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Background: Obesity is a known risk factor for breast cancer development; however, it is unclear whether obesity is associated with more aggressive disease. We sought to determine the relationship between obesity and tumor characteristics in breast cancer patients., Methods: Medical records of invasive breast cancer patients undergoing mastectomy at our institution between January 2010 and April 2018 were reviewed. Patients who had received neoadjuvant therapy were excluded. Patients were separated into obese (body mass index [BMI] ≥ 30 kg/m 2 ) and nonobese (BMI < 30 kg/m 2 ) categories and compared using nonparametric statistical analyses., Results: Of the 415 patients in this cohort, 124 (29.9%) were obese. Obese patients were more likely to present with larger tumors (tumor size ≥ 2 cm: 53.2% vs 41.0%, P = .024) and more node-positive disease (46.8% vs 28.9%, P = .001). Controlling for confounders, obesity was independently associated with node-positive disease (odds ratio [OR] = 2.00; 95% CI 1.24-3.21, P = .004), but not with tumor size ≥ 2 cm (OR = 1.38; 95% CI 0.87-2.21, P = .174)., Conclusion: Obesity is associated with node-positive disease at presentation independent of other factors.

Introduction: We sought to determine rates of complications, reoperation, and length of stay (LOS) between nipple-sparing (NSM) and skin-sparing (SSM) mastectomy patients, hypothesizing that rates would be higher in the former., Methods: Patients undergoing NSM or SSM at our institution between January 1, 2010 and December 31, 2017 were compared., Results: 217 patients underwent NSM; 581 underwent SSM. NSM patients were more likely to be younger, with private insurance, lower BMI, lighter breasts, have bilateral mastectomy, with implant-based reconstruction, for BRCA, and/or lower stage disease and were less likely to have diabetes, axillary dissection, and/or neoadjuvant therapy. Controlling for these factors, NSM patients had a higher complication rate than SSM patients (OR: 1.822; 95% CI: 1.163-2.853, p = 0.009). Length of stay and reoperation rates were not significantly different between the two groups., Conclusion: NSM and SSM patients have similar reoperation rates and LOS; however, complication rate is higher in NSM patients., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: Exercise after breast cancer diagnosis is associated with lower cancer-specific mortality, but the biological mechanisms through which exercise impacts breast cancer are not fully understood. The Pre-Operative Health and Body (PreHAB) Study was a randomized window-of-opportunity trial designed to test the impact of exercise on Ki-67, gene expression, and other biomarkers in women with breast cancer., Experimental Design: Inactive women with newly diagnosed breast cancer were randomized to an exercise intervention or mind-body control group, and participated in the study between enrollment and surgery (mean 29.3 days). Tumor and serum were collected at baseline and surgery., Results: Forty-nine women were randomized (27 exercise, 22 control). At baseline, mean age was 52.6, body mass index was 30.2 kg/m 2 , and exercise was 49 minutes/week. Exercise participants significantly increased exercise versus controls (203 vs. 23 minutes/week, P < 0.0001). There were no differences in changes of expression of Ki-67, insulin receptor, and cleaved caspase-3 in exercise participants versus controls. KEGG pathway analysis demonstrated significant upregulation of 18 unique pathways between the baseline biopsy and surgical excision in exercise participants and none in control participants ( q < 0.1). Top-ranked pathways included several implicated in immunity and inflammation. Exploratory analysis of tumor immune infiltrates demonstrated a trend toward a decrease in FOXP3 + cells in exercise versus control participants over the intervention period ( P = 0.08)., Conclusions: A window-of-opportunity exercise intervention did not impact proliferation but led to alterations in gene expression in breast tumors, suggesting that exercise may have a direct effect on breast cancer. See related commentary by Koelwyn and Jones, p. 5179 ., (©2019 American Association for Cancer Research.)

Both skin-sparing mastectomy (SSM) and nipple-sparing mastectomy (NSM) are well accepted in the management of breast cancer. Factors that influence the decision of choosing one of these techniques over the other, however, remain to be well elucidated. From January 2010 to December 2017, 734 patients at our institution underwent one of these two procedures. Factors differentiating these patient cohorts were compared. In this study, 196 (26.7%) underwent NSM and 538 (73.3%) underwent SSM. The median age of patients at the time of surgery was 50 years (range, 22-78 years). On multivariate analysis, younger patient age, insurance type, BRCA+ mutation status, smaller breast size (by weight), and those who did not undergo neoadjuvant chemotherapy were more likely to undergo NSM. Surgeon also was an independent predictor of whether patients had NSM or SSM. There may be many factors that play into the decision to pursue NSM versus SSM, but younger patient age, BRCA mutation status, breast size, and whether the patient had neoadjuvant chemotherapy may be key among them. Insurance status may also be a factor for some patients. Aside from these factors, some surgeons may be more or less inclined to perform NSM.

Purpose: The age at which women present with breast cancer varies widely among nations, and breast cancer may behave differently in younger women. Differences in clinicopathological characteristics based on age have not been well characterized in Pakistani patients with breast cancer., Methods: We conducted a retrospective review of patients with symptoms of breast cancer presenting to Aga Khan University Hospital (AKUH), a large tertiary care center in Pakistan, between 2001 and 2010; we compared young (≤ 40 years) versus older (> 40 years) patients in terms of their clinicopathological characteristics. We also compared this Pakistani cohort with the US population using data from the National Cancer Database (NCDB)., Results: A total of 1,334 patients with breast cancer presented to our center over the 10-year review period. The median age at diagnosis was 50 years, compared with 60 years for patients in the NCDB. In the AKUH cohort, younger patients were significantly more likely than their older counterparts to present with metastatic disease (13.1% v 10.8%; P < .01). They also were more likely to present with higher-grade tumors (grade 3: 40.1% v 28.3%; P < .001), have triple hormone receptor-negative phenotype (25.4% v 14.1%, P < .001), and have positive axillary lymph node involvement (70.9% v 57.5%; P < .001) compared with older women. Younger and older patients in the AKUH cohort tended to present with higher-stage disease ( P < .001) and were more likely to have triple hormone receptor-negative disease ( P < .001), compared with all patients in the NCDB and with those of Indo-Pakistani origin., Conclusion: Young Pakistani women, similar to their Western counterparts, present with more advanced disease and more aggressive tumor biology than their older counterparts.

