Abstract PS7-16: Increased cancer mortality after second primary malignancy among breast cancer survivors
Authors: Deng Zhengyi , Jones Miranda R , Visvanathan Kala 
Published: February 2021

Abstract
Background: Due to advances in early detection and treatment, the number of breast cancer survivors in the US is expected to increase to 5 million by 2030. Although it is well established that breast cancer survivors are at increased risk of second primary malignancy (SPM), there is limited data on the impact of a SPM on overall and cancer-specific mortality compared to women with a first primary cancer. This information could inform prognosis for women with breast cancer as well as screening and treatment recommendations.
Methods: A retrospective cohort study was conducted using the Surveillance, Epidemiology, and End Results (SEER) 18 database, which collected cancer incidence and mortality from 18 US cancer registries (represents 28% of US population) between 2000 and 2016. For this analysis, we focused on the top 10 SPM in breast cancer survivors: breast cancer, lung cancer, colorectal cancer, uterine cancer, lymphoma, melanoma, thyroid cancer, pancreatic cancer, ovarian cancer, and leukemia. Propensity scores were used to match SPM with first primary cancer 1:1 on race, primary site, year of diagnosis, age of diagnosis, tumor stage, and treatments (surgery, chemotherapy, and radiotherapy). Hazard ratio (HR) and 95% confidence interval (CI) for cancer-specific death comparing SPM to first primary cancer were estimated from Cox proportional hazard regression, accounting for competing risk of death from conditions other than cancer. Subgroup analyses were conducted by SPM tumor stage, SPM primary site, and time interval between first breast cancer and SPM diagnosis.
Results: The study population included 31,712 breast cancer survivors with SPM and 1,471,886 women with first primaries. Women with SPM were older (mean age of 66.6 years) than first primary cancers (mean age of 62.1 years). 52.8% of SPM and 47.5% of first primary cancers were diagnosed at local stage. Women with SPM had higher cancer mortality than women with first primary cancer (HR: 1.27, 95%CI: 1.23-1.30). Mortality difference was larger among local stage SPM (HR: 1.95, 95%CI: 1.82-2.08) and regional stage (HR: 1.40, 95%CI: 1.33-1.47) than for distant stage (HR:1.10, 95%CI:1.06-1.14). Among the top 10 SPM, increased mortality was observed for thyroid cancer (HR: 3.02, 95%CI: 1.96-4.67), breast cancer (HR: 2.26, 95%CI: 2.11-2.42), and melanoma (HR: 1.76, 95%CI: 1.36-2.28). There was no statistically significant difference in mortality for second lung (HR: 1.06, 95%CI: 1.00-1.17) and pancreatic cancer (HR: 0.93, 95%CI: 0.82-1.06). Larger mortality difference comparing SPM to first primary cancer was observed for SPM diagnosed within 5 years (HR: 1.39, 95%CI: 1.35-1.44) than after 5 years (HR: 1.09, 95%CI: 1.04-1.13).
Conclusion: Breast cancer survivors with a SPM had higher cancer-specific mortality overall and for several cancers compared to women diagnosed with the same type of cancer for the first time suggesting that prior breast cancer is an important prognostic factor. Our results support the evaluation of improved risk stratification and/or novel screening and treatment approaches to improve outcomes from second cancer in breast cancer survivors.
Citation Format: Zhengyi Deng, Miranda R Jones, Kala Visvanathan. Increased cancer mortality after second primary malignancy among breast cancer survivors [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS7-16.