Faculty Bibliography

Advances in bioelectrical impedance analysis (BIA) permit the assessment of lymphedema by directly measuring lymph fluid changes. The objective of the study was to examine the reliability, sensitivity, and specificity of cross-sectional assessment of BIA in detecting lymphedema in a large metropolitan clinical setting. BIA was used to measure lymph fluid changes. Limb volume by sequential circumferential tape measurement was used to validate the presence of lymphedema. Data were collected from 250 women, including healthy female adults, breast cancer survivors with lymphedema, and those at risk for lymphedema. Reliability, sensitivity, specificity and area under the ROC curve were estimated. BIA ratio, as indicated by L-Dex ratio, was highly reliable among healthy women (ICC=0.99; 95% CI = 0.99 - 0.99), survivors at-risk for lymphedema (ICC=0.99; 95% CI = 0.99 - 0.99), and all women (ICC=0.85; 95% CI = 0.81 - 0.87); reliability was acceptable for survivors with lymphedema (ICC=0.69; 95% CI = 0.54 to 0.80). The L-Dex ratio with a diagnostic cutoff of >+7.1 discriminated between at-risk breast cancer survivors and those with lymphedema with 80% sensitivity and 90% specificity (AUC=0.86). BIA ratio was significantly correlated with limb volume by sequential circumferential tape measurement. Cross-sectional assessment of BIA may have a role in clinical practice by adding confidence in detecting lymphedema. It is important to note that using a cutoff of L-Dex ratio >+7.1 still misses 20% of true lymphedema cases, it is important for clinicians to integrate other assessment methods (such as self-report, clinical observation, or perometry) to ensure the accurate detection of lymphedema.

BACKGROUND: : Nipple-sparing mastectomy has gained popularity, but the question remains of whether it can be offered safely to women with a history of reduction mammaplasty or mastopexy. The authors present their experience with nipple-sparing mastectomy in this patient population. METHODS: : Patients at the authors' institution who had reduction mammaplasty or mastopexy before nipple-sparing mastectomy were identified. Outcomes measured include nipple-areola complex viability, mastectomy flap necrosis, infection, presence of cancer in the nipple-areola complex, and breast cancer recurrence. RESULTS: : The records of the nipple-sparing mastectomy patients at the authors' institution from 2006 through 2012 were reviewed. The authors identified 13 breasts in eight patients that had nipple-sparing mastectomy following reduction mammaplasty or mastopexy. Within this subset of patients, the mean age was 46.6 years and the mean body mass index was 25.1. Nine of 13 breasts had therapeutic resections, whereas the remaining four were for prophylactic indications. Average time elapsed between reduction mammaplasty or mastopexy and nipple-sparing mastectomy was 51.8 months (range, 33 days to 11 years). In all cases, prior reduction mammaplasty/mastopexy incisions were used for nipple-sparing mastectomy. Ten breasts underwent reconstruction immediately with tissue expanders, one with a latissimus dorsi flap with immediate implant and two with immediate abdominally based free flaps. Complications included one hematoma requiring evacuation and one displaced implant requiring revision. There were no positive subareolar biopsy results, and the nipple viability was 100 percent. Mean follow-up time was 10.5 months. CONCLUSIONS: : The authors' experience demonstrates that nipple-sparing mastectomy can be offered to patients with a history of reduction mammaplasty or mastopexy with reconstructive outcomes comparable to those of nipple-sparing mastectomy alone. CLINICAL QUESTION/LEVEL OF EVIDENCE: : Therapeutic, IV.

Nipple-sparing mastectomy (NSM) as a therapeutic or prophylactic procedure for breast cancer is rapidly gaining popularity as the literature continues to support it safety. The lateral inframammary fold (IMF) approach provides adequate exposure and eliminates visible scars on the anterior surface of the breast, making this incision cosmetically superior to radial or periareolar approaches. We reviewed 55 consecutive NSMs performed through a lateral IMF incision with immediate implant-based reconstruction, with or without tissue expansion, between June 2008 and June 2011. Prior to incision, breasts were lightly infiltrated with dilute anesthetic solution with epinephrine. Sharp dissection, rather than electrocautery, was used as much as possible to minimize thermal injury to the mastectomy flap. When indicated, acellular dermal matrix was placed as an inferolateral sling. Subsequent fat grafting to correct contour deformities was performed in select patients. Three-dimensional (3D) photographs assessed changes in volume, antero-posterior projection, and ptosis. Mean patient age was 46 years, and mean follow-up time was 12 months. Twelve mastectomies (22%) were therapeutic, and the remaining 43 (78%) were prophylactic. Seven of the nine sentinel lymph node biopsies (including one axillary dissection) (78%) were performed through the lateral IMF incision without the need for a counter-incision. Acellular dermal matrix was used in 34 (62%) breasts. Average permanent implant volume was 416 cc (range 176-750 cc), and average fat grafting volume was 86 cc (range 10-177 cc). In one patient a positive intraoperative subareolar biopsy necessitated resection of the nipple-areola complex (NAC), and in two other patients NAC resection was performed at a subsequent procedure based on the final pathology report. Mastectomy flap necrosis, requiring operative debridement, occurred in two breasts (4%), both in the same patient. One of these breasts required a salvage latissimus dorsi myocutaneous flap to complete the reconstruction. Three nipples (6%) required office debridement for partial necrosis and operative reconstruction later. No patient had complete nipple necrosis. No statistically significant differences existed between therapeutic and prophylactic mastectomies for developing partial skin and/or nipple necrosis (p = 0.35). Three episodes (5%) of cellulitis occurred, which responded to antibiotics without the need for explantation. Morphological outcomes using 3D scan measurements showed reconstructed breasts were larger, more projected, and less ptotic than the preoperative breasts (196 versus 248 cc, 80 versus 90 mm, 146 versus 134 mm, p < 0.01 for each parameter). Excellent results can be achieved with immediate implant-based reconstruction of NSM through a lateral IMF incision. NAC survival is reliable, and complication rates are low.

