Abstract
We aimed to evaluate the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression discordance in matched pairs of primary breast cancer and lymph node metastasis specimens and determine the effect of discordance on prognosis. Among all patients diagnosed with lymph node metastases from 2004 to 2007, primary tumors and paired lymph node metastases were resected from 209 patients. The status of ER, PR, and HER2 expression was analyzed immunohistochemically in 200, 194, and 193 patients, respectively. Discordance was correlated with prognosis. Biomarker discordance between primary tumors and paired lymph node metastases was 25.0% (50/200) for ER status, 28.9% (56/194) for PR status, and 14.0% (27/193) for HER2 status. ER positivity was a significant independent predictor of improved survival when analyzed in primary tumors and lymph node metastases. Patients with PR-positive primary tumors and paired lymph node metastases displayed significantly enhanced survival compared to patients with PR-positive primary tumors and PR-negative lymph node metastases. Patients with ER- and PR-positive primary tumors and paired lymph node metastases who received endocrine therapy after surgery displayed significantly better survival than those not receiving endocrine therapy. Similalry treated patients with PR-negative primary tumors and PR-positive paired lymph node metastases also displayed better survival than those not receiving endocrine therapy. Biomarker discordance was observed in matched pairs of primary tumors and lymph node metastases. Such cases displayed poor survival. Thus, it is important to reassess receptor biomarkers used for lymph node metastases.
Highlights
Breast cancer is one of the most common causes of cancer-related deaths worldwide
progesterone receptor (PR) status PR positivity in the primary tumor did not correlate with 5-year overall survival (OS) (c2=5.377, P=0.101); different results were obtained for PR positivity in the lymph node (c2=11.253, P=0.001) (Figure 2c)
We sought to investigate differences in receptor expression levels between primary tumors and paired lymph nodal metastases, which may serve as an alternative explanation for resistance to targeted therapy in breast cancer
Summary
The prediction of clinical outcome and the selection of patients for adjuvant therapy are currently based on prognostic factors [age, hormone receptor status, human epidermal growth factor receptor 2 (HER2) expression, tumor size, and lymph node involvement] according to international guidelines (Cinieri et al, 2007). Among these factors, the number of metastatic axillary lymph nodes is the most powerful prognostic factor (Nemoto et al, 1980). Conclusions: Biomarker discordance was observed in matched pairs of primary tumors and lymph node metastases It is important to reassess receptor biomarkers used for lymph node metastases
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