TARGIT-R (Retrospective): 5-Year Follow-Up Evaluation of Intraoperative Radiation Therapy (IORT) for Breast Cancer Performed in North America.

BACKGROUND: Intraoperative radiation therapy (IORT) has been investigated for patients with low-risk, early-stage breast cancer. The The North American experience was evaluated by TARGIT-R (retrospective) to provide outcomes for patients treated in "real-world" clinical practice with breast IORT. This analysis presents a 5-year follow-up assessment. METHODS: TARGIT-R is a multi-institutional retrospective registry of patients who underwent lumpectomy and IORT between the years 2007 and 2013. The primary outcome of the evaluation was ipsilateral breast tumor recurrence (IBTR). RESULTS: The evaluation included 667 patients with a median follow-up period of 5.1 years. Primary IORT (IORT at the time of lumpectomy) was performed for 72%, delayed IORT (after lumpectomy) for 3%, intended boost for 8%, and unintended boost (primary IORT followed by whole-breast radiation) for 17% of the patients. At 5 years, IBTR was 6.6% for all the patients, with 8% for the primary IORT cohort and 1.7% for the unintended-boost cohort. No recurrences were identified in the delayed IORT or intended-boost cohorts. Noncompliance with endocrine therapy (ET) was associated with higher IBTR risk (hazard ratio [HR], 3.67). Patients treated with primary IORT who were complaint with ET had a 5-year IBTR rate of 3.9%. CONCLUSION: The local recurrence rates in this series differ slightly from recent results of randomized IORT trials and are notably higher than in previous published studies using whole-breast radiotherapy for similar patients with early-stage breast cancer. Understanding differences in this retrospective series and the prospective trials will be critical to optimizing patient selection and outcomes going forward.

Assessment of hospital-level adjusted breast cancer sentinel lymph node positivity rates.

BACKGROUND/OBJECTIVES: Proficiency of performing sentinel lymph node biopsy (SLNB) for breast cancer varies among hospitals and may be reflected in the hospital's SLNB positivity rate. Our objectives were to examine whether hospital characteristics are associated with variation in SLNB positivity rates and whether hospitals with lower-than-expected SLNB positivity rates have worse patient survival. METHODS: Using the National Cancer Data Base, stage I to III breast cancer patients were identified (2004-2012). Hospital-level SLNB positivity rates were adjusted for tumor and patient factors. Hospitals were divided into terciles of SLNB positivity rates (lower-, higher-, as-expected). Hospital characteristics and survival were examined across terciles. RESULTS: Of 438 610 SLNB patients (from 1357 hospitals), 78 104 had one or more positive SLN (21.3%). Hospitals in the low and high terciles were more likely to be low volume (low: RRR, 4.40; 95% CI, 2.89-6.57; P < 0.001; and high: RRR, 1.79; 95% CI, 1.21-2.64; P < 0.001) compared to hospitals with as-expected (middle tercile) SLNB positivity rates. Stage I patients at low- and high-tercile hospitals had statistically worse survival. CONCLUSIONS: There is a wide variation in hospital SLNB positivity rates. Hospitals with lower- or higher-than-expected SLNB positivity rates were associated with survival differences. Hospital SLNB positivity rates may be a novel 'process measure' to report to hospitals for internal quality assessment.

National Evaluation of the New Commission on Cancer Quality Measure for Postmastectomy Radiation Treatment for Breast Cancer.

BACKGROUND: Current guidelines recommend postmastectomy radiotherapy (PMRT) for patients with ≥4 positive lymph nodes and suggest strong consideration of PMRT in those with 1-3 positive nodes. These recommendations were incorporated into a Commission on Cancer quality measure in 2014. However, national adherence with these recommendations is unknown. Our objectives were to describe PMRT use in the United States in patients with stage I to III invasive breast cancer and to examine possible factors associated with the omission of PMRT. METHODS: From the National Cancer Data Base, 753,536 mastectomies at 1123 hospitals were identified from 1998 to 2011. PMRT use over time was examined using random effects logistic regression analyses, adjusting for patient, tumor, and hospital characteristics. Analyses were stratified by nodal status (≥4 nodes positive, 1-3 nodes positive, node negative). RESULTS: The proportion of patients receiving PMRT increased from 1998 to 2011 (>4 positive nodes: 56.2 to 66.6 %; 1-3 positive nodes: 28.0 to 39.1 %; node-negative: 8.3 to 10.0 %, p < 0.001 for all). In adjusted analyses, patients with ≥4 positive nodes were more likely to have PMRT omitted if they had smaller tumors. Patients with 1-3 positive nodes were more likely to have PMRT omitted if they had lower grade or smaller tumors. Irrespective of patients' nodal status, PMRT utilization rates decreased as age increased. CONCLUSIONS: Though PMRT rates increased over time in patients with ≥4 and 1-3 positive nodes, PMRT in patients with ≥4 positive nodes remains underutilized. Feedback to hospitals using the new Commission on Cancer PMRT measure may help to improve adherence rates.

