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Background: The objective of this study was to examine the effect of Paget disease (PD) on axillary lymph node metastases and survival in patients who had concomitant invasive ductal carcinoma (PD-IDC)., Methods: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify women who were diagnosed with PD-IDC from 2000 to 2011, comparing baseline demographic and tumor characteristics with those who were diagnosed with IDC alone during the same period. Multivariable logistic regression was used to examine the association of PD-IDC with axillary lymph node metastasis, and breast cancer-specific survival and overall survival were compared between the PD-IDC and IDC groups using the Kaplan-Meier method and Cox proportional hazards regression., Results: The study cohort included 1102 patients with PD-IDC and 302,242 controls with IDC alone. PD-IDC tumors were more likely to be centrally located (26.9% vs 5.5%; P < .001), high grade (63.5% vs 40.3%; P < .001), >2 cm in greatest dimension (47.1% vs 35.7%; P < .001), and estrogen/progesterone receptor-negative (45.2% vs 22.1%; P < .001). In adjusted analyses, patients with PD-IDC had higher odds of axillary lymph node metastasis (odds ratio, 1.83; P < .001). The unadjusted 10-year breast cancer-specific and overall survival rates were lower for the PD-IDC group compared with the IDC-alone group, although, after adjusting for disease stage, tumor characteristics, and local therapy, no significant differences in mortality risk were observed between the 2 groups (hazard ratio, 0.91; P = .24)., Conclusions: PD-IDC is associated with an increased risk of axillary lymph node metastasis, but not with inferior survival, compared with IDC alone after adjustment for other disease factors., (© 2015 American Cancer Society.)

Purpose: Recent consensus guidelines on margins for breast-conserving surgery (BCS) recommend the use of "no ink on tumor" as the standard for an adequate margin. The recommendations extend to invasive lobular carcinoma (ILC), but the data on this subset are limited. We reviewed our modern dataset on margin status with outcomes of ILC., Methods: We performed a retrospective cohort study on 736 patients with a diagnosis of stage I-III ILC treated at our cancer center between May 1997 and December 2007. Clinicopathologic data were extracted from the Clinical Research Information Systems Database. Margin status was defined using the latest ASCO/ASTRO/SSO consensus guideline criteria., Results: The initial surgery performed was mastectomy in 352 patients (48 %) and BCS in 384 patients (52 %). In multivariate analysis, tumor size and multifocality were significantly associated with high rates of mastectomy and positive surgical margins at initial BCS. After initial BCS, additional surgery was performed in 92 patients (24 %). During a 72-month median follow-up period, 12 (3.1 %) ipsilateral breast tumor recurrences (IBTR) and 5 (1.3 %) other locoregional recurrences (LRR) were observed. Patients with margins with ink on tumor who did not receive further surgery were found to have significantly increased LRR [odds ratio (OR) 5.5; p = 0.02] and IBTR (OR 8.5; p = 0.006), whereas patients with close margins (1-3 mm) and margins within 1 mm were not., Conclusions: Our study supports the validity of using "no ink on tumor" as the standard for a negative margin for pure and mixed ILC treated with multimodality therapy.

Background: In the multidisciplinary care model, breast imagers frequently provide second-opinion reviews of imaging studies performed at outside institutions. However, the need for additional imaging and timeliness of obtaining these studies has yet to be established. We sought to evaluate the frequency of additional imaging orders by breast surgeons and to evaluate the impact of this supplementary imaging on timeliness of surgery., Methods: We identified 2489 consecutive women with breast cancer who underwent first definitive surgery (FDS) at our comprehensive cancer center between 2011 and 2013. The number of breast-specific imaging studies performed for each patient between initial consultation and FDS was obtained. χ (2) tests were used to quantify the proportion of patients undergoing additional imaging by surgeon. Interval time between initial consultation and additional imaging and/or biopsy was calculated. The delay of additional imaging on time to FDS was assessed by t test., Results: Of 2489 patients, 615 (24.7 %) had at least one additional breast-specific imaging study performed between initial consultation and FDS, with 222 patients undergoing additional biopsies (8.9 %). The proportion of patients receiving imaging tests by breast surgeon ranged from 15 to 39 % (p < 0.0001). Patients receiving additional imaging had statistically longer wait times to FDS for BCT (21.4-28.5 days, p < 0.0001)., Conclusions: Substantial variability exists in the utilization of additional breast-specific imaging and in the timeliness of obtaining these tests among breast surgeons. Further research is warranted to assess the sources and impact of this variation on patient care, cost, and outcomes.

Preoperative bevacizumab and chemotherapy may benefit a subset of breast cancer (BC) patients. To explore potential mechanisms of this benefit, we conducted a phase II study of neoadjuvant bevacizumab (single dose) followed by combined bevacizumab and adriamycin/cyclophosphamide/paclitaxel chemotherapy in HER2-negative BC. The regimen was well-tolerated and showed a higher rate of pathologic complete response (pCR) in triple-negative (TN)BC (11/21 patients or 52%, [95% confidence interval (CI): 30,74]) than in hormone receptor-positive (HR)BC [5/78 patients or 6% (95%CI: 2,14)]. Within the HRBCs, basal-like subtype was significantly associated with pCR (P = 0.007; Fisher exact test). We assessed interstitial fluid pressure (IFP) and tissue biopsies before and after bevacizumab monotherapy and circulating plasma biomarkers at baseline and before and after combination therapy. Bevacizumab alone lowered IFP, but to a smaller extent than previously observed in other tumor types. Pathologic response to therapy correlated with sVEGFR1 postbevacizumab alone in TNBC (Spearman correlation 0.610, P = 0.0033) and pretreatment microvascular density (MVD) in all patients (Spearman correlation 0.465, P = 0.0005). Moreover, increased pericyte-covered MVD, a marker of extent of vascular normalization, after bevacizumab monotherapy was associated with improved pathologic response to treatment, especially in patients with a high pretreatment MVD. These data suggest that bevacizumab prunes vessels while normalizing those remaining, and thus is beneficial only when sufficient numbers of vessels are initially present. This study implicates pretreatment MVD as a potential predictive biomarker of response to bevacizumab in BC and suggests that new therapies are needed to normalize vessels without pruning.

Background: Rates of contralateral prophylactic mastectomy (CPM) have increased in the United States, with younger women with breast cancer the most likely to have CPM., Methods: As part of an ongoing cohort study of young women diagnosed with breast cancer at age ≤40 years, we conducted multinomial logistic regression of data from 560 women with unilateral Stage I-III disease to identify factors associated with: (1) CPM versus unilateral mastectomy (UM); (2) CPM versus breast-conserving surgery (BCS)., Results: Median age at diagnosis was 37 years; 66 % of women indicated that their doctor said that BCS was an option or was recommended. Of all women, 42.9 % had CPM, 26.8 % UM, and 30.4 % BCS. Among women who said the surgical decision was patient-driven, 59.9 % had CPM, 22.8 % BCS, and 17.3 % UM. Clinical characteristics associated with CPM versus BCS included HER2 positivity, nodal involvement, larger tumor size, lower BMI, parity, and testing positive for a BRCA mutation. Emotional and decisional factors associated with CPM versus UM and BCS included anxiety, less fear of recurrence, and reporting a patient-driven decision. Women who reported a physician-driven decision were less likely to have had CPM than both of the other surgeries, whereas higher confidence with the decision was associated with having CPM versus BCS., Conclusions: Many young women with early-stage breast cancer are choosing CPM. The association between CPM and emotional and decisional factors suggest that improved communication together with better psychosocial support may improve the decision-making process.

