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Background: Women with breast cancer in northwest Syria, an area of protracted armed conflict, face multiple intersecting challenges to accessing care which may relate to gender, social structures, and financial constraints. Our aim was to explore the perspectives of women with breast cancer in northwest Syria about the impact of their diagnosis and experiences of accessing care., Methods: Women who accessed diagnosis or clinical care at the Syrian American Medical Society (SAMS) oncology centre in Idlib city during 2022 were identified from hospital records; they were invited to participate in semi-structured interviews conducted in Arabic by four local female-trained researchers. Participation was voluntary and informed consent was sought. Semi-structured interviews were conducted in August and September 2022 until thematic saturation was reached. Data were audio recorded and transcribed in Arabic before translation and thematic analysis using Nvivo to identify key emerging themes., Results: 22 women with breast cancer were interviewed. Findings were categorised into three themes: 1. Challenges to accessing oncology care in northwest Syria 2. Interactions with healthcare workers 3. The role of community and society. All participants noted the financial strains which the breast cancer diagnosis placed on them and their families. Most also noted the additional strains of travelling long distances, either in northwest Syria or to Turkey, where referral would entail additional costs, bureaucracy or isolation from family or social support. Some participants described social impacts including the expectation that they would continue with household chores and childcare even while ill. Patients reported that strong faith, having children, compassion from healthcare staff and peer support as being important factors for coping with their diagnosis and treatment., Conclusion: Though there have been improvements to breast cancer care in northwest Syria, stock-outs and the lack of availability of radiotherapy may still force women to travel to Turkey for further investigations or treatment. Our findings suggest increased support for women with breast cancer as well as their families is required. This work is a starting point for future research on this topic both in northwest Syria and other areas in Syria., Competing Interests: Declaration of competing interest The authors have declared that no competing interests exist., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Successful completion of chemotherapy is critical to improve breast cancer outcomes. Relative dose intensity (RDI), defined as the ratio of chemotherapy delivered to prescribed, is a measure of chemotherapy completion and is associated with cancer mortality. The effect of exercise and eating a healthy diet on RDI is unknown. We conducted a randomized trial of an exercise and nutrition intervention on RDI and pathologic complete response (pCR) in women diagnosed with breast cancer initiating chemotherapy., Methods: One hundred seventy-three women with stage I-III breast cancer were randomly assigned to usual care (UC; n = 86) or a home-based exercise and nutrition intervention with counseling sessions delivered by oncology-certified registered dietitians (n = 87). Chemotherapy dose adjustments and delays and pCR were abstracted from electronic medical records. T-tests and chi-square tests were used to examine the effect of the intervention versus UC on RDI and pCR., Results: Participants randomly assigned to intervention had greater improvements in exercise and diet quality compared with UC ( P < .05). RDI was 92.9% ± 12.1% and 93.6% ± 11.1% for intervention and UC, respectively ( P = .69); the proportion of patients in the intervention versus UC who achieved ≥85% RDI was 81% and 85%, respectively ( P = .44). The proportion of patients who had at least one dose reduction and/or delay was 38% intervention and 36% UC ( P = .80). Among 72 women who received neoadjuvant chemotherapy, women randomly assigned to intervention were more likely to have a pCR than those randomly assigned to UC (53% v 28%; P = .037)., Conclusion: Although a diet and exercise intervention did not affect RDI, the intervention was associated with a higher pCR in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative and triple-negative breast cancer undergoing neoadjuvant chemotherapy.

Background: Breast-conserving surgery (BCS) is a mainstay for breast cancer management, and obtaining negative margins is critical. Some have advocated for the use of preoperative magnetic resonance imaging (MRI) in reducing positive margins after BCS. We sought to determine whether preoperative MRI was associated with reduced positive margins., Patients and Methods: The SHAVE/SHAVE2 trials were multicenter trials in ten US centers with patients with stage 0-3 breast cancer undergoing BCS. Use of preoperative MRI was at the discretion of the surgeon. We evaluated whether or not preoperative MRI was associated with margin status prior to randomization regarding resection of cavity with shave margins., Results: A total of 631 patients participated. Median age was 64 (range 29-94) years, with a median tumor size of 1.3 cm (range 0.1-9.3 cm). Patient factors included 26.1% of patients (165) had palpable tumors, and 6.5% (41) received neoadjuvant chemotherapy. Tumor factors were notable for invasive lobular histology in 7.0% (44) and extensive intraductal component (EIC) in 32.8% (207). A preoperative MRI was performed in 193 (30.6%) patients. Those who underwent preoperative MRI were less likely to have a positive margin (31.1% versus 38.8%), although this difference was not statistically significant (p = 0.073). On multivariate analysis, controlling for patient and tumor factors, utilization of preoperative MRI was not a significant factor in predicting margin status (p = 0.110). Rather, age (p = 0.032) and tumor size (p = 0.040) were the only factors associated with margin status., Conclusion: These data suggest that preoperative MRI is not associated margin status; rather, patient age and tumor size are the associated factors., (© 2023. Society of Surgical Oncology.)