TARGIT-R (Retrospective): North American Experience with Intraoperative Radiation Using Low-Kilovoltage X-Rays for Breast Cancer.

BACKGROUND: Single-dose intraoperative radiotherapy (IORT) is an emerging treatment for women with early stage breast cancer. The objective of this study was to define the frequency of IORT use, patient selection, and outcomes of patients treated in North America. METHODS: A multi-institutional retrospective registry was created, and 19 institutions using low-kilovoltage IORT for the treatment of breast cancer entered data on patients treated at their institution before July 31, 2013. Patient selection, IORT treatment details, complications, and recurrences were analyzed. RESULTS: From 2007 to July 31, 2013, a total of 935 women were identified and treated with lumpectomy and IORT. A total of 822 patients had at least 6 months' follow-up documented and were included in the analysis. The number of IORT cases performed increased significantly over time (p < 0.001). The median patient age was 66.8 years. Most patients had disease that was <2 cm in size (90 %) and was estrogen positive (91 %); most patients had invasive ductal cancer (68 %). Of those who had a sentinel lymph node procedure performed, 89 % had negative sentinel lymph nodes. The types of IORT performed were primary IORT in 79 %, secondary IORT in 7 %, or planned boost in 14 %. Complications were low. At a median follow-up of 23.3 months, crude in-breast recurrence was 2.3 % for all patients treated. CONCLUSIONS: IORT use for the treatment of breast cancer is significantly increasing in North America, and physicians are selecting low-risk patients for this treatment option. Low complication and local recurrence rates support IORT as a treatment option for selected women with early stage breast cancer.

Tumescent technique does not increase the risk of complication following mastectomy with immediate reconstruction.

BACKGROUND: Despite the growing interest in the advantages of tumescent mastectomy technique, there remain concerns that tumescent solution may increase postoperative complication rates. This study evaluates patient outcomes following tumescent mastectomy in the setting of immediate prosthetic reconstruction. METHODS: Retrospective review of 1,491 breasts (1,030 patients) treated by 4 oncologic and 2 reconstructive surgeons between 2004 and 2012 at a single institution. The primary outcomes of interest included seroma, hematoma, infection, and mastectomy flap necrosis, as well as conversion to autologous reconstruction. Multiple logistic regression was used to determine the adjusted influence of tumescence on outcomes. RESULTS: The tumescent cohort (n = 890 breasts) was younger and experienced lower rates of preoperative radiation than the nontumescent cohort (n = 601 breasts). Mean follow-up was 21.2 months. While tumescent procedures were on average 20 min faster, postoperative complication rates did not significantly differ between cohorts. Regression analysis controlling for potential confounders, including differences in surgeon technique, failed to identify tumescent mastectomy as an independent risk factor for complication [odds ratio (OR) = 1.2, 95% confidence interval (CI) = 0.8-1.8, p = 0.385]. Individually, neither seroma, hematoma, infection, nor flap necrosis was affected significantly by the use of tumescence (OR = 1.66, 95% CI = 0.73-3.78, p = 0.229; OR = 1.11, 95% CI = 0.42-2.95, p = 0.837; OR = 0.84, 95% CI = 0.4-1.75, p = 0.689; OR = 1.19, 95% CI = 0.7-2.03, p = 0.67, respectively). DISCUSSION: This longitudinal study is well equipped to assess the influence of tumescent mastectomy technique in the hands of experienced and high-volume oncologic surgeons on postoperative outcomes. Our analysis suggests that in the setting of an immediate prosthetic reconstruction, tumescent mastectomy does not independently affect postoperative complication rates.