Purpose: We examined the incidence and modern national trends in the management of Paget's disease (PD), including the use of breast-conserving surgery (BCS), mastectomy, axillary surgery, and receipt of radiotherapy., Methods: Using surveillance, epidemiology and end results (SEER) data, we identified 2631 patients diagnosed with PD during 2000-2011. Of these patients, 185 (7%) had PD of the nipple only, 953 (36.2%) had PD with ductal carcinoma in situ (PD-DCIS), and 1493 (56.7%) had PD with invasive ductal carcinoma (PD-IDC). Trends in age-adjusted incidence, primary surgery, sentinel lymph node biopsy (SLNB), and axillary lymph node dissection were examined. Multivariable logistic regression was used to evaluate factors associated with receipt of BCS and radiotherapy., Results: A decrease in the age-adjusted incidence of PD occurred from 2000 to 2011 (-4.3% per year, p < 0.05). The overall rates of mastectomy in the PD only, PD-DCIS, and PD-IDC groups were 47, 69, and 88.9%, respectively. Only in the PD-IDC group did the proportion of patients undergoing BCS increase significantly, from 8.5% in 2000 to 15.7% in 2011 (p = 0.01). Of those who underwent axillary surgery, the proportion of patients undergoing SLNB increased from 2000 to 2011. In adjusted analyses, Paget's subgroup, older age, central tumor location, low/intermediate grade, tumor size <2.0 cm, SEER region, and year of diagnosis after 2006 were significantly associated with receipt of BCS., Conclusions: The incidence of Paget's disease has decreased over time while modern trends in local therapy suggest that BCS, SLNB, and adjuvant radiotherapy remain underutilized.

Multiple randomized trials, as well as a meta-analysis of these studies, have confirmed the equivalence of breast-conservation and mastectomy. In addition, in unselected populations, adjuvant radiation therapy following lumpectomy has been shown to decrease in-breast recurrence and improve overall survival. However, radiation has morbidity, and is costly and inconvenient. Multiple efforts to minimize treatment have been studied, including omitting radiation in low-risk populations, as well as in those with significant competing risks. Central to these efforts has been an increased awareness of the inherent biology, allowing treatment to be more precisely tailored to the risks posed by each individual patient's disease. In addition, an improved understanding of the radio-responsiveness of both tumor and adjacent normal tissue has permitted safe use of short-course (hypofractionated) radiation. Studies are ongoing to determine the most appropriate candidates for both hypofractionated treatment and omission of radiation entirely. The optimal management of ductal carcinoma in situ is also a subject of intense study. Multiple trials have attempted to identify patients who can safely forego radiation and, more recently, molecular predictors of recurrence have been developed to further fine-tune this low-risk population.

Approximately five percent of all breast cancer patients in developed countries present with distant metastases at initial diagnosis. Due to its incurability, metastatic breast cancer is generally treated with systemic therapies to achieve disease control and reduce tumor-related symptoms. Primary treatments for metastatic breast cancer are chemotherapy, endocrine- and biologic therapy, whereas surgery with or without radiotherapy is usually performed to treat impending wound issues. Since 2002, several retrospective non-randomized clinical studies have shown that extirpation of the primary tumor correlates with a significantly improved survival in patients with primary metastatic breast cancer. Others have argued that this survival benefit associated with surgery may be due to selection biases. Therefore, in the absence of published results from randomized controlled trials carried out in India and Turkey and completion of a trial in the United States, there is no clear conclusion on whether surgical excision of the primary breast cancer translates into a survival benefit for patients with de novo metastatic disease. Furthermore, timing and type of surgical procedure, as well as selection of patients who could benefit the most from this approach, represent additional points of uncertainty. Despite the epidemiological burden of this condition, there are no guidelines on how to manage breast cancer patients presenting with de novo metastatic breast cancer; and decisions are often left to provider and patient preferences. Here, we present a critical overview of the literature focusing on the rationale and potential role of primary tumour excision in patients with de novo metastatic breast cancer., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Patients referred to comprehensive cancer centers arrive with clinical data requiring review. Radiology consultation for second opinions often generates additional imaging requests; however, the impact of this service on breast cancer management remains unclear. We sought to identify the incidence of additional imaging requests and the effect additional imaging has on patients' ultimate surgical management., Methods: Between November 2013 and March 2014, 153 consecutive patients with breast cancer received second opinion imaging reviews and definitive surgery at our cancer center. We identified the number of additional imaging requests, the number of fulfilled requests, the modality of additional imaging completed, the number of biopsies performed, and the number of patients whose management was altered due to additional imaging results., Results: Of 153 patients, the mean age was 55 years; 98.9% were female; 23.5% (36) had in situ carcinoma (35 DCIS/1 LCIS), and 76.5% (117) had invasive carcinoma. Additional imaging was suggested for 47.7% (73/153) of patients. After multidisciplinary consultation, 65.8% (48/73) of patients underwent additional imaging. Imaging review resulted in biopsy in 43.7% (21/48) of patients and ultimately altered preliminary treatment plans in 37.5% (18/48) of patients (Fig. 1). Changes in management included: conversion to mastectomy or breast conservation, neoadjuvant therapy, additional wire placement, and need for contralateral breast surgery. Fig. 1 Impact of second-opinion imaging reviews on the management of breast cancer patients, Conclusions: Our analysis of second opinion imaging consultation demonstrates the significant value that this service has on breast cancer management. Overall, 11.7% (18/153) of patients who underwent breast surgery had management changes as a consequence of radiologic imaging review.

Background: Several studies indicate that lymph node (LN) ratio (LNR) is more predictive than the traditional LN-positive stratification (pNs). We assessed whether LNR can provide additional prognostic information on node-positive breast cancer patients, particularly with breast cancer subtypes (BCS)., Methods: We retrospectively reviewed the medical records of 2,049 patients with primary breast cancer treated between January 2006 and December 2011 and identified 511 subjects with positive axillary LN. Clinicopathological findings, types of treatment, and the 5-year overall survival (OS) were included., Results: The results of multivariate analysis of the cohort showed that the correlations of pNs and LNR in regard to OS were P < .001 and P < .001, respectively, with adjustment for tumor characteristics and treatment factors. Moreover, our data revealed that LNR was more predictive in luminal A, luminal B, and luminal human epidermal growth factor receptor 2 in a comparison of pNs and LNR with regard to OS among BCS., Conclusion: LNR and pNs are important prognostic factors with regard to OS for patients with node-positive breast cancer, but LNR has a more correlated value in BCS., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: To assess the efficacy of neoadjuvant systemic therapy (NST) at increasing the rate of successful breast-conserving therapy (BCT) in triple negative breast cancer., Background: Inducing tumor regression to permit BCT is often cited to support administration of NST. To quantify this benefit, we conducted a surgical companion study to CALGB40603, a randomized phase II, 2×2 factorial trial of neoadjuvant paclitaxel ± carboplatin ± bevacizumab (B) followed by doxorubicin plus cyclophosphamide ± B in stage II-III triple negative breast cancer., Methods: Before and after NST, treating surgeons evaluated BCT candidacy by clinico-radiographic criteria; surgery performed was at surgeon and patient discretion. We measured (1) conversion rates from BCT-ineligible to BCT-eligible, (2) surgical choices in BCT candidates, and (3) rates of successful BCT with tumor-free margins., Results: Four hundred four patients were assessable for surgical outcomes. Two hundred nineteen (54%) were BCT candidates before NST. One hundred ninety-seven (90%) remained BCT candidates after NST, of whom 138 (70%) chose BCT, which was successful in 130 (94%). Of 185 (46%) who were not BCT candidates before NST, 78 (42%) converted to candidates with NST. Of these, 53 (68%) chose BCT with a 91% (48/53) success rate. The overall BCT-eligibility rate rose from 54% to 68% (275/404) with NST. Addition of carboplatin, B, or both increased conversion rates., Conclusions: This is the first study to document prospectively a 42% conversion rate from BCT-ineligible to BCT-eligible, resulting in a 14% absolute increase in BCT eligibility. BCT was successful in 93% of patients who opted for it, but 31% of BCT-eligible patients still chose mastectomy.

Radio-guided localization (RGL) for identifying occult breast lesions has been widely accepted as an alternative technique to other localization methods, including those using wire guidance. An appropriate phantom model would be an invaluable tool for practitioners interested in learning the technique of RGL prior to clinical application. The aim of this study was to devise an inexpensive and reproducible training phantom model for RGL. We developed a simple RGL phantom model imitating an occult breast lesion from inexpensive supplies including a pimento olive, a green pea and a turkey breast. The phantom was constructed for a total cost of less than $20 and prepared in approximately 10 min. After the first model's construction, we constructed approximately 25 additional models and demonstrated that the model design was easily reproducible. The RGL phantom is a time- and cost-effective model that accurately simulates the RGL technique for non-palpable breast lesions. Future studies are warranted to further validate this model as an effective teaching tool., (© 2015 Wiley Periodicals, Inc.)