Background: Breast cancer patients may not be well-informed about palliative care, hindering its integration into cancer self-management., Objective: The aim of this study was to test Managing Cancer Care: A Personal Guide (MCC-PT), an intervention to improve palliative care literacy and cancer self-management., Methods: This was a single-blind pilot randomized controlled trial to evaluate the feasibility/acceptability and intervention effects of MCC-PT on palliative care literacy, self-management behaviors/emotions, and moderation by demographic/clinical characteristics. We enrolled 71 stages I to IV breast cancer patients aged at least 21 years, with >6-month prognosis at an academic cancer center. Patients were randomized to MCC-PT (n = 32) versus symptom management education as attention-control (n = 39). At baseline, 1 month, and 3 months, participants completed the Knowledge of Care Options Test (primary outcome), Control Preferences Scale, Goals of Care Form, Medical Communication Competence Scale, Measurement of Transitions in Cancer Scale, Chronic Disease Self-efficacy Scale, Hospital Anxiety and Depression Scale, and the Mishel Uncertainty in Illness Scale., Results: Mean participant age was 51.5 years (range, 28-74 years); 53.5% were racial/ethnic minority patients, and 40.8% had stage III/IV cancer. After adjusting for race/ethnicity, MCC-PT users improved their palliative care literacy with a large effect size (partial η2 = 0.13). Patients at late stage of disease showed increased self-management (partial η2 = 0.05) and reduced anxiety (partial η2 = 0.05) and depression (partial η2 = 0.07) with medium effect sizes., Conclusions: Managing Cancer Care: A Personal Guide is feasible and appears most effective in late-stage cancer. Research is needed to elucidate relationships among cancer stage, race/ethnicity, and self-management outcomes., Implications for Practice: Integration of palliative care into cancer care can assist in creation of appropriate self-management plans and improve emotional outcomes., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: We developed a virtual interactive course for female faculty/practicing physicians and trainees to hone their skills in negotiation and sought to evaluate the impact of this on their knowledge, comfort, and skill in negotiation., Methods: We surveyed participants as to their comfort and experience with negotiation before and after the course, as well as three months later., Results: Of the 102 participants in the faculty course, 55 (53.9%) were academic ladder faculty, and 47 (46.1%) were in surgery or a surgical subspecialty. Participants were significantly more comfortable with negotiation initiation, strategy, and post-settlement settlement after the course ( p  < 0.001 for each). 91.1% found the course valuable, 92.9% felt their knowledge about negotiation increased, and 85.7% wished they would have taken this course earlier. 98.2% stated they were likely to use some of the things they learned in this course in future. Three months later, 40.7% of respondents stated they had used what they had learned: 57.7, 41.7, and 32.0% had negotiated for pay, promotion, or job-related perks, respectively. These negotiations went "better than expected" in 26.6, 30, and 37.5%, respectively. Prior to the course, only 3 (2.9%) felt that their last negotiation went "very well" or better; three months after the course, 28% felt their last negotiation after the course went "very well" or "extremely well" ( p  = 0.002)., Conclusion: Negotiation training can have a significant impact on female physicians' comfort in initiating negotiation, negotiation strategy and post-settlement discussions. Such training significantly increases "better than expected" negotiations., (© The Author(s), under exclusive licence to Association for Surgical Education 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: Negotiation training has been posited to help reduce gender wage disparities. We sought to evaluate the impact of a virtual negotiations training course (VNTC) on female trainees., Methods: 111 female trainees participated in the course; 42 completed both pre- and post-course surveys., Results: 95.5% had no prior negotiation training. After the course, more trainees reported feeling "pretty comfortable" or "extremely comfortable" with initiating negotiation (8.3% vs. 94.1%, p < 0.001) and negotiation strategy (0% vs. 50.0%, p < 0.001). Three months later, 44% had negotiated for compensation; 63.6% felt the negotiation went "better than expected". Compared to the last major negotiation they had prior to taking the course, trainees were more likely to state that their last major negotiation after the course went "very well" or "extremely well" (2.0% vs. 50.0%, p < 0.001)., Conclusion: Most female medical trainees do not get negotiation training; however, these data demonstrate a significant benefit of such training., Competing Interests: Declaration of competing interest This work was funded by the American Medical Association's Joan Giambalvo Award for the advancement of women, and resulted in the creation of a virtual negotiation training course (negotiation-101.square.site). Other conflicts of interest (unrelated to the current work): I sit on the Board of Directors of Protean Biodiagnostics. I receive royalties from Uptodate (where I am the Breast Surgery Section editor) as well as from Yale University (for my course called “An Introduction to Breast Cancer” on the Coursera platform). I have also received honoraria from Sanofi Aventis, Guardant, Athenex, Puma Therapeutics, Novartis, and Lumicell. I am on the speakers bureau for Merck., (Copyright © 2022. Published by Elsevier Inc.)