Risk factors for unplanned readmissions following excisional breast surgery.

Thirty-day hospital readmission has emerged as an important variable in health care quality improvement. Our purpose was to investigate the unplanned readmission rate following excisional breast surgery and to identify risk factors associated with readmission. The 2011 National Surgical Quality Improvement Program registry was retrospectively reviewed for patients undergoing excisional breast surgery. Logistic regression was used to investigate the relationship between pre- and perioperative variables and 30-day readmission. Of 13,610 women identified, 292 (2.15%) were readmitted within the 30-day tracking period. The readmitted cohort demonstrated significantly more comorbidities and postoperative complications, as well as longer operative times and hospital stays. Postoperative complications were the best predictors for readmission; however, age, a history of bleeding disorders, immunosuppression, cardiovascular disease, and inpatient hospitalization were also significant independent predictors for readmission. Risk factors for readmission include both pre- and perioperative variables. Perioperative complications, most often infectious in nature, are the strongest predictors; however, comorbidities including immunosuppression, bleeding disorders, and cardiovascular disease also significantly increase the risk for readmission. Although readmission is relatively rare, identifying and managing high-risk patients in addition to more effective methods to prevent and manage postoperative complications will be critical to reducing readmissions and improving patient care.

Selective Progesterone Receptor Modulators in Early-Stage Breast Cancer: A Randomized, Placebo-Controlled Phase II Window-of-Opportunity Trial Using Telapristone Acetate.

PURPOSE: Selective progesterone receptor modulators (SPRMs) show preclinical activity against hormone-sensitive breast cancer, but have not been tested in patients with early, treatment-naïve tumors. PATIENTS AND METHODS: In a double-blind presurgical window trial of oral telapristone acetate (TPA) 12 mg daily versus placebo, 70 patients with early-stage breast cancer were randomized 1:1 (stratified by menopause) and treated for 2 to 10 weeks. The primary endpoint was change in Ki67 between diagnostic biopsy and surgical specimens. Gene expression pre- and posttherapy was assessed using RNA-sequencing and gene set enrichment analysis was performed to determine pathways enriched in response to TPA and placebo treatments. RESULTS: Among 61 evaluable women (29 placebo and 32 telapristone acetate), 91% of tumors were ER/PR positive. The mean Ki67 declined by 5.5% in all women treated with telapristone acetate (P = 0.003), and by 4.2% in all women treated with placebo (P = 0.04). After menopausal stratification, the Ki67 decline remained significant in 22 telapristone acetate-treated premenopausal women (P = 0.03). Differential gene expression analysis showed no significant modulation overall. However, in a subset of tumors that demonstrated ≥30% relative reduction in Ki67 in the telapristone acetate group, genes related to cell-cycle progression, and those in the HER2 amplicon were significantly downregulated. In contrast, no significantly enriched pathways were identified in the placebo group. CONCLUSIONS: Patients treated with telapristone acetate whose Ki67 decreased by ≥30% demonstrated a selective antiproliferative signal, with a potentially important effect on HER2 amplicon genes. Evaluation of SPRMs in a neoadjuvant trial is merited, with attention to predictors of response to SPRM therapy, and inclusion of pre- and postmenopausal women.

Impact of breast MRI in women eligible for breast conservation surgery and intra-operative radiation therapy.