Importance: While the prevalence of ductal carcinoma in situ (DCIS) of the breast has increased substantially following the introduction of breast-screening methods, the clinical significance of early detection and treatment for DCIS remains unclear., Objective: To investigate the survival benefit of breast surgery for low-grade DCIS., Design, Setting, and Participants: A retrospective longitudinal cohort study using the Surveillance, Epidemiology, and End Results (SEER) database from October 9, 2014, to January 15, 2015, at the Dana-Farber/Brigham Women's Cancer Center. Between 1988 and 2011, 57,222 eligible cases of DCIS with known nuclear grade and surgery status were identified., Exposures: Patients were divided into surgery and nonsurgery groups., Main Outcomes and Measures: Propensity score weighting was used to balance patient backgrounds between groups. A log-rank test and multivariable Cox proportional hazards model was used to assess factors related to overall and breast cancer-specific survival., Results: Of 57,222 cases of DCIS identified in this study, 1169 cases (2.0%) were managed without surgery and 56,053 cases (98.0%) were managed with surgery. With a median follow-up of 72 months from diagnosis, there were 576 breast cancer-specific deaths (1.0%). The weighted 10-year breast cancer-specific survival was 93.4% for the nonsurgery group and 98.5% for the surgery group (log-rank test, P < .001). The degree of survival benefit among those managed surgically differed according to nuclear grade (P = .003). For low-grade DCIS, the weighted 10-year breast cancer-specific survival of the nonsurgery group was 98.8% and that of the surgery group was 98.6% (P = .95). Multivariable analysis showed there was no significant difference in the weighted hazard ratios of breast cancer-specific survival between the surgery and nonsurgery groups for low-grade DCIS. The weighted hazard ratios of intermediate- and high-grade DCIS were significantly different (low grade: hazard ratio, 0.85; 95% CI, 0.21-3.52; intermediate grade: hazard ratio, 0.23; 95% CI, 0.14-0.42; and high grade: hazard ratio, 0.15; 95% CI, 0.11-0.23) and similar results were seen for overall survival., Conclusions and Relevance: The survival benefit of performing breast surgery for low-grade DCIS was lower than that for intermediate- or high-grade DCIS. A prospective clinical trial is warranted to investigate the feasibility of active surveillance for the management of low-grade DCIS.

Background: Several studies have showed an increased prevalence of airflow obstruction in first degree relatives of individuals with chronic obstructive pulmonary disease (COPD). Considering no specific research had evaluated airway resistance in offspring of patients with severe COPD, we utilized a spirometry and a impulse oscillometry (IO) to evaluate this population., Materials and Methods: In this case control study, from November 2011 to July 2012, we consecutively evaluated 54 offsprings of severe COPD patients (case group) admitted in the pulmonary ward, affiliated to the Isfahan University of Medical Sciences and control group. Pulmonary function tests and the IO were obtained for both groups. Student's t-test was used for inter-group comparisons, and P values below 0.05 were taken as significant., Results: Abnormal increased airway resistance was seen in cases in comparison with controls (R5 Hz [46.29%, P = 0.01], R25 Hz [42.59%, P < 0.001]). Also, considering the spirometry, case group had pulmonary function parameters less than control group (forced vital capacity [FVC]; P = 0.02, forced expiratory volume in 1(st) s; P < 0.001, forced expiratory flow (FEF) 25-75; P < 0.001, FEF 25-75/FVC; P < 0.001) but they were in normal range., Conclusion: This study demonstrated increased airway resistance among the severe COPD offsprings. The IO may be a sensitive tool for detection of high risk subjects in families with COPD.

Di-(2-ethylhexyl) phthalate (DEHP) interferes with male reproductive endocrine system in mammals, however its effects on fish reproduction are largely unknown. We evaluated sperm quality and investigated reproductive endocrine system in mature goldfish (Carassius auratus) exposed to nominal 1, 10, and 100μg/L DEHP. To examine DEHP estrogenic activity, one group of goldfish was exposed to 17β-estradiol (5μg/L E2) for comparison. Following 30d of exposure, sperm production was decreased and suppressed in DEHP and E2 treated goldfish, respectively. Sperm motility and velocity were decreased in goldfish exposed to 100 and 10μg/L DEHP at 15s post-sperm activation, respectively. Compared to control, 11-ketotestosterone (11-KT) levels were decreased at 10 and 1μg/L DEHP at day 15 and 30, respectively. In E2 treated goldfish, 11-KT levels were decreased compared to control during the period of exposure. E2 levels were increased in goldfish exposed to E2, but remained unchanged in DEHP treated goldfish during the period of exposure. StAR mRNA levels encoding regulator of cholesterol transfer to steroidogenesis were decreased in DEHP and E2 treated goldfish following 15 and 30d of exposure, respectively. Luteinizing hormone (LH) levels were decreased in DEHP and E2 treated goldfish following 15 and 30d of exposure, respectively. In DEHP treated goldfish, gnrh3, kiss1 and its receptor (gpr54) mRNA levels did not change during the experimental period. In E2 treated goldfish, gnrh3 mRNA levels were decreased at day 7, but kiss1 and gpr54 mRNA levels were increased at day 30 of exposure. The mRNA levels of genes encoding testicular LH and androgen receptors remained unchanged in DEHP and E2 treated goldfish. In contrast to E2 treated goldfish, vitellogenin production was not induced in DEHP treated goldfish and mRNA levels of genes with products mediating estrogenic effects remained unchanged or decreased. In conclusion, DEHP interferes with testis and pituitary hormonal functions to reduce sperm quality in goldfish and does not exhibit estrogenic activity., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Intraductal papillomas (IPs) are commonly seen breast lesions with variable clinical presentation. For a palpable lesion and/or evidence of cellular atypia and/or pathologic nipple discharge, excision is warranted to rule out adjacent carcinoma, while for asymptomatic IPs lacking atypia current data for excision vs. observation are controversial. We reviewed outcomes of IPs diagnosed at our institution., Methods: With IRB approval, we reviewed consecutive patients with IPs seen on core biopsy (CBx) between 2005 and 2013. All patients had an excision, with subspecialty breast pathology review of CBx and excisions. The rate of upgrade to cancer on excision was recorded. Differences between atypia and no-atypia groups were determined by two-tailed t test and Fisher's exact test., Results: We identified 97 patients (age range 31-83 years) with IPs on CBx. Among 52 atypical IPs, DCIS was seen in 11 (upgrade 21 %). In 45 IPs without atypia, 3 cancers were seen (upgrade 6. %): 2 had palpable lesions and were found to have DCIS, and 1 invasive cancer was found in a non-palpable mammographically detected BIRADS 4C lesion, whose Cbx result was discordant. If the 2 palpable lesions are excluded, the upgrade rate for IPs without atypia is 2.2 %., Conclusions: This series shows a low upgrade rate for IP without atypia seen on CBx in the absence of a palpable mass and radiographic/pathologic discordance, suggesting that a surgical biopsy may not be necessary. Further prospective studies to better estimate the upgrade rate for IPs without atypia may be helpful.

Background: Breast cancer diagnosed in young women may be more aggressive, with higher rates of local and distant recurrence compared to the disease in older women. Epidemiologic evidence suggests that Korean women have a lower incidence of breast cancer than women in the United States, but that they present at a younger age than their American counterparts. We sought to compare risk factors and management of young women with breast cancer in Boston, Massachusetts (US) with those in Seoul, South Korea (KR)., Materials and Methods: A retrospective review was performed of consecutive patients less than 35 years old with a diagnosis of breast cancer at academic cancer centers in the US and KR from 2000-2005. Patient data were obtained by chart review. Demographic, tumor and treatment characteristics were compared utilizing Pearson's chi- square or Wilcoxon rank-sum tests where appropriate. All differences were assessed as significant at the 0.05 level., Results: 205 patients from the US and 309 from KR were analyzed. Patients in US were more likely to have hormone receptor positive breast cancer, while patients in KR had a higher rate of triple negative lesions. Patients in US had a higher mean body mass index and more often reported use of birth control pills, while those in the KR were less likely to have a sentinel node procedure performed or to receive post mastectomy radiation., Conclusions: Patients under 35 diagnosed with breast cancer in the US and KR differ with respect to demographics, tumor characteristics and management. Although rates of breast conservation and mastectomy were similar, US patients were more likely to receive post mastectomy radiation. The lower use of sentinel node biopsy is explained by the later adoption of the technique in KR. Further evaluation is necessary to evaluate recurrence rates and survival in the setting of differing disease subtypes in these patients.

