Contralateral Breast Cancer Risk Is Highly Overestimated

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When they see the risk, compared to the small benefit, patients start to change their decisions.

— Courtney Vito, MD

Breast cancer is highly unlikely to develop in the contralateral breast of women treated for primary breast cancer, yet many women continue to fear it and undergo prophylactic mastectomies.

“Regardless, the perceived risk of developing and dying from a contralateral breast cancer is highly overestimated, and this has been shown to be a driving force for aggressive surgical intervention,” said Lori Uyeno, MD, MPH. Dr. Uyeno and colleagues documented the incidence of contralateral breast cancer and its impact on overall survival after mastectomy for unilateral breast cancer. They presented their findings at the 2012 Breast Cancer Symposium.1

While contralateral breast cancer is the most common malignancy among breast cancer survivors, it is still incredibly rare. The risk figure usually quoted is 0.5% to 1.0% per year, said senior author Courtney Vito, MD. “But our study found the risk to be less than 1% at 51 months, and this is a very big difference,” she noted. Previous estimates may be higher because they originated during an era of less effective systemic therapies.

“We also found that when a contralateral breast cancer does occur, the only patients with a decrease in overall survival are those with a late-stage presentation (stage IIB/III/IV),” Dr. Vito added.

SEER Database Explored

Investigators used the Surveillance, Epidemiology and End Results (SEER) database of 109,411 women (median age, 54 years) with a primary diagnosis of unilateral breast cancer between 1998 and 2006. Patients underwent mastectomy, and about 10% also had a contralateral prophylactic mastectomy. The median follow-up was 51 months beyond the 1-year survival landmark.

The researchers divided the population into two similar groups: a test sample (n = 54,706) and a validation sample (n = 54,705). The patients’ primary tumors were mostly early stage (1–IIA, 63%), moderately or poorly differentiated (78%), and hormone receptor–positive (52%).

Low Incidence of Contralateral Cancer

After 51 months’ follow-up, contralateral breast cancer was diagnosed in 867 women (0.79%) at a median age of 61 years after a median observation time of about 2 years. The majority of these (66.2%) were detected at an early stage (0–IIA) and were moderately/poorly differentiated and estrogen receptor–positive.

The analysis showed a stage-specific effect on overall survival. “Only contralateral tumors that were stage IIB to IV increased mortality. Early-stage contralateral breast cancer had no effect on overall survival,” Dr. Uyeno reported.

The survival analysis was adjusted for primary tumor characteristics and treatment (including contralateral prophylactic mastectomy), patient demographics, and aging.

The adjusted hazard ratios were 3.04 for stage IIB/III/IV on the test sample (P < .0001) and 2.72 (P < .0001) on the validation sample. Stage I/I/IIA and tumors of unknown stage carried hazard ratios of 0.73 (P = .05) and 1.20 (P = 0.21), respectively.

Factors Linked to
Later-stage Tumors

“We then wanted to know which patients are most at risk. This is not information we generally have when we see the patient upfront and are making decisions about treatment,” Dr. Vito said.

The 247 cases of stage IIB/III/IV contralateral tumors were compared with 559 cases of stage 0/I/IIA tumors. The likelihood of having an advanced-stage contralateral tumor was greater when the patient’s original tumor was aggressive (extensive disease, large size, positive nodes) and when the patient was African American. Although African-American race is a risk factor nationwide (twofold risk compared to other races), it was much greater for patients living in the Southeast (sixfold risk compared to other races), which the investigators attributed to the possibility of reduced access to health care or cultural biases. Shorter time since the primary diagnosis was also associated with having a contralateral tumor of an advanced stage.

Efforts to improve survival after unilateral breast cancer should emphasize early detection of contralateral breast cancer, the researchers advised. Intensive monitoring should begin early after treatment of the primary tumor, and any barriers to follow-up should be addressed.

Dr. Vito said she counsels patients by “giving them the true numbers,” which come as a surprise to many women, she said. She also informs them that their risk for a surgical complication is at least 20%, for prophylactic mastectomy with reconstruction, according to series from Mayo Clinic and The University of Texas MD Anderson Cancer Center.

“When they see the risk, compared to the small benefit, patients start to change their decisions,” she said.

Cornelia Liedtke, MD, of the University of Muenster, Germany, commented on the study. “Patients tend to opt for more safe therapies because of their anxiety, but several analyses of contralateral breast cancer risk show that risk is only really increased in families with known mutations. I advise against prophylactic mastectomies unless the patient has a proven mutation,” she told The ASCO Post.

Disclosure: Drs. Uyeno, Vito, and Liedtke reported no potential conflicts of interest.


1. Uyeno L, Behrendt, Vito C: Contralateral breast cancer: Impact on survival after unilateral breast cancer is stage-dependent. 2012 Breast Cancer Symposium. Abstract 69. Presented September 14, 2012.