Although radiotherapy is integral to the multidisciplinary therapy used in the treatment of common childhood and adolescent and young adult (AYA) cancers, including Hodgkin lymphomas, sarcomas, and breast cancer, the treatment is a strong risk factor for a secondary breast malignancy, especially when used to treat AYA cancers. A study investigating the breast cancer–specific survival of premenopausal secondary breast cancer after radiotherapy in survivors of AYA and childhood cancer has found that breast cancer–specific survival is significantly decreased among these survivors, including women with good prognostic features, such as a diagnosis of early-stage breast cancer, low histologic grade, and estrogen receptor positivity.

Results from the study by Sauder et al suggest that alternative and more aggressive treatment may need to be considered in women previously thought to be at low risk for secondary breast cancer. The study is published in Cancer Epidemiology, Biomarkers & Prevention.

Study Methodology

To better understand how radiation used to treat primary malignancies affects the clinical characteristics of secondary breast cancers diagnosed in premenopausal women, the researchers analyzed data from the large population-based California Cancer Registry, which is estimated to represent more than 99% of all invasive cancers diagnosed in California. They examined data from women ages 12 to 50, to capture premenopausal breast cancer based on approximations of age at menarche and menopause, who were diagnosed with primary breast cancer from 1988 to 2014 (n = 107,751) and compared the data of similarly aged patients with secondary breast cancer who were treated with radiotherapy for their primary tumor (n = 1,147) from ages 12 to 39.

The researchers compared demographic and clinical factors between women with secondary primary breast cancer and those with primary breast cancer. They then compared breast cancer–specific survival between these groups, both collectively and for specific subgroups, including age, race/ethnicity, lymph node involvement, hormone receptor status, and HER2 status.

The researchers examined breast cancer–specific survival using multivariable Cox proportional hazards regression.

Results

Overall, the researchers found that compared with premenopausal women with primary breast cancer, those with secondary primary breast cancer treated with radiation were more likely to be Hispanic or Black, 35 to 45 years of age, have earlier stage tumors and higher grade tumors, no lymph node involvement, and be hormone receptor–negative. All the women showed worse breast cancer–specific survival for large tumor size, lymph node involvement, and hormone receptor–negative status. Breast cancer–specific survival 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.

“Breast cancer–specific survival 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. Therefore, we may need to consider alternative and even more aggressive treatment in what were considered low-risk populations previously,” concluded the study authors.

Evaluating How Treatments Affect Secondary Primary Breast Cancer Outcomes

“We found that the negative impact of second primary breast cancer among women previously treated with radiation was particularly strong in subgroups of patients that have superior survival after primary breast cancer,” said Candice A. Sauder, MD, MEd, Assistant Professor of Surgery at the University of California Davis Comprehensive Cancer Center and lead author of this study, in a statement. “It will be important to prospectively evaluate how certain treatments, such as specific radiation fields or chemotherapeutic agents, can affect second primary breast cancer outcomes.”

Dr. Sauder, of the University of California Davis Comprehensive Cancer Center, is the corresponding author of this study.

Disclosure: Funding for this study was provided by University of California Davis Health and University of California Davis Comprehensive Cancer Center. The study authors declared no potential conflicts of interest.