Clinical and sociodemographic risk factors associated with the development of second primary cancers among postmenopausal breast cancer survivors

Background: Advancement in breast cancer (BC) diagnosis and treatment have increased the number of long-term survivors. Consequently, primary BC survivors are at a greater risk of developing second primary cancers (SPCs). The risk factors for SPCs among BC survivors including sociodemographic characteristics, cancer treatment, comorbidities, and concurrent medications have not been comprehensively examined. The purpose of this study is to assess the incidence and clinicopathologic factors associated with risk of SPCs in BC survivors. Methods: We analyzed 171, 311 women with early-stage primary BC diagnosed between January 2000 and December 2015 from the Medicare-linked Surveillance Epidemiology and End Results (SEER-Medicare) database. SPC was defined as any diagnosis of malignancy occurring within the study period and at least 6 months after primary BC diagnosis. Univariate analyses compared baseline characteristics between those who developed a SPC and those who did not. We evaluated the cause-specific hazard of developing a SPC in the presence of death as a competing risk. Results: Of the study cohort, 21,510 (13%) of BC survivors developed a SPC and BC was the most common SPC type (28%). The median time to SPC was 44 months. Women who were white, older, and with fewer comorbidities were more likely to develop a SPC. While statins [hazard ratio (HR) 1.066 (1.023–1.110)] and anti-hypertensives [HR 1.569 (1.512–1.627)] increased the hazard of developing a SPC, aromatase inhibitor therapy [HR 0.620 (0.573–0.671)] and bisphosphonates [HR 0.905 (0.857–0.956)] were associated with a decreased hazard of developing any SPC, including non-breast SPCs. Conclusion: Our study shows that specific clinical factors including type of cancer treatment, medications, and comorbidities are associated with increased risk of developing SPCs among older BC survivors. These results can increase patient and clinician awareness, target cancer screening among BC survivors, as well as developing risk-adapted management strategies.