PURPOSE: The current standard of care for women diagnosed with early stage breast cancer is breast-conserving surgery (BCS) followed by external beam radiation therapy, commonly delivered over 3-6 weeks. As an alternative, select patients can undergo intra-operative radiation therapy (IORT) at the time of BCT. This technique delivers a single fraction of radiation at the time of surgery, enabling patients to undergo both surgery and radiation in a single session. Our current study analyzed the value of incorporating breast MRI into the routine work-up of patients deemed eligible for IORT, to quantify the impact on patient eligibility and requirement for additional work-up. MATERIALS AND METHODS: We retrospectively identified patients treated by a single surgeon who were eligible for IORT based on institutional eligibility criteria which included: women age ≥55, grades 1-2, size <3 cm, estrogen receptor (ER) positive, Her-2 neu non-amplified and low/intermediate Ki-67, unifocal invasive ductal/mixed histology carcinomas. All patients must have undergone a physical exam and bilateral diagnostic mammography with ultrasound. From this population, we identified all patients who had undergone bilateral breast MRI as part of pre-operative evaluation. RESULTS: A total of 215 women were identified who met all eligibility criteria. MRI detected additional abnormalities in the breast in 89 patients (41%). Sixty-eight women underwent additional biopsies, with a total of 117 separate lesions biopsied. Of these, pathology was benign in 61 (52.1%), atypical ductal hyperplasia (ADH) in 21 (18%), ductal carcinoma in-situ (DCIS) in 17 (14.5%) and invasive disease in 18 (15.4%). Six patients had MRI-detected abnormalities in the contralateral breast only, with biopsies identifying invasive disease (3), DCIS (1) and benign (2) findings. MRI showed abnormalities in both breasts in 6 patients and 18 additional lesions were biopsied which reveled invasive carcinoma (6), DCIS (7), ADH (3) and benign findings (2). Fifteen patients had either multifocal/multicentric disease or index lesion >3 cm on MRI and were deemed ineligible for IORT. Based on either MRI size or biopsy results, management was ultimately changed for 27 patients (12.5%). Extramammary findings were observed in 17 patients and 11 of these patients underwent further imaging studies all of which returned negative results. CONCLUSION: Preoperative bilateral breast MRI is a valuable tool in the proper selection of patients best suited for IORT. Even in highly selected, favorable risk patients, MRI detected additional lesions that changed surgical and radiation therapy recommendations in 12.5% of patients. However, the cost/benefit ratio needs to be taken into consideration given the high frequency of benign biopsies and additional radiological work-up.

Evaluating the impact of preoperative breast magnetic resonance imaging on the surgical management of newly diagnosed breast cancers.

HYPOTHESIS: Women with newly diagnosed breast cancers may harbor additional ipsilateral or contralateral breast malignancies that are undetected by mammography and ultrasonography. Magnetic resonance imaging (MRI) has demonstrated excellent sensitivity in the detection of breast cancers. However, the impact of routine MRI on the surgical management of new, biopsy-proven breast cancers remains unclear. DESIGN: Retrospective analysis of a prospective database. SETTING: An academic, tertiary care center in a large metropolitan area. PATIENTS: A total of 155 women with breast cancer newly diagnosed by mammography, ultrasonography, and needle biopsy underwent preoperative bilateral breast MRI in a single-institution, single-surgeon setting during 1 year. MAIN OUTCOME MEASURES: Change in surgical management based on breast MRI findings. RESULTS: The MRI demonstrated 124 additional suspicious lesions in 73 patients. Post-MRI follow-up mammograms or ultrasonograms were required in 65 patients, and 41 patients underwent additional image-guided biopsies. There was a change in surgical management as MRI discovered additional, otherwise undetected malignancies in 36 patients based on radiographic-pathologic correlation. Lumpectomy was converted to mastectomy in 10 patients (8 beneficial), wider excision was performed in 21 patients (10 beneficial), and 5 patients (2 beneficial) underwent contralateral surgery. Larger tumor size was an independent predictor of a beneficial change in surgical management (odds ratio, 1.66; 95% confidence interval, 1.04-2.66). CONCLUSIONS: Breast MRI results in a beneficial change in surgical management in 9.7% of newly diagnosed breast cancers. The detection of additional, otherwise undetected ipsilateral and contralateral breast malignancies with MRI suggests that breast MRI may have a role in the evaluation of new breast cancers.

Tamoxifen Acceptance and Adherence among Patients with Ductal Carcinoma In Situ (DCIS) Treated in a Multidisciplinary Setting.

