Hormone responsive breast cancer is usually determined by the presence of estrogen receptors (ER) or progesterone receptors (PR) on primary invasive breast cancers. Adjuvant and metastatic hormone therapy are recommended based on primary ER and PR determination. Little information is available to determine if primary hormone receptors correlate with metastatic disease and if survival is influenced by metastatic receptor status. We retrospectively compared primary to metastatic tumor ER and PR content from 200 metastatic breast cancer patients. ER and PR analyses were available in both primary and metastatic disease in 200 and 173 patients, respectively. There was a correlation between both the ER and PR in the primary and metastatic lesion (p < 0.001). However, in 60 of 200 (30%) patients, discordance between primary and metastatic ER was noted. Tumors from 68 of 173 (39.3%) showed discordance for PR. In 39 (19.5%) patients, the ER primary status was positive and metastatic status was negative and in 21 (10.5%) patients, the primary status was negative and metastatic status was positive. Survival from the time of metastatic diagnosis was calculated. Those patients with ER positive primary and metastatic tumors (Positive/Positive) or only the metastatic lesion (Negative/Positive) had similar median survival (1131 and 1111 days, respectively). However, patients with tumors that changed from positive primary to negative metastasis (Positive/Negative) experienced significantly shorter median survival (669 days, p < 0.05). Likewise, median survival (580 days) was significantly shorter for patients with primary and metastasis ER negative (Negative/Negative, p < 0.001) compared to Positive/Positive (p < 0.001) or compared to Negative/Positive (p < 0.02). The changes in PR status were not associated with a change in survival. We found a significant discordance between hormone receptor content of primary versus metastatic breast cancer. The ER status of the metastatic lesion was a better predictor of survival. Therefore, optimal metastatic treatment cannot be determined solely on primary ER and PR analysis.

Introduction Trastuzumab is a highly effective therapy for the treatment of HER-2/neu positive breast cancer. To maximize benefit and minimize unnecessary toxicity, patient selection is essential. Currently HER-2/neu analysis is routinely performed only for primary invasive breast cancers, and trastuzumab therapy is recommended based on primary analysis only. Methods Using immunohistochemistry, we performed a retrospective study comparing HER-2/neu expression in original primary to subsequent metastatic breast cancers. Results Tumors from 382 patients with metastatic breast cancer were studied. In 254 cases (66%) both primary and metastatic lesions were concordant. In 90 cases the primary lesion was HER-2/neu positive with the metastatic lesion negative; whereas, in 37 cases the primary lesion was HER-2/neu negative and the metastatic lesion positive. Primary HER-2/neu immunostaining was associated with a negative predictive value of 35.7%. Although all four groups were similar at diagnosis, survival differences were noted with the best survival experienced by patients with initial primary lesions HER-2/neu negative and subsequent metastatic lesions positive. Patients with hormone receptor and HER-2/neu positive primary lesions who received tamoxifen were more likely to have HER-2/neu positive metastasis. Conclusions The significant discordance between HER-2/neu expression in primary and metastatic tumors suggests that determination of HER-2/neu status in metastatic disease should be attempted.