Multi-region sequencing is used to detect intratumor genetic heterogeneity (ITGH) in tumors. To assess whether genuine ITGH can be distinguished from sequencing artifacts, we performed whole-exome sequencing (WES) on three anatomically distinct regions of the same tumor with technical replicates to estimate technical noise. Somatic variants were detected with three different WES pipelines and subsequently validated by high-depth amplicon sequencing. The cancer-only pipeline was unreliable, with about 69% of the identified somatic variants being false positive. Even with matched normal DNA for which 82% of the somatic variants were detected reliably, only 36%-78% were found consistently in technical replicate pairs. Overall, 34%-80% of the discordant somatic variants, which could be interpreted as ITGH, were found to constitute technical noise. Excluding mutations affecting low-mappability regions or occurring in certain mutational contexts was found to reduce artifacts, yet detection of subclonal mutations by WES in the absence of orthogonal validation remains unreliable., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Oncotype Dx is a genetic test that has been incorporated into the 2017 AJCC breast cancer staging system for ER positive, HER2-negative, lymph node-negative patients to predict the risk of recurrence. Recent data suggest that immunohistochemistry (ER, PR, HER2, and Ki-67) and histologic subtype may identify patients that will not benefit from Oncotype Dx testing., Methods: A total of 371 patients underwent Oncotype Dx testing at our institution from 2012 to 2016. Oncotype recurrence score was categorized as low- (ORS = 0-10), intermediate- (11-25), or high risk (26-100). Invasive carcinomas were categorized based on histologic subtype as "favorable" (mucinous, tubular, cribriform, tubulolobular, and lobular) and "unfavorable" (ductal, mixed ductal and lobular, and micropapillary carcinoma). All cases were estrogen receptor positive and HER2-negative. Clinical and histologic predictors of low-risk ORS were assessed in univariate and multivariate logistic regression., Results: A total of 371 patients were categorized by ORS as low risk (n = 85, 22.9%), intermediate risk (n = 244, 65.8%), and high risk (n = 42, 11.3%). The histologic subtypes with the highest percentage of high-risk ORS were invasive micropapillary (n = 4/17, 23.5%), pleomorphic lobular (n = 2/10, 20%), and ductal carcinoma (n = 28/235, 11.9%). Low-grade invasive carcinomas with favorable histology rarely had a high-risk ORS (n = 1/97, 1%). In a simple multivariable model, favorable histologic subtype (OR = 2.39, 95% CI: 1.10 to 5.15, P = 0.026), and histologic grade (OR = 1.76, 95% CI: 1.07 to 2.90, P = 0.025) were the only significant predictors of an ORS less than 11 in estrogen receptor positive, HER2-negative, and lymph node-negative patients., Conclusion: We question the utility of performing Oncotype Dx in subtypes of invasive carcinoma that are associated with excellent prognosis. We propose that immunohistochemistry for ER, PR, and HER2 is sufficient for patients with low-grade invasive carcinomas and can be used as a surrogate for Oncotype Dx., (© 2018 Wiley Periodicals, Inc.)

Background: We sought to determine the impact of time after surgery on quality of life (QoL) and body image in breast cancer patients undergoing mastectomy., Methods: Female patients with unilateral breast cancer who had undergone mastectomy were surveyed regarding their body image (Body Image After Breast Cancer Questionnaire; BIBCQ) and QoL (FACT-B). Data were analyzed using nonparametric statistics (SPSS version 24)., Results: Ninety-four of the 109 patients approached completed both surveys (86.2% response rate). Median patient age at the time of surgery was 49.5 (range 29-82); the survey was administered at a median of 14.2 months postoperatively (range 0.3-192.1 months). Seventy-four patients (78.7%) had reconstruction, and 52 patients (55.3%) chose to undergo contralateral prophylactic mastectomy. Patients who reported an above average overall body image perception on the BIBCQ tended to be further out from their surgery than those who reported a below average perception (median 20.9 vs. 8.1 months, respectively, p = 0.009). Patients who reported above average QoL also tended to be further out from their surgery compared with those with below average overall QoL (median 21.8 vs. 6.4 months, respectively, p = 0.004). Receipt of reconstruction, contralateral prophylactic mastectomy, disease stage, patient race, education, insurance type, income, marital status, employment status, and age at surgery did not significantly affect body image nor QoL in this cohort., Conclusions: Better body image perception and higher QoL were associated with being further out from surgery. These findings suggest that body image and QoL may improve with time, as patients acclimatize to their "new normal."

Poor breast cancer-related quality of life is associated with flattened cortisol rhythms and inflammation in breast cancer survivors and women with advanced disease. We explored the associations of cancer-specific distress (Impact of Events Scale), mood (Profile of Mood States), activity/sleep (wake after sleep onset, 24-hour autocorrelation coefficient) and cortisol (diurnal slope) circadian rhythms, and inflammation (interleukin-6) with quality of life (Functional Assessment of Cancer Therapy-Breast) among patients awaiting breast cancer surgery ( N = 57). Models were adjusted for differences in age and cancer stage. Distress and mood disturbance were significantly correlated with lower quality of life. Ethnic differences in the relationship between distress and mood disturbance with global quality of life and subscales of quality of life were observed. Actigraphic measures showed that in comparison with non-Hispanic patients, African Americans had significantly poorer activity/sleep (wake after sleep onset, 24-hour autocorrelation coefficient). Circadian disruption and inflammation were not associated with quality of life. Physiological dysregulation and associated comorbidities may take time to develop over the course of disease and treatment.

Background: Age is one of the most important risk factors for developing breast cancer. However, age-related changes in normal breast tissue that potentially lead to breast cancer are incompletely understood. Quantifying tissue-level DNA methylation can contribute to understanding these processes. We hypothesized that occurrence of breast cancer should be associated with an acceleration of epigenetic aging in normal breast tissue., Results: Ninety-six normal breast tissue samples were obtained from 88 subjects (breast cancer = 35 subjects/40 samples, unaffected = 53 subjects/53 samples). Normal tissue samples from breast cancer patients were obtained from distant non-tumor sites of primary mastectomy specimens, while samples from unaffected women were obtained from the Komen Tissue Bank (n = 25) and from non-cancer-related breast surgery specimens (n = 28). Patients were further stratified into four cohorts: age < 50 years with and without breast cancer and age ≥ 50 with and without breast cancer. The Illumina HumanMethylation450k BeadChip microarray was used to generate methylation profiles from extracted DNA samples. Data was analyzed using the "Epigenetic Clock," a published biomarker of aging based on a defined set of 353 CpGs in the human genome. The resulting age estimate, DNA methylation age, was related to chronological age and to breast cancer status. The DNAmAge of normal breast tissue was strongly correlated with chronological age (r = 0.712, p < 0.001). Compared to unaffected peers, breast cancer patients exhibited significant age acceleration in their normal breast tissue (p = 0.002). Multivariate analysis revealed that epigenetic age acceleration in the normal breast tissue of subjects with cancer remained significant after adjusting for clinical and demographic variables. Additionally, smoking was found to be positively correlated with epigenetic aging in normal breast tissue (p = 0.012)., Conclusions: Women with luminal breast cancer exhibit significant epigenetic age acceleration in normal adjacent breast tissue, which is consistent with an analogous finding in malignant breast tissue. Smoking is also associated with epigenetic age acceleration in normal breast tissue. Further studies are needed to determine whether epigenetic age acceleration in normal breast tissue is predictive of incident breast cancer and whether this mediates the risk of chronological age on breast cancer risk.