Tamoxifen and other endocrine agents have proven benefits for women with ductal carcinoma in situ (DCIS), but low patient acceptance is widely reported. We examined factors associated with tamoxifen acceptance and adherence among DCIS patients who received a recommendation for therapy in a multidisciplinary setting. Using our institutional database, we identified women diagnosed with DCIS, 1998 to 2009, who were offered tamoxifen. We recorded data on demographics, tumor and therapy variables, tamoxifen acceptance, and adherence to therapy for ≥4 years. Univariable and multivariable analyses were conducted using logistic regression to identify factors specific to each group that were related to acceptance and adherence. A total of 555 eligible women identified, of whom 369 were offered tamoxifen; 298 (81%) accepted, among whom 214 (72%) were adherent, 59 of 298 (20%) were nonadherent, and for 25 (8%), adherence was undetermined. After stepwise elimination in adjusted logistic regression models, acceptance of breast radiotherapy was associated with acceptance of tamoxifen [OR, 2.22; 95% confidence interval (CI), 1.26-3.90; P < 0.01], as was a medical oncology consultation (OR, 1.76; 95% CI, 0.99-3.15; P = 0.05). Insured patients were more likely to adhere to tamoxifen (OR, 6.03; 95% CI, 2.60-13.98; P < 0.01). The majority of nonadherent women (n = 38/56, 68%) discontinued the drug during the first year of treatment with 48 (86%) citing adverse effect(s) as the reason. In a multidisciplinary, tertiary care setting, we observed relatively high rates of acceptance and adherence of tamoxifen. Acceptance of tamoxifen and radiotherapy were associated, and adherence was influenced by insurance status.Key Message: Tamoxifen acceptance and adherence following resection of DCIS of the breast is related to acceptance of radiotherapy and may be improved by confirmation of the recommendation by a medical oncologist. Despite the low cost of tamoxifen, adherence to therapy is significantly impacted by lack of insurance; those who discontinue therapy report adverse effects as a major reason. Cancer Prev Res; 10(7); 389-97. ©2017 AACR.

Cytologic atypia in the contralateral unaffected breast is related to parity and estrogen-related genes.

PURPOSE: The contralateral unaffected breast (CUB) of women with unilateral breast cancer provides a model for the study of breast tissue-based risk factors. Using random fine needle aspiration (rFNA), we have investigated hormonal and gene expression patterns related to atypia in the CUBs of newly diagnosed breast cancer patients. METHODS: 83 women underwent rFNA of the CUB. Cytologic analysis was performed using the Masood Score (MS), atypia was defined as MS > 14. RNA was extracted using 80% of the sample. The expression of 20 hormone related genes was quantified using Taqman Low Density Arrays. Statistical analysis was performed using 2-tailed t tests and linear regression. RESULTS: Cytological atypia was more frequent in multiparous women (P = 0.0392), and was not associated with any tumor-related features in the affected breast. Masood Score was higher with shorter interval since last pregnancy (R = 0.204, P = 0.0417), higher number of births (R = 0.369, P = 0.0006), and estrogen receptor (ER) negativity of the index cancer (R = -0.203, P = 0.065). Individual cytologic features were associated with aspects of parity. Specifically, anisonucleosis was correlated with shorter interval since last pregnancy (R = 0.318, P = 0.0201), higher number of births (R = 0.382, P = 0.0004), and ER status (R = -0.314, P = 0.0038). Eight estrogen-regulated genes were increased in atypical samples (P < 0.005), including TFF1, AGT, PDZK1, PGR, GREB1, PRLR, CAMK2B, and CCND1. CONCLUSIONS: Cytologic atypia, and particularly anisonucleosis, is associated with recent and multiple births and ER negative status of the index tumor. Atypical samples showed increased expression of estrogen-related genes, consistent with the role of estrogen exposure in breast cancer development.

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.

Local transdermal therapy to the breast for breast cancer prevention and DCIS therapy: preclinical and clinical evaluation.

PURPOSE: Women at high risk of breast cancer and those with carcinoma in situ need non-toxic, well-tolerated preventive interventions. One promising approach is drug delivery through the breast skin (local transdermal therapy, LTT). Our goal was to test novel drugs for LTT, to establish that LTT is applicable to non-steroidal drugs. METHODS: Athymic nude rats were treated with oral tamoxifen, transdermal 4-hydroxytamoxifen (4-OHT) or endoxifen gel applied daily to the axillary mammary gland for 6 weeks (Study 1). Study 2 was identical to Study 1, testing transdermal telapristone acetate (telapristone) gel versus subcutaneous implant. At euthanasia, mammary glands and blood were collected. In Study 3, consenting women requiring mastectomy were randomized to diclofenac patch applied to the abdomen or the breast for 3 days preoperatively. At surgery, eight tissue samples per breast were collected from predetermined locations, along with venous blood. Drug concentrations were measured using liquid chromatography-tandem mass spectroscopy. RESULTS: Mammary tissue concentrations of 4-OHT, endoxifen, and telapristone were significantly higher in the axillary glands of the gel-treated animals, compared to inguinal glands or to systemically treated animals. Plasma concentrations were similar in gel and systemically treated animals. The clinical trial showed significantly higher mammary concentrations when diclofenac was applied to the breast skin versus the abdominal skin, but concentrations were variable. CONCLUSIONS: These results demonstrate that lipophilic drugs can be developed for LTT; although the nude rat is suitable for testing drug permeability, delivery is systemic. In human, however, transdermal application to the breast skin provides local delivery.

