A Breast Cancer Paradox: Study Finds Cancer in a Second Breast Increases Risk of Death, but a Double Mastectomy to Prevent Cancer in Second Breast Makes No Mortality Difference

Women newly diagnosed with breast cancer are opting for bilateral mastectomy more frequently. The surgery should help prevent cancer in the other breast, many intuitively believe, reducing their anxiety about that possibility. Bilateral mastectomy is also preferred by some because they believe it will result in more symmetrical appearance after breast reconstruction.

Women who get a bilateral mastectomy usually are not choosing the procedure due to medical advice. Multiple studies have found that removing the second breast does not improve survival rates.

A new study, believed to be the largest and longest running of its kind, reaffirmed those findings. But it also revealed a paradox.

Women with cancer in one breast, known as unilateral breast cancer, who chose a procedure limited to that breast — either a lumpectomy or mastectomy — were significantly more likely to later develop cancer in the other breast, known as a contralateral breast cancer, compared with women who opted for bilateral mastectomy. But those who chose to be treated with bilateral mastectomy gained no additional protection against death: Their survival rate was the same as group that was treated with more limited surgery.

Steven A. Narod, M.D.

Corresponding author Steven A. Narod, M.D., a professor in the Department of Medicine at the University of Toronto, a physician at Women’s College Hospital and a senior scientist at Women’s College Research Institute, where he leads the Familial Breast Cancer Research Unit, and his colleagues identified women diagnosed with unilateral breast cancer between 2000 and 2019 in the Surveillance, Epidemiology, and End Results (SEER) Program registry database.

They divided them into three matched treatment groups of approximately 36,000 each – lumpectomy, unilateral mastectomy and bilateral mastectomy – and followed them for up to 20 years, ending in November 2021. The results were published last week in JAMA Oncology.

Cumulative breast cancer mortality was four times greater for women with contralateral breast cancer 15 years after developing it compared with those who did not develop it. Yet overall breast cancer mortality was nearly indistinguishable among the three treatment groups: 8.54% in the lumpectomy group, 9.07% in the unilateral mastectomy group and 8.50% in the bilateral mastectomy group.

Although the study could not determine the reason for the seemingly contradictory findings, the authors noted that contralateral breast cancer is generally assumed to be a new primary tumor with the potential to metastasize. If the increase in deaths in such cases were due to metastasis of the second cancer, the authors wrote, “we would expect bilateral mastectomy to be beneficial.”

Seema Khan, M.D., M.S.

In an accompanying editorial, Seema Khan, M.D., M.S., a professor of at Northwestern University Feinberg School of Medicine, wrote that a “tenable” explanation is that the higher risk of death after contralateral breast cancer may actually be due to the original tumor. Primary breast cancer tends to be diagnosed at a younger age, which increases the overall risk of death, and treated with older, less effective regimens.

In other words, contralateral breast cancer might actually be a metastasis of the original cancer in the other breast.

Still, Khan wrote that caution is needed when interpreting the analysis for several reasons. She also noted that, despite the study’s successful matching, some higher-risk patients who had undergone a bilateral mastectomy could not be matched. As a result of that omission, the findings should perhaps be generalized only to women with lower-risk disease, Khan suggested.