Background: Positive margins have been reported in 20% to 40% of patients undergoing a partial mastectomy, often resulting in re-excision. How often the re-excision yields additional cancer and whether there are predictors of residual disease remain unknown., Study Design: Patients who had a positive margin (defined as tumor at ink for patients with invasive disease or within 1 mm for patients with ductal carcinoma in situ) in the SHAVE (A Randomized Controlled Trial of Routine Shave Margins Versus Standard Partial Mastectomy in Breast Cancer Patients) trial before randomization were evaluated to determine the rate of additional disease either in cavity shave margins or at re-excision. Details of the SHAVE trial can be found elsewhere., Results: Of the 235 patients in the trial, 82 (34.9%) had a positive margin before randomization; 58 of these patients underwent either cavity shave margins excision or a re-excision of the positive margin(s). Twenty-one (36.2%) patients had residual disease. On bivariate analysis, residual disease was associated with younger patient age (median 51 vs 62 years; p = 0.007), and the presence of high-grade ductal carcinoma in situ (57.1% vs 31.3% for grade 2 and 0% for grade 1; p = 0.025). The following factors were not associated with further disease: patient race; ethnicity; BMI; volume of resection; number of positive margins; extent of ductal carcinoma in situ; and extent, grade, and histologic subtype of invasive cancer. On multivariate analysis, only patient age younger than 60 years remained a significant predictor of residual disease (odds ratio 3.920; 95% CI 1.081 to 14.220; p = 0.038)., Conclusions: Positive margins are associated with further disease in more than one-third of patients and, aside from young age, there are no predictors of this. These findings support continued re-excision of positive margins, particularly in patients younger than 60 years of age., (Copyright © 2018 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Dedicated to the memory of Dr. William Hunter Harridge and Nonie Lowry, this manuscript discusses the ups and downs associated with novel therapies in breast cancer, and applies the lessons of persistence learned from baseball to our quest for more optimal treatments, particularly in triple negative breast cancer., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Ductal carcinoma in situ (DCIS) is a premalignant condition, whose incidence is increasing in the current era of widespread screening mammography. While eminently treatable, there are innumerable controversies that surround this disease in terms of its diagnosis and treatment. We discuss these issues and review the data to date regarding this condition which affects roughly 20 per cent of all patients presenting with breast cancer.

Purpose: The 21-gene recurrence score (RS) assay is used to help formulate adjuvant chemotherapy recommendations for patients with estrogen receptor-positive, early-stage breast cancer. Most frequently, medical oncologists order RS after surgery. Results take an additional 2 weeks to return, which can delay decision making. We conducted a prospective quality-improvement project to assess the impact of early guideline-directed RS ordering by surgeons before the first visit with a medical oncologist on adjuvant therapy decision making., Materials and Methods: Surgical oncologists ordered RS testing following National Comprehensive Cancer Network guidelines at time of diagnosis or at time of surgery between July 1, 2015 and December 31, 2015. We measured the testing rate of patients eligible for RS, time to chemotherapy decisions, rates of chemotherapy use, accrual to RS-based clinical trials, cost, and physician acceptance of the policy and compared the results to patients who met eligibility criteria for early guideline-directed testing during the 6 months before the project., Results: Ninety patients met eligibility criteria during the testing period. RS was ordered for 91% of patients in the early testing group compared with 76% of historical controls ( P < .001). Median time to chemotherapy decision was significantly shorter in the early testing group (20 days; 95% CI, 17 to 23 days) compared with historical controls (32 days; 95% CI, 29 to 35 days; P < .001). There were no significant differences in time to chemotherapy initiation, chemotherapy use, RS-based trial enrollment, or calculated costs between the groups., Conclusion: Early guideline-directed RS testing in selected patients is an effective way to shorten time to treatment decisions.

Background: Women ≥70 years old with clinically (c) lymph node (LN) negative (-), hormone receptor (HR) positive (+) breast cancer are recommended not to be routinely staged with a sentinel LN biopsy. We sought to determine how this affects adjuvant decision-making., Methods: Statistical analyses were performed to determine the association of LN evaluation with adjuvant chemotherapy and radiation therapy in cLN-, HR + breast cancer patients in the National Cancer Database., Results: Between 2004 and 2013, there were 193,728 patients aged 70-90 with cLN-, HR + breast cancer; 15.0% were LN+. LN + patients were more likely to receive chemotherapy (28.3% vs. 5.5%, p < 0.001), hormonal therapy (83.6% vs. 71.4%, p < 0.001), post-lumpectomy radiation therapy (81.4% vs. 73.6%, p < 0.001) and post-mastectomy radiation therapy (30.3% vs. 5.1%, p < 0.001)., Conclusion: 15% of patients aged 70-90 will be LN+. These patients more frequently receive systemic and radiation therapy. LN status may affect treatment in these patients., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Early studies have shown significant regional differences in the utilization of breast-conserving therapy (BCT) and mastectomy with reconstruction. It is expected that with the passage of time and the adoption of national treatment guidelines, these disparities would disappear., Methods: Patients with non-metastatic breast cancer who underwent surgery between 2004 and 2013 were analyzed using the National Cancer Database (NCDB). Trends in BCT and reconstruction were evaluated and multivariate logistic regression performed., Results: The highest rate of BCT was in New England (69%) and the lowest in East South Central (49%), p < 0.001. The rate of reconstruction was highest in the Middle Atlantic (44%) and the lowest in East South Central (26%), p < 0.001. Compared to East South Central, the odds ratio (OR) for BCT in New England was 2.2 (95% CI 2.1-2.3), and the OR for reconstruction in Middle Atlantic was 1.7 (95% CI 1.6-1.8)., Conclusion: There continue to be significant regional differences in breast surgery., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Some suggest that lymph node (LN) evaluation not be performed routinely in women aged ≥70 years with clinically (c) LN-negative (-), hormone receptor (HR)-positive (+) breast cancer. We sought to determine the association of omission of LN evaluation on survival., Methods: Patients who met the above criteria and were diagnosed from 2004 to 2012 were identified in the NCDB and SEER databases. Overall survival (OS) and breast cancer-specific survival (BCSS) were determined., Results: Using the NCDB, we identified 157,584 cLN- HR+ patients aged ≥70 years in whom survival and LN evaluation data were available. A total of 126,638 patients (80.2%) had regional LN surgery. With a median follow-up of 41.6 months, there was a significant difference in OS between those who had LN evaluation and those who did not (median OS: 100.5 vs. 70.9 months, respectively, p < 0.001). After adjusting for patient age, race, insurance, income, comorbidities, tumor characteristics and treatment, patients who had undergone LN evaluation still had a lower hazard rate for death than those who had not (hazard ratio = 0.633; 95% confidence interval [CI] 0.613-0.654, p < 0.001). We then did a parallel analysis using SEER data that showed LN evaluation was associated with a lower hazard rate for both BCSS (hazard ratio = 0.452; 95% CI 0.427-0.479, p < 0.001) and non-BCSS (hazard ratio = 0.465; 95% CI 0.447-0.482, p < 0.001)., Conclusions: Roughly 20% of patients older than aged 70 years with cLN-, HR+ breast cancer did not have LN evaluation. Those who did had better OS controlling for sociodemographic, pathologic, and treatment variables; however, this may be due to patient selection.