Background: There are several techniques for localization of non-palpable breast tumors, but comparisons of these techniques in terms of margin positivity and volume of tissue resected are lacking., Methods: Between 2011-2013 and 2016-2018, 2 randomized controlled trials involving 10 centers across the United States accrued 631 patients with stage 0-3 breast cancer, all of whom underwent breast conserving surgery. Of these, 522 had residual non-palpable tumors for which localization was required. The localization technique was left to the discretion of the individual surgeon. We compared margin positivity and volume of tissue resected between various localization techniques., Results: The majority of the patients (n = 465; 89.1%) had wire localization (WL), 50 (9.6%) had radioactive seed (RS) localization, and 7 (1.3%) had Savi Scout (SS) localization. On bivariate analysis, there was no difference in terms of margin positivity (37.8% vs. 28.0% vs. 28.6%, P = .339) nor re-excision rates (13.3% vs. 12.0% vs. 14.3%, P = .961) for the WL, RS, and SS groups, respectively. Further, the volume of tissue removed was not significantly different between the 3 groups (71.9 cm 3 vs. 55.8 cm 3 vs. 86.6 cm 3 for the WL, RS, and SS groups, respectively, P = .340). On multivariate analysis, margin status was affected by tumor size (OR = 1.336; 95% CI: 1.148-1.554, P <.001) but not by type of localization ( P = .670)., Conclusions: While there are a number of methods for tumor localization, choice of technique does not seem to influence volume of tissue resected nor margin status.

Introduction: De-escalation of breast cancer treatment aims to reduce patient and financial toxicity without compromising outcomes. Level I evidence and National Comprehensive Cancer Network guidelines support omission of adjuvant radiation in patients aged >70 y with hormone-sensitive, pT1N0M0 invasive breast cancer treated with endocrine therapy. We evaluated radiation use in patients eligible for guideline concordant omission of radiation., Methods: Subgroup analysis of patients eligible for radiation omission from two pooled randomized controlled trials, which included stage 0-III breast cancer patients undergoing breast conserving surgery, was performed to evaluate factors associated with radiation use., Results: Of 631 patients, 47 (7.4%) met radiation omission criteria and were treated by 14 surgeons at eight institutions. The mean age was 75.3 (standard deviation + 4.4) y. Majority of patients identified as White (n = 46; 97.9%) and non-Hispanic (n = 44; 93.6%). The mean tumor size was 1.0 cm; 37 patients (88.1%) had ductal, 4 patients (9.5%) had lobular, and 17 patients (40.5%) had low-grade disease. Among patients eligible for radiation omission, 34 (72.3%) patients received adjuvant radiation. Those who received radiation were significantly younger than those who did not (74 y, interquartile range = 4 y, versus 78 y, interquartile range = 11 y, P = 0.03). There was no difference in radiation use based on size (P = 0.4), histology (P = 0.5), grade (P = 0.7), race (P = 1), ethnicity (P = 0.6), institution (P = 0.1), gender of the surgeon (P = 0.7), or surgeon (P = 0.1)., Conclusions: Fewer than 10% of patients undergoing breast conservation met criteria for radiation omission. Nearly three-quarters received radiation therapy with younger age being a driver of radiation use, suggesting ample opportunity for de-escalation, particularly among younger eligible patients., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Context.—: Breast carcinoma grade, as determined by the Nottingham Grading System (NGS), is an important criterion for determining prognosis. The NGS is based on 3 parameters: tubule formation (TF), nuclear pleomorphism (NP), and mitotic count (MC). The advent of digital pathology and artificial intelligence (AI) have increased interest in virtual microscopy using digital whole slide imaging (WSI) more broadly., Objective.—: To compare concordance in breast carcinoma grading between AI and a multi-institutional group of breast pathologists using digital WSI., Design.—: We have developed an automated NGS framework using deep learning. Six pathologists and AI independently reviewed a digitally scanned slide from 137 invasive carcinomas and assigned a grade based on scoring of the TF, NP, and MC., Results.