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      Prognostic Value of Clinicopathological Factors for Indonesian Breast Carcinomas of Different Molecular Subtypes

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          Abstract

          Background:

          Breast carcinoma (BC) is a heterogeneous disease due to its different molecular profiles i.e. luminal (luminal A and luminal B) and non-luminal (HER2 positive and triple negative) subtypes. Prognostic value of clinicopathological factors of Indonesian BC of different molecular subtypes has never been reported previously. This study aims to elaborate prognostic impacts on Indonesian BCs focusing on separate molecular subtypes.

          Methods:

          A hundred and fifty cases of invasive BC, stage I-IIIA, in Sardjito Hospital, Indonesia, were stained using anti ER, PR, HER2 and Ki-67 antibodies. Survival and prognostic values were statistically analyzed.

          Results:

          Compared to the luminal subtypes, the non-luminal subtypes demonstrated higher proportions of intermediate-to-high grade, stage IIIA, positive lymph node infiltration and mortality. The triple negative subtype was typically intermediate-to-high grade, stage IIIA and with a high relative death risk. Luminal A lesions were characteristically low grade, stage I-II and less likely to cause death.

          Conclusion:

          In non-luminal BC, staging and lymph node metastasis are independent prognostic factors for survival in HER2 positive and triple negative subtypes, respectively. In luminal BC, clinicopathological factors demonstrated no influence on survival. This study suggests that staging and lymph node metastasis are correlated with survival in non-luminal Indonesian BCs.

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          Most cited references24

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          Breast cancer molecular subtypes respond differently to preoperative chemotherapy.

          Molecular classification of breast cancer has been proposed based on gene expression profiles of human tumors. Luminal, basal-like, normal-like, and erbB2+ subgroups were identified and were shown to have different prognoses. The goal of this research was to determine if these different molecular subtypes of breast cancer also respond differently to preoperative chemotherapy. Fine needle aspirations of 82 breast cancers were obtained before starting preoperative paclitaxel followed by 5-fluorouracil, doxorubicin, and cyclophosphamide chemotherapy. Gene expression profiling was done with Affymetrix U133A microarrays and the previously reported "breast intrinsic" gene set was used for hierarchical clustering and multidimensional scaling to assign molecular class. The basal-like and erbB2+ subgroups were associated with the highest rates of pathologic complete response (CR), 45% [95% confidence interval (95% CI), 24-68] and 45% (95% CI, 23-68), respectively, whereas the luminal tumors had a pathologic CR rate of 6% (95% CI, 1-21). No pathologic CR was observed among the normal-like cancers (95% CI, 0-31). Molecular class was not independent of conventional cliniocopathologic predictors of response such as estrogen receptor status and nuclear grade. None of the 61 genes associated with pathologic CR in the basal-like group were associated with pathologic CR in the erbB2+ group, suggesting that the molecular mechanisms of chemotherapy sensitivity may vary between these two estrogen receptor-negative subtypes. The basal-like and erbB2+ subtypes of breast cancer are more sensitive to paclitaxel- and doxorubicin-containing preoperative chemotherapy than the luminal and normal-like cancers.
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            Meeting highlights: international expert consensus on the primary therapy of early breast cancer 2005.

            The ninth St Gallen (Switzerland) expert consensus meeting in January 2005 made a fundamental change in the algorithm for selection of adjuvant systemic therapy for early breast cancer. Rather than the earlier approach commencing with risk assessment, the Panel affirmed that the first consideration was endocrine responsiveness. Three categories were acknowledged: endocrine responsive, endocrine non-responsive and tumors of uncertain endocrine responsiveness. The three categories were further divided according to menopausal status. Only then did the Panel divide patients into low-, intermediate- and high-risk categories. It agreed that axillary lymph node involvement did not automatically define high risk. Intermediate risk included both node-negative disease (if some features of the primary tumor indicated elevated risk) and patients with one to three involved lymph nodes without additional high-risk features such as HER 2/neu gene overexpression. The Panel recommended that patients be offered chemotherapy for endocrine non-responsive disease; endocrine therapy as the primary therapy for endocrine responsive disease, adding chemotherapy for some intermediate- and all high-risk groups in this category; and both chemotherapy and endocrine therapy for all patients in the uncertain endocrine response category except those in the low-risk group.
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              Keeping abreast of the mammary epithelial hierarchy and breast tumorigenesis.

              The epithelium of the mammary gland exists in a highly dynamic state, undergoing dramatic morphogenetic changes during puberty, pregnancy, lactation, and regression. The recent identification of stem and progenitor populations in mouse and human mammary tissue has provided evidence that the mammary epithelium is organized in a hierarchical manner. Characterization of these normal epithelial subtypes is an important step toward understanding which cells are predisposed to oncogenesis. This review summarizes progress in the field toward defining constituent cells and key molecular regulators of the mammary epithelial hierarchy. Potential relationships between normal epithelial populations and breast tumor subtypes are discussed, with implications for understanding the cellular etiology underpinning breast tumor heterogeneity.
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                Author and article information

                Journal
                Asian Pac J Cancer Prev
                Asian Pac. J. Cancer Prev
                Asian Pacific Journal of Cancer Prevention : APJCP
                West Asia Organization for Cancer Prevention (Iran )
                1513-7368
                2476-762X
                2017
                : 18
                : 5
                : 1251-1256
                Affiliations
                [1 ] Department of Anatomical Pathology, Oncology Division Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia
                [2 ] Department of Surgery, Oncology Division Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia
                Author notes
                [* ] For Correspondence: : ery_malueka@ 123456ugm.ac.id
                Article
                APJCP-18-1251
                10.22034/APJCP.2017.18.5.1251
                5555531
                28610410
                a56c9b9a-5e49-478d-8ed6-e2bb87a4b9f9
                Copyright: © Asian Pacific Journal of Cancer Prevention

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License

                History
                Categories
                Research Article

                indonesian breast carcinoma,molecular subtypes,clinicopathological factors,prognostic value,survival

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