Background: Sentinel lymph node biopsy (SLNB) should be performed in patients with ductal carcinoma in situ (DCIS) undergoing mastectomy. Yet, the same logic is controversial in the setting of prophylactic mastectomy., Methods: Surgeons were surveyed as to their practices. Statistical analyses were performed to identify associated factors., Results: 238 surgeons responded to the survey. 73.1% of respondents stated they would always perform SLNB in the setting of mastectomy for DCIS, but only 6.6% would always do so in the prophylactic setting. While generally perceived that the rate of SLN positivity in the setting of pure DCIS and prophylactic mastectomy was <5% (96.9% and 99.5%, respectively), 61.8% of surgeons who reported "always" performing SLNB in the setting of DCIS treated with mastectomy stated they "never" performed a SLNB for prophylactic mastectomy., Conclusion: SLNB practice patterns for these low risk settings are disparate. Consensus is required to rationalize practice., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The SHAVE trial is a prospective trial in which 235 women with stage 0 to 3 disease undergoing partial mastectomy were randomized intraoperatively to either have cavity shave`s (CSMs) taken at the time of initial surgery or not. In this study, 9 of the 76 patients (11.8%) with initially negative margins randomized to the "shave" group had occult cancers found in the CSM. Seven of these patients had sufficient primary tumor tissue available for further analysis. These patients were age and stage matched in a 1:2 ratio to other patients in the trial who had no further disease found in their CSM. A tissue microarray was created, stained for E-cadherin, MUC1, and beta-catenin, and evaluated by two independent pathologists (blinded to outcome). There were no significant differences between cases and controls in terms of median invasive tumor size, ductal carcinoma in situ size, volume of initial resection, and volume of CSM. Further, no differences were noted between cases and controls for median (staining intensity × per cent of cells staining) for each marker. Hence, although nearly 12 per cent of breast cancer patients with negative margins will have occult disease, this could not be predicted by primary tumor markers in this study.

Over the past several years, there has been an increasing rate of bilateral prophylactic mastectomy (BPM) and contralateral prophylactic mastectomy (CPM) surgeries. Since publication of the 2007 SSO position statement on the use of risk-reducing mastectomy, there have been significant advances in the understanding of breast cancer biology and treatment. The purpose of this manuscript is to review the current literature as a resource to facilitate a shared and informed decision-making process regarding the use of risk-reducing mastectomy.

Background: Although identification of human epidermal growth factor receptor 2 (Her2) positive breast cancer represents one of the greatest advances over the past 3 decades, it has not been studied extensively on a national level., Methods: The National Cancer Database is a joint project of the American Cancer Society and the American College of Surgeons and contains data on about 70% of the cancer cases in the United States. Data on Her2 have been collected since 2010 and was used for this study., Results: Of 298,937 cases of invasive breast cancer with known Her2 status diagnosed in 2010 and 2011, 43,485 (14.5%) were Her2 positive. Her2 positivity was greatest in Asian/Pacific Islanders and least in non-Hispanic Whites and was markedly more common in younger women. The incidence of Her2 positive tumors ranged from a low of 13.9% in the Mountain West region to a high of 16.0% in the West South Central region (P < .001). Compared with Her2 negative tumors, Her2 positive tumors were larger (2.6 vs 2.2 cm, P < .001), more likely to have positive nodes (39% vs 31% P < .001), have lymphovascular invasion (30% vs 20%, P < .001), and be high grade (56% vs 29%, P < .001). There were also differences by histology: invasive ductal 16.4%, invasive lobular 5.5%, tubular 2.3%, inflammatory 36%, and Paget's with invasion 59%. When adjusted for age, race, tumor size, and nodal status Her2 positive tumors were much more likely to receive chemotherapy (odds ratio = 5.5, confidence interval = 5.2 to 6.0) and somewhat less likely to undergo breast preservation (odds ratio = .78, confidence interval = .76 to .80)., Conclusions: Her2 positive tumors have distinct epidemiologic, clinical, and treatment characteristics., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background . Most institutions require a patient undergoing sentinel lymph node biopsy to go through nuclear medicine prior to surgery to be injected with radioisotope. This study describes the long-term results using intraoperative injection of radioisotope. Methods . Since late 2002, all patients undergoing a sentinel lymph node biopsy at the Yale-New Haven Breast Center underwent intraoperative injection of technetium-99m sulfur colloid. Endpoints included number of sentinel and nonsentinel lymph nodes obtained and number of positive sentinel and nonsentinel lymph nodes. Results . At least one sentinel lymph node was obtained in 2,333 out of 2,338 cases of sentinel node biopsy for an identification rate of 99.8%. The median number of sentinel nodes found was 2 and the mean was 2.33 (range: 1-15). There were 512 cases (21.9%) in which a sentinel node was positive for metastatic carcinoma. Of the patients with a positive sentinel lymph node who underwent axillary dissection, there were 242 cases (54.2%) with no additional positive nonsentinel lymph nodes. Advantages of intraoperative injection included increased comfort for the patient and simplification of scheduling. There were no radiation related complications. Conclusion . Intraoperative injection of technetium-99m sulfur colloid is convenient, effective, safe, and comfortable for the patient.

Objective: The aim of the study was to compare costs associated with excision of routine cavity shave margins (CSM) versus standard partial mastectomy (PM) in patients with breast cancer., Background: Excision of CSM reduces re-excision rates by more than 50%. The economic implications of this is, however, unclear., Methods: Between October 21, 2011 and November 25, 2013, 235 women undergoing PM for Stage 0-III breast cancer were randomized to undergo either standard PM ("no shave", n = 116) or have additional CSM taken ("shave", n = 119). Costs from both a payer and a hospital perspective were measured for index surgery and breast cancer surgery-related care through subsequent 90 days., Results: The 2 groups were well-matched in terms of baseline characteristics. Those in the "shave" group had a longer operative time at the initial surgery (median 76 vs 66 min, P < 0.01), but a lower re-excision rate for positive margins (13/119 = 10.9% vs 32/116 = 27.6%, P < 0.01). Actual direct hospital costs associated with operating room time ($1315 vs. $1137, P = 0.03) and pathology costs ($1195 vs $795, P < 0.01) were greater for the initial surgery in patients in the "shave" group. Taking into account the index surgery and the subsequent 90 days, there was no significant difference in cost from either the payer ($10,476 vs $11,219, P = 0.40) or hospital perspective ($5090 vs $5116, P = 0.37) between the "shave" and "no shave" groups., Conclusions: Overall costs were not significantly different between the "shave" and "no shave" groups due to significantly fewer reoperative surgeries in the former.

Effective communication is a requirement in the teamwork necessary for improved coordination to deliver patient-centered, value-based cancer care. Communication is particularly important when care providers are geographically distributed or work across organizations. We review organizational and teams research on communication to highlight psychological safety as a key determinant of high-quality communication within teams. We first present the concept of psychological safety, findings about its communication effects for teamwork, and factors that affect it. We focus on five factors applicable to cancer care delivery: familiarity, clinical hierarchy-related status differences, geographic dispersion, boundary spanning, and leader behavior. To illustrate how these factors facilitate or hinder psychologically safe communication and teamwork in cancer care, we review the case of a patient as she experiences the treatment-planning process for early-stage breast cancer in a community setting. Our analysis is summarized in a key principle: Teamwork in cancer care requires high-quality communication, which depends on psychological safety for all team members, clinicians and patients alike. We conclude with a discussion of the implications of psychological safety in clinical care and suggestions for future research.

