The risk of a second primary lung cancer after a first invasive breast cancer according to estrogen receptor status

Lung cancers account for 5 % of second primary cancers after breast cancer. The low overall 5-year relative survival rate of lung cancer makes it a particularly concerning new malignancy for breast cancer survivors. It is unknown whether second lung cancer risk varies by estrogen receptor (ER) expression of the first breast cancer. We evaluated second primary lung cancer risks using standardized incidence ratios (SIRs) (95 % confidence intervals (CIs)) among 222,148 one-year breast cancer survivors in the NCI-SEER Program registry database (1992-2008). Relative risks (RRs) and 95 % CIs for lung cancer following ER- compared with ER+ breast cancer were estimated using Poisson regression, adjusted for age, year, and stage of breast cancer diagnosis, attained age, latency, and radiotherapy. We also examined the reciprocal association of second ER- and ER+ breast cancers among 28,107 1-year lung cancer survivors. There were 418 and 1,444 second lung cancers diagnosed following 50,781 ER- and 171,367 ER+ breast cancers. Second lung cancer rates were significantly elevated after ER- (SIR = 1.20 (1.09-1.33)), but not ER+ (SIR = 0.96 (0.91-1.01)) breast cancer. The adjusted RR for a second lung cancer following ER- compared with ER+ breast cancer was 1.22 (1.10-1.37). The reciprocal adjusted RR for a second ER- compared with ER+ breast cancer following lung cancer was 1.29 (0.98-1.70). The parallel increase for a second lung cancer following an ER- first breast cancer and for a second ER- breast cancer after a first lung cancer suggests that there may be shared etiologic factors for these cancers. Further evaluation of lung cancer risk after ER- breast cancer may identify women at high risk for this fatal malignancy.