9 Background: Traditionally, breast cancer-related lymphedema is considered to be mainly due to the mechanical injury from cancer surgery. Recent research identified that inflammation-infection may be one of the important predictors for lymphedema. This pilot study aimed to explore the associations between lymphatic and pro-inflammatory candidate gene variations and lymphedema. METHODS: A prospective, longitudinal, repeated-measure, and comparative design was used to recruit 178 breast cancer survivors. To ensure the accuracy of lymphedema phenotype, lymphedema was classified into lymphedema of arm and breast. Arm lymphedema must have been validated by infra-red perometer and a bioimpedance device. Breast lymphedema was validated by an observational scale since no objective measure is available. Saliva samples were collected for DNA extraction. Candidate Gene Association Research Method was used to examine the eight genes known for inflammation and lymphatic specific growth factors: cytokines (IL1A, IL6, IL8, IL10, IL13) and PTGS2 (COX2), and lymphatic specific growth factors [VEGF-C and D]. Descriptive statistics, Chi-Squared tests for contingency tables and one-way analysis of variance for continuous variables were used to compare the genotypes for each of these genes in patients with and without lymphedema. Odds ratios of developing lymphedema are estimated. RESULTS: Among 178 survivors, 39 women were confirmed to have arm lymphedema and 43 women had breast lymphedema. Five genes were significantly associated with breast cancer-related lymphedema. Specific single nucleic polymorphisms (SNPs) for lymphatic specific growth factors VEGF-C (rs4604006) and cytokine IL13 (rs1800925) were related to arm lymphedema. Specific SNPs of cytokine IL1A (rs1800587) and PTGS2 (COX2) (rs20417) were associated with breast lymphedema. CONCLUSIONS: Our findings provided preliminary data on genetic susceptibility as a risk factor for breast cancer-related lymphedema. Findings of our study may serve as a preliminary foundation for a priori recognition of genetic risk that may facilitate lymphedema risk prediction prior to surgery and raises the potential for early intervention for a high-risk group.

112 Background: Maintaining a healthy weight after breast cancer diagnosis has been associated with improved survival outcomes. Lifestyle interventions are particularly important in overweight women who are at an increased risk of overall and breast-cancer specific death compared to non-overweight women. The purpose of this study is to examine the barriers and acceptance of a lifestyle intervention program among overweight women with newly diagnosed breast cancer. METHODS: The Breast Cancer Database of NYU Langone Medical Center was queried for women who were newly diagnosed with breast cancer and who had a body mass index (BMI) >/=25kg/m2. Eligible patients participated in the Moving for Life (MFL) exercise program for 16 sessions. Questionnaires were administered at baseline and at the end of the intervention. Descriptive statistics were used to summarize patient characteristics and paired t-tests were used to see if there were any significant differences before and after the intervention. RESULTS: A total of 40 women were eligible to participate in the MFL exercise program. A total of 20 women declined to participate due to location, transportation limitations, and conflicts in schedule. Of the 18 women who enrolled in the MFL program, 13 (72%) were regular attendees and completed the study. The median age was 61 years (range: 38-76) and the average baseline BMI was 31kg/m2(range: 25-42). After completing the MFL intervention, there was a significant decrease in weight and BMI (p=0.04). The average weight loss was 10lbs. Participants also reported a greater enjoyment of exercise (p=0.02), as well as a decrease in pain related to treatment (p=0.05). CONCLUSIONS: Moving for Life is a unique exercise program for breast cancer patients and had a high rate of acceptance and completion in a cohort of overweight breast cancer patients. This study resulted in a statistically significant average weight loss of 10lbs, as well as a greater enjoyment of exercise and decrease in treatment-related pain which may impact long-term lifestyle changes. Longitudinal follow-up at 6- and 12-months will allow assessment of secondary endpoints, including exercise frequency and attitudes about exercise, allowing us to examine sustainability and changes in behaviors and attitudes over time.