Background: Whether rates of breast-conservation surgery (BCS) vary based on race and ethnicity has not been clearly elucidated on a national leve., Methods: The National Cancer Data Base (NCDB) was used to identify women who underwent surgery for invasive breast cancer during 2010 and 2011. The effect of race and ethnicity on BCS rates was determined, independent of patient demographics, tumor-related variables, and geographic region., Results: There were 299,827 patients with known race and ethnicity who underwent definitive breast surgery. BCS rates by race were as follows: 135,065/241,236 (56.0 %) for whites, 17,819/33,301 (53.5 %) for blacks, 4,722/9,508 (49.7 %) for Asian/Pacific Islanders, and 7,919/15,782 (50.2 %) for Hispanics (p < 0.001). Mean tumor size differed among the racial groups: 2.07 cm in whites, 2.54 cm in blacks, 2.23 cm in Asians, and 2.48 cm in Hispanics (p < 0.001). When stratified by tumor size, BCS was most common in blacks and least common in Asians for all tumors >2 cm (p < 0.001). On multivariable analysis adjusted for age, tumor size, nodal status, grade, molecular type, geographic area, urban/rural residence, insurance status, and census-derived median income and education for the patient's zip code, the odds ratio for BCS for blacks compared to whites was 1.23 (95 % confidence interval [CI] 1.20-1.27, p < 0.001), for Asians was 0.84 (95 % CI 0.80-0.88, p < 0.001), and for Hispanics was 1.00 (95 % CI 0.96-1.05, p = 0.885)., Conclusions: When adjusted for patient demographics, tumor-related variables, and geographic area, BCS rates are higher in blacks and lower in Asians compared to whites.

Background: Performing a sentinel lymph node biopsy (SLNB) is the standard of care for axillary nodal staging in patients with invasive breast cancer and clinically negative nodes. The procedure provides valuable staging information with few complications when performed by experienced surgeons. However, variation in proficiency exists for this procedure, and a great amount of experience is required to master the technique, especially when faced with challenging cases. The purpose of this paper was to provide a troubleshooting guide for commonly encountered technical difficulties in SLNB, and offer potential solutions so that surgeons can improve their own technical performance from the collective knowledge of experienced specialists in the field., Methods: Information was obtained from a convenience sample of six experienced breast cancer specialists, each actively involved in training surgeons and residents/fellows in SLNB. Each surgeon responded to a structured interview in order to provide salient points of the SLNB procedure., Results: Four of the key opinion surgical specialists provided their perspective using technetium-99 m sulfur colloid, and two shared their experience using blue dye only. Distinct categories of commonly encountered problem scenarios were presented and agreed upon by the panel of surgeons. The responses to each of these scenarios were collected and organized into a troubleshooting guide., Discussion: We present a compilation of 'tips' organized as a troubleshooting guide to be used to guide surgeons of varying levels of experience when encountering technical difficulties with SLNB.

The burden of cancer in low- to middle-income countries is growing and is expected to rise dramatically while resources to manage this disease remain inadequate. All authorities for the management of cancer recommend multidisciplinary care. Educational efforts by international organizations to assist local professionals in caring for their patients tend to have a lasting impact because they empower local professionals and enhance their skills. A multidisciplinary cancer management course was designed by American Society of Clinical Oncology staff and local experts to provide a roadmap for cross-specialty interaction and coordination of care in Zimbabwe. The outcome of the course was measured through feedback obtained from participants and impact on local workforce. The cancer management course was relevant to daily practice and fostered long-lasting partnerships and collaborations. Furthermore, it resulted in a more motivated local workforce and strengthened existing multidisciplinary practices. Cancer care is in a critical state in low- to middle-income countries. Educational efforts and collaborative partnerships may provide a cost-effective strategy with sustainable benefits. A multidisciplinary approach to optimize therapy is desirable. Evaluation of the course impact after a period of 6 months to 1 year is needed to determine the sustainability and impact of such efforts., Competing Interests: The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO’s conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/site/ifc. Sandra NdarukwaNo relationship to discloseAnna Mary NyakabauTravel, Accommodations, Expenses: Genentech, AstraZeneca, NovartisAnees B. ChagparNo relationship to discloseDavid RabenEmployment: AstraZeneca Consulting or Advisory Role: AstraZeneca Travel, Accommodations, Expenses: AstraZenecaNtokozo NdlovuNo relationship to discloseWebster KadzatsaNo relationship to discloseVanessa J. EatonNo relationship to disclosePaida MafundaNo relationship to discloseEvangelia RazisHonoraria: Roche, AstraZeneca, GlaxoSmithKline, Amgen, Novartis, Zeincro, Merck, Pfizer, Bristol-Myers Squibb Consulting or Advisory Role: Roche, Amgen, AstraZeneca, Janssen-Cilag, Astellas Pharma, Novartis, Bristol-Myers Squibb, Merck, Pfizer, Zeincro Research Funding: Sanofi, Genentech, Novartis, AstraZeneca, Demo Pharmaceutical, Celldex, PAREXEL International Travel, Accommodations, Expenses: Genesis Pharmaceuticals, LEO Pharma, Pfizer, Roche, GlaxoSmithKline, Sanofi, Amgen, Bristol-Myers Squibb, Genekor, Eisai, Merck, Pierre Fabre, Novartis

Purpose Indoor tanning is associated with an increased risk of non-melanoma skin cancers (NMSC), yet little is known about indoor tanning habits of individuals with a history of NMSC. Methods We examined self-reported history of NMSC and tanning bed use among non-Hispanic white respondents in the 2010 National Health Interview Survey (NHIS), a cross-sectional population-based survey designed to be representative of the civilian US population. We computed weighted population estimates and standard errors using the Taylor series linearization method. We then evaluated chi-square tests of independence and conducted weighted logistic regression analyses to evaluate if NMSC status was a predictor of indoor tanning. Results In our analytic sample of 14,400 non-Hispanic white participants, representing 145,287,995 in the population, 543 participants (weighted proportion = 3.45%) self-reported a history of NMSC or "skin cancer type not known." In multivariate analyses, non-melanoma skin cancer survivors were no less likely to use tanning beds in the last 12 months than skin cancer free controls (OR = 0.70, 95% CI: 0.34-1.43, p = 0.33). Conclusions Non-melanoma skin cancer survivors should be educated on their increased risk of recurrence and other skin cancers and in particular the role of indoor tanning in skin tumorigenesis.

