Evidence-Based Clinical Practice Guideline: Autologous Breast Reconstruction with DIEP or Pedicled TRAM Abdominal Flaps.

The American Society of Plastic Surgeons commissioned a multistakeholder Work Group to develop recommendations for autologous breast reconstruction with abdominal flaps. A systematic literature review was performed and a stringent appraisal process was used to rate the quality of relevant scientific research. The Work Group assigned to draft this guideline was unable to find evidence of superiority of one technique over the other (deep inferior epigastric perforator versus pedicled transverse rectus abdominis musculocutaneous flap) in autologous tissue reconstruction of the breast after mastectomy. Presently, based on the evidence reported here, the Work Group recommends that surgeons contemplating breast reconstruction on their next patient consider the following: the patient's preferences and risk factors, the setting in which the surgeon works (academic versus community practice), resources available, the evidence shown in this guideline, and, equally important, the surgeon's technical expertise. Although theoretical superiority of one technique may exist, this remains to be reported in the literature, and future methodologically robust studies are needed.

Gene Methylation and Cytological Atypia in Random Fine-Needle Aspirates for Assessment of Breast Cancer Risk.

Methods to determine individualized breast cancer risk lack sufficient sensitivity to select women most likely to benefit from preventive strategies. Alterations in DNA methylation occur early in breast cancer. We hypothesized that cancer-specific methylation markers could enhance breast cancer risk assessment. We evaluated 380 women without a history of breast cancer. We determined their menopausal status or menstrual cycle phase, risk of developing breast cancer (Gail model), and breast density and obtained random fine-needle aspiration (rFNA) samples for assessment of cytopathology and cumulative methylation index (CMI). Eight methylated gene markers were identified through whole-genome methylation analysis and included novel and previously established breast cancer detection genes. We performed correlative and multivariate linear regression analyses to evaluate DNA methylation of a gene panel as a function of clinical factors associated with breast cancer risk. CMI and individual gene methylation were independent of age, menopausal status or menstrual phase, lifetime Gail risk score, and breast density. CMI and individual gene methylation for the eight genes increased significantly (P < 0.001) with increasing cytological atypia. The findings were verified with multivariate analyses correcting for age, log (Gail), log (percent density), rFNA cell number, and body mass index. Our results demonstrate a significant association between cytological atypia and high CMI, which does not vary with menstrual phase or menopause and is independent of Gail risk and mammographic density. Thus, CMI is an excellent candidate breast cancer risk biomarker, warranting larger prospective studies to establish its utility for cancer risk assessment. Cancer Prev Res; 9(8); 673-82. ©2016 AACR.

Clinical outcomes with the MammoSite radiation therapy system: results of a prospective trial.

OBJECTIVE: The purpose of this study was to report the treatment-induced adverse events and cosmetic and treatment outcomes of accelerated partial breast irradiation (APBI) delivered with the MammoSite radiation therapy system (RTS) in breast cancer patients undergoing breast-conserving therapy (BCT). METHODS: This is a prospective clinical trial that was approved by the institutional review board. The study included female breast cancer patients undergoing breast-conserving therapy in the form of surgery and APBI delivered with the MammoSite RTS. Patients and tumor characteristics, treatment-induced acute adverse events based on the Common Toxicity Criteria for Adverse Events (CTCAE) version 2.0, chronic AEs according to Radiation Therapy Oncology Group (RTOG) scale, treatment outcomes (including local control, disease-free survival, and overall survival), and cosmetic outcomes are reported. RESULTS: The study included 36 eligible patients treated consecutively in our institution between November 2003 and August 2009. The age range was 45-83 years. A total of 29 patients had invasive disease (median size 1.1 cm), while 7 patients had in situ disease only (median size 0.8 cm). The skin distance in most of the patients (91.7 %) was ≥1 cm; only three patients (8.3 %) had skin distance <1 cm. The median balloon diameter was 5 cm (range 4-6 cm). At a median follow-up of 42 months (range 4-65 months), local control, disease-free survival, and overall survival were 100 %. None of the patients experienced any grade 3 or 4 toxicities; 16.7 and 5.6 % of the patients had late grade 2 fibrosis and telangiectasia, respectively. At last follow-up, cosmetic outcome was rated as good or excellent in 94 % of the patients. CONCLUSION: APBI delivered with the MammoSite RTS is a feasible, tolerable, and effective treatment modality. Multicenter, randomized, controlled clinical trials with a larger number of patients are required for verification.

