Breast cancer research and treatment
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Breast Cancer Res. Treat. · Nov 2010
Randomized Controlled Trial Multicenter StudyEffect of neoadjuvant anthracycline-taxane-based chemotherapy in different biological breast cancer phenotypes: overall results from the GeparTrio study.
In order to explore the effect of neoadjuvant chemotherapy (NACT) on clinical mid-course and pathological complete response (pCR) at surgery in different biological breast cancer subtypes. The GeparTrio study included 2,072 patients with operable or locally advanced breast cancer. After two cycles with docetaxel, doxorubicin and cyclophosphamide (TAC) patients were randomized according to their clinical response. ⋯ Grading gave independent information for mid-course response within the triple negative group. No factor predicted mid-course response within the other groups. Grading and age can identify subgroups within the luminal and triple negative patients who have an increased benefit from NACT.
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Breast Cancer Res. Treat. · Nov 2010
Multicenter Study Comparative StudyEvaluation of established breast cancer risk factors as modifiers of BRCA1 or BRCA2: a multi-center case-only analysis.
The incomplete penetrance of mutations in BRCA1 and BRCA2 suggests that some combination of environmental and genetic factors modifies the risk of breast cancer in mutation carriers. This study sought to identify possible interactions between established breast cancer risk factors and BRCA1 or BRCA2 mutations using a case-only study design. Breast cancer cases that had been tested for BRCA1 and BRCA2 mutations were identified from 11 collaborating centers. ⋯ Compared with non-carriers, statistically significant IRRs were observed for later age at menarche among BRCA2 mutation carriers, for a greater number of pregnancies among both BRCA1 and BRCA2 mutation carriers, and for alcohol use among BRCA1 mutation carriers. Our data suggest that the risk for breast cancer among BRCA1 or BRCA2 carriers may be modified by reproductive characteristics and alcohol use. However, our results should be interpreted cautiously given the overall inconsistency in the epidemiologic literature on modifiers of BRCA1 and BRCA2.
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Breast Cancer Res. Treat. · Nov 2010
Comparative StudyHuman epidermal growth factor receptor 2 expression in early breast cancer patients: a Swiss cost-effectiveness analysis of different predictive assay strategies.
Trastuzumab has conferred significant clinical benefits in HER-2-positive breast carcinomas. HER-2 status is determined by immunohistochemistry (IHC) and/or fluorescence in situ hybridisation (FISH), but appropriate assessment of HER2 status remains subject to considerable debate. Data on the health economic impact of HER-2 test strategies are limited. ⋯ FISH as primary HER-2 testing modality remained the preferred option in deterministic and probabilistic sensitivity analysis. Predictive testing to identify adjuvant breast cancer patients who benefit from trastuzumab treatment is a clinical and economic necessity. Our model identifies FISH as the most cost-effective approach.
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Breast Cancer Res. Treat. · Nov 2010
Association of CYP1B1 with hypersensitivity induced by taxane therapy in breast cancer patients.
Taxanes represent a group of anticancer drugs with a wide range of activity against breast cancer. Therapy side effects include haematologic toxicity (neutropenia, leucopenia), peripheral neuropathy and hypersensitivity, and demonstrate inter-individual variations. Since it is known that three genes are implicated in taxane turnover, namely ABCB1 in the transport, CYP2C8 in the metabolism and CYP1B1 in the activity, we explored the association among polymorphisms (single nucleotide polymorphisms, SNPs) in these three genes and the occurrence of taxane-induced toxicity. ⋯ We observed a significant association between the CYP1B1*3 allele and a lower occurrence of hypersensitivity reactions to taxane treatment. We speculate that the highest production of 4-hydroxyestradiol (4-OHE2) metabolite by CYP1B1*3 allele could increase the formation of the 4-OHE2-taxane adduct and possibly inhibit taxane toxicity. We suggest that CYP1B1 might affect taxane hypersensitivity therefore representing, if confirmed in a large cohort of patients, an exploratory hypersensitivity predictive biomarker.
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Breast Cancer Res. Treat. · Nov 2010
Tocotrienols induce apoptosis in breast cancer cell lines via an endoplasmic reticulum stress-dependent increase in extrinsic death receptor signaling.
Tocotrienols are naturally occurring forms of vitamin E based on their structural similarity. This study focused on investigating anticancer effects of tocotrienols and the mechanisms of apoptosis induction by tocotrienols in vivo and in vitro. Dietary delivery of γ-tocotrienol (γ-T3) suppressed tumor growth in a syngeneic implantation mouse mammary cancer model by inhibiting cell proliferation and inducing apoptosis. ⋯ Both DR5 and CHOP upregulation were required for γ-T3-induced apoptosis, and DR5 was transcriptionally regulated by CHOP after γ-T3 treatment. Moreover, γ-T3 increased the level of other ER-stress markers. Taken together, these results suggest that upregulation of DR5 by γ-T3 treatment is dependent on JNK and p38 MAPK activation which is mediated by ER-stress.