The aim of this study was to determine the features of triple-negative breast cancer (TNBC) using a large national database. TNBC is known to be an aggressive subtype, but national epidemiologic data are sparse. All patients with invasive breast cancer and known molecular subtype diagnosed in 2010 to 2011 were identified from the National Cancer Data Base (NCDB). Patients with and without TNBC were compared with respect to their sociodemographic and clinicopathologic features. TNBC was present in 38,628 of 295,801 (13%) female patients compared to 185 of 3136 (6%) male patients (P < 0.001). The incidence of TNBC varied by region from 10.8% in New England to 15.8% in the east south central US (P < 0.001), as well as by race with the highest rates in African-Americans (23.7%), and lowest in Filipino patients (8.9%). The incidence of TNBC also varied by histology, accounting for 76% of metaplastic cancers, but only 2% of infiltrating lobular carcinomas. TNBCs were significantly larger than non-TNBC (mean 2.8 cm vs 2.1 cm, P < 0.001), and more TNBC were poorly differentiated compared to other subtypes (79.7% vs 25.8%, P < 0.001). On univariate analysis, TNBC was no more likely than non-TNBC to have node-positive disease (32.0% vs 31.7%, respectively, P = 0.218) but in a multivariable analysis controlling for tumor size and grade, TNBC was associated with significantly less node-positivity (OR = 0.59; 95% confidence interval [CI]: 0.57-0.60). TNBC has distinct features regarding age, gender, geographic, and racial distribution. Compared to non-TNBC, TNBC is larger and higher grade, but less likely to have lymph node metastases., Competing Interests: The authors have no conflicts of interest to declare.

Background: Recently, it has been suggested that screening mammography may result in some degree of overdiagnosis (ie, detection of breast cancers that would never become clinically important within the lifespan of the patient). The extent and biology of these overdiagnosed cancers, however, is not well understood, and the effect of newer screening modalities on overdiagnosis is unknown., Methods: We performed a retrospective review of a prospectively collected database of breast cancers diagnosed at the Yale Breast Center from 2004-2014. The mode of initial presentation was categorized into 5 groups: screening mammogram, screening magnetic resonance imaging, screening ultrasonography, self-detected masses, and physician-detected masses., Results: Compared with cancers presenting with masses, cancers detected by image-based screening were more likely to present with ductal carcinoma-in-situ or T1 cancers (P < .001). In addition to a simple stage shift, however, cancers detected by image-based screening were also more likely to be luminal and low-grade cancers; symptomatic cancers were more likely high-grade and triple-negative (P < .001, respectively). On a multivariate analysis, adjusting for age, race, and tumor size, cancers detected by mammogram, US, and magnetic resonance imaging had greater odds of being luminal (odds ratio 1.8, 95% confidence interval, 1.5-2.3; odds ratio 2.2, 95% confidence interval, 1.1-4.7; and odds ratio 4.7, 95% confidence interval, 2.1-10.6, respectively), and low-grade (odds ratio 2.2, 95% confidence interval, 1.6-2.9; odds ratio 4.9, 95% confidence interval, 2.7-8.9; and odds ratio 4.6, 95% confidence interval, 2.6-8.1, respectively) compared with cancers presenting with self-detected masses., Conclusion: Screening detects cancers with more indolent biology, potentially contributing to the observed rate of overdiagnosis. With magnetic resonance imaging and US being used more commonly for screening, the rate of overdiagnosis may increase further., (Copyright © 2016. Published by Elsevier Inc.)

Margin status after definitive breast-conserving surgery (BCS) is a key predictor of local tumor recurrence. This study utilized the National Cancer Database, which captures 70 per cent of all cancer cases nationally, to determine factors associated with persistently positive margins status post-BCS. From 1998 to 2010, there were 1,170,284 patients with stage 0 to 3 breast cancer who underwent BCS. After final definitive surgery, 7.3 per cent of patients had positive margins. On bivariate analysis, persistently positive margin status post-BCS was correlated with patient age, race, ethnicity, comorbidities, facility type and location, tumor size, grade, presence of invasive disease, lymph node positivity, as well as receipt of neoadjuvant chemotherapy and adjuvant radiation therapy (P < 0.001). On multivariate analysis, patients who were black, with multiple comorbidities, living in a Pacific state, who had larger, high-grade, node-positive invasive tumors, who did not receive neoadjuvant chemotherapy, and who did not receive adjuvant radiation therapy were more likely to have persistently positive margins (P < 0.05). Although the goal of BCS is the attainment of negative margins, 7.3 per cent of patients have persistently positive margins after definitive surgery. These patients tend to have more aggressive disease and greater comorbidities, and are less likely to receive adjuvant radiation therapy.

Background: Tumor-infiltrating lymphocyte (TIL) count in breast cancer carries prognostic information and represents a potential predictive marker for emerging immunotherapies. However, the distribution of the lymphocyte subpopulations is not well defined. The goals of this study were to examine intratumor heterogeneity in TIL subpopulation counts in different fields of view (FOV) within each section, in different sections from the same biopsy, and between biopsies from different regions of the same cancer using quantitative immunofluorescence (QIF)., Methods: We used multiplexed QIF to quantify cytokeratin-positive epithelial cells, and CD3-positive, CD8-positive and CD20-positive lymphocytes in tissue sections from multiple biopsies obtained from different areas of 31 surgically resected primary breast carcinomas (93 samples total). Log2-transformed QIF scores or concordance and variance component analyses with linear mixed-effects models were used. Cohen's kappa index [k] of high versus low scores, defined as above and below the median, was used to measure sample similarity between areas., Results: We found a strong positive correlation between CD3 and CD8 levels across all patients (Pearson correlation coefficient [CC] = 0.827). CD3 and CD8 showed a weaker but significant association with CD20 (CC = 0.446 and 0.363, respectively). For each marker, the variation between different FOVs in the same section was higher than the variation between sections or between biopsies of the same cancer. The intraclass correlation coefficients (ICC) were 0.411 for CD3, 0.324 for CD8, and 0.252 for CD20. In component analysis, 66-69 % of the variance was attributable to differences between FOVs in the same section and 30-33 % was due to differences between biopsies from different areas of the same cancer. Section to section differences were negligible. Concordance for low versus high marker status assignment in single biopsies compared to all three biopsies combined yielded k = 0.705 for CD3, k = 0.655 for CD8, and k = 0.603 for CD20., Conclusions: T and B lymphocytes show more heterogeneity across the dimensions of a single section than between different sections or regions of a given breast tumor. This observation suggests that the average lymphocyte score from a single biopsy of a tumor is reasonably representative of the whole cancer.

Conventional wisdom holds that physicians are slow to abandon ineffective medical practices. We evaluated this theory in the case of axillary lymph node dissection, a procedure to remove the lymph nodes near the breast to prevent the spread of breast cancer following breast-conserving surgery. A major trial conducted from 1999 to 2004, with results presented in 2010 and published in 2011, found that patients who met certain criteria could forgo axillary lymph node dissection. Using cancer registry data, we estimated that the proportion of patients undergoing axillary dissection declined by 32.6 percentage points after the trial was published. The decline began immediately after the trial was presented at a medical conference. The rapid decline in the use of axillary dissection belies the common belief that practice patterns are slow to change in response to new evidence, and it highlights the value of trials of established medical practices to patients and the health system., (Project HOPE—The People-to-People Health Foundation, Inc.)

