Abstract 3057: Second primary cancer risks for female and male breast cancer survivors
Authors: Allen Isaac , Rahman Tameera , Bacon Andrew , Knott Craig , Jose Sophie , Vernon Sally , Hassan Hend , Huntley Catherine , Loong Lucy , Walburga Yvonne , Lavelle Katrina , Morris Eva , Hardy Steven , Torr Beth , Eccles Diana , Turnbull Clare , Tischkowitz Marc , Pharoah Paul , Antoniou Antonis C. 
Published: April 2023

Background: Second primary cancer (SPC) incidence is rising among breast cancer (BC) survivors, but these risks remain unclear. We estimated SPC risks for male and female BC survivors using large-scale electronic health record data from a linkage of National Cancer Registration and Analysis Service data and Hospital Episode Statistics surgical records in England.

Material and Methods: We used a retrospective cohort study design comprising 763,578 female and 4,795 male BC survivors first diagnosed with BC between 1995-2018. We calculated overall and site-specific SPC standardized incidence ratios (SIRs) by comparing observed and expected SPC counts for 19 cancer sites. Study participants were followed from one year after the first BC diagnosis until either a SPC diagnosis (excluding ipsilateral breast and non-melanoma skin cancers), death, migration, relevant surgical procedures, or the end of 2019. Expected SPC counts were calculated using year-, age- and sex-specific cancer incidence rates in the general English population. We stratified the SIRs by age group, sex, and cancer site. We estimated Kaplan-Meier absolute risks of site-specific SPCs and assessed the influence of age at first BC diagnosis using Cox proportional hazards models.

Results: There were 68,550 and 720 incident SPCs among female and male BC survivors, respectively. There was a significant increased risk of all SPCs combined for female BC survivors (SIR: 1.19, 95%CI: 1.18-1.20). There were significant increased risks for SPC at all sites combined, all non-breast sites combined, and at 12 further specific sites for females and at 2 specific sites for males. Among females, the increase was greatest for contralateral breast (SIR: 1.82, 95%CI: 1.79-1.85) and uterine cancers (SIR: 1.80, 95%CI: 1.76-1.85). The risk at all sites combined was higher for women first diagnosed with BC before age 50 (SIR: 1.89, 95%CI: 1.85-1.92) compared to women diagnosed with BC at age 50 or over (SIR: 1.11, 95%CI: 1.10-1.12). The largest associations were observed for contralateral breast (SIR: 3.19, 95%CI: 3.11-3.29) and uterine (SIR: 1.77, 95%CI: 1.73-1.82) SPCs in the younger and older age groups, respectively. Increasing age at first female BC diagnosis was associated with decreasing CBC absolute risks, but significantly increased absolute risks of all other SPCs. Male BC survivors were at increased risk of contralateral breast (SIR: 42.39, 95%CI: 28.39-60.89) and prostate (SIR: 1.29, 95%CI: 1.13-1.46) SPCs.

Conclusions: This is the largest study to date to assess SPC risks following BC in either men or women. SPC risks were significantly increased, both in combination and at specific sites. These findings could help guide clinical management, such as screening recommendations, for BC survivors. Further analysis is underway to investigate the effects of chemotherapy, radiotherapy, hormonal therapy, comorbidities, or germline BC susceptibility.

Citation Format: Isaac Allen, Tameera Rahman, Andrew Bacon, Craig Knott, Sophie Jose, Sally Vernon, Hend Hassan, Catherine Huntley, Lucy Loong, Yvonne Walburga, Katrina Lavelle, Eva Morris, Steven Hardy, Beth Torr, Diana Eccles, Clare Turnbull, Marc Tischkowitz, Paul Pharoah, Antonis C. Antoniou. Second primary cancer risks for female and male breast cancer survivors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3057.