Purpose: One third of patients with triple-negative breast cancer (TNBC) achieve pathologic complete response (pCR) with standard neoadjuvant chemotherapy (NACT). CALGB 40603 (Alliance), a 2 × 2 factorial, open-label, randomized phase II trial, evaluated the impact of adding carboplatin and/or bevacizumab., Patients and Methods: Patients (N = 443) with stage II to III TNBC received paclitaxel 80 mg/m(2) once per week (wP) for 12 weeks, followed by doxorubicin plus cyclophosphamide once every 2 weeks (ddAC) for four cycles, and were randomly assigned to concurrent carboplatin (area under curve 6) once every 3 weeks for four cycles and/or bevacizumab 10 mg/kg once every 2 weeks for nine cycles. Effects of adding these agents on pCR breast (ypT0/is), pCR breast/axilla (ypT0/isN0), treatment delivery, and toxicities were analyzed., Results: Patients assigned to either carboplatin or bevacizumab were less likely to complete wP and ddAC without skipped doses, dose modification, or early discontinuation resulting from toxicity. Grade ≥ 3 neutropenia and thrombocytopenia were more common with carboplatin, as were hypertension, infection, thromboembolic events, bleeding, and postoperative complications with bevacizumab. Employing one-sided P values, addition of either carboplatin (60% v 44%; P = .0018) or bevacizumab (59% v 48%; P = .0089) significantly increased pCR breast, whereas only carboplatin (54% v 41%; P = .0029) significantly raised pCR breast/axilla. More-than-additive interactions between the two agents could not be demonstrated., Conclusion: In stage II to III TNBC, addition of either carboplatin or bevacizumab to NACT increased pCR rates, but whether this will improve relapse-free or overall survival is unknown. Given results from recently reported adjuvant trials, further investigation of bevacizumab in this setting is unlikely, but the role of carboplatin could be evaluated in definitive studies, ideally limited to biologically defined patient subsets most likely to benefit from this agent., (© 2014 by American Society of Clinical Oncology.)

Background: Considering the effectiveness of craniofacial photographic analysis for diagnosis and management of obstructive sleep apnea-hypopnea syndrome (OSAHS) as well as ethnic differences in indexes measured by this method, this study designed to compare the surface facial dimensions, including nose width, intercanthal width and mandibular width of Iranian patients with mild, moderate and severe OSAHS., Materials and Methods: In this cross sectional study subjects with mild, moderate and severe OSAHS based on apnea-hypopnea index, were studied. To determine cephalometric measurements, face and neck digital photographs were taken from participants following a standardized procedure. Cephalometric measurements including face, intercanthal and mandibular widths were compared between studied groups., Results: In this study, 100 participants enrolled. From which 20 (20.8%), 35 (36.45%) and 41 (42.7%) of them had mild, moderate and severe OSAHS, respectively. Mean of nose, intercanthal and mandibular width were significantly higher in patients with severe OSAHS than those with mild or moderate OSAHS (P < 0.05). In both genders, mandibular width were higher in severe forms of OSAHS. Disease severity was significantly associated with increased age and mandibular width (P < 0.05)., Conclusion: Mandibular width was the most important index, which had a significant association with the disease severity. It seems that our results could be used both for diagnosis and follow-up of OSAHS management. They could be used as baseline information as well as a clinical and research tool in the field of OSAHS.

Background: Neoadjuvant chemotherapy (NCT) downstages advanced primary tumors, with magnetic resonance imaging (MRI) being the most sensitive imaging predictor of response. However, the impact of MRI evaluation on surgical treatment decisions in the neoadjuvant setting has not been well described. We report surgical patterns of care across 8 National Cancer Institute comprehensive cancer centers in women receiving both NCT and MRI to evaluate the impact of MRI findings on surgical planning., Methods: Seven hundred seventy women from 8 institutions received NCT with MRI obtained both before and after systemic treatment. Univariate and multivariate analyses of imaging, patient-, and tumor-related covariates associated with choice of breast surgery were conducted., Results: MRI and surgical data were available on 759 of 770 patients. A total of 345 of 759 (45 %) patients received breast-conserving surgery and 414 of 759 (55 %) received mastectomy. Mastectomy occurred more commonly in patients with incomplete MRI response versus complete (58 vs. 43 %) (p = 0.0003). On multivariate analysis, positive estrogen receptor status (p = 0.02), incomplete MRI response (p = 0.0003), higher baseline T classification (p < 0.0001), younger age (p < 0.0006), and institution (p = 0.003) were independent predictors of mastectomy. A statistically significant trend toward increasing use of mastectomy with increasing T stage at presentation (p < 0.0001) was observed in patients with incomplete response by MRI only. Among women with complete response on MRI, 43 % underwent mastectomy., Conclusions: Within a multi-institutional cohort of women undergoing neoadjuvant treatment for breast cancer, MRI findings were not clearly associated with extent of surgery. This study shows that receptor status, T stage at diagnosis, young age, and treating institution are more significant determinants of surgical treatment choice than MRI response data.

Few studies have examined care processes within providers' and institutions' control that expedite or delay care. The authors investigated the timeliness of breast cancer care at a comprehensive cancer center, focusing on factors influencing the time from initial consultation to first definitive surgery (FDS). The care of 1,461 women with breast cancer who underwent surgery at Dana-Farber/Brigham and Women's Cancer Center from 2011 to 2013 was studied. The interval between consultation and FDS was calculated to identify variation in timeliness of care based on procedure, provider, and patients' sociodemographic characteristics. Targets of 14 days for lumpectomy and mastectomy and 28 days from mastectomy with immediate reconstruction were set and used to define delay. Mean days between consultation and FDS was 21.6 (range 1-175, sd 15.8) for lumpectomy, 36.7 (5-230, 29.1) for mastectomy, and 37.5 (7-111, 16) for mastectomy with reconstruction. Patients under 40 were less likely to be delayed (OR = 0.56, 95 % CI = 0.33-0.94, p = 0.03). Patients undergoing mastectomy alone (OR = 2.64, 95 % CI = 1.80-3.89, p < 0.0001) and mastectomy with immediate reconstruction (OR = 1.34 95 % CI = 1.00-1.79, p = 0.05) were more likely to be delayed when compared to lumpectomy. Substantial variation in surgical timeliness was identified. This study provides insight into targets for improvement including better coordination with plastic surgery and streamlining pre-operative testing. Cancer centers may consider investing in efforts to measure and improve the timeliness of cancer care.

Purpose: Our purpose was to review needle aspiration of breast abscesses and identify factors associated with treatment by aspiration alone versus aspiration with surgical incision and drainage (I/D)., Methods: This Institutional Review Board-approved, retrospective review of the breast ultrasound database from 2008 to 2010 identified 40 patients (41 abscesses) who underwent aspiration, with or without I/D. Demographics, imaging, number of aspirations, and microbiology were reviewed., Results: Twenty-two abscesses underwent aspiration only, 16 > 3 cm, 6 ≤ 3 cm (mean 4.3 cm, range 0.9-10 cm). Known risk factors included lactational (11), 3 weeks post partum (1), pregnancy (1), recent biopsy/lumpectomy (5). Nineteen abscesses underwent aspiration and I/D, 15 > 3 cm, 4 ≤ 3 cm (mean 4.1 cm, range 2.2-7.5 cm). Known risk factors included lactational (4), recurrent subareolar abscess (4), diabetes (3), hydradenitis suppuritiva (1), nipple piercing (2), smoking (1), pregnancy (1), HIV (1), and lumpectomy (1). Identified reasons for I/D included lack of improvement/recurrence (12), fistula (3), and one electively after clinical improvement of a recurrent subareolar abscess., Conclusions: Abscesses associated with pregnancy and lactation or breast biopsy are effectively managed with aspiration, even when large. Recurrence, chronicity, or fistula may require surgical intervention., (© 2014 Wiley Periodicals, Inc.)

