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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    ABSTRACT: Neoadjuvant chemotherapy is the standard treatment for patients with locally advanced breast cancer and is increasingly considered for patients with operable disease. Recently, as many clinical trials have demonstrated favorable outcomes of anthracycline-taxane based regimen, this approach has been widely used in the neoadjuvant setting. We compared women who received adriamycine and docetaxel (AD) with adriamycin, cyclophosphamide followed by paclitaxel (AC-T) as neoadjuvant chemotherapy. The AD group was scheduled for six cycles of AD (50 mg/m(2) and 75 mg/m(2), respectively) at a 3-week interval. The AC-T group was scheduled for four cycles of adriamycin and cyclophosphamide (50 mg/m(2) and 500 mg/m(2), respectively) followed by four cycles of paclitaxel (175 mg/m(2)) at a 3-week interval. The responses of chemotherapy were equivalent (overall response rate [AD, 75.7% vs. AC-T, 80.9%; P = 0.566], pathologic complete response [pCR] rate [breast and axilla: AD, 10.8% vs. AC-T, 12.8%; P = 1.000; breast only: AD, 18.9% vs. AC-T, 14.9%, P = 0.623], breast conserving surgery rate [P = 0.487], and breast conserving surgery conversion rate [P = 0.562]). The pCR rate in the breast was higher in the human epidermal growth factor receptor 2 (HER2) positive cases (HER2 positive 33.3% vs. negative 10%, P = 0.002). Although nonhematologic toxicities were comparable, hematologic toxicities were more severe in the AD group. Most women in the AD group suffered from grade 3/4 neutropenia (P < 0.001) and neutropenic fever (P < 0.001). Tumor responses were not different in various variables between the two groups. However, AC-T was a more tolerable regimen than AD in patients with breast cancer receiving neoadjuvant chemotherapy.
    Journal of the Korean Surgical Society 07/2013; 85(1):7-14. DOI:10.4174/jkss.2013.85.1.7 · 0.73 Impact Factor
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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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    ABSTRACT: Objective: To evaluate the predictive value of GST gene polymorphisms with regard to prognosis of breast cancer patients receiving neoadjuvant chemotherapy. Methods: A total of 159 patients were included in our study between January 2005 and January 2007. All the patients were followed up until January 2012. Genotyping was based upon the duplex polymerase-chain-reaction with the PCR-CTPP method. Results: Patients with null GSTM1 and GSTP1 Val/Val genotypes had significantly had better response rates to chemotherapy when compared with non-null GSTM1 and GSTP1 Ile/ Ile genotypes (OR=1.96 and OR=2.14, respectively). Patients with the GSTM1 null genotype had a longer average survival time and significantly lower risk of death than did those with non-null genotypes (HR=0.66). Similarly, those carrying the GSTP1 Val/Val genotype had 0.54- fold the risk of death of those with GSTP1 Ile/ Ile (HR=0.54). Conclusion: A significant association was found between GSTM1 and GSTP1 gene polymorphisms and clinical outcomes in breast cancer cases.
    Asian Pacific journal of cancer prevention: APJCP 10/2012; 13(10):5019-22. DOI:10.7314/APJCP.2012.13.10.5019 · 2.51 Impact Factor
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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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    ABSTRACT: Previous studies suggested that estrogen receptor alpha (ERα) plays an important role in the chemoresistance of breast cancers. However, large random trials failed to demonstrate any benefit of the concurrent estrogen antagonist tamoxifen on the chemotherapy efficacy. Thus, in the present study, the importance of the role of ERα in the chemoresistance of breast cancer cells was investigated. The ERα-transfected Bcap37 cells and natural ERα-positive T47D breast cancer cells were treated using chemotherapeutic agents with or without 17-beta estradiol (E2) pretreatment. Their viabilities were assessed using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assays. The dead cell rates were determined using propidium iodide dye exclusion tests, and the expression levels of Bcl-2 and Bax were detected through Western blot analysis. The effects of E2 on the growth of breast cancer cells were also determined via cell growth curve and cell cycle analysis. ERα activation by E2 increased the sensitivity of natural ERα-positive T47D breast cancer cells to chemotherapeutic agents. However, the increase in ERα expression in ERα-negative Bcap37 breast cancer cells also significantly increased their resistance. These phenomena cannot be explained by asserting that ERα mediated the chemoresistance of breast cancer cells by regulating the expression of Bcl-2 and Bax. Our findings show that ERα activation upregulated the expression of Bcl-2 in natural ERα-positive T47D breast cancer cells, whereas ERα activation by E2 downregulated and upregulated the Bcl-2 and Bax expression levels, respectively, in ERα-transfected Bcap37 cells. This phenomenon was due to the influence of ERα on the growth of breast cancer cells. Specifically, ERα activation enhanced the growth of natural ERα-positive breast cancer cells and thus increased their sensitivity to chemotherapeutic agents. However, ERα activation also inhibited the growth of ERα-transfected Bcap37 cells and increased the resistance of cancer cells to chemotherapeutic agents. Chemoresistance of ERα-transfected Bcap37 cells was only due to the specific growth inhibition by E2, which is not applicable to common ERα-positive breast cancer cells. Although ERα was associated with chemoresistance of breast cancers, ERα itself did not mediate this resistance process.
    Journal of Experimental & Clinical Cancer Research 05/2012; 31(1):42. DOI:10.1186/1756-9966-31-42 · 4.43 Impact Factor
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