A Multi-institutional Analysis of Insurance Status as a Predictor of Morbidity Following Breast Reconstruction.

BACKGROUND: Although recent literature suggests that patients with Medicaid and Medicare are more likely than those with private insurance to experience complications following a variety of procedures, there has been limited evaluation of insurance-based disparities in reconstructive surgery outcomes. Using a large, multi-institutional database, we sought to evaluate the potential impact of insurance status on complications following breast reconstruction. METHODS: We identified all breast reconstructive cases in the 2008 to 2011 Tracking Operations and Outcomes for Plastic Surgeons clinical registry. Propensity scores were calculated for each case, and insurance cohorts were matched with regard to demographic and clinical characteristics. Outcomes of interest included 15 medical and 13 surgical complications. RESULTS: Propensity-score matching yielded 493 matched patients for evaluation of Medicaid and 670 matched patients for evaluation of Medicare. Overall complication rates did not significantly differ between patients with Medicaid or Medicare and those with private insurance (P = 0.167 and P = 0.861, respectively). Risk-adjusted multivariate regressions corroborated this finding, demonstrating that Medicaid and Medicare insurance status does not independently predict surgical site infection, seroma, hematoma, explantation, or wound dehiscence (all P > 0.05). Medicaid insurance status significantly predicted flap failure (odds ratio = 3.315, P = 0.027). CONCLUSIONS: This study is the first to investigate the differential effects of payer status on outcomes following breast reconstruction. Our results suggest that Medicaid and Medicare insurance status does not independently predict increased overall complication rates following breast reconstruction. This finding underscores the commitment of the plastic surgery community to providing consistent care for patients, irrespective of insurance status.

Individualized risk of surgical-site infection: an application of the breast reconstruction risk assessment score.

BACKGROUND: Risk factors for surgical-site infection following beast reconstruction have been thoroughly investigated at a population level. However, traditional population-based measures may not always capture the nuances of individual patients. The authors aimed to develop a validated breast reconstruction risk assessment calculator for surgical-site infection that informs risk at an individual level. METHODS: Mastectomies with immediate reconstruction (n = 16,069) from 2005 to 2011 were identified from the National Surgical Quality Improvement Program database. A multiple logistic regression model was created for postoperative surgical-site infection. Hosmer-Lemeshow, C statistic, and Brier score were computed to assess model performance. Bootstrap analysis validated the model. RESULTS: A robust, validated risk model for surgical-site infection was developed using 11 covariates. The model Hosmer-Lemeshow p value was 0.371, the Brier score was 0.0357, and the C statistic was 0.682 (optimism-corrected C statistic, 0.678). The distribution of individual risks demonstrated a positive skew. Population-derived risk underestimated or overestimated individual risk by at least 1.5-fold in nearly one-fifth of all patients. CONCLUSIONS: The breast reconstruction risk assessment score risk calculator for surgical-site infection mitigates the potentially inaccurate interpolation of population-based risk to individual patients. The authors concomitantly developed an online interface-accessible by patients and surgeons alike-to quantify a patient's risk for surgical-site infection, better informing evidence-based decisions and managing patient expectations. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

A randomized phase II presurgical trial of transdermal 4-hydroxytamoxifen gel versus oral tamoxifen in women with ductal carcinoma in situ of the breast.

