Breast Cancer Biomarker Changes after Neoadjuvant Chemotherapy: A Single Institution Experience and Literature Review

Chemotherapy and hormonal treatment decisions for breast cancer are influenced by the expression of tumor biomarkers, including estrogen receptor, progesterone receptor and human epidermal growth hormone receptor 2 (HER2/neu). These biomarkers are most commonly assessed by immunohistochemical staining and fluorescence in situ hybridization studies performed on breast cancer biopsy specimens. Biomarker studies performed on excisional specimens may be discordant with those performed on core needle biopsy, especially after neoadjuvant chemotherapy. We evaluated 195 cases at our institution from 2002 to 2015 to determine the effects of neoadjuvant chemotherapy on the expression of the aforementioned biomarkers and Ki-67. Forty-nine (25.1%) cases showed complete pathologic response after neoadjuvant chemotherapy. Twelve cases (8.6%) showed a change in estrogen receptor status after neoadjuvant chemotherapy. Twenty-four cases (17.1%) showed a change in progesterone receptor status, predominantly from positive to negative (p = 0.0002). HER2/neu expression was evaluated by both immunohistochemical staining and fluorescence in situ hybridization, where two (1.5%) (p = 1.000) and eight (8.2%) (p = 0.4795) cases changed expression status, excluding equivocal cases, respectively. Ki-67 was also evaluated, with 49 cases (48%) (p <0.0001) showing altered proliferation indices after neoadjuvant therapy. The differences were statistically significant for progesterone receptor and Ki-67. Overall survival was also evaluated, and showed statistically significant differences between groups that changed progesterone receptor status after neoadjuvant therapy. Given the therapeutic implications of altered biomarker status after neoadjuvant chemotherapy, we recommend repeating biomarker studies on resection specimens to most appropriately guide adjuvant chemotherapy decisions.