The Research Of Clinicopathologic Characteristics And Individual Chemotherapy Based On Breast Cancer Different Molecular Subtypes In Chinese Women

ObjectiveBreast cancer is regarded as a heterogeneous disease classified into different molecular subtypes, resulting in different biologic behavior and sensitivity to treatment respectively. The aim of the study was to identify the prevalence and clinicopathologic features of each breast cancer subtype and try to find the independent prognosis factor of different subtypes in Chinese population. Furthermore, This study validate the expression of drug resistance drug in different molecular subtypes and measure the drug sensitivity in different molecular subtypes of breast carcinoma cell lines and breast neoplasms, which aim to identify the primary drug-resistance in the different molecualr subtypes.MethodsClassification of the btreast cancer case into molecular subtypes was based on the of expression of ER,PR,C-erbB-2,CK5/6,EGFR,Ki-67,p53 by IHC and the amplification status of HER/neu gene by FISH. A retrospective analysis of 1840 chinese women diagnosed with breast cancer to investigate the prevalence and the clinical and histopathologic characteristics of molecular breast cancer subtypes, and independent prognosis factor in Chinese population. We detected the expression of drug resistance genes,including Topoâ…¡,GST-Ï€,P-gp,LRP in 548 cases of differentt molecualr subtypes on the tissue microarray by IHC.224 cases of different breast caner subtype tissue were cultured through primary cell culturing technology. Identifying different molecular subtypes of breast carcinoma cell lines by western blot. The three-dimensional culture drug-sensitivity test detected the sensitivity to different drug (paclitaxel, anthracyclines, platinum, fluorouracil, navelbine) in different subtypes.Result1. The clinicopathologic feather of molecular subtypes showed significantly different. Compared with other subtypes, the basal cell-like subtype was associated with a higher prevalence in the postmenopausal group and the earliest age at menarche. (P<0.001, P=0.006). And it wasassociated with the youngest, a bigger tumor, a higher tumor grade, a higher prevalence of node positivity and the stronger heredity (P<0.0001), Whereas luminal A tumors were related to the oldest mean age at first full-term birth (P<0.001), a smaller tumor, a lower tumor grade, a lower prevalence of node positivity luminal A tumors were related to the oldest mean age at first full-term birth (P<0.001)2. The survivl analysis showed the significantly different of the 5-year actuarial OS and RFS of different subtypes (P<0.001, P<0.001). In the Cox multivariate analysis, breast cancer subtypes were proved to be independent risk factors for OS and RFS. The basal cell-like and HER-2/neu subtype were identified as negative prognostic factors for OS and RFS. And the breast family history was proved to be independent risk factors for OS and RFS in the basal cell-like breast cancer subtype.3. The expression of drug resistance genes were significant difference in the different molecular subtypes. Topoâ…¡was the more positive rate and positive intensity in the basal cell-like and HER2/neu subtype,whereas the lowest in the luminal A subtype (P=0.005). The positive rate of P-gp expression was 67.3% in the basal cell-like subtype, which was the highest among the four subtypes, and the HER2/neu subtype was the lowest positive rate (P=0.000). LRP was the more positive rate in the HER2/neu subtype and luminal A subtype and GST-Ï€was the most positive rate in the luminal A subtype. In the basal cell-like subtype, the expression of LRP and GST-Ï€were the lowest positive rate compared other subtypes. In the corrrelation analysis, the significant coeeelation were showed in the expression of GST-Ï€between P-gp and GST-Ï€between LRP (P=0.04; P=0.000)4. The T47D cell line showed strong sensitivity to the fluorouracil and the cell lines of MDA-MB-435 and MDA-MB-231 showed the strong sensitivity to the paclitaxel and anthracyclines. Moreover, platinum and fluorouracil are still effective to the MDA-MB-231 cell line.5. The results of three-dimensional culture drug-sensitivity test detecting primary breast neoplasms showed the basal cell-like subtype were obvious responsivity to paclitaxel, anthracyclines and platium, but did not showed the sensitivity to the navelbine. Anthracyclines drug showd the most effective to the HER2/neu subtypes, meanwhile this subtype also has good response to paclitaxel, but resistance to platinum, fluorouracil and navelbine. However, any chemotherapy drug showed the effectiveness to the luminal subtypes except the fluorouracil. ConclusionsThe study showed the significantly different biologic behavior and sensitivity to different drug treatment respectively.The basal cell-like subtype showed the strong sensitivity to the chemotherapy, so the chemotherapy is the major treatment to it and choose paclitaxel and anthracyclines as the first line drug. And platinum can be as supplementary methods. The HER2/neu subtypes is the most sensitivity to the anthracyclines, which should be choosed as the fist line drug for this sub types. Wheras the luminal subtype showed drug resisitance to the chemothreapy, and the endocrine therapy is still effective therapeutic method to it.