| Malignant tumor threats people’s physical and mental health seriously. With the development of economy and the improvement of living standards, the incidence of cancer is rising. By 2030, the incidence of cancer worldwide is expected to rise to 26.4 million with 17 million deaths, and most of these new cases of cancer are expected to occur in the developing world, particularly India and China. Up to now, breast cancer is the most prevalent malignant tumor in females. Breast cancer not only presents heterogeneous histologically and molecularly, but also shows significant differences in areas, populations and ethnics. In recent years, some large sample reports about breast cancer have been found in developed countries while the clinicopathological data have not been discovered in Chinese patients. This study analyzed the epidemiological features, clinicopathological characteristics and molecular subtypes of breast cancer at National Cancer Center with large sample to establish Chinese breast cancer clinicopatho logical database. It will be useful for future researches, individualized treatments and prognostic evaluation of breast cancer. At the same time, we explored the highly heterogeneous, refractory and poor prognostic triple-negative breast cancer to understand the pathogenesis and prognostic factors. The contents of this study are divided into two sections as followed:Section 1:3,198 cases of surgical resection mammary carcinomas without any treatments previously were assessed immunohistochemically for ER, PR and HER2 expressions to explore the correlation of these markers to clinical features and pathological characteristics. This study was an important documentation of Chinese breast cancer patients and the report would serve as a baseline for other future studies. In this research, we found that ER、PR and HER2 status were associated with onset age and tumor grade. Luminal A, Luminal B, HER2 overexpression and triple-negative breast cancer (TNBC) differed from onset age, tumor size, lymph node metastasis, and tumor grade.Section 2:We evaluated the clinicopatho logical characteristics and prognostic significance of BRCA1 gene methylation in triple-negative breast cancer which is refractory and has worse prognosis to determine the relationship between BRCA1 gene methylation and clinicopathological features. In hereditary breast cancer with BRCA1 mutations, over 80% of the cases are triple-negative breast cancer. Given the contribution that BRCA1 mutations to the development of hereditary triple-negative breast cancer, it is unexpected that BRCA1 mutation can be rarely found in sporadic triple-negative breast cancer. Despite sporadic triple-negative breast cancer patients do not have germline alternation of BRCAl, they often share similar histological characteristics and clinical outcomes with BRCA1-mutation carriers. Herein, it was postulated that BRCA1 inactivation might also have a role in sporadic triple-negative breast cancers. Epigenetic alterations are now well recognized as another mean to silence tumor suppressor genes independent of mutation or deletion. Recently, a few studies have shown that the epigenetic alterations was aberrant methylation. By detecting BRCAl gene methylation status in 239 cases of sporadic triple-negative breast cancer, the study aimed to investigate the correlation of BRCA1 gene methylation to clinicopathological features, molecular subtypes treatments and prognosis. Among the 239 triple-negative breast cancer cases,137(57.3%) showed methylation of the BRCAl. According to the immuno histo chemistry results, triple-negative breast cancer cases were classified into basal-like breast cancer (BLBC,60.7%) and non-basal-like breast cancer (non-BLBC, 39.3%). The frequency of BRCA1 methylation was significantly higher in basal-like breast cancer subtype than the non-basal subtype. Multivariate analyses further showed that BRCA1 promoter methylation is an independent predictor of overall survival and disease-free survival in triple-negative breast cancer. Future researches based on this study are expected to provide the potential targets in TNBC/BLBC, to elevate the integrative level of personalized treatment and to promote the development of precision medicine for breast cancer. |
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