Bilateral mastectomy cuts contralateral cancer risk, but not mortality

For women with unilateral breast cancer, bilateral mastectomy helps prevent the occurrence of a second cancer in the opposite breast, but this benefit does not translate to improved survival outcomes, as reported in a study.

In a propensity-score matched cohort of women who underwent a surgical procedure for unilateral breast cancer, the 20-year cumulative incidence rate of contralateral breast cancer (CBC) was much lower with bilateral mastectomy at 0.7 percent as opposed to 6.1 percent with unilateral mastectomy and 7.8 percent with lumpectomy. [JAMA Oncol 2024;doi:10.1001/jamaoncol.2024.2212]

Bilateral mastectomy conferred a significant protective effect on the risk of CBC when compared with lumpectomy (hazard ratio [HR], 0.12, 95 percent confidence interval [CI], 0.10–0.15; p<0.001)—an effect that was not observed with unilateral mastectomy (HR, 0.93, 95 percent CI, 0.87–1.01; p=0.08).

However, preventing CBC through surgery did not appear to improve survival rates, as the investigators noted. The 20-year cumulative incidence rate of breast cancer mortality was 16.3 percent with lumpectomy and 16.7 percent both with unilateral and bilateral mastectomy (bilateral mastectomy vs lumpectomy: HR, 0.99, 95 percent CI, 0.95–1.03, p=0.57; unilateral mastectomy vs lumpectomy: HR, 1.07, 95 percent CI, 1.02–1.11, p=0.003).

What’s more is that the occurrence of CBC increased the risk of death by fourfold (HR, 4.00, 95 percent CI, 3.52–4.54), based on an analysis of data from the lumpectomy and unilateral mastectomy groups combined. This risk, according to the investigators, was consistently elevated, regardless of the time elapsed since the initial diagnosis (first 5 years: HR, 3.89, 95 percent CI, 3.36–4.49; 5–10 years: HR, 4.12, 95 percent CI, 3.24–5.23; 10–15 years: HR, 4.48, 95 percent CI, 2.73–7.35).

Similar findings were observed in the California Cancer Registry, where CBCs, despite being smaller and less aggressive, were linked to poorer survival compared with unilateral breast cancers. In contrast, a Swedish cohort study suggested that the prognosis for CBC depended primarily on the timing of its onset, with earlier diagnoses linked to higher mortality rates. [Ann Surg Oncol 2023;30:6178-6187; J Clin Oncol 2007;25:4210-4216]

The investigators proposed that CBC might be similar to ipsilateral breast tumour recurrence (IBTR) in its effect on mortality, citing earlier research suggesting that IBTR is a marker of increased mortality but not the cause itself. [Lancet 1991;338:327-331]

“It is generally presumed that a CBC is a new primary tumour with the potential to metastasize. Our findings question this interpretation. If the increase in deaths after a CBC were due to metastasis of the second cancer, we would expect bilateral mastectomy to be beneficial,” they said. “[Furthermore,] early detection of CBC may not be an effective means of reducing mortality.”

For the study, the investigators used data from the Surveillance, Epidemiology, and End Results (SEER) Program registry and identified 661,270 women (mean age 58.7 years) who underwent a surgical procedure for unilateral breast cancer. After matching, 36,028 women in each of the lumpectomy, unilateral mastectomy, and bilateral mastectomy groups were included in the analyses.

The role of primary tumour

In an accompanying editorial, Drs Seema Ahsan Khan and Masha Kocherginsky from the Northwestern University in Chicago, Illinois, US, pointed to the possibility that the primary tumour, rather than the CBC, may be the main factor affecting survival. [JAMA Oncol 2024;doi:10.1001/jamaoncol.2024.2205]

“Because patients with breast cancer are diagnosed with the index primary tumour at a younger age (which increases the hazard of death) and are treated with older, less effective regimens, it is possible that the risk of death from CBC 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 post-treatment screening,” they wrote. “Consequently, surgical measures to prevent a second primary tumour do not extend survival.”

Khan and Kocherginsky emphasized the need for more detailed information, such as the interval to the development of distant disease and/or breast cancer death among the patients who develop a CBC, to be able to accurately assess the unique contributions of the primary and secondary breast cancers to survival. Such analyses are crucial for future research, they added.

“The education of patients as well as surgeons regarding the risks and benefits of bilateral mastectomy is a continuing and necessary endeavour given that existing interventions have not impacted the rates of contralateral phylactic mastectomy so far,” Khan and Kocherginsky stated. [Surgery 2024;175:677-686; Breast Cancer Res Treat 2023;199:119-126]