Distinguishing tumor from normal glandular breast tissue is an important step in breast-conserving surgery. Because this distinction can be challenging in the operative setting, up to 40% of patients require an additional operation when traditional approaches are used. Here, we present a proof-of-concept study to determine the feasibility of using desorption electrospray ionization mass spectrometry imaging (DESI-MSI) for identifying and differentiating tumor from normal breast tissue. We show that tumor margins can be identified using the spatial distributions and varying intensities of different lipids. Several fatty acids, including oleic acid, were more abundant in the cancerous tissue than in normal tissues. The cancer margins delineated by the molecular images from DESI-MSI were consistent with those margins obtained from histological staining. Our findings prove the feasibility of classifying cancerous and normal breast tissues using ambient ionization MSI. The results suggest that an MS-based method could be developed for the rapid intraoperative detection of residual cancer tissue during breast-conserving surgery.

The objective of the present study was to establish multiethnic, all-age prediction equations for estimating stature from arm span in males and females. The arm span/height ratio (ASHR) from 13 947 subjects (40.9% females), aged 5-99 years, from nine centres (in China, Europe, Ghana, India and Iran) was used to predict ASHR as a function of age using the lambda, mu and sigma method. Z-scores for forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC in 1503 patients were calculated using measured height and height calculated from arm span and age. ASHR varied nonlinearly with age, was higher in males than in females and differed significantly between the nine sites. The data clustered into four groups: Asia, Europe, Ghana and Iran. Average predicted FEV1, FVC and FEV1/FVC using measured or predicted height did not differ, with standard deviations of 4.6% for FEV1, 5.0% for FVC and 0.3% for FEV1/FVC. The percentages of disparate findings for a low FEV1, FVC and FEV1/FVC in patients, calculated using measured or predicted height, were 4.2%, 3.2% and 0.4%, respectively; for a restrictive pattern, there were 1.0% disparate findings. Group- and sex-specific equations for estimating height from arm span and age to derive predicted values for spirometry are clinically useful., (©ERS 2014.)

Background: The rate of reexcision in breast-conserving surgery remains high, leading to delay in initiation of adjuvant therapy, increased cost, increased complications, and negative psychological impact to the patient.1 (-) 3 We initiated a phase 1 clinical trial to determine the feasibility of the use of intraoperative magnetic resonance imaging (MRI) to assess margins in the advanced multimodal image-guided operating (AMIGO) suite., Methods: All patients received contrast-enhanced three-dimensional MRI while under general anesthesia in the supine position, followed by standard BCT with or without wire guidance and sentinel node biopsy. Additional margin reexcision was performed of suspicious margins and correlated to final pathology (Fig. 1). Feasibility was assessed via two components: demonstration of safety and sterility and acceptable duration of the operation and imaging; and adequacy of intraoperative MRI imaging for interpretation and its comparison to final pathology. Fig. 1 Schema of AMIGO trial, Results: Eight patients (mean age 48.5 years), 4 with stage I breast cancer and 4 with stage II breast cancer, were recruited. All patients underwent successful BCT in the AMIGO suite with no AMIGO-specific complications or break in sterility during surgery. The mean operative time was 113 min (range 93-146 min)., Conclusions: Our experience with AMIGO suggests that it is feasible to use intraoperative MRI imaging to evaluate margin assessment in real time. Further research is required to identify modalities that will lead to a reduction in reexcision in breast cancer therapy.

The fungicide vinclozolin (VZ) is in use globally and known to disrupt reproductive function in male. The present study tested the hypothesis that VZ disrupts testicular function in goldfish (Carassius auratus) by affecting brain-pituitary-testis axis. Goldfish were exposed to 100, 400 and 800 μg/L VZ and 5 μg/L 17β-estradiol (E2) for comparison. In VZ treated goldfish, 11-ketotesteosterone (11-KT) secretion was changed depending on dose and duration period of treatment. Following 7 days of exposure, 11-KT was decreased in goldfish exposed to 800 μg/L VZ, while it was increased in goldfish exposed to 100 μg/L VZ after 30 days of exposure. Circulating E2 level was unchanged in VZ treated goldfish, however the E2/11-KT ratio was increased in a concentration-related manner. In E2 treated goldfish, circulatory 11-KT and E2 levels were decreased and increased, respectively, which resulted in an increase in the E2/11-KT ratio. Exposure to VZ at 100 μg/L caused a significant increase in the circulatory luteinizing hormone (LH) after 30 days. In E2 treated fish circulatory LH was decreased, significantly. Transcripts of genes encoding gonadotropin-releasing hormone and androgen receptor in the brain, and those of genes encoding LH and follicle-stimulating hormone receptors, StAR, CYP17, and 3β-HSD in the testis changed in VZ-treated goldfish depending on concentration and period of treatment. mRNA of genes encoding vitellogenin and estrogen receptor in the liver and cytochrome P450 aromatase in the brain were increased in E2-treated goldfish. The results suggest that VZ-induced changes in 11-KT were due to disruption in brain-pituitary-testis axis and provide integrated characterization of VZ-related reproductive disorders in male fish., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: Pulmonary impairment in patients suffering ulcerative colitis (UC) has been suggested by several investigators using standard pulmonary function tests (PFTs). This changes in pulmonary function associated with minimal respiratory symptoms have been documented, especially in patients with active disease. The aim of this prospective study was to determine airway resistance and lung volumes in patients with UC who have no respiratory symptoms in comparisons to a healthy control group., Materials and Methods: We evaluated a total of 30 patients with UC by means of spirometry, body plethysmography, and impulse oscillometry. The patients were not complaining of any pulmonary symptoms and did not present any history of previous respiratory diseases. As controls we examined 30 healthy subjects matched for gender, age, and smoking status. The relationship between PFT, lung volume, and airway resistance; and the activity, localization, and duration of the UC disease were analyzed., Results: There was a significant difference between airway resistances (kPa/L/s) measured by body plethysmography in patients with UC and those of the controls (R5hz; 0.60 ± 0.44 vs. 0.39 ± 0.13; P < 0.001) and R20hz (0.37 ± 0.19 vs. 0.29 ± 0.1, P = 0.02). There were no correlation between PFT, airway resistance and site and scoring activity (P > 0.05)., Conclusion: Despite the lack of pulmonary symptoms, increased airway resistance was found in UC patients. We also have not found correlation between PFT, lung volume and airway resistance values and scoring of UC activity.

Conventional preoperative chemotherapy regimens have only limited efficacy in hormone receptor positive (HR+) breast cancer and new approaches are needed. We hypothesized that capecitabine, which is effective in metastatic breast cancer, may be an active preoperative treatment for HR+ breast cancer. Women with HR+, HER2-negative operable breast cancer received capecitabine, 2000 mg/m(2) daily in divided doses for 14 days, followed by a 7-day rest period. Treatment was repeated every 21 days for a total of four cycles. The primary endpoint of the study was to determine the rate of pathological complete response (pCR). Because of slow accrual, the study was closed after 24 patients were enrolled. Three patients had a complete clinical response, and eight patients had a partial clinical response, for an overall clinical response rate of 45.8%. There were no cases of pCR. Of the 22 patients who had pathological response assessment by the Miller-Payne grading system, there were six grade 3 responses, and no grade 4 or 5 responses. Toxicity was manageable: the only grade 3 toxicities observed were one case each of diarrhea, palmar plantar erythrodysesthesia, hypokalemia, and mucositis. There was no association between baseline levels, or change in level from baseline to cycle 1, or from baseline to time of surgery, of thymidine phosphorylase (TYMP), thymidylate synthase (TYMS), dihydropyrimidine dehydrogenase (DPYD), or Ki67 and pathological, clinical, or radiographic response. Preoperative capecitabine is a well-tolerated regimen, but appears not lead to pCR when used as monotherapy in HR+ breast cancer., (© 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

The authors sought to measure the timeliness of care for patients with breast cancer at Dana-Farber/Brigham and Women's Cancer Center throughout the treatment continuum, and to identify sources of variation that may serve as targets for improving care delivery. This report describes the methods that were developed to measure and analyze baseline performance.

Background: The goal of this study was to determine the length of operative time and its effect on surgeon productivity with the use of intraoperative digital specimen mammography (IDSM) compared to standard specimen mammography (SSM)., Methods: A retrospective chart review was performed on 344 consecutive patients from a single breast surgeon from 2003 to 2010. Operative time was compared between procedures using SSM vs IDSM. Surgeon productivity was evaluated by the number of wire-localized excisions performed prior to and after implementation of IDSM., Results: Two hundred thirty patients underwent SSM and 114 underwent IDSM. Average operative time in the SSM group was 78 minutes vs 68 minutes in the IDSM group (P < .0001). In the first 2 years after implementation of IDSM, the number of wire-localized excisions performed increased by 20%., Conclusions: Operative times were significantly shorter with the use of IDSM vs SSM, and this was associated with an increase in surgeon productivity., (Copyright © 2013 Elsevier Inc. All rights reserved.)

