Bilateral mastectomy may not reduce mortality risk

Abstract

Although rates of contralateral prophylactic mastectomy and bilateral mastectomy are increasing among women with unilateral sporadic breast cancer, a new study reports that despite the procedure diminishing the risk of contralateral breast cancer, the patients experienced mortality rates similar to those of patients treated with lumpectomy or unilateral mastectomy.

The primary goal of the study, appearing in JAMA Oncology (doi:10.1001/jamaoncol.2024.2212), was to determine the 20-year cumulative risk of breast cancer mortality among women with stage 0–III unilateral breast cancer divided by each patient’s initial surgical procedures.

In an editorial accompanying the study, Seema A. Khan, MD, Bluhm Family Professor of Cancer Research at the Feinberg School of Medicine at Northwestern University in Chicago, Illinois, and Masha Kocherginsky, PhD, professor of biostatistics and director of the Quantitative Data Sciences Core at the Robert H. Lurie Comprehensive Cancer Center at Northwestern Medicine, wrote that although contralateral breast cancer is the most frequent second malignant tumor among women who have experienced a diagnosis of primary breast cancer, it is less frequent and less ominous than recurrence of the initial cancer. “Nevertheless,” they wrote, “for many patients with newly diagnosed unilateral breast cancer, it can be a prominent source of worry as they navigate their treatment decisions. This worry is accentuated among young patients and those with early-stage disease.”

The cohort study included patients from the Surveillance, Epidemiology, and End Results Program registry database. The researchers identified 661,270 eligible women with unilateral breast cancer diagnosed from 2000 to 2019. The average age of the patients was 58.7 years. In each treatment group, approximately 83% were White, just over 8% were Black, approximately 2% were East Asian, and 2% were Southeast Asian. The remainder of the patients were American Indian/Alaska Native, Pacific Islander, South Asian, or “unknown” (approximately 1% in each category).

The research team identified 564,062 cases of invasive breast cancer (85.3%) and 97,208 cases of ductal carcinoma in situ (14.7%). According to study author Steven A. Narod, MD, a professor in the Dalla Lana School of Public Health and the Department of Medicine at the University of Toronto, the researchers matched 90.7% of the patients with bilateral mastectomy into three surgical groups of equal size (36,028 women in each treatment group): lumpectomy, unilateral mastectomy, and bilateral mastectomy. All three groups were similar across demographic, clinical, and treatment variables and propensity scores. More than 70% of the cohort had undergone breast-conserving surgery, whereas 23.4% had undergone unilateral mastectomy, and 6.0% had undergone bilateral mastectomy.

Nearly two-thirds of the patients underwent radiotherapy, whereas approximately 37% received chemotherapy. The researchers reported that patients who underwent mastectomy tended to be younger than those who underwent lumpectomy and were more likely to have a lobular or mixed breast cancer. They also were more likely to have advanced clinical features, including a high tumor grade, larger size, and greater nodal involvement. Excluded from the study were bilateral mastectomy patients who received a diagnosis at a young age, were more likely to have unfavorable tumor characteristics, and likely received chemotherapy and radiotherapy.

According to Dr Narod, the researchers noted that although, in general, it is believed that a contralateral breast cancer is a new primary tumor with the potential to metastasize, their findings question this interpretation. “If the increase in deaths after a contralateral breast cancer was due to metastasis of the second cancer, we would expect bilateral mastectomy to be beneficial.”

Dr Narod adds, “The findings of this cohort study indicate that women with unilateral breast cancer should be advised that bilateral mastectomy greatly reduces the risk of a second cancer but does not affect mortality.”

Dr Monique Gary, DO, medical director of the Grand View Health Surgery/Penn Cancer Network in Sellersville, Pennsylvania, notes, “While it’s been known for some time in the surgical literature that bilateral mastectomy does not impact mortality, this study more clearly confirms that through large sample sizes, length of prospective follow-up, and thoughtful subgroup analysis.”

Dr Gary adds, “The importance of the study from my opinion lies in the contemporary population-based cohort, with longer follow-up than prior studies and more diversity represented than prior studies as well. Additionally, the proportion of patients who were stage 2 or 3 that are represented in this trial is valuable, as I have [seen] in over 10 years of practice that patients who are stage 2 or 3 relay concerns over confidence in the data about their specific risk for mortality and recurrence that impacts their mental health in survivorship and clinical surveillance.”

As for discussions with patients considering their options, Dr Gary says that the risk of contralateral breast cancer in women with unilateral primary breast cancer seems to remain constant, and this fact should not be avoided in conversation with patients. She adds that “mortalities not decreasing with bilateral mastectomy may reflect several factors, including the benefit of systemic therapy, tumor biology, and other comorbid factors not considered in this study.”

Dr Gary believes what clinicians and researchers should take away from this article is that the conversation is much more nuanced than simply the survival benefit of double mastectomy. “The reasons why patients pursue this surgical option over others relates to factors including, but not limited to, survival such as risk of recurrence, hereditary mutations, anxiety, and mammographically occult disease. All of these things should be taken into account when counseling patients regarding their surgical options.”