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The pathogenesis of breast cancers that do not express estrogen receptors or Her-2/neureceptors (ER−/HER2− phenotype) is incompletely understood. We had observed markedly elevated gene expression of gamma-aminobutyric acid type A (GABAA) receptor subunit π (GABAπ, GABRP) in some breast cancers with ER−/HER2− phenotype. In this study, transcriptional profiles (TxPs) were obtained from 82 primary invasive breast cancers by oligonucleotide microarrays. Real-time reverse transcription–polymerase chain reaction (RT–PCR) was used to measure GABAπ gene expression in a separate cohort of 121 invasive breast cancers. GABAπ gene expression values from TxP and RT–PCR were standardized and compared with clinicopathologic characteristics in the 203 patients. GABAπ gene expression was increased in 16% of breast cancers (13/82 TxP, 20/ 121 RT–PCR), particularly in breast cancers with ER−/HER2− phenotype (60%), and breast cancers with basal-like genomic profile (60%). The profile of genes coexpressed with GABAπ in these tumors was consistent with an immature cell type. In multivariate linear regression analysis, the level of GABAπ gene expression was associated with ER−/HER2− phenotype (P<0.0001), younger age at diagnosis (P=0.0003), and shorter lifetime duration of breastfeeding (≤ 6 months) in all women (P=0.017) and specifically in parous women (P=0.013). GABAπ gene expression was also associated with combinations of high grade with ER−/HER2− phenotype (P=0.002), and with Hispanic ethnicity (P=0.036). GABAπ gene expression is increased in breast cancers of immature (undifferentiated) cell type and is significantly associated with shorter lifetime history of breastfeeding and with high-grade breast cancer in Hispanic women.

The triglyceride content of skeletal muscle samples determined by lipid extraction correlates with the severity of insulin-resistant glucose metabolism in muscle. To determine whether this reflects increased triglyceride within muscle fibers and to test the hypothesis that the lipid content in muscle fibers is increased in obesity, the present study was undertaken using quantitative histochemistry of Oil Red O staining of vastus lateralis muscle. A percutaneous muscle biopsy was performed in 9 lean subjects, 15 obese subjects without type 2 diabetes mellitus (DM), and 10 obese subjects with type 2 DM (body mass index [BMI], 23.4 +/- 1.0, 33.6 +/- 0.6, and 36.0 +/- 1.1 kg . m^-^2 for lean, obese, and DM, respectively). Eight obese and 7 DM subjects had a weight loss and reassessment of muscle lipid content. Transverse muscle cryosections were examined by light microscopy with quantitative image analysis (grayscale images obtained by analog to digital conversion) to determine a lipid accumulation index (LAI) based on the percentage of cross-sectional fiber area occupied by lipid droplets. Muscle fiber lipid content was greater in obese individuals with DM than in lean individuals (3.62% +/- 0.65% v 1.42% +/- 0.28%, P < .05) but was not different in obese individuals without DM (2.53% +/- 0.41%). Weight loss reduced the LAI from 3.43% +/- 0.53% to 2.35% +/- 0.31%. In summary, lipid accumulation within muscle fibers is significantly increased in obesity and is reduced by weight loss. This provides important information regarding the accumulation and distribution of skeletal muscle triglyceride in type 2 DM and obesity.

Ten patients (pts) with MBC who had primary/secondary resistance to Taxol (135−250mg/m2over 3−24 hours) were treated with Taxotere 100mg/m2every 21 days.

Twelve patients (pts) received cyclophosphamide (CTX) as a 1hr infusion followed by Taxotere (TXT) as a 1hr infusion every 21 days. Dose levels were 0: CTX/TXT 600/60mg/m2(6 pts), 1: CTX/TXT 600/75mg/m2(3 pts), 2: CTX/TXT 700/75mg/m2(3 pts). Pts were premedicated with dexamethasone 8mg B. I. D. at day 0–4 and oral ondansetron.