In vitro techniques for investigating the toxic effects of environmental contaminants (EC) on fish spermatozoa motility kinetics and fertilizing ability are valuable tools to understand toxicity mechanisms and sites of action. In vitro techniques may also be well-suited to studies of endocrine disruption in male fertility in vivo. This review shows ECs to decrease or suppress spermatozoa motility kinetics and fertilizing ability in a dose-dependent manner, with toxic concentrations being much higher than those reported in the aquatic environment. Sites of action depend on EC concentration and duration of exposure. Both instant (immediate) and incubated exposure of spermatozoa to ECs results in damage to the plasma membrane and the axoneme, while disruption of energy metabolism appears only during incubated exposure. Spermatozoa lose fertilizing ability following exposure to ECs in vitro, not only due to inhibition or suppression of the initiation of motility, but also through damage to DNA. This review highlights the significant lack of information about disruption of spermatozoa function associated with exposure to water from polluted areas as well as combined effects of ECs. Specifics of alterations in intracellular signaling cascades involved in the initiation of spermatozoa motility following exposure to sublethal concentrations of ECs remain unknown. Further studies are also needed to elucidate in vitro EC effects during spermatozoa maturation, when spermatozoa acquire the potential for motility., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Objective: To compare the extraction time and infection rate of umbilical cord by applying ethanol, humanmilk or dry care., Method: The parallel single-blinded randomised clinical trial was performed on 300 neonates at Shahid Sadougi University of Medical Sciences and Health Service, Yazd, Iran, between March and September 2010. The neonates were divided into three random but numerically equal groups. Each group was assigned the application of ethanol or mother's milk or to keep the stump dry. The neonates were visited on the 3rd and the 7th day after birth and follow-up was maintained telephonically until umbilical separation. Umbilical separation time and umbilical local infection frequency were considered as the study outcome, which was compared among the three groups according to age, gender and delivery type of the neonates., Results: Umbilical separation time in neonates of the human milk group had significant difference with the ethanol group (p=0.0001) and drying groups (p = 0.003). Frequency of omphalitis had no significant difference among the three groups., Conclusion: Topical usage of human milk on umbilical cord stamp decreased separation time and incidence rate of omphalitis.

Neoadjuvant therapy (NAC) is commonly used in operable breast cancer. Previous studies have suggested a high rate of postoperative complications after NAC. We prospectively evaluated the surgical complications in a cohort of patients who underwent mastectomy following neoadjuvant adriamycin/cytoxan/taxol (AC/T) plus bevacizumab (bev) and compared the rate of complications to a matched cohort of neoadjuvant AC/T without bev. One hundred patients with HER2-negative breast cancer enrolled in a single-arm trial of neoadjuvant AC/T plus bev (cohort 1), 60 of these patients underwent mastectomy and were matched with 59 patients who received standard neoadjuvant AC/T (cohort 2) over a similar time period in the same healthcare system. All patients underwent mastectomy with or without reconstruction. Fisher's exact tests were used to compare complication rates, with p < 0.05 considered significant. Patients were matched well in terms of demographics. The overall complication rate was 32 % in cohort 1 and 31 % in cohort 2 (p value = 1, Table 1). In cohort 1, 7 of 23 (30 %) patients who underwent immediate expander/implant reconstruction had complications, including 2 patients who had explantation of their reconstructions. In cohort 2, 0 of 8 (0 %) had complications (p value = 0.15). Nearly a third of patients undergoing NAC with AC/T with or without bev developed a postoperative complication after mastectomy. The use of bev was not associated with a significant increase in surgical complications, although this is a nonrandomized data set with a small sample size. As larger data sets become available with the use of neoadjuvant bevacizumab with mastectomy, further refinement may be necessary.

We sought to assess whether a close surgical margin (>0 and <2 mm) after breast-conserving therapy (BCT) confers an increased risk of local recurrence (LR) compared with a widely negative margin (≥2 mm). We studied 906 women with early-stage invasive breast cancer treated with BCT between January 1998 and October 2006; 91 % received adjuvant systemic therapy. Margins were coded as: (1) widely negative (n = 729), (2) close (n = 85), or (3) close (n = 84)/positive (n = 8) but having no additional tissue to remove according to the surgeon. Cumulative incidence of LR and distant failure (DF) were calculated using the Kaplan-Meier method. Gray's competing-risk regression assessed the effect of margin status on LR and Cox proportional hazards regression assessed the effect on DF, controlling for biologic subtype, age, and number of positive lymph nodes (LNs). Three hundred seventy-seven patients (41.6 %) underwent surgical re-excision, of which 63.5 % had no residual disease. With a median follow-up of 87.5 months, the 5-year cumulative incidence of LR was 2.5 %. The 5-year cumulative incidence of LR by margin status was 2.3 % (95 % CI 1.4-3.8 %) for widely negative, 0 % for close, and 6.4 % (95 % CI 2.7-14.6 %) for no additional tissue, p = 0.3. On multivariate analysis, margin status was not associated with LR; however, triple-negative subtype (AHR 3.7; 95 % CI 1.6-8.8; p = 0.003) and increasing number of positive LNs (AHR 1.6; 95 % CI 1.1-2.3; p = 0.025) were associated. In an era of routine adjuvant systemic therapy, close surgical margins and maximally resected close/positive margins were not associated with an increased risk of LR compared to widely negative margins. Additional studies are needed to confirm this finding.

Background: Admission of low birth-weight (LBW) neonates in neonatal intensive care unit (NICU) causes their deprivation of tactile and sensory stimulation., Objective: The purpose of this study was to evaluate efficacy of body massage on growth parameters (weight, height and head circumference) gain velocity of LBW in Yazd, Iran., Materials and Methods: A randomized clinical trial study was conducted on LBW neonates whom were admitted to NICU of Shahid Sadoughi Hospital, Yazd, Iran from March to December 2011. Neonates were randomly assigned to two groups. In group one, 20 neonates were received massage three times in a day for consecutive 14 days by their mothers. In group two, intervention consisted of standard and routine care as control group. The primary endpoints were efficacy in increase of mean of weight, height and head circumference that were evaluated 14 days after intervention, at ages one and two months. Secondary outcome was clinical side effects., Results: 17 girls and 23 boys with mean gestational age of 34.4±1.22 weeks were evaluated. In the body massage group, only weight at the age of two months was significantly higher than the control group (mean±SD: 3250±305 vs. 2948±121 gr, p=0.005). No adverse events were seen in the two groups., Conclusion: Body massage might be used as an effective and safe non-medical intervention for increasing of weight gain velocity in LBW preterm neonates.

Background: Increased pathologic complete response (pCR) rates observed with neoadjuvant chemotherapy (NCT) for some subsets of patients with invasive breast cancer have prompted interest in whether patients who achieved a pCR can be identified preoperatively and potentially spared the morbidity of surgery. The objective of this multicenter, retrospective study was to estimate the accuracy of preoperative magnetic resonance imaging (MRI) in predicting a pCR in the breast., Methods: MRI studies at baseline and after the completion of NCT plus data regarding pathologic response were collected retrospectively from 746 women who received treatment at 8 institutions between 2002 and 2011. Tumors were characterized by immunohistochemical phenotype into 4 categories based on receptor expression: hormone (estrogen and progesterone) receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative (n = 327), HR-positive/HER2-positive, (n = 148), HR-negative/HER2-positive, (n = 101), and triple-negative (HR-negative/HER2 negative; n = 155). In all, 194 of 249 patients (78%) with HER2-positive tumors received trastuzumab. Univariate and multivariate analyses of factors associated with radiographic complete response (rCR) and pCR were performed., Result: For the total group, the rCR and pCR rates were 182 of 746 patients (24%) and 179 of 746 patients (24%), respectively, and the highest pCR rate was observed for the triple-negative subtype (57 of 155 patients; 37%) and the HER2-positive subtype (38 of 101 patients; 38%). The overall accuracy of MRI for predicting pCR was 74%. The variables sensitivity, negative predictive value, positive predictive value, and accuracy differed significantly among tumor subtypes, and the greatest negative predictive value was observed in the triple-negative (60%) and HER2-positive (62%) subtypes., Conclusions: The overall accuracy of MRI for predicting pCR in invasive breast cancer patients who were receiving NCT was 74%. The performance of MRI differed between subtypes, possibly influenced by differences in pCR rates between groups. Future studies will determine whether MRI in combination with directed core biopsy improves the predictive value of MRI for pathologic response., (Copyright © 2013 American Cancer Society.)