Background: Smoking is known to be carcinogenic and an important factor in the outcome of cancer treatment. However, to the authors' knowledge, smoking habits and smoking cessation counseling in patients with cancer have been poorly studied. The authors sought to analyze smoking habits among Americans diagnosed with cancer in a nationally representative dataset., Methods: The cancer supplement of the National Health Interview Survey (NHIS) in 2010 was used to obtain information regarding self-reported smoking behavior in a representative sample of the US population. Cancer history, smoking history, quitting behavior, cessation counseling, cessation approaches, and sociodemographic variables were analyzed., Results: A total of 27,157 individuals were interviewed for the NHIS in 2010, representing 216,052,891 individuals, 7,058,135 of whom had ever smoked and 13,188,875 of whom had been told that they had cancer. Approximately 51.7% of individuals diagnosed with cancer and who were active smokers reported being counseled to quit smoking by a health professional within the previous 12 months. Cancer survivors were no more likely to quit smoking than individuals in the general population. Those diagnosed with a tobacco-related cancer were found to be no more likely to report quitting smoking than those with other types of cancers. Rates of quitting did not appear to vary based on the type of smoking cessation method used (P = .50)., Conclusions: Patients with cancer, including those diagnosed with a tobacco-related cancer, do not appear to be more likely to quit smoking than the general population. Only approximately one-half of patients with cancer who smoke are counseled to quit. Smoking cessation in patients with cancer is an important area for intervention and investigation., (© 2016 American Cancer Society.)

Introduction: Breast cancer is frequently diagnosed, yet variation remains in terms of practice patterns in presurgical workup. We sought to determine factors associated with this variation., Methods: An anonymous web-based survey was distributed to surgeons regarding their practices. Statistical analyses were conducted using SPSS., Results: A total of 253 surgeons responded to the survey. 17.0% were in academic practice, 37.5% were hospital employed, and 41.5% were in private practice. 53.3% claimed that >50% of their practice was breast related. Surgeons were asked how often they would use various tests in the workup of an otherwise healthy asymptomatic patients, presenting with a non-palpable mammographic abnormality and a core needle biopsy showing invasive breast cancer. 23.5% stated that they always would obtain a breast ultrasound, 17.2% stated that they never would. 12.8% stated that they never order a breast MRI; 4.1% always would. Workup of patients did not vary significantly based on number of years in practice nor practice setting. However, those whose practice was >50% breast were more likely to state that they would always order a breast ultrasound (32.5 vs. 12.9%, p < 0.001), and less likely to state that they would never order a breast MRI (3.4 vs. 25.8%, p < 0.001). However, the proportions of surgeons who would always order a breast MRI were similar in the two groups (3.4 and 3.2%, respectively)., Conclusion: These data highlight the lack of uniformity in the workup of asymptomatic patients presenting with non-palpable breast cancers, pointing to potential areas for improving value by minimizing variability.

Purpose: Obesity is associated with a higher risk of breast cancer mortality. The gold standard approach to weight loss is in-person counseling, but telephone counseling may be more feasible. We examined the effect of in-person versus telephone weight loss counseling versus usual care on 6-month changes in body composition, physical activity, diet, and serum biomarkers., Methods: One hundred breast cancer survivors with a body mass index ≥ 25 kg/m(2) were randomly assigned to in-person counseling (n = 33), telephone counseling (n = 34), or usual care (UC) (n = 33). In-person and telephone counseling included 11 30-minute counseling sessions over 6 months. These focused on reducing caloric intake, increasing physical activity, and behavioral therapy. Body composition, physical activity, diet, and serum biomarkers were measured at baseline and 6 months., Results: The mean age of participants was 59 ± 7.5 years old, with a mean BMI of 33.1 ± 6.6 kg/m(2), and the mean time from diagnosis was 2.9 ± 2.1 years. Fifty-one percent of the participants had stage I breast cancer. Average 6-month weight loss was 6.4%, 5.4%, and 2.0% for in-person, telephone, and UC groups, respectively (P = .004, P = .009, and P = .46 comparing in-person with UC, telephone with UC, and in-person with telephone, respectively). A significant 30% decrease in C-reactive protein levels was observed among women randomly assigned to the combined weight loss intervention groups compared with a 1% decrease among women randomly assigned to UC (P = .05)., Conclusion: Both in-person and telephone counseling were effective weight loss strategies, with favorable effects on C-reactive protein levels. Our findings may help guide the incorporation of weight loss counseling into breast cancer treatment and care., (© 2015 by American Society of Clinical Oncology.)

Background: We performed an analysis to determine the relative contribution of the Oncotype DX (ODX) recurrence score (RS) results in adjuvant therapy delivery compared with traditional pathologic factors., Methods and Materials: We performed a retrospective review of women with stage I-IIIA breast cancer treated at the Yale Comprehensive Cancer Center from 2006 to 2012 with available ODX results. We constructed separate logistic models with the clinicopathologic factors alone and also integrating RS and compared these models using the likelihood ratio test and c-statistic to determine whether integration of the RS will result in better prediction of chemotherapy (CTx) delivery., Results: We identified 431 women with a median age of 58 years. The RS was low (< 18), intermediate (18-30), and high (> 30) in 56%, 37%, and 7%, respectively. CTx was delivered to 30% of the patients. Age, differentiation, lymphovascular invasion, and progesterone receptor (PR) positivity < 50% were associated with CTx delivery in multivariable logistic regression of clinicopathologic factors alone (P < .05). In the model integrating the RS, an intermediate or a high RS was the most influential factor for CTx delivery (odds ratio, 7.87 vs. 265.35, respectively; P < .0001). The PR results and grade were no longer significant (P = .74 and P = .06, respectively). The integration of the RS resulted in improved model fit and precision, indicated by the likelihood ratio test (ΔG2, 100.782; df = 2; P < .0001) and an improved c-statistic (0.720 vs. 0.856)., Conclusion: Gene expression profiling appears to account for a substantial amount of variability in CTx delivery in current practice. Further work is needed to ensure appropriate test usage and cost-effectiveness., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: Pathologic complete response (pCR) to neoadjuvant chemotherapy reflects the cytotoxic efficacy of a drug, but patient survival is influenced by many other factors. The purpose of this study was to assess the relationship between increased pCR rate and trial-level survival benefit in triple-negative breast cancer (TNBC)., Experimental Design: We used bootstrap resampling from a neoadjuvant trial to simulate trials with different pCR rates. We used estimates from Adjuvant!Online to simulate trial populations with different baseline prognosis and estimated survival improvements associated with changes in pCR rate., Results: Assuming that survival is similar for patients with pCR regardless of treatment arm, a linear relationship exists between increasing pCR rate and increasing recurrence-free survival (RFS). The slope is equal to the difference in survival between those with pCR and residual disease, which in turn is influenced by (i) the baseline prognosis of the trial population, (ii) interactions between prognostic variables and pCR, and (iii) the efficacy of the postneoadjuvant therapies. For example, if the pCR rates are 30% and 60% (OR = 3.5) and the 10-year RFS of the control arm is 0.74, the trial would require 3,550 patients per arm, whereas if the RFS is 0.54, the trial would require only 425 patients per arm to detect significant survival benefit., Conclusions: We provide a framework for understanding the relationship between pCR and overall survival benefit that can help inform the design of neoadjuvant trials aiming to demonstrate improved survival from a regimen that results in higher pCR rate., (©2015 American Association for Cancer Research.)

