The potential biomarkers in predicting pathologic response of breast cancer to three different chemotherapy regimens: A case control study

Department of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University College of Medicine, Hangzhou, PR China.
BMC Cancer (Impact Factor: 3.36). 07/2009; 9(1):226. DOI: 10.1186/1471-2407-9-226
Source: PubMed


Preoperative 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.
118 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.
There 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.
ER 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.

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Available from: Weimin Fan, Sep 16, 2015
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    • "HER2 was often co-amplified with topoisomerase IIa which was located at chromosome 17, close to the HER2 gene. These genes played a role in the target and mediator of anthracycline-induced cytotoxicity [21,22]. However, the clear mechanism has not been established and more research should be necessary. "
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    • "Several in vitro studies using various human cells have indicated that GSTM1, GSTT1 and GSTP1 expression is associated with resistance to chemotherapy (Satta et al., 1992; Whelan et al., 1992; Lourenço et al., 2010). However, the results of GSTs polymorphisms and response to chemotherapy in breast cancer are conflicting (Wang et al., 2009; Arun et al., 2010; Franco et al., 2012). Moreover, there is no study conducted in Chinese population on the association of GSTs expression with response to chemotherapy in breast cancer patients. "
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    • "Our and other studies have suggested that ERα-positive breast cancer is more resistant to chemotherapy than ERα-negative cancer [4-9]. In vitro studies have also shown that ERα plays an important role in determining the sensitivity of breast cancer cells to chemotherapeutic agents [2,10-14]. "
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