PURPOSE: Local transdermal therapy to the breast may achieve effective target-organ drug delivery, while diminishing systemic effects. We conducted a randomized, double-blind, placebo-controlled phase II trial comparing transdermal 4-hydroxytamoxifen gel (4-OHT) to oral tamoxifen (oral-T) in women with ductal carcinoma in situ (DCIS). METHODS: Twenty-seven pre- and postmenopausal women were randomized to 4-OHT (4 mg/day) or oral-T (20 mg/day) for 6 to 10 weeks before surgery. Plasma, nipple aspirate fluid, and breast adipose tissue concentrations of tamoxifen and its major metabolites were determined by liquid chromatography/tandem mass spectrometry. The primary endpoint was Ki67 labeling in DCIS lesions, measured by immunohistochemistry. In plasma, insulin-like growth factor-1 (IGFI), sex hormone-binding globulin (SHBG), and coagulation protein concentrations were determined. RESULTS: Posttherapy Ki67 decreased by 3.4% in the 4-OHT and 5.1% in the oral-T group (P ≤ 0.03 in both, between-group P = 0. 99). Mean plasma 4-OHT was 0.2 and 1.1 ng/mL in 4-OHT and oral groups, respectively (P = 0.0003), whereas mean breast adipose tissue concentrations of 4-OHT were 5.8 ng/g in the 4-OHT group and 5.4 ng/g in the oral group (P = 0.88). There were significant increases in plasma SHBG, factor VIII, and von Willebrand factor and a significant decrease in plasma IGFI with oral-T, but not with 4-OHT. The incidence of hot flashes was similar in both groups. CONCLUSIONS: The antiproliferative effect of 4-OHT gel applied to breast skin was similar to that of oral-T, but effects on endocrine and coagulation parameters were reduced. These findings support the further evaluation of local transdermal therapy for DCIS and breast cancer prevention.

Two surgeons, one patient: the impact of surgeon-surgeon familiarity on patient outcomes following mastectomy with immediate reconstruction.

BACKGROUND: Mastectomy with immediate reconstruction requires the coordination and expertise of two distinct surgeons. This often results in several different combinations of mastectomy and reconstructive surgeons, but with an unknown impact on patient outcomes. We evaluate the effect of different surgical teams on complication rates following mastectomy and immediate reconstruction. METHODS: Retrospective review of consecutive patients that underwent mastectomy with immediate prosthetic reconstruction from 4/1998 to 10/2008 at one institution was performed. Patients of the three highest-volume mastectomy and reconstructive surgeons were stratified by their individual combination of surgeons, resulting in nine different surgical teams. Complications were categorized by end-outcome. Appropriate statistics, including multiple linear regression, were performed. RESULTS: Clinical characteristics were similar among patients (n = 511 patients, 699 breasts) with the same mastectomy surgeon but different reconstructive surgeon. Mean follow-up was 38.4 ± 25.7 months. For each mastectomy surgeon, the choice of reconstructive surgeon did not affect complication rates. Furthermore, the combined complication rates of the three highest-volume teams (n = 384 breasts) were similar to the remaining lower-volume teams (n = 315 breasts). Patient factors, but not the individual surgeon or surgical team, were independent risk factors for complications. DISCUSSION: Our study suggests that among high-volume surgeons, complication rates following mastectomy with immediate reconstruction are not affected by the surgeon-surgeon familiarity. The individual surgeon's expertise, and patient risk factors, may have a greater impact on outcomes than the team's experience with each other. These results validate the efficacy and safety of the surgeon distribution model currently used by many breast surgery practices.

Autologous options for postmastectomy breast reconstruction: a comparison of outcomes based on the American College of Surgeons National Surgical Quality Improvement Program.

BACKGROUND: The postmastectomy patient faces a plethora of choices when opting for autologous breast reconstruction; however, multi-institutional data comparing the available techniques are lacking. The National Surgical Quality Improvement Program (NSQIP) database provides a robust patient cohort for comparing outcomes and determining independent predictors of complications for each autologous method. STUDY DESIGN: The NSQIP database was retrospectively reviewed from 2006 to 2010, identifying 3,296 autologous breast reconstruction patients. Univariate analyses compared complication and reoperation rates. Multivariable logistic regression analyses of 4 cohorts (free flaps, pedicled transverse rectus abdominis myocutaeous (TRAM) flaps, latissimus, and all flaps in aggregate) determined complication rates and independent risk factors for complications and specific outcomes of interest (surgical site infection [SSI], flap failure, reoperation) in all flap types. RESULTS: American Society of Anesthesiologists (ASA) classification ≥ 3, body mass index > 30 kg/m(2), recent surgery, delayed reconstruction, and prolonged operative times are significant predictors of increased complications in autologous reconstructions. Rates of complications, flap failure, and reoperation were highest in the free tissue transfer group (p < 0.001). Latissimus flaps showed significantly lower rates of complications than other autologous methods (p < 0.001). Pedicled TRAM patients had the highest incidences of venous thromboembolic disease and SSI. CONCLUSIONS: This large-scale, multicenter evaluation of outcomes in autologous breast reconstruction found that free flaps have the highest captured 30-day complication and reoperation rates of any autologous reconstructive method; complications in latissimus flaps were surprisingly few. Pedicled TRAM and latissimus flaps remain the most commonly used autologous reconstructive methods. In addition to providing statistically robust outcomes data, this study contributes significantly to patient education and preoperative planning discussions.

