Bilateral mastectomy reduces risk for contralateral breast cancer, not mortality
Click Here to Manage Email Alerts
Key takeaways:
- Bilateral mastectomy reduced risk for contralateral breast cancer vs. other surgical options.
- Researchers observed no difference in mortality with bilateral mastectomy vs. lumpectomy or unilateral mastectomy.
Women with unilateral breast cancer who underwent bilateral mastectomy had a significantly lower risk for contralateral breast cancer than those who underwent other surgical procedures, results of a cohort study showed.
However, even though women who developed contralateral breast cancer were four times more likely to die than those who did not, overall mortality rates did not differ between those who had bilateral mastectomy, unilateral mastectomy or lumpectomy.
“This raises several key questions related to breast cancer itself: Is contralateral breast cancer truly a new independent cancer that can metastasize and cause death, or is it a marker of an increased risk [for] metastasis in that patient?” investigator Vasily Giannakeas, PhD, MPH, scientist and epidemiologist at Women’s College Hospital Research and Innovation Institute in Toronto, told Healio.
Background and methods
Many women diagnosed with unilateral breast cancer choose bilateral mastectomy because they consider it the best strategy to prevent another breast tumor, thereby reducing risk for death. The potential for breast reconstruction after bilateral mastectomy to produce a more symmetrical appearance also appeals to some, according to study background.
Prior research showed risk for contralateral breast cancer is approximately 0.4% per year for 20 years after initial breast cancer diagnosis. Studies showed removing an unaffected breast decreases incidence of second breast cancers; however, none have demonstrated reductions in breast cancer mortality.
Giannakeas and colleagues used the SEER 17 registry to investigate whether risk for contralateral breast cancer or breast cancer mortality differed based on whether patients underwent bilateral mastectomy, unilateral mastectomy or lumpectomy.
They identified 661,270 women (median age, 58.7 years) diagnosed with in situ or invasive breast cancer between 2000 and 2019.
Researchers narrowed the study population to three cohorts, each with 36,028 women who underwent lumpectomy, unilateral mastectomy or bilateral mastectomy. Investigators matched women in each cohort for age, year of diagnosis, histologic subtype, ER status and propensity score.
Results and next steps
Results showed significantly lower rates of contralateral breast cancer among women who underwent bilateral mastectomy (0.3%) than unilateral mastectomy (2%) or lumpectomy (2.1%).
The bilateral mastectomy cohort had a lower 20-year cumulative incidence of contralateral invasive breast cancer (0.7%; 95 CI, 0.5-0.9) than the unilateral mastectomy cohort (6.1%; 95% CI, 5.3-7) or lumpectomy cohort (7.8%; 95% CI, 6.3-9.5).
Women who underwent lumpectomy or unilateral mastectomy who developed contralateral breast cancer had a higher cumulative breast cancer mortality rate at 15 years than those who develop contralateral breast cancer (32.1% vs. 14.5%; HR = 4; 95% CI, 3.52-4.54).
However, the percentage of women who died of breast cancer did not differ significantly between those who underwent bilateral mastectomy (8.5%), unilateral mastectomy (9.07%) or lumpectomy (8.54%).
Additionally, the 20-year cumulative incidence of breast cancer death for women who underwent bilateral mastectomy (16.7%) did not differ significantly from those who had unilateral mastectomy (16.7%) or lumpectomy (16.3%).
“We believe this may be because contralateral breast cancer is correlated with the risk [for] latent metastasis, possibly originating from the original cancer, but is not causing metastasis,” Giannakeas said. “If this were the case, we would question the benefit of screening for contralateral breast cancer after the initial breast cancer diagnosis, as we would not expect a mortality benefit by catching the cancer earlier. Roughly one-third of patients with contralateral breast cancer were also treated with chemotherapy, and we would question the value of chemotherapy in this context. We hope to address these questions in future research.”
Giannakeas and colleagues acknowledged study limitations. They included lack of data on BRCA1/BRCA2 status or family history — which elevate risk for contralateral breast cancer — or endocrine therapy use. Researchers also lacked access to screening records, noteworthy because detection of contralateral cancers may have been due to intensified screening.
“Although lack of survival benefit [with contralateral prophylactic mastectomy] may seem counterintuitive, a tenable explanation is that the dominant hazard to survival derives from the index primary tumor rather than the contralateral breast cancer,” Seema Ahsan Khan, MD, Bluhm family professor of cancer research at Northwestern University Feinberg School of Medicine, and colleagues wrote in an accompanying editorial.
“Because patients with breast cancer are diagnosed with the index primary tumor at a younger age — which increases the hazard of death — and are treated with older, less effective regimens, it is possible that the risk [for] death from contralateral breast cancer is subsumed by the risk from the index cancer, particularly if second cancers are diagnosed at earlier stages in survivors who tend to be more adherent to posttreatment screening. Consequently, surgical measures to prevent a second primary tumor do not extend survival.”
However, the higher mortality risk observed among women who develop contralateral breast cancer is “the main disturbing finding,” Khan and colleagues wrote.
Patient preferences and their risk tolerance are equally important, they added.
“There are certainly those who, with a good understanding of the risks and quality-of-life problems associated with bilateral mastectomy with or without reconstruction, would prefer to avoid both the imaging experience of breast surveillance and the burden of undergoing treatment for a second breast cancer — even if highly likely to be cured,” they wrote. “The education of patients as well as surgeons regarding the risks and benefits of bilateral mastectomy is a continuing and necessary endeavor given that existing interventions have not impacted the rates of contralateral prophylactic mastectomy so far.”
References:
- Giannakeas V, et al. JAMA Oncol. 2024;doi:10.1001/jamaoncol.2024.2212.
- Khan SA, et al. JAMA Oncol. 2024;doi:10.1001/jamaoncol.2024.2205.
For more information:
Vasily Giannakeas, PhD, MPH, can be reached at vasily.giannakeas@mail.utoronto.ca.
Perspective
Back to Top
Lauren Kopicky, DO, FACS, FACOS, FSSO
Women diagnosed with breast cancer are faced with many decisions, including surgical choice. Many desire bilateral mastectomy to minimize the risk for another breast cancer. Surgically removing the contralateral breast inherently decreases the opportunity for contralateral breast cancer to arise, as mastectomy surgically removes nearly 100% of breast tissue. However, studies to date have not demonstrated a survival benefit among those who undergo contralateral prophylactic mastectomy.This study showed that bilateral mastectomy reduced the risk for contralateral breast cancer but did not reduce mortality risk. The authors comment that perhaps the larger impact on survival is from the initial cancer, not a subsequent cancer.
However, the study did not include important data such as family history or genetic mutation status that can impact surgical desires and subsequent contralateral breast cancer risk. More importantly, the study did not include endocrine therapy use, which confers protective risk reduction of the contralateral breast tissue.
It is somewhat surprising that although overall mortality rates did not differ between patient cohorts, the risk for breast cancer mortality increased fourfold after experiencing contralateral breast cancer. The authors note that the new contralateral breast cancer may be indicative of already present distant disease rather than a new primary source, and why preventive surgery may not be beneficial. There is an opportunity to further improve systemic therapy control of disease at primary diagnosis when local therapy such as surgery may not confer future benefit. We also must recognize the many advancements that have been made in systemic therapy treatments for breast cancer during this study time period which could influence outcomes.
Patient and clinician education of risks and benefits of contralateral prophylactic mastectomy is necessary, and shared decision-making should continue to be employed.
Collapse
Giannakeas V, et al. JAMA Oncol. 2024;doi:10.1001/jamaoncol.2024.2212.
Click Here to Manage Email Alerts