The results of a contemporary U.S. population–based cohort study published by Giannakeas et al in JAMA Oncology revealed that patients with unilateral breast cancer had an increased risk of breast cancer–related death after developing contralateral disease. Although the findings also showed a decreased risk of developing such a second malignancy in those who underwent bilateral mastectomy, the approach did not seem to affect mortality.

“It is generally presumed that a contralateral breast cancer is a new primary tumor with the potential to metastasize, [but] our findings question this interpretation,” the investigators remarked. “If the increase in deaths after a contralateral breast cancer were due to metastasis of the second cancer, we would expect bilateral mastectomy to be beneficial.”

Study Details

Using the Surveillance, Epidemiology, and End Results Program registry database, the investigators identified 661,270 patients (mean age = 58.7 years) who were diagnosed with stage 0 to III unilateral invasive breast cancer (n = 564,062; 85.3%) or ductal carcinoma in situ (n = 97,208; 14.7%) between 2000 and 2019. Nearly three-quarters of this population initially underwent breast-conserving surgery; the remaining patients had either a unilateral (23.4%) or bilateral (6.0%) mastectomy. A total of 90.7% of those who underwent bilateral mastectomy were successfully matched to establish three surgical cohorts of equal size (n = 36,028). After the cohorts were matched, similar demographic, clinical, and treatment variables, as well as similar propensity scores, were demonstrated across the cohorts.

The cohorts were followed for a 20-year period for contralateral breast cancer and breast cancer mortality. Data analysis was conducted between October 2023 and February 2024. 

Contralateral Breast Cancer Risk

During the 20-year follow-up, a total of 766 (2.1% of the cohort), 728 (2.0%), and 97 (0.3%) contralateral breast cancers were documented in the patients who underwent lumpectomy, unilateral mastectomy, and bilateral mastectomy, respectively. The median duration of time that had elapsed from the first primary tumor to contralateral breast cancer was 5.0 years (range = 2.3–8.6 years). The investigators reported an annual risk of contralateral breast cancer of 0.3% and a 20-year risk of 6.9% (95% confidence interval [CI] = 6.1%–7.9%) in the lumpectomy and unilateral mastectomy groups combined.

Breast Cancer Mortality

At 15 years, in the lumpectomy and unilateral mastectomy groups combined, the cumulative breast cancer mortality rate was 32.1% in patients who developed contralateral disease and 14.5% in those who did not; with contralateral disease being used as a time-dependent covariate, the hazard ratio for death from breast cancer was 4.00 (95% CI = 3.52–4.54). A total of 3,077 (8.5%), 3,269 (9.1%), and 3,062 (8.5%) patients who underwent lumpectomy, unilateral mastectomy, and bilateral mastectomy, respectively, experienced a breast cancer–related death. The 20-year rate of cumulative mortality from breast cancer was 16.3% after lumpectomy, 16.7% after unilateral mastectomy, and 16.7% after bilateral mastectomy.

“Based on these data, we expect that 69 in 1,000 women with breast cancer will develop a contralateral cancer within 20 years of diagnosis,” the investigators concluded. “After experiencing a contralateral breast cancer, the mortality rate increased fourfold from the time of contralateral cancer until the end of follow-up among the study cohort; however, the patients treated with bilateral mastectomy for unilateral breast cancer experienced similar mortality rates compared with those treated with unilateral surgery.”

Steven A. Narod, MD, of Women’s College Hospital, Toronto, is the corresponding author of the JAMA Oncology article.

Disclosure: The study was funded by the Peter Gilgan Centre for Women’s Cancers at Women’s College Hospital, the Canadian Cancer Society, and others. For full disclosures of the study authors, visit jamanetwork.com.