Purpose: To examine the rate of local recurrence according to the margin status for patients with pure ductal carcinoma in situ (DCIS) treated by mastectomy., Methods and Materials: One hundred forty-five consecutive women who underwent mastectomy with or without radiation therapy for DCIS from 1998 to 2005 were included in this retrospective analysis. Only patients with pure DCIS were eligible; patients with microinvasion were excluded. The primary endpoint was local recurrence, defined as recurrence on the chest wall; regional and distant recurrences were secondary endpoints. Outcomes were analyzed according to margin status (positive, close (≤2 mm), or negative), location of the closest margin (superficial, deep, or both), nuclear grade, necrosis, receptor status, type of mastectomy, and receipt of hormonal therapy., Results: The primary cohort consisted of 142 patients who did not receive postmastectomy radiation therapy (PMRT). For those patients, the median follow-up time was 7.6 years (range, 0.6-13.0 years). Twenty-one patients (15%) had a positive margin, and 23 patients (16%) had a close (≤2 mm) margin. The deep margin was close in 14 patients and positive in 6 patients. The superficial margin was close in 13 patients and positive in 19 patients. One patient experienced an isolated invasive chest wall recurrence, and 1 patient had simultaneous chest wall, regional nodal, and distant metastases. The crude rates of chest wall recurrence were 2/142 (1.4%) for all patients, 1/21 (4.8%) for those with positive margins, 1/23 (4.3%) for those with close margins, and 0/98 for patients with negative margins. PMRT was given as part of the initial treatment to 3 patients, 1 of whom had an isolated chest wall recurrence., Conclusions: Mastectomy for pure DCIS resulted in a low rate of local or distant recurrences. Even with positive or close mastectomy margins, the rates of chest wall recurrences were so low that PMRT is likely not warranted., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Contemporary clinical outcomes of microinvasive breast cancer (MIBC), defined as no focus >1 mm, are not well characterized. We document the immunophenotype, incidence of axillary metastases, and rate of recurrence in a well-defined case series., Methods: We reviewed 83 consecutive patients with MIBC from 1997 to 2005. Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2/neu) receptor status were assessed. The cumulative incidence of local recurrence (LR) and nodal/distant recurrence was calculated. Predictors of recurrence were identified and effect estimates determined., Results: Fifty-two patients (63%) underwent breast-conserving therapy (BCT) and 31 (37%) underwent mastectomy. Sixty-one percent had ER-positive disease and 49% had HER-2/neu-positive disease. Three (4%) of 68 patients with sentinel node mapping or axillary dissection had single node micrometastases, and none had macrometastases or multiple nodes involved. Median follow-up was 6.4 years, with 6 LRs, 2 regional nodal recurrences, and 2 concurrent local/distant recurrences. The 5-year cumulative incidence of recurrence (local, nodal, or distant) was 5.3% (95% confidence interval [CI] 2.0-13.4) for all patients, and among BCT patients, the 5-year cumulative incidence of LR was 4.2% (95% CI 0.7-12.7). HER-2/neu overexpression was not associated with recurrence (P = 0.46). Close/positive margins (≤2 mm) were significantly associated with an increased risk of LR after BCT or mastectomy (hazard ratio 8.8; 95% CI 1.6-48.8; P = 0.003)., Conclusions: MIBC has a favorable prognosis, and HER-2/neu overexpression, although highly prevalent, is not significantly associated with recurrence. Axillary metastases at diagnosis are small and infrequent. The cumulative incidence of LR after BCT is acceptable; however, our data confirm that negative margins (>2 mm) are required for optimal BCT outcomes.

Background: Obstructive sleep apnea (OSA) is a common but usually under-diagnosed sleep disorder. Objective diagnosis is based on polysomnography, which is an expensive test. We assessed the reliability and diagnostic accuracy of the Berlin questionnaire (BQ) in diagnosis of OSA in Iranian sleep clinic patients., Methods: A cross-sectional linguistic validation study was conducted on consecutive Iranian patients with Persian language attending one sleep clinic in Isfahan (Iran) were studied. Patients completed the Persian BQ (contains 10 questions in 3 categories), developed by forward-backward translation method. The patients underwent an overnight polysomnographic study at the clinic. Apneas/hypopnea index of >5/Hour was considered for diagnosis of OSA., Results: One hundred and fifty seven patients (55.4% male, mean age = 52.3 ± 13.6 years) were evaluated. Sleep study confirmed OSA diagnosis in 91.7% of the studied patients. The reliability analysis of the BQ categories showed alpha Cronbach's as 0.70 and 0.50 for category 1 and category 2, respectively. BQ categories 1-3 were positive respectively in 88.5%, 67.5%, and 66.9% of the patients. The BQ and sleep study were in agreement for 82.1% of the cases. The sensitivity, specificity, positive and negative predictive values, and positive, and negative likelihood ratio of the BQ were calculated as 84.0%, 61.5%, 96.0%, 25.8%, 2.18%, and 0.26% respectively., Conclusions: BQ is useful as a screening test for diagnosing OSA in Iranian patients with sleep complaints; however, the test cannot be used for rolling out the OSA. Further studies on editing, modifying, and applying the BQ in a larger sample of patients are warranted in our society.

Context: Paget disease is an uncommon skin manifestation of breast cancer, associated with either invasive carcinoma or ductal carcinoma in situ in the underlying breast. In very rare cases, tumor cells within the epidermis invade through the basement membrane of the skin into the dermis., Objectives: To identify a series of cases of Paget disease with direct dermal invasion and to investigate the clinicopathologic features and outcome., Design: Cases were identified during a 6-year period from the files of 2 hospitals. The clinical histories, imaging studies, and pathology reports were reviewed., Results: Seven patients were identified, 5 with microinvasion (<0.1 cm) and 2 with 0.2- or 0.3-cm invasive carcinomas in the dermis. No lymphovascular invasion was seen. Sentinel nodes were negative in 3 patients who underwent biopsy. Five patients were treated with breast conservation with radiation. Three patients were at high risk for breast cancer because of prior breast cancer, Li-Fraumeni syndrome, or radiation for Hodgkin disease. The latter 2 patients underwent bilateral mastectomies. Three patients received hormonal therapy and 1 oophorectomy. No patient received chemotherapy. At follow-ups ranging from 4 to 66 months (median, 20 months), there have been no recurrences., Conclusions: Patients with direct dermal invasion from Paget disease had a favorable outcome during the available follow-up period. This type of dermal involvement must be distinguished from locally advanced invasive carcinomas with skin invasion classified as T4b in the American Joint Cancer Commission staging system, as cancers with other types of skin invasion are associated with a poor prognosis.

