Bcl-2 Downregulation Is Predictive of Complete Pathologic Response Following Neoadjuvant Chemotherapy in Breast Cancer
Steven Goodman, Thomas Stockl, Stephen Lyle, Dina Kandil, Kathryn Edmiston, Robert Quinlan, Ashraf Khan. UMass Memorial Medical Center, Worcester, MA
Background: Neoadjuvant chemotherapy has become standard of care in a subset of breast cancer. Certain chemotherapeutic agents including docetaxel act by binding tubulin, inhibiting mitsosis, and by phosphorylating bcl-2 to inactivate its overexpression. Bcl-2 is an oncogene, which inhibits apoptosis and restrains cell cycle entry. Overexpression of Bcl-2 prevents apoptosis in damaged cells and can eventually lead to cancer. The aim of this study was to evaluate the expression pattern and predictive value of Bcl-2 in the outcome of breast cancer by examining the effect of neoadjuvant therapy on breast cancer.
Design: A total of 27-paired cases (pre-treatment biopsy and post-treatment resection specimens) over a six year period (2006-2011) were obtained from the surgical pathology files. All the slides were reviewed to confirm the diagnosis and evaluate pathologic response in post treatment specimens. These consisted of invasive carcinoma of both lobular (n=3) and ductal types (n=24). Immunohistochemistry for Bcl-2 was performed on pretreatment biopsies and in post treatment specimens in which residual tumor was present. Positive bcl-2 staining in tumor cells was graded into three groups by intensity of cytoplasmic staining, 1 as weak and 3 as strong. The chemotherapy used varied, and included paclitaxel, docetaxel, cycophosphamide, doxorubicin, and in Her-2 positive cases, Transtuzumab (Herceptin). Complete pathologic response (CPR) was defined as no residual tumor seen in post treatment surgical resection specimen.
Results: Of the 27-paired cases, complete pathologic response (CPR) to therapy occurred in 9. Of these nine cases, 8 of them were Bcl-2 negative, and 1 was Bcl-2 positive. Of the remaining 18 cases, 7 were Bcl-2 negative, and 11 were Bcl-2 positive (P value = 0.019, Fisher's exact test). Of the cases with CPR, all 9 were invasive ductal carcinoma (8 grade III, 2 grade II). Positive Her-2 receptor status did not correlate with Bcl-2 expression. Of the 9 cases with complete response, five cases were Her-2 positive and received Transtuzumab. Bcl-2 expression did not change after treatment with neoadjuvant chemotherapy.
Conclusions: In summary bcl-2 down regulation is significantly associated with CPR following neoadjuvant chemotherapy in breast cancer suggesting that a pro-apoptotic molecular signature may play a role in response to chemotherapy and bcl-2 expression may be used to predict response following neoadjuvant chemotherapy.
Wednesday, March 6, 2013 9:30 AM
Poster Session V # 23, Wednesday Morning