—: Interobserver agreement for the pathologists and AI for overall grade was moderate (κ = 0.471). Agreement was good (κ = 0.681), moderate (κ = 0.442), and fair (κ = 0.368) for grades 1, 3, and 2, respectively. Observer pair concordance for AI and individual pathologists ranged from fair to good (κ = 0.313-0.606). Perfect agreement was observed in 25 cases (27.4%). Interobserver agreement for the individual components was best for TF (κ = 0.471 each) followed by NP (κ = 0.342) and was worst for MC (κ = 0.233). There were no observed differences in concordance amongst pathologists alone versus pathologists + AI., Conclusions.—: Ours is the first study comparing concordance in breast carcinoma grading between a multi-institutional group of pathologists using virtual microscopy to a newly developed WSI AI methodology. Using explainable methods, AI demonstrated similar concordance to pathologists alone., Competing Interests: Authors Mantrala, Mitkari, Joshi, Prabhala, Ramachandra, Kini, and Koka are current employees of Onward Assist., (© 2022 College of American Pathologists.)

Introduction: Asian American women have lower breast cancer incidence and mortality than their non-Hispanic White (NHW) counterparts. We sought to determine whether differences in screening practices could explain, in part, the variation in breast cancer detection rate., Methods: The 2015 National Health Interview Survey, an annual survey that is representative of the civilian, noninstitutionalized American population, was used to determine whether mammography usage was different between Asian and NHW women. Women ≥40 y of age who identified as either Asian or NHW were included., Results: A total of 7990 women ≥40 y of age (6.12% Asian, 93.88% NHW), representing 53,275,420 women in the population, were included in our cohort of interest; 71.49% of Asian and 74.46% of NHW women reported having had a mammogram within the past 2 y (P = 0.324). Controlling for education, insurance, family income, marital status, and whether they were born in the United States, Asians were less likely to have had a mammogram within the past 2 y than their NHW counterparts (odds ratio = 0.68; 95% confidence interval: 0.46-0.99, P = 0.047). Of patients who had an abnormal mammogram, there was no difference in the biopsy rate (20.35% versus 25.97%, P = 0.4935) nor in the rate of cancer diagnosis among those who had a biopsy (7.70% versus 12.86%, P = 0.211) between Asian and NHW women, respectively., Conclusions: Our findings suggest that the lower breast cancer incidence among the Asian population may, in part, be explained by a lower screening mammography rate in this population., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Approximately one-quarter of annual global cervical cancer deaths occur in India, possibly due to cultural norms promoting vaccine hesitancy. We sought to determine whether people of Indian ancestry (POIA) in the USA exhibit disproportionately lower human papilloma virus (HPV) vaccination rates than the rest of the US population. We utilised the 2018 National Health Interview Survey to compare HPV vaccine initiation and completion rates between POIA and the general US population and determined factors correlating with HPV vaccine uptake among POIA. Compared to other racial groups, POIA had a significantly lower rate of HPV vaccination (8.18% vs. 12.16%, 14.70%, 16.07% and 12.41%, in White, Black, Other Asian and those of other/mixed ancestry, respectively, P = 0.003), but no statistically significant difference in vaccine series completion among those who received at least one injection (3.17% vs. 4.27%, 3.51%, 4.31% and 5.04%, P = 0.465). Among POIA, younger individuals ( vs. older), single individuals ( vs. married), those with high English proficiency ( vs. low English proficiency), those with health insurance and those born in the USA ( vs. those born outside the USA) were more likely to obtain HPV vaccination ( P = 0.018, P = 0.006, P = 0.029, P = 0.020 and P = 0.019, respectively). Public health measures promoting HPV vaccination among POIA immigrants may substantially improve vaccination rates among this population.

