Abstract 896: Comparison of tumor profiles of second cancers among breast cancer survivors to first cancers in the SEER registries: A nationwide study

Background: In the US, the number of breast cancer (BC) survivors is expected to increase to 5 million by 2030. Although it is well established that BC survivors are at increased risk of second primary cancer (SPC), little is known about the characteristics of these tumors. Methods: We conducted a retrospective cohort study using the Surveillance, Epidemiology, and End Results (SEER) 18 database to compare the tumor characteristics of first primary cancer (FPC) to SPC among women diagnosed with BC between 2000-2016. For this analysis, we focused on breast, lung, colorectal, uterine, and cervical cancer. Odds ratio (OR) and 95% confidence interval (CI) for tumor characteristics comparing SPC to FPC were estimated from logistic or multinomial logistic regression, adjusting for race/ethnicity, year of diagnosis, and age at diagnosis. Tumor characteristics included summary tumor stage, T stage, tumor grade, hormone receptor (HR) status of BC, molecular subtype of BC, Oncotype DX score of BC for a subset (N=48,826), and histologic subtype of lung cancer. Results: The study population included 14,392 second and 586,788 first BC, 5,202 second and 246,543 first lung cancers, 3,525 second and 190,640 first colorectal cancers, 2,517 second and 125,818 first uterine cancers, as well as 230 second and 42,601 first cervical cancers. Women with SPC were older than women with FPC. Compared to FPC, SPC were more likely to be diagnosed at local stage for breast (OR: 1.30, 95%CI: 1.25-1.34), lung (OR: 1.57, 95%CI: 1.47-1.68), colorectal (OR: 1.20, 95%CI: 1.12-1.28), and cervical cancer (OR: 1.59, 95%CI: 1.19-2.12), but not for uterine cancer (OR: 1.07, 95%CI: 0.98-1.17). Second breast (OR: 1.26, 95%CI: 1.21-1.31) and uterine (OR: 1.83, 95%CI: 1.65-2.03) cancers were more likely to present at poorly or undifferentiated tumor grade after adjusting for tumor stage. No difference in tumor grade was found for lung, colorectal, and cervical cancer. Second BC were more likely to be of hormone receptor (HR) negative (OR: 1.64, 95%CI: 1.57-1.71), human epidermal growth factor receptor 2 (HER2) enriched (OR:1.30, 95%CI: 1.16-1.45) and triple negative (OR: 1.66, 95%: 1.55-1.77) subtype, and having Oncotype DX score above 26 (OR: 1.73, 95%CI: 1.47-2.04). Second lung cancers were more likely to be of small cell histology compared to first lung cancers (OR =1.15, 95%CI: 1.06-1.25). Conclusion: Screen-detectable second cancers were diagnosed at an earlier stage compared with first cancers. Further, second breast, uterine, and lung cancer had a more aggressive tumor profile compared to women with a similar type of first cancer suggestive of underlying biological differences between the two groups. It is plausible that more intensive screening strategies akin to screening recommendations for women at high risk of BC may be needed for survivors at risk for certain second cancers. Citation Format: Zhengyi Deng, Miranda R. Jones, Kala Visvanathan. Comparison of tumor profiles of second cancers among breast cancer survivors to first cancers in the SEER registries: A nationwide study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 896.