Hormonal determinants of nipple aspirate fluid yield among breast cancer cases and screening controls.

BACKGROUND: Nipple aspiration fluid (NAF) use as a biosample is limited by the variable yield across studies. We investigated the endocrine determinants of yield in an ongoing breast cancer case-control study. METHODS: One-hundred and eighteen women yielding ≥2 µL NAF and 120 non-yielders were included; serum hormones were measured; differences in median hormones were assessed using the Wilcoxon rank-sum test. ORs and 95% confidence intervals (95% CI) for yielder status relative to hormone levels were estimated using logistic regression, adjusting for parity and lactation, and, in premenopausal women, menstrual cycle phase (MCP). RESULTS: Prolactin concentrations were higher in yielders than non-yielders (premenopausal: 7.6 and 2.5 ng/mL, P < 0.01; postmenopausal 5.3 and 2.2 ng/mL; P < 0.01). Among premenopausal-yielders, estradiol was lower (64.3 vs. 90.5 pg/mL, MCP-adjusted P = 0.02). In separate menopausal status and parity-adjusted models, significant case-control differences persisted in prolactin: case OR 1.93 (95% CI, 1.35-2.77), control OR 1.64 (95% CI, 1.17-2.29). Premenopausal control yielders had higher progesterone (OR, 1.70; 95% CI, 1.18-2.46) and sex-hormone binding-globulin (OR, 2.09; 95% CI, 1.08-4.05) than non-yielders. Among parous women, further adjustment for lactation suggested a stronger positive association of serum prolactin with yield in cases than controls. CONCLUSION: NAF-yielders show higher prolactin than non-yielders, regardless of menopause and parity; implications of this and other endocrine differences on NAF biomarkers of breast cancer risk deserve further study. IMPACT: NAF yield is associated with a distinct endocrine environment that must be considered in studies of NAF-based breast cancer risk markers.

Physical inactivity and percent breast density among Hispanic women.

Results of epidemiologic studies suggest an inverse association between breast cancer risk and physical activity; this is one of the few modifiable breast cancer risk factors identified to date. However, only 2 previous studies assessed the association between physical activity and the extent of mammographically-detected fibroglandular breast density, a marker of breast cancer risk. Moreover, there has been no study of physical inactivity and percent breast density, nor a study of this relationship in Hispanic women, who are less physically active than non-Hispanic whites. In the Chicago Breast Health Project, we collected information on sociodemographic, reproductive, medical and lifestyle factors and percent breast density, assessed quantitatively using full-field digital mammography, from 294 Hispanic women. In our study, we examined the independent associations of hours per day of physical inactivity with percent breast density using multivariate linear regression analysis adjusting for age, education, body mass index, parity, menopausal status, use of hormone replacement therapy and smoking status. Overall, the mean percent breast density was low (i.e., 17.7%) and ranged from 1.9% to 54.6%. There was no difference in percent breast density for women who reported 1.5-3.0 hr of physical inactivity per day compared to women who reported 0-1 hr per day (beta = -0.08, p = 0.95), but percent density was marginally significantly higher for women who were reported at least 3.5 hr per day of physical inactivity (beta = 3.18, p = 0.056). Results were similar, albeit less statistically significant, in analyses of pre/perimenopausal and postmenopausal women separately. These results support the need for further research investigating the effect of physical activity on breast cancer risk.