Background: Molecular subtype in invasive breast cancer guides systemic therapy. It is unknown whether molecular subtype should also be considered to tailor surgical therapy. The present investigation was designed to evaluate whether breast cancer subtype impacted surgical margins in patients with invasive breast cancer stage I through III undergoing breast-conserving therapy., Methods: Data from 2 randomized trials evaluating cavity shave margins (CSM) on margin status in patients undergoing partial mastectomy (PM) were used for this analysis. Patients were included if invasive carcinoma was present in the PM specimen and data for all 3 receptors (ER, PR, and HER2) were known. Patients were classified as luminal if they were ER and/or PR positive; HER2 enriched if they were ER and PR negative but HER2 positive; and TN if they were negative for all 3 receptors. The impact of subtype on the margin status was evaluated at completion of standard PM, prior to randomization to CSM versus no CSM. Non-parametric statistical analyses were performed using SPSS Version 26., Results: Molecular subtype was significantly correlated with race ( P = .011), palpability ( P = .007), and grade ( P < .001). Subtype did not correlate with Hispanic ethnicity ( P = .760) or lymphovascular invasion ( P = .756). In this cohort, the overall positive margin rate was 33.7%. This did not vary based on molecular subtype (positive margin rate 33.7% for patients with luminal tumors vs 36.4% for those with TN tumors, P = .425)., Discussion: Molecular subtype does not predict margin status. Therefore, molecular subtype should not, independent of other factors, influence surgical decision-making.

Introduction: Factors contributing to the use of preoperative MRI remain poorly understood., Methods: Data from a randomized controlled trial of stage 0-3 breast cancer patients undergoing breast conserving surgery between 2016 and 2018 were analyzed., Results: Of the 396 patients in this trial, 32.6% had a preoperative MRI. Patient age, race, ethnicity, tumor histology, and use of neoadjuvant therapy were significant predictors of MRI use. On multivariate analysis, younger patients with invasive lobular tumors were more likely to have a preoperative MRI. Rates also varied significantly by individual surgeon (p < 0.001); in particular, female surgeons (39.9% vs. 24.0% for male surgeons, p = 0.001) and those in community practice (58.9% vs. 14.2% for academic, p < 0.001) were more likely to order preoperative MRI. Rates declined over the two years of the study, particularly among female surgeons., Conclusions: Preoperative MRI varies with patient age and tumor histology; however, there remains variability by individual surgeon., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Patient and tumor characteristics often coincide with obesity, potentially affecting treatment decision-making in obese breast cancer patients. Independent of all of these factors, however, it is unclear whether obesity itself impacts the decision to offer patients undergoing mastectomy breast reconstruction, postmastectomy radiation therapy (PMRT), or neoadjuvant chemotherapy. We sought to determine whether implicit bias against obese breast cancer patients undergoing mastectomy plays a role in their treatment., Methods: Medical records of breast cancer patients undergoing mastectomy from January 2010 to April 2018 from a single institution were retrospectively reviewed, separated into obese (BMI ≥30) and nonobese (BMI <30) categories, and compared using nonparametric statistical analyses., Results: Of 972 patients, 291 (31.2%) were obese. Obese patients were more likely to have node-positive, triple-negative breast cancers ( P = .026) and were also more likely to have other comorbidities such as a history of smoking ( P = .026), hypertension ( P < .001), and diabetes ( P < .001). Receipt of immediate reconstruction and contralateral prophylactic mastectomy did not vary between obese and nonobese patients. While obese patients were more likely to undergo neoadjuvant chemotherapy (26.5% vs. 18.1%, P = .004) and PMRT (33.0% vs. 23.4%, P = .003), this did not remain significant when controlling for comorbidities and clinicopathologic confounders., Conclusion: Obese patients present with more aggressive tumors and often have concomitant comorbidities. Independent of these factors, however, differences in the treatment of patients undergoing mastectomy do not seem to be affected by an implicit bias against obese patients.

Background: We sought to determine factors affecting time to surgery (TTS) to identify potential modifiable factors to improve timeliness of care., Methods: Patients with clinical stage 0-3 breast cancer undergoing partial mastectomy in 2 clinical trials, conducted in ten centers across the US, were analyzed. No preoperative workup was mandated by the study; those receiving neoadjuvant therapy were excluded., Results: The median TTS among the 583 patients in this cohort was 34 days (range: 1-289). Patient age, race, tumor palpability, and genomic subtype did not influence timeliness of care defined as TTS ≤30 days. Hispanic patients less likely to have a TTS ≤30 days ( P = .001). There was significant variation in TTS by surgeon ( P < .001); those practicing in an academic center more likely to have TTS ≤30 days than those in a community setting (55.1% vs 19.3%, P < .001). Patients who had a preoperative ultrasound had a similar TTS to those who did not (TTS ≤30 days 41.9% vs 51.9%, respectively, P = .109), but those who had a preoperative MRI had a significantly increased TTS (TTS ≤30 days 25.0% vs 50.9%, P < .001). On multivariate analysis, patient ethnicity was no longer significantly associated with TTS ≤30 ( P = .150). Rather, use of MRI (OR: .438; 95% CI: .287-.668, P < .001) and community practice type (OR: .324; 95% CI: .194-.541, P < .001) remained independent predictors of lower likelihood of TTS ≤30 days., Conclusions: Preoperative MRI significantly increases time to surgery; surgeons should consider this in deciding on its use.