Soy isoflavone supplementation for breast cancer risk reduction: a randomized phase II trial.

Soy isoflavone consumption may protect against breast cancer development. We conducted a phase IIB trial of soy isoflavone supplementation to examine its effect on breast epithelial proliferation and other biomarkers in the healthy high-risk breast. One hundred and twenty-six consented women underwent a random fine-needle aspiration (rFNA); those with 4,000 or more epithelial cells were randomized to a double-blind 6-month intervention of mixed soy isoflavones (PTIG-2535) or placebo, followed by repeat rFNA. Cells were examined for Ki-67 labeling index and atypia. Expression of 28 genes related to proliferation, apoptosis, and estrogenic effect was measured using quantitative reverse transcriptase PCR. Hormone and protein levels were measured in nipple aspirate fluid (NAF). All statistical tests were two-sided. Ninety-eight women were evaluable for Ki-67 labeling index. In 49 treated women, the median Ki-67 labeling index was 1.18 at entry and 1.12 post intervention, whereas in 49 placebo subjects, it was 0.97 and 0.92 (P for between-group change: 0.32). Menopausal stratification yielded similar results between groups, but within premenopausal soy-treated women, Ki-67 labeling index increased from 1.71 to 2.18 (P = 0.04). We saw no treatment effect on cytologic atypia or NAF parameters. There were significant increases in the expression of 14 of 28 genes within the soy, but not the control group, without significant between-group differences. Plasma genistein values showed excellent compliance. A 6-month intervention of mixed soy isoflavones in healthy, high-risk adult Western women did not reduce breast epithelial proliferation, suggesting a lack of efficacy for breast cancer prevention and a possible adverse effect in premenopausal women.

Comparison of sentinel lymph node biopsy alone and completion axillary lymph node dissection for node-positive breast cancer.

PURPOSE: For women with breast cancer, the role of completion axillary lymph node dissection (ALND) after identification of nodal metastases by sentinel lymph node biopsy (SLNB) has been questioned. Our objectives were to assess national nodal evaluation practice patterns and to examine differences in recurrence and survival for SLNB alone versus SLNB with completion ALND. PATIENTS AND METHODS: From the National Cancer Data Base (1998 to 2005), women with clinically node-negative breast cancer who underwent SLNB and who had nodal metastases were identified. Practice patterns and outcomes were examined for patients who underwent SLNB alone versus SLNB with completion ALND (median follow-up, 63 months). RESULTS: Of 97,314 patients, 20.8% underwent SLNB alone, and 79.2% underwent SLNB with completion ALND. In 2004 to 2005, patients were significantly more likely to undergo SLNB alone if they were older, had smaller tumors, or were treated at non-National Cancer Institute-designated cancer centers. In patients with macroscopic nodal metastases (n = 20,075 during 1998 to 2000), there was a nonsignificant trend toward better outcomes for completion ALND (v SLNB alone) after analysis was adjusted for differences between the two groups: axillary recurrence (hazard ratio [HR], 0.58; 95% CI, 0.32 to 1.06) and overall survival (HR, 0.89; 95% CI, 0.76 to 1.04). In patients with microscopic nodal metastases (n = 2,203 during 1998 to 2000), there were no significant differences in axillary recurrence or survival for patients who underwent SLNB alone versus completion ALND. CONCLUSION: Compared with SLNB alone, completion ALND does not appear to improve outcomes for breast cancer patients with microscopic nodal metastases; however, there was a nonsignificant trend toward better outcomes with completion ALND for those with macroscopic disease.