Estrogen receptor, progesterone receptor, and HER2-neu expression in first primary breast cancers and risk of second primary contralateral breast cancer

Breast cancer survivors have a 60 % higher risk of developing a second primary asynchronous contralateral breast cancer (CBC) compared to women’s risk of developing a first primary breast cancer (FBC). However, little is known about how expression of tumor markers in first breast cancers influences CBC risk. We conducted a population-based nested case–control study among women 20–74 years of age diagnosed with a first breast cancer between 1996 and 2008 in western Washington State to evaluate the association between their tumor’s estrogen receptor (ER), progesterone receptor (PR) and HER2-neu (HER2) expression, and risk of CBC. The study included 482 cases diagnosed with both a FBC and a CBC and 1,506 control women diagnosed only once with breast cancer identified through our local Surveillance, Epidemiology and End Results (SEER) cancer registry. Compared to the women whose FBC was ER+/PR+, those with ER−/PR− first tumors had a 1.6-fold (95 % confidence interval (CI): 1.2–2.3) increased risk of developing a CBC. When evaluated by joint ER/PR/HER2 status, compared to women with ER+/HER2− first cancers, those with HER2-overexpressing (ER−/HER2+) and triple-negative disease (ER−/PR−/HER2−) had 2.0-fold (95 % CI: 1.1–3.8) and 1.4-fold (95 % CI: 0.9–2.3) elevated risks of developing CBC, respectively. Beyond the known higher risks of mortality among patients diagnosed with more aggressive BC subtypes, here, we observe that they may also have increased risks of developing CBC.