Purpose: Although positive surgical margins are generally associated with a higher risk of local-regional recurrence (LRR) for most solid tumors, their significance after mastectomy remains unclear. We sought to clarify the influence of the mastectomy margin on the risk of LRR., Methods and Materials: The retrospective cohort consisted of 397 women who underwent mastectomy and no radiation for newly diagnosed invasive breast cancer from 1998-2005. Time to isolated LRR and time to distant metastasis (DM) were evaluated by use of cumulative-incidence analysis and competing-risks regression analysis. DM was considered a competing event for analysis of isolated LRR., Results: The median follow-up was 6.7 years (range, 0.5-12.8 years). The superficial margin was positive in 41 patients (10%) and close (≤2 mm) in 56 (14%). The deep margin was positive in 23 patients (6%) and close in 34 (9%). The 5-year LRR and DM rates for all patients were 2.4% (95% confidence interval, 0.9-4.0) and 3.5% (95% confidence interval, 1.6-5.3) respectively. Fourteen patients had an LRR. Margin status was significantly associated with time to isolated LRR (P=.04); patients with positive margins had a 5-year LRR of 6.2%, whereas patients with close margins and negative margins had 5-year LRRs of 1.5% and 1.9%, respectively. On univariate analysis, positive margins, positive nodes, lymphovascular invasion, grade 3 histology, and triple-negative subtype were associated with significantly higher rates of LRR. When these factors were included in a multivariate analysis, only positive margins and triple-negative subtype were associated with the risk of LRR., Conclusions: Patients with positive mastectomy margins had a significantly higher rate of LRR than those with a close or negative margin. However, the absolute risk of LRR in patients with a positive surgical margin in this series was low, and therefore the benefit of postmastectomy radiation in this population with otherwise favorable features is likely to be small., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Data reviewed at the Kyoto Breast Cancer Consensus Conference (KBCCC) showed that preoperative systemic therapy (PST) could optimize surgery through the utilization of information relating to pre- and post-PST tumor stage, therapeutic sensitivity, and treatment-induced changes in the biological characteristics of the tumor. As such, it was noted that the biological characteristics of the tumor, such as hormone receptors, human epidermal growth factor receptor-2, histological grade, cell proliferative activity, mainly defined by the Ki67 labeling index, and the tumor's multi-gene signature, should be considered in the planning of both systemic and local therapy. Furthermore, the timing of axillary sentinel lymph node diagnosis (i.e., before or after the PST) was also noted to be critical in that it may influence the likelihood of axillary preservation, even in node positive cases. In addition, axillary diagnosis with ultrasound and concomitant fine needle aspiration cytology or core needle biopsy (CNB) was reported to contribute to the construction of a treatment algorithm for patient-specific or individualized axillary surgery. Following PST, planning for breast surgery should therefore be based on tumor subtype, tumor volume and extent, therapeutic response to PST, and patient preference. Nomograms for predicting nodal status and drug sensitivity were also recognized as a tool to support decision-making in the selection of surgical treatment. Overall, review of data at the KBCCC showed that PST increases the likelihood of patients receiving localized surgery and individualized treatment regimens.

In mammals, vinclozolin (VZ) is known as anti-androgen, which causes male infertility via androgen receptor (AR) antagonism. In aquatic animals, the VZ effects on reproductive functions are largely unknown and results are somewhat contradictory. To understand VZ adverse effects on male reproduction, mature goldfish (Carassius auratus) were exposed to three nominal VZ concentrations (100, 400, and 800 μg/L) and alternations in gonadosomatic (GSI) and hepatosomatic indices (HSI), 17β-estradiol (E(2)), 11-ketotestosterone (11-KT) and sperm quality were investigated compared to the solvent control. One group was exposed to E(2) (nominal concentration of 5 μg/L), an estrogenic compound, as a negative control. Following one month exposure, GSI and HSI were unchanged in all VZ treated groups compared to solvent control. Sperm volume, motility and velocity were reduced in fish exposed to 800 μg/L VZ. This was associated with the decrease in 11-KT level, suggesting direct VZ effects on testicular androgenesis and sperm functions. In goldfish exposed to 100 μg/L VZ, 11-KT was increased but E(2) remained unchanged. This is, probably, the main reason for unchanged sperm quality at 100 μg/L VZ. In goldfish exposed to E(2), GSI and 11-KT were decreased, E(2) was increased and no sperm was produced. The present study shows different dose-dependent VZ effects, which lead to impairment in sperm quality via disruption in steroidogenesis. In addition to VZ effects through competitive binding to AR, our data suggests potential effects of VZ by direct inhibition of 11-KT biosynthesis in fish as well as abnormalities in sperm morphology., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: Paget's disease constitutes between 1% and 3% of all breast malignancies, which makes defining standard surgical therapy difficult. We sought to identify preoperative factors that would select patients for successful breast conservation., Methods: Fifty-one patients with Paget's disease underwent surgical therapy between October 1998 and January 2010. Clinical presentation of Paget's disease, preoperative imaging, pathologic tumor characteristics, as well as surgical, radiation, and adjuvant therapies were reviewed., Results: Thirty-seven percent underwent breast conservation whereas 63% underwent mastectomy. Twelve patients presented with a palpable mass, and all were treated with mastectomy. Twenty-two patients underwent a mammogram, identifying extensive abnormality requiring mastectomy. Magnetic resonance imaging added to surgical planning in 52% of patients who participated in the study. None of our patients had a local/regional recurrence at 29 months of follow-up evaluation., Conclusions: Paget's disease of the breast can be treated with breast conservation in a properly selected subset of patients. Successful breast conservation was achieved in patients without a palpable finding, a benign mammogram, and a normal magnetic resonance imaging scan., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Motor vehicle accidents are the second highest cause of mortality in Iran. Sleep apnea symptoms have been associated with increased risk of motor vehicle accidents in other countries. However, we have limited data in Iran. We conducted a study to evaluate sleep apnea symptoms and sleepiness in professional drivers and to assess the predictors of motor vehicle accidents in Iran., Methods: A questionnaire-based cross-sectional study of drivers was done in Shahrekord, Iran. This study used a self-administered questionnaire that included personal information, the Epworth sleepiness scale (ESS), the Berlin questionnaire, and history of previous automobile accidents. Nine hundred thirty-one male drivers (62% of invited drivers), aged 40.2 ± 10.1 years (mean±SD), were included in the study. The mean number of hours spent driving was 48.9 h/week. The median distance covered weekly was 2,905 km/week. Statistical analysis included logistic models with covariate-adjusted P values of <0.01 s (odds ratios and 95% confidence intervals or limits). Independent accident predictors were sought., Result: The professional drivers with car accidents had a higher risk in Berlin questionnaire (P < 0.02), a larger mean neck circumference (P < 0.04), and more witnessed apneas (P < 0.04). There was no significant association between in drivers with car accident and ESS above 10., Conclusions: In Persian professional drivers, high-risk Berlin questionnaire, larger neck circumference, and a history of witnessed apneas were the most important predictors of motor vehicle accident.

Background: Sleep apnea is associated with increased risk of diabetes mellitus. However, no studies have compared sleep apnea symptoms in diabetic patients and their first degree relatives. The purpose of our study was to investigate high risk for sleep apnea syndrome, in diabetics and their first degree relatives for prevention of diabetes in family., Methods: As a part of a cohort study, all of diabetic and their first degree relatives who came for glucose control in diabetes clinic were invited to take part in the survey. Two thousand, four hundred and sixty-two individuals (82% of invited) agreed to fill out the Berlin and Epworth sleep questionnaire. Participants consisted of 2462 subjects of 15-70 years of age, both males and females with diabetes and family history of type 2 diabetes mellitus. A total of 1234 participants had diabetes and 11,231 were relatives of diabetic patients. High risk for sleep apnea regarding Berlin questionnaire and Epworth sleepiness scale, diabetic and relative were analyzed., Results: Prevalences of high risk for sleep apnea were higher among diabetics than relatives (P-value<0.001). In a multiple regression analysis, "age, body mass index, education, high blood pressure" were risk factor for sleep apnea symptoms while isolated blood glucose level was not by Berlin questionnaire. By Epworth sleep scale only education level was a risk factor for sleep apnea symptoms while isolated blood glucose level was not risk factor., Conclusions: Sleep apnea symptoms may not have significant difference between diabetics and their relatives. We need more study on sleep apnea in the family of diabetic patients. We hope that more studies on mentioned field may help prevention of diabetes in their family.

Axillary node dissection (ALND) is the standard of care for patients who have a positive sentinel lymph node (SLN) on sentinel lymph node biopsy (SLNB). We sought to identify a low-risk patient population with positive SLN that may not need cALND. We analyzed SLNB for breast cancer at our institutions between 1999 and 2007. We identified 130 patients who had a positive SLN but did not undergo completion ALND. We evaluated clinical data, adjuvant treatment patterns and intermediate locoregional and distant events. The median patient age was 50; 19% had N0(i+) disease, 53% had micrometastatic (N1mi) disease, and 28% had macrometastasis. Eighty-eight percent of patients underwent radiation therapy; 66 patients (51%) had documented nodal radiation (of these 50 were treated with three fields and 14 with high tangents. Local recurrence in the breast occurred in two patients (2%) and nine patients (7%) developed distant metastases; there were no axillary/nodal recurrences. In this highly selected group of patients who had a positive SLNB but did not undergo cALND, we observed no axillary recurrences., (© 2011 Wiley Periodicals, Inc.)