Cancer Rose, May 17, 2025
Three publications look at the relationship between false-positive events and the development of subsequent breast cancers.
All three papers suggest that women who have undergone several mammographic tests showing false-positive results are at increased risk of breast cancer.
What are false positives?
Along with overdiagnosis and radiation, false positives are one of the major drawbacks of mammographic screening. Another problem is interval cancer, i.e. a cancer that develops after a screening mammogram classified as normal; interval cancers are rather to be considered as screening failures.
A false alarm, or false positive, is defined as the suspicion of cancer, on a mammographic image, which will not be confirmed, but only after further complementary examinations.
In other words, it’s a non-cancer, which we only know after carrying out additional tests to the mammogram.
The additional tests required to rule out this suspicion can be costly, and sometimes even result in biopsies, which have become much more frequent since screening began. This situation is facilitated by the double reading carried out as part of the mammography screening procedure (a second radiologist examines the images taken in the first radiology office).
Experiencing a false alarm is often very stressful, as women sometimes have to wait several days or even weeks for confirmation of the absence of disease, particularly for biopsy results, which can take from a week to a month depending on the geographical region.
Its figures:
For every 1,000 women aged over 50 participating in screening for 20 years, there would be around 1,000 false alarms in France, leading to 150 to 200 unnecessary biopsies. (Revue Prescrire, February 2015/Tome 35 N°376)
But other assessments exist, giving higher figures. Here, for example, is an Australian assessment [1]. It gives a result over 25 years, a period corresponding to the overall duration of screening in a woman’s life if she undergoes screening from age 50 to 74.
Read the full article here: https://cancer-rose.fr/en/2021/10/19/what-is-the-difference-between-a-false-alarm-and-cancer-overdiagnosis/
Three studies on the false-positive/breast cancer relationship
Here we summarize the findings of three publications, by Blanch et al, published in PLOS One in 2014, by Castells et al, published in Radiology in 2016, and by Mao et al, published in JAMA oncology in 2023.
The first publication is a retrospective study of a cohort of 645,764 women screened in 32 radiology departments in five regions of Spain, who had mammography between January 1, 2000 and December 31, 2006 and were followed up until June 30, 2009 for interval cancer. These women underwent a total of 1,508,584 screening mammograms.
X.Castells’ study is a retrospective cohort study including 521,200 women aged 50 to 69 who were screened as part of the Spanish breast cancer screening program between 1994 and 2010, and who were observed until December 2012.
The latest publication is also a population-based and paired cohort study in Sweden from January 1, 1991 to March 31, 2020. It included 45,213 women who received a first false-positive mammography result between 1991 and 2017, and 452,130 female controls paired on age, calendar year for mammography and screening history (this group had no previous false-positive results).
The study also included 1,113 women who had a false-positive result and 11,130 controls paired with information on breast density from the Karolinska Mammography Project for Risk Prediction of Breast Cancer.
These are therefore large-scale cohort studies.
Blanch’s study shows that women’s premenopausal status, family history of breast cancer and previous benign breast biopsy were risk factors for interval cancer and cancer detected by screening.
Interval cancer, remember, is the cancer that occurs between two screening mammograms, i.e. after a normal mammogram and before the next scheduled mammogram. It’s a screening failure that can be explained by very rapid cancers with aggressive characteristics, which screening cannot anticipate, or occult cancers, missed at mammography.
For Blanch et al. the presence of a previous false-positive result was a risk factor for both screen-detected and interval cancer, but the association with interval cancer was more powerful.
Castelles et al. concluded that “women who had a false-positive result were at increased risk of breast cancer, particularly those with calcifications on mammography. Women who underwent multiple exams showing false-positive results and who experienced changes in mammographic characteristics over time had a strongly increased risk of breast cancer.”
Mao’s publication is perhaps the most interesting, bringing several detailed findings:
In this large population-based cohort study with extended follow-up, women who had a false-positive mammography result had an increased risk of subsequent breast cancer, persisting for up to 20 years, and the risk was highest in women aged 60 to 75.
In addition, the authors found a higher risk of large tumors (≥ 20 mm) and tumors on the breast on which a false-positive result had been established. An increased risk of breast cancer on the homolateral side (the same side) was highest during the first 4 years of follow-up, while a stable rate of increased long-term risk was observed for cancers arising on the contralateral breast.
However, the prognosis of breast cancer patients did not differ according to whether or not they had previously obtained false-positive results.
The authors write: “Given that false-positive results are frequent (i.e., approximately half [49.0%] of women in the U.S. and 20.0% of women in Europe will have at least one false-positive result after 10 screenings, our results highlight that they constitute a crucial public health problem.”
There is therefore a link between the false alarm events experienced by screened women and the subsequent risk of breast cancer.
Possible explanations
Only the most recent study cited, by Mao et al in Jama Oncology, attempts to provide an explanation.
According to the authors, the first mechanism that could explain the correlation between false positives and cancer is the possible co-existence of a small, as yet undetected lesion that could become malignant. This begs the question: should these women with false positives be considered for more intensive surgical procedures, or more intensive follow-up? It’s clear that we’re entering a spiral of invasive procedures and endless imaging, which could be harmful and anxiety-provoking for the women concerned.
A second explanation put forward is that the false-positive event is an indicator of a generally higher risk of breast cancer.
A hypothesis that has never been put forward in any of these studies, and that we could reasonably put forward, is that it is precisely our diagnostic procedures (repeated x-rays and irradiation, traumatic compression of the breast, biopsies that are themselves traumatic) that lead to alteration of the breast tissue and the development of invasive cancer.
The iatrogenicity of our procedures, although intrusive in character not negligible, is never mentioned, because it goes against the current of the innocuous image that we want to give them, and that is found in the messages of the health authorities as well as in the incitative Pink October campaigns, but very few informants.
This relationship between false alarms, which some women may experience several times in their screening career, and the subsequent occurrence of cancer, clearly raises the question of the aggressiveness of our diagnostic procedures, on both a physical and psychological level. The anxiety generated by these events is itself insufficiently studied, and its physical repercussions certainly underestimated.
In conclusion
In view of the very disappointing results of this screening, which is not delivering the expected benefits, it’s more than time to ask ourselves the right questions about our practices. Primum non nocere is the first pillar of our profession. More than ever, we must give priority to the choice of women, who must be aware of the pitfalls of mammographic screening (false positives, overdiagnosis, irradiation, interval cancers) and their consequences for their health.
Most women are under-informed about the drawbacks and failures of this health measure, to which they are strongly encouraged.
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What’s the difference between false alarm and overdiagnosis of cancer?
[1] Jolyn Hersch. Decision aid for breast cancer screening for women aged 50 and over. It’s your choice. (Australian brochure).
https://drive.google.com/file/d/16yDg3f71DytiDTNbNaJIHYPgNsx9x2N0/preview
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