristics of cancer, but would have remained asymptomatic throughout the woman's life if the screening had not occurred.
The authors add: "Cancer overdiagnosis refers to cancer excess in women invited to screen divided by the total number of cancers which would be diagnosed in the absence of screening (on a population of the same profile, with the same age group, without screening)."
"If overdiagnosis is calculated using the number of screened cancers as a denominator, then for 100 screened breast cancers, 30 to 50 will be overdiagnosed."
Our conclusion
Breast cancer is clearly shown to be a very heterogeneous disease; indolent cancers with the probability of better healing outcomes are easily detected by mammography screening, abusively increasing the overall incidence of breast cancer, making believe that there are always more, but it is this mechanism of public health that produces them.
And they also give the illusion that the cure rate is improving because their host will never have been killed by all these cancers.
On the other hand, many of the aggressive and lethal types of breast cancers remain unnoticed or develop in the mammography interval.
Other strategies, particularly a deeper understanding of the natural history of cancer, which includes referring to fundamental studies on cancer growth models, are needed to improve the rate of breast cancer death and overall population mortality.
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.