Purpose. In November 2009, the U.S. Preventative Service Task Force (USPSTF) revised their breast cancer screening guidelines. We evaluated the pattern of screening subsequent to the altered guidelines in a cohort of women. Methods. Our database was queried for the following variables: age, race, method of diagnosis, mass palpability, screening frequency, histology, and stage. Statistical analyses were performed using Pearson's chi-square and Fisher's exact tests. Results. 1112 women were diagnosed with breast cancer from January 2010 to 2012. The median age at diagnosis was 60 years. Most cancers were detected on mammography (61%). The majority of patients had invasive ductal carcinoma (59%), stage 0 (23%), and stage 1 (50%) cancers. The frequency of screening did not change significantly over time (P = 0.30). However, nonregular screeners had an increased risk of being diagnosed with later stage breast cancer (P < 0.001) and were more likely to present with a palpable mass compared to regular screeners (56% versus 21%; P < 0.001). Conclusions. In our study, screening behavior did not significantly change in the years following the USPSTF guidelines. These results suggest that women who are not screened annually are at increased risk of a delay in breast cancer diagnosis, which may impact treatment options and outcomes.

Background: Advances in breast cancer screening and treatment have fostered the use of surgical procedures that increasingly optimize cosmetic outcome, while ensuring oncologic safety remains the primary concern of the oncologic surgeon. The role of nipple-sparing mastectomy (NSM) for risk-reducing surgery and breast cancer is evolving. It can be difficult to demonstrate involvement of the nipple-areolar complex (NAC) preoperatively, and and in this report we examine the utility of intraoperative subareolar frozen section (FS). Methods: Records of patients undergoing NSM at the NYU Langone Medical Center from 2006-2011 were reviewed retrospectively. Use of subareolar FS was at surgeon's discretion. Results: 237 NSM were performed (146 prophylacytic, 91 theraputic). FC was not utilized in 58 mastectomies (28 prophylactic), with 2 (+) on paraffin. Among the remaining 180 mastectomies, 11 biopsies were (+)(7.2%); 5 subareolar biopsies were (+) on FS and paraffin histologic slides (PS)(2.8%); 6 were negative on FS and (+) on PS. Among the 3 prophylactic NSM with (+) subareolar biopsies there was 1 (+) FS, 1 (-) FS, and 1 with no FS performed. There were no false (+) FS. Four of the 5 patients with (+)FS underwent simultaneous excision of the NAC. The 5th patient had atypia on FS and DCIS on PS, and returned to the OR during the same hospitalization for removal of NAC. The remaining patients underwent subsequent excision of the NAC either during planned 2nd stage reconstruction or following completion of chemotherapy. 8 NAC were free of disease and 5 were positive for in situ or invasive disease. There has been no local recurrence in these patients to date. Conclusions: The rate of NAC involvement is low, 5.5% in this series, and FS, while utilized in the majority of these cases, detected only 46% of subareolar disease. While FS can direct intraoperative decision making, the predictive power is low, and these considerations must be addressed in preoperative patient discussions. Furthermore, among th!

PURPOSE: Skin metastases of breast cancer remain a therapeutic challenge. Toll-like receptor 7 agonist imiquimod is an immune response modifier and can induce immune-mediated rejection of primary skin malignancies when topically applied. Here we tested the hypothesis that topical imiquimod stimulates local antitumor immunity and induces the regression of breast cancer skin metastases. EXPERIMENTAL DESIGN: A prospective clinical trial was designed to evaluate the local tumor response rate of breast cancer skin metastases treated with topical imiquimod, applied 5 d/wk for 8 weeks. Safety and immunologic correlates were secondary objectives. RESULTS: Ten patients were enrolled and completed the study. Imiquimod treatment was well tolerated, with only grade 1 to 2 transient local and systemic side effects consistent with imiquimod's immunomodulatory effects. Two patients achieved a partial response [20%; 95% confidence interval (CI), 3%-56%]. Responders showed histologic tumor regression with evidence of an immune-mediated response, showed by changes in the tumor lymphocytic infiltrate and locally produced cytokines. CONCLUSION: Topical imiquimod is a beneficial treatment modality for breast cancer metastatic to skin/chest wall and is well tolerated. Importantly, imiquimod can promote a proimmunogenic tumor microenvironment in breast cancer. Preclinical data generated by our group suggest superior results with a combination of imiquimod and ionizing radiation and we are currently testing in patients whether the combination can further improve antitumor immune and clinical responses.