Breast cancer research and treatment
-
Breast Cancer Res. Treat. · Sep 2011
Common genetic variation in adiponectin, leptin, and leptin receptor and association with breast cancer subtypes.
Adipocytokines are produced by visceral fat, and levels may be associated with breast cancer risk. We investigated whether single nucleotide polymorphisms (SNPs) in adipocytokine genes adiponectin (ADIPOQ), leptin (LEP), and the leptin receptor (LEPR) were associated with basal-like or luminal A breast cancer subtypes. 104 candidate and tag SNPs were genotyped in 1776 of 2022 controls and 1972 (200 basal-like, 679 luminal A) of 2311 cases from the Carolina Breast Cancer Study (CBCS), a population-based case-control study of whites and African Americans. Breast cancer molecular subtypes were determined by immunohistochemistry. ⋯ There was no evidence of interaction with waist-hip ratio. Data suggest associations between LEPR candidate SNPs and luminal A breast cancer in the CBCS and LEPR intron 2 tag SNPs and basal-like breast cancer. Replication in additional studies where breast cancer subtypes have been defined is necessary to confirm these potential associations.
-
Breast Cancer Res. Treat. · Sep 2011
Multicenter StudyObesity and breast cancer survival in ethnically diverse postmenopausal women: the Multiethnic Cohort Study.
Breast cancer survival has been found to be lower in obese women, but few studies have evaluated ethnic variations in this association. This study examined all-cause and breast cancer-specific survival by body mass index (BMI) in the Multiethnic Cohort (MEC) study for African American, Native Hawaiian, Japanese American, Latino, and Caucasian women. Female MEC participants free of breast cancer, aged ≥50 years at cohort entry, and diagnosed with primary invasive breast cancer during follow-up were included in the analyses (n = 3,842). ⋯ After adjustment for breast cancer characteristics, including hormone receptor status, stage at diagnosis, and treatment, obese women had a higher risk of all-cause [hazard ratio (HR) = 1.54; 95% confidence interval (CI): 1.23, 1.91] and breast cancer-specific (HR = 1.45; 95% CI: 1.05, 2.00) mortality compared to women with high-normal BMI; however, being overweight did not affect survival. There was no evidence of ethnic differences in the BMI effect on all-cause (P (interaction) = 0.87) or breast cancer-specific (P (interaction) = 0.63) mortality. Our findings are consistent with the literature that maintaining moderate weight throughout adult life may be beneficial for breast cancer survival in women and this appears to hold for all ethnic groups.
-
Breast Cancer Res. Treat. · Sep 2011
Multicenter StudySurgery of the primary tumor does not improve survival in stage IV breast cancer.
We sought to evaluate the survival of patients who received breast surgery prior to any other breast cancer therapy following a metastatic diagnosis. Standard treatment for stage IV breast cancer is systemic therapy without resection of the primary tumor. Registry-based studies suggest that resection of the primary tumor may improve survival in stage IV cancer. ⋯ Survival was similar between the groups with a median of 3.4 years in the nonsurgery group and 3.5 years in the surgery group. The groups were similar after adjusting for the presence of lung metastases and use of trastuzumab therapy (HR=0.94, CI 0.83-1.08, P=0.38). When matching for the variables associated with a survival benefit in previous studies, surgery was not shown to improve survival in the stage IV setting for this subset.
-
Breast Cancer Res. Treat. · Sep 2011
Case ReportsTwo patients with germline mutations in both BRCA1 and BRCA2 discovered unintentionally: a case series and discussion of BRCA testing modalities.
When a family is known to have a BRCA mutation, genetic testing for family members is typically limited to single site analysis of the known mutation. The exception to this is in Ashkenazi Jewish families, where testing for the three common Ashkenazi Jewish BRCA mutations is recommended. ⋯ These cases raise the question of whether or not Single Site BRACAnalysis for a known familial BRCA mutation is always the appropriate test when testing an affected individual. The implications of missing a second mutation are discussed.
-
Breast Cancer Res. Treat. · Sep 2011
The PI3 kinase/mTOR blocker NVP-BEZ235 overrides resistance against irreversible ErbB inhibitors in breast cancer cells.
Resistance against first and second generation (irreversible) ErbB inhibitors is an unsolved problem in clinical oncology. The purpose of this study was to examine the effects of the irreversible ErbB inhibitors pelitinib and canertinib on growth of breast and ovarian cancer cells. Although in vitro growth-inhibitory effects of both drugs exceeded by far the effects of all reversible ErbB blockers tested (lapatinib, erlotinib, and gefitinib), complete growth inhibition was usually not reached. ⋯ In a next step, we applied PI3K/AKT/mTOR blockers including the dual PI3K/mTOR kinase inhibitor NVP-BEZ235. These agents were found to cooperate with pelitinib and canertinib in producing in vitro growth inhibition in cancer cells resistant against ErbB-targeting drugs. In conclusion, our data show that ErbB drug-refractory activation of the PI3K/AKT/mTOR pathway plays a crucial role in resistance against classical and second-generation irreversible ErbB inhibitors, and NVP-BEZ235 can override this form of resistance against pelitinib and canertinib.