Mortality after second malignancy in breast cancer survivors compared to a first primary cancer: a nationwide longitudinal cohort study

Abstract

Limited information exists about survival outcomes after second primary cancers (SPCs) among breast cancer survivors. Studies suggest that mortality after certain SPCs may be higher than mortality after first primary cancers (FPCs) of the same type. A cohort study was conducted among 63,424 US women using the Surveillance, Epidemiology, and End Results 18 database (2000-2016) to compare mortality after a SPC among breast cancer survivors to mortality among women after a FPC using Cox proportional hazard regression. Propensity scores were used to match survivors with SPCs to women with FPCs 1:1 based on cancer type and prognostic factors. During a median follow-up of 42 months, 11,532 cancer deaths occurred after SPCs among survivors compared to 9305 deaths after FPCs. Cumulative cancer mortality was 44.7% for survivors with SPCs and 35.2% for women with FPCs. Survivors with SPCs had higher risk of cancer death (hazard ratio (HR): 1.27, 95% CI: 1.23-1.30) and death overall (HR: 1.18, 95% CI: 1.15-1.21) than women with FPCs. Increased risk of cancer death after SPCs compared to FPCs was observed for cancer in breast, lung, colon and/or rectum, uterus, lymphoma, melanoma, thyroid, and leukemia. Estrogen receptor status and treatment of the prior breast cancer as well as time between prior breast cancer and SPC significantly modified the mortality difference between women with SPC and FPC. A more tailored approach to early detection and treatment could improve outcomes from second cancer in breast cancer survivors.

Fig. 1. Study design using second colorectal cancer as an example.

Colorectal cancer is one of the top 10 cancers we studied. FPC first primary cancer, SPC second primary cancer.

Fig. 2. Hazard function and cumulative mortality comparing SPC to matched FPC.

Non-parametric hazard functions with hazard ratios (HRs) and 95% confidence intervals (CIs) for cancer mortality (a) and all-cause mortality (b). Cumulative mortality functions for cancer mortality (c) and all-cause mortality (d). SPC and FPC were matched by propensity scores calculated from race, age at diagnosis, cancer type, year of diagnosis, surgery, chemotherapy, and radiotherapy. Shaded areas in c and d show the 95% CIs of cumulative mortality. The absolute differences in 5 year, 10 year and overall mortality are provided below the figures. FPC first primary cancer, SPC second primary cancer.