Age-related risk factors associated with primary contralateral breast cancer among younger women versus older women.

PURPOSE: Contralateral prophylactic mastectomy is increasing, despite unclear evidence of improving survival. To investigate the age-related risk factors for contralateral breast cancer (CBC).

METHODS: This study included 8716 patients diagnosed with non-metastatic unilateral invasive breast cancer between 1989 and 2008. Data on primary tumor size, node metastasis, grade and subtype using individual matching were used to adjust for differences in the primary tumor and treatment between younger and older age groups. CBC risk factors, CBC-free survival, and annual CBC risk were analyzed by age.

RESULTS: The younger group included 652 patients aged under 35 years, and the older group included 2608 women aged 35 years or older. The median time to CBC development was 6.1 years. CBC was detected in 6.6% of the women in the younger group and 2.5% of those in the older group. Multivariable analysis revealed a relative CBC risk of 2.48 in younger women compared to older women. The risk was significantly higher among women with human epidermal growth factor receptor 2 (HER2)-overexpressing tumors (hazard ratio [HR] 4.98), a family history of breast cancer (HR 7.79), and anti-hormone therapy (HR 3.46). In younger women with HER2-positive cancer, CBC occurrence peaked at 4.6 years after surgery, in those with hormone receptor-positive cancer, it peaked at 7.1 years after surgery, and in triple-negative disease cases, and it increased steadily over time.

CONCLUSIONS: After adjusting for primary breast tumor characteristics, patients < 35 years old had 2.5 times the risk of CBC development compared to the older women. CBC occurrence peaked within 5 years after primary breast cancer in younger women with the HER2-positive subtype and after 5 years in cases with the hormone receptor-positive subtype.