A Strategy to Lower Breast Cancer Risk in BRCA Mutation Carriers: Preventive Surgery
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Does Risk-Reducing Mastectomy Lower Breast Cancer and Mortality Risks?
Breast cancer is the most common cancer among women worldwide. Inherited genetic factors, particularly BRCA1 and BRCA2 genetic variants, play an important role in its development. Approximately 10-15% of all breast cancers result from certain inherited cancer-related genetic changes, particularly in BRCA1-2. Lifetime breast cancer risk is substantially increased for BRCA1-2 carriers. Potentially lifesaving measures for these at-risk individuals include risk-reducing mastectomy (preventive breast surgery). Detailed information about the actual effects and outcomes of this radical step can guide patients and healthcare professionals in making decisions.
The image below has two sections comparing inherited genetic mutations associated with breast, ovarian, and endometrial (uterine) cancers, and the incidence (number of new cases) and mortality rates of these cancers.
Panel A: The upper section contains a Venn diagram showing genetic mutations associated with three different cancer types. Mutations that increase the risk of each cancer type are indicated.
- Blue Area (Left): Shows genetic mutations associated with breast cancer (for example, BARD1, MRE11A, CDH1, ATM, and CHEK2).
- Yellow Area (Right): Shows genetic mutations associated with ovarian cancer (for example, BRCA1, BRCA2, RAD51C, and RAD51D).
- Pink Area (Bottom): Shows genetic mutations associated with endometrial cancer.
- Overlapping Areas: These sections show genetic mutations associated with more than one cancer type. For example, BRCA1 and BRCA2 increase the risks of both breast and ovarian cancer.
Panel B: The lower section contains a bar chart showing incidence (blue) and mortality rates (red) for various cancer types. The number of new cases (incidence) and the mortality rate per 100000 people are compared for each cancer type.
The chart shows a particularly high incidence (number of new cases) of breast cancer, but a relatively low mortality rate compared with other cancers. Incidence and mortality rates differ across the other cancer types, and some cancers (such as thyroid and corpus uteri cancers) have very low mortality rates.
The Current Study
Research published by Metcalfe and colleagues on 29 November 2023 in the British Journal of Cancer provides valuable evidence that risk-reducing mastectomy lowers both the risk of a breast cancer diagnosis and the likelihood of death among women with BRCA1 or BRCA2 gene variants (genetic changes). The study examines the potential benefits of preventive mastectomy in people with genetic risk in detail and aims to give patients more information and support when making this difficult decision.
Study Details
Women with inherited BRCA1 or BRCA2 genetic variants have a lifetime breast cancer risk of 80%. Research has shown that risk-reducing mastectomy, one of the most effective methods of preventing breast cancer in women with this risk profile, can reduce breast cancer risk by 90%. However, in Canada, for example, only 30% of women with pathogenic variants undergo this surgery.
To date, however, only one previous study has quantitatively examined risk-reducing mastectomy's effect on mortality rates and its benefits in this patient group.
Deciding whether to undergo risk-reducing mastectomy is often difficult and complex for patients. Having as much information as possible is key, because it enables patients to make informed choices about their own treatment pathways. As cancer specialists, we should support our patients at every stage of this important decision and provide strong, clear evidence to inform their choices. This approach helps patients become the authors of their own health stories and empowers them to manage their treatment more effectively.
Study Methods and Results
In this quasi-randomized study, researchers examined how risk-reducing mastectomy might affect mortality in 1,600 women with pathogenic BRCA1 or BRCA2 variants who had not been diagnosed with breast cancer. Approximately 50% had undergone risk-reducing mastectomy.
After 6 years of follow-up, researchers found 20 breast cancer cases and two deaths in the risk-reducing mastectomy group, compared with 100 breast cancer cases and seven deaths in the control group.
Risk-reducing mastectomy also reduced breast cancer risk by 80%, and the risk of dying from breast cancer 15 years after the procedure was less than 1%.
The chart below compares cumulative breast cancer incidence (the proportion of new cancer cases) over the years between patients who underwent risk-reducing mastectomy and the control group. The red line represents controls, while the gray line represents the mastectomy group.
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Control Group (Red Line): In the control group, 100 breast cancer events (cases) occurred among 827 patients. These patients had not undergone risk-reducing mastectomy. The chart shows increasing cumulative cancer incidence in this group over time.
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RRM Group (Gray Line): In the mastectomy group, 20 breast cancer events occurred among 827 patients. These patients underwent risk-reducing mastectomy to prevent breast cancer. The chart shows that their cumulative cancer incidence over time was much lower than that of controls.
The expression “p < 0.0001” on the chart is a p-value, the result of a statistical test, indicating a highly significant difference in incidence rates between the two groups (because the p-value is smaller than 0.0001). This means that the observed difference is not the result of random variation and that the groups differ significantly in breast cancer incidence.
Conclusion
“Although there was no significant difference in deaths between the two groups in this study, we know that risk-reducing mastectomy substantially reduces the risk of developing breast cancer,” emphasized the lead researcher, Dr. Metcalfe.
The researchers stated that following participants for longer could provide more evidence for assessing mortality after risk-reducing mastectomy and clarifying the benefits associated with this type of surgery.
Today, we have powerful tools such as magnetic resonance imaging (MRI), an effective method of breast cancer screening. Thus, although surgery is an available alternative, it is not recommended as standard practice. Detailed studies of the long-term health and risk factors of patients who undergo risk-reducing mastectomy will help define this approach's future role. With current knowledge, choosing this surgery remains a decision based entirely on individual health circumstances and risk assessments. New scientific evidence may require updates to our existing preventive-surgery guidelines in the future.
Sources
2. Bertozzi, S.; Londero, A.P.; Xholli, A.; Azioni, G.; Di Vora, R.; Paudice, M.; Bucimazza, I.; Cedolini, C.; Cagnacci, A. Risk-Reducing Breast and Gynecological Surgery for BRCA Mutation Carriers: A Narrative Review. J. Clin. Med. 2023, 12, 1422. https://doi.org/10.3390/jcm12041422
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