Background: Radiotherapy is used to treat many adolescent and young adult (AYA) and childhood cancer patients and is a risk factor for secondary breast cancer. While premenopausal breast cancer is inherently more aggressive, no studies to date have evaluated the characteristics and breast cancer-specific survival (BCSS) of premenopausal secondary breast cancer after radiotherapy in AYA and childhood cancer survivors.Methods: Female patients ages 12 to 50 diagnosed with primary breast cancer from 1988 to 2014 (n ¼ 107,751) were obtained from the California Cancer Registry and compared with similar aged patients with secondary breast cancer who were treated with radiotherapy for their primary tumor (n ¼ 1,147) from ages 12 to 39. We examined BCSS using multivariable Cox proportional hazards regression.Results: The secondary breast cancer cohort was more likely to be Hispanic or Black, be 35 to 45 years of age, have earlier stage tumors, be higher grade, have no lymph node involvement, and be hormone receptor negative. All women showed worse BCSS for large tumor size, lymph node involvement, and hormone receptor-negative status. BCSS was worse for women with secondary breast cancer both overall (hazard ratio, 1.98; 95% confidence interval, 1.77-2.23) and in all subgroups considered. Associations were most pronounced in Hispanics, Asian/Pacific Islanders, and younger women, as well as those with earlier stage, lymph node-negative, and hormone receptor-positive disease.Conclusions: BCSS is significantly decreased among all survivors of childhood and AYA cancer treated with radiotherapy that develop a secondary breast cancer, including women with good prognostic features.Impact: Therefore, we may need to consider alternative and even more aggressive treatment in what were considered low-risk populations previously.

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