Purpose: To explore racial differences in the use and outcome of neoadjuvant chemotherapy for breast cancer., Methods: The National Cancer Data Base was queried to identify women with stage 1 to 3 breast cancer diagnosed in 2010 and 2011. Chemotherapy use and rate of pathologic complete response (pCR) was determined for various racial/ethnic groups., Results: Of 278,815 patients with known race and ethnicity, 127,417 (46%) received chemotherapy, and of 121,446 where the timing of chemotherapy was known, 27,300 (23%) received neoadjuvant chemotherapy. Chemotherapy, and neoadjuvant chemotherapy in particular, was given more frequently to black, Hispanic, and Asian women than to white women (P < 0.001). This difference was largely explained by more advanced stage, higher grade tumors, and a greater proportion of triple-negative and human epidermal growth factor receptor 2 (HER2)-positive tumors in these women. Of 17,970 patients with known outcome, 5,944 (33%) had a pCR. No differences in response rate for estrogen receptor (ER)/progesterone receptor (PR)-positive tumors were found, but compared with white women, black but not Hispanic or Asian women had a lower rate of pCR for ER/PR-negative, HER2-positive (43% v 54%, P = 0.001) and triple-negative tumors (37% v 43%, P < 0.001). This difference persisted when adjusted for age, clinical T stage, clinical N stage, histology, grade, comorbidity index, facility type, geographic region, insurance status, and census-derived median income and education for the patient's zip code (odds ratio, 0.84; 95% CI, 0.77 to 0.93)., Conclusion: Neoadjuvant chemotherapy is given more frequently to black, Hispanic, and Asian women than to white women. Black women have a lower likelihood of pCR for triple-negative and HER2-positive breast cancer. Whether this is due to biologic differences in chemosensitivity or to treatment or socioeconomic differences that could not be adjusted for is unknown., (© 2015 by American Society of Clinical Oncology.)

Background: Standard two-dimensional (2D) specimen radiography may guide intraoperative re-excision of margins in patients undergoing breast conserving surgery. We sought to determine the impact of three-dimensional (3D) specimen imaging in further reducing positive margin rates., Methods: A prospective study of 100 patients in which both 2D and 3D specimen radiographies were performed. The impact of orthogonal view on intraoperative surgical management and final margins was assessed., Results: Ten patients had no residual tumor; therefore, 90 patients formed the cohort of interest. Of them, 21 patients (23.3%) had ductal carcinoma in situ; 18 (20.0%) had invasive cancer; and 51 (56.7%) had both. Median tumor size was 1.7 cm (range, .2 to 8.1 cm). On the basis of 2D imaging, surgeons stated they would take more tissue in 26 patients (28.9%). Three-dimensional imaging changed management in 4 patients (6.3%). One of these patients would have had positive margins if the intraoperative resection done on the basis of the 3D imaging would have been omitted., Conclusions: Three-dimensional specimen imaging results in further intraoperative re-excision in 6.3% of patients and may reduce re-excision rates in 2.2%., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Routine resection of cavity shave margins (additional tissue circumferentially around the cavity left by partial mastectomy) may reduce the rates of positive margins (margins positive for tumor) and reexcision among patients undergoing partial mastectomy for breast cancer., Methods: In this randomized, controlled trial, we assigned, in a 1:1 ratio, 235 patients with breast cancer of stage 0 to III who were undergoing partial mastectomy, with or without resection of selective margins, to have further cavity shave margins resected (shave group) or not to have further cavity shave margins resected (no-shave group). Randomization occurred intraoperatively after surgeons had completed standard partial mastectomy. Positive margins were defined as tumor touching the edge of the specimen that was removed in the case of invasive cancer and tumor that was within 1 mm of the edge of the specimen removed in the case of ductal carcinoma in situ. The rate of positive margins was the primary outcome measure; secondary outcome measures included cosmesis and the volume of tissue resected., Results: The median age of the patients was 61 years (range, 33 to 94). On final pathological testing, 54 patients (23%) had invasive cancer, 45 (19%) had ductal carcinoma in situ, and 125 (53%) had both; 11 patients had no further disease. The median size of the tumor in the greatest diameter was 1.1 cm (range, 0 to 6.5) in patients with invasive carcinoma and 1.0 cm (range, 0 to 9.3) in patients with ductal carcinoma in situ. Groups were well matched at baseline with respect to demographic and clinicopathological characteristics. The rate of positive margins after partial mastectomy (before randomization) was similar in the shave group and the no-shave group (36% and 34%, respectively; P=0.69). After randomization, patients in the shave group had a significantly lower rate of positive margins than did those in the no-shave group (19% vs. 34%, P=0.01), as well as a lower rate of second surgery for margin clearance (10% vs. 21%, P=0.02). There was no significant difference in complications between the two groups., Conclusions: Cavity shaving halved the rates of positive margins and reexcision among patients with partial mastectomy. (Funded by the Yale Cancer Center; ClinicalTrials.gov number, NCT01452399.).

Psychological distress, which can begin with cancer diagnosis and continue with treatment, is linked with circadian and endocrine disruption. In turn, circadian/endocrine factors are potent modulators of cancer progression. We hypothesized that circadian rest-activity rhythm disruption, distress, and diurnal cortisol rhythms would be associated with biomarkers of tumor progression in the peripheral blood of women awaiting breast cancer surgery. Breast cancer patients (n=43) provided actigraphic data on rest-activity rhythm, cancer-specific distress (IES, POMS), saliva samples for assessment of diurnal cortisol rhythm, cortisol awakening response (CAR), and diurnal mean. Ten potential markers of tumor progression were quantified in serum samples and grouped by exploratory factor analysis. Analyses yielded three factors, which appear to include biomarkers reflecting different aspects of tumor progression. Elevated factor scores indicate both high levels and strong clustering among serum signals. Factor 1 included VEGF, MMP-9, and TGF-β; suggesting tumor invasion/immunosuppression. Factor 2 included IL-1β, TNF-α, IL-6R, MCP-1; suggesting inflammation/chemotaxis. Factor 3 included IL-6, IL-12, IFN-γ; suggesting inflammation/TH1-type immunity. Hierarchical regressions adjusting age, stage and socioeconomic status examined associations of circadian, distress, and endocrine variables with these three factor scores. Patients with poor circadian coordination as measured by rest-activity rhythms had higher Factor 1 scores (R(2)=.160, p=.038). Patients with elevated CAR also had higher Factor 1 scores (R(2)=.293, p=.020). These relationships appeared to be driven largely by VEGF concentrations. Distress was not related to tumor-relevant biomarkers, and no other significant relationships emerged. Women with strong circadian activity rhythms showed less evidence of tumor promotion and/or progression as indicated by peripheral blood biomarkers. The study was not equipped to discern the cause of these associations. Circadian/endocrine aberrations may be a manifestation of systemic effects of aggressive tumors. Alternatively, these results raise the possibility that, among patients with active breast tumors, disruption of circadian activity rhythms and elevated CAR may facilitate tumor promotion and progression., (Copyright © 2015 Elsevier Inc. All rights reserved.)