Abstract
BackgroundPreoperative chemotherapy (PCT) has become the standard of care in locally advanced breast cancer. The identification of patient-specific tumor characteristics that can improve the ability to predict response to therapy would help optimize treatment, improve treatment outcomes, and avoid unnecessary exposure to potential toxicities. This study is to determine whether selected biomarkers could predict pathologic response (PR) of breast tumors to three different PCT regimens, and to identify a subset of patients who would benefit from a given type of treatment.Methods118 patients with primary breast tumor were identified and three PCT regimens including DEC (docetaxel+epirubicin+cyclophosphamide), VFC (vinorelbine/vincristine+5-fluorouracil+cyclophosphamide) and EFC (epirubicin+5-fluorouracil+cyclophosphamide) were investigated. Expression of steroid receptors, HER2, P-gp, MRP, GST-pi and Topo-II was evaluated by immunohistochemical scoring on tumor tissues obtained before and after PCT. The PR of breast carcinoma was graded according to Sataloff's classification. Chi square test, logistic regression and Cochran-Mantel-Haenszel assay were performed to determine the association between biomarkers and PR, as well as the effectiveness of each regimen on induction of PR.ResultsThere was a clear-cut correlation between the expression of ER and decreased PR to PCT in all three different regimens (p < 0.05). HER2 expression is significantly associated with increased PR in DEC regimen (p < 0.05), but not predictive for PR in EFC and VFC groups. No significant correlation was found between biomarkers PgR, Topo-II, P-gp, MRP or GST-pi and PR to any tested PCT regimen. After adjusted by a stratification variable of ER or HER2, DEC regimen was more effective in inducing PR in comparison with VFC and EFC regimens.ConclusionER is an independent predictive factor for PR to PCT regimens including DEC, VFC and EFC in primary breast tumors, while HER2 is only predictive for DEC regimen. Expression of PgR, Topo-II, P-gp, MRP and GST-pi are not predictive for PR to any PCT regimens investigated. Results obtained in this clinical study may be helpful for the selection of appropriate treatments for breast cancer patients.
Highlights
Preoperative chemotherapy (PCT) has become the standard of care in locally advanced breast cancer
No significant correlation was found between biomarkers progesterone receptor (PgR), Topo-II, P-gp, multidrug resistance-related protein (MRP) or glutathione S-transferase pi (GST-pi) and pathologic response (PR) to any tested PCT regimen
estrogen receptor (ER) is an independent predictive factor for PR to PCT regimens including DEC, VFC and EFC in primary breast tumors, while human epidermal growth factor receptor 2 (HER2) is only predictive for DEC regimen
Summary
Preoperative chemotherapy (PCT) has become the standard of care in locally advanced breast cancer. This study is to determine whether selected biomarkers could predict pathologic response (PR) of breast tumors to three different PCT regimens, and to identify a subset of patients who would benefit from a given type of treatment. Preoperative chemotherapy has become the standard of care in locally advanced breast cancers [1,2]. Several different classes of chemotherapeutic drugs are applied in the preoperative setting include taxanes, anthracyclines and vinca alkaloids, etc., there are currently no standard regimens or protocols for preoperative chemotherapy in breast cancer patients [2]. Drug resistance has become the major cause of cancer chemotherapy failure and is largely responsible for breast cancer mortality. The identification of patient-specific tumor characteristics that can improve the ability to predict response to therapy would help optimize treatment, improve treatment outcomes, and avoid unnecessary exposure to potential toxicities
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