Breast cancer research and treatment
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Breast Cancer Res. Treat. · Feb 2012
Transcriptomic and proteomic profiling of KEAP1 disrupted and sulforaphane-treated human breast epithelial cells reveals common expression profiles.
Sulforaphane (SFN), an isothiocyanate found in cruciferous vegetables, is a potent inhibitor of experimental mammary carcinogenesis and may be an effective, safe chemopreventive agent for use in humans. SFN acts in part on the Keap1/Nrf2 pathway to regulate a battery of cytoprotective genes. In this study, transcriptomic and proteomic changes in the estrogen receptor negative, non-tumorigenic human breast epithelial MCF10A cell line were analyzed following SFN treatment or KEAP1 knockdown with siRNA using microarray and stable isotopic labeling with amino acids in culture (SILAC), respectively. ⋯ Moreover, these pathways were most prominent in both the transcriptomic and the proteomic analyses. The aldo-keto reductase family members, AKR1B10, AKR1C1, AKR1C2 and AKR1C3, as well as NQO1 and ALDH3A1, were highly upregulated at both the transcriptomic and the proteomic levels. Collectively, these studies served to identify potential biomarkers that can be used in clinical trials to investigate the initial pharmacodynamic action of SFN in the breast.
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Breast Cancer Res. Treat. · Feb 2012
Incidence and risk factors for axillary web syndrome after breast cancer surgery.
The objective of the study is to estimate the incidence and risk factors of axillary web syndrome (AWS) in early postoperative period (45 days). From the prospective cohort of women undergoing breast cancer surgery, we collected the variables related to patient characteristics, treatment, tumor, and postoperative complications. We performed bivariate and logistic regression. ⋯ The presence of pain in the ipsilateral upper-limb associated with AWS was reported in 5.4% of the patients, and the shoulder joint restriction was observed in 11.4%. When controlling for confounding between AWS and the factors that showed statistical significance in bivariate analysis, the variables that explain the occurrence of the AWS were the type of axillary surgery, where women who underwent sentinel lymph node biopsy showed 68% less risk compared with those that underwent axillary lymphadenectomy (AL) (RR = 0.32; 95% CI, 0.13-0.79; P value = 0.014) and numbness in the arm after an injury of the intercostobrachial nerve, which is 3.19 times the risk of the AWS (RR = 3.19; 95% CI, 1.40-7.29, P value = 0.006). From the above findings, we concluded that the incidence of AWS was 28.1%, and it was associated with AL and numbness in the arm after injury of the intercostobrachial nerve.
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For Hispanic women, the Breast Cancer Risk Assessment Tool (BCRAT; "Gail Model") combines 1990-1996 breast cancer incidence for Hispanic women with relative risks for breast cancer risk factors from non-Hispanic white (NHW) women. BCRAT risk projections have never been comprehensively evaluated for Hispanic women. We compared the relative risks and calibration of BCRAT risk projections for 6,353 Hispanic to 128,976 NHW postmenopausal participants aged 50 and older in the Women's Health Initiative (WHI). ⋯ The AUC was higher for Hispanic women than NHW women (0.63 vs. 0.58, P = 0.03). Updating the BCRAT with contemporaneous breast cancer incidence rates improved calibration in the WHI. The modest discriminatory accuracy of the BCRAT for Hispanic women might improve by using risk factor relative risks specific to Hispanic women.
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Breast Cancer Res. Treat. · Feb 2012
Can we avoid axillary dissection in the micrometastatic sentinel node in breast cancer?
There is considerable interest in foregoing axillary dissection (AD) when the sentinel node (SN) is positive in early breast cancer, particularly when involvement is minimal (micrometastases or isolated tumor cells). To address this issue we analyzed outcomes in patients with a single micrometastatic SN who did not receive AD. We selected 377 consecutive patients treated at the European Institute of Oncology between 1999 and 2007 for invasive breast cancer. ⋯ By multivariable analysis, tumor size and grade were significantly associated with axillary recurrence. The high five-year survival and low cumulative incidence of axillary recurrence in this cohort provide justification for the increasingly common practice of foregoing AD in women with minimal SN involvement, and suggest in particular that AD can safely be avoided in women with small, low-grade tumors. Nevertheless, a subset of patients might be at high risk of developing overt axillary disease and efforts should be made to identify such patients by ancillary analyses of the results of ongoing or recently published clinical trials.
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Breast Cancer Res. Treat. · Feb 2012
Prevalence of BRCA1/2 mutations in sporadic breast/ovarian cancer patients and identification of a novel de novo BRCA1 mutation in a patient diagnosed with late onset breast and ovarian cancer: implications for genetic testing.
In order to adequately evaluate the clinical relevance of genetic testing in sporadic breast and ovarian cancer patients, we offered comprehensive BRCA1/2 mutation analysis in patients without a family history for the disease. We evaluated the complete coding and splice site regions of BRCA1/2 in 193 sporadic patients. In addition, a de novo mutation was further investigated with ultra deep sequencing and microsatellite marker analysis. ⋯ As a consequence, a family history for the disease and an early age of onset should not be used as the only criteria for mutation analysis of BRCA1/2. The relatively high mutation detection ratio suggests that the prevalence of BRCA1/2 may be underestimated, especially in sporadic patients who developed breast and ovarian cancer. In addition, although rare, the possibility of a de novo occurrence in a sporadic patient should be considered.