Introduction: Breast cancer survivors are often prescribed medications for at least 5 years to reduce recurrence risk, yet some forego this treatment due to cost. We sought to elucidate the prevalence of this and the factors contributing to it., Methods: The National Health Interview Survey (NHIS) is a population-based survey, representative of the civilian non-institutionalized US population, administered annually by the CDC. People diagnosed with breast cancer within the past 5 years surveyed in the 2018 NHIS formed the cohort of interest., Results: Of the 24,858 breast cancer survivors surveyed, representing 244,607,304 in the population, 6.32% stated that they needed a prescription medicine within the past 12 months, but didn't get it filled because they couldn't afford it. Of those who had gotten a prescription within the past 12 months, 5.71, 5.94 and 7.48% had either skipped doses, taken less medication than prescribed, or delayed filling a prescription, respectively, to save money. 11.99% of people had done at least one of these, thereby foregoing treatment. On bivariate analyses, factors associated with foregoing treatment included age, race, education, family income, and insurance status (p < 0.001 for all). On multivariable analysis, age, race, family income, and insurance status were all independent predictors of foregoing treatment (p < 0.001 for all); education status was not significant in the model (p = 0.211)., Conclusion: Roughly 12% of breast cancer survivors who are prescribed medications within the first 5 years of their diagnosis will forego treatment due to cost. Family income and insurance status are key modifiable drivers of this., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The coronavirus disease 2019 pandemic prompted a surge in telemedicine, with the presumption that patients had computer and internet access. We sought to determine, in a population-based sample, how many Americans were using computers and the internet before the pandemic, and whether disparities existed in this., Methods: The National Health Interview Survey is conducted annually by the Centers for Disease Control and Prevention and is representative of the entire United States civilian non-institutionalized population. In 2018, questions were fielded regarding computer and web utilization. We evaluated sociodemographic factors associated with this., Results: Twenty-five thousand and forty-nine people, representing 245,842,992 in the population, responded to these questions. Of the responses, 19% stated they used a computer "never or almost never," 18% stated they did not use the internet, and 25% did not use email. Over the previous 12 months, 55% of responders stated they had looked up health information on the internet, 11% had filled a prescription online, 16% had scheduled a medical appointment on the internet, and 17% had communicated with a healthcare provider by email. Internet usage varied by region, age, race, education, family income, and insurance status, but not by gender., Conclusion: As telemedicine becomes more prevalent, sociodemographic factors limiting computer and internet use may disadvantage certain segments of the population., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Breast cancer survivors may experience sleep disturbances that can affect their physical and mental well-being. We sought to determine the association, if any, between yoga and sleep among breast cancer survivors in a population-based cohort., Methods: The National Health Interview Survey is designed to be representative of the US civilian non-institutionalized population. We evaluated breast cancer survivors in the 2017 cohort to determine the association between yoga and self-reported quality of sleep., Results: Of the 25,905 people surveyed, representing 238,738,039 in the population, 1.59% reported a previous history of breast cancer. Breast cancer survivors were less likely to report having practiced yoga in the preceding 12 months, compared to those without a history of breast cancer (9.98% vs 13.78%, P = .011). In addition, they were more likely to report having had trouble falling asleep (44.64% vs 36.32%, P = .002), staying asleep (53.72% vs 39.43%, P < .001), and using sleep medication on at least 1 day within the previous week (23.80% vs 13.49%, P < .001) than those without breast cancer. Among breast cancer survivors, there were no significant differences in difficulty falling asleep (39.16% vs 44.98%, P = .482), difficulty staying asleep (61.17% vs 52.70%, P = .305), and needing sleep medication (19.03% vs 24.53%, P = .395) between those who practiced yoga and those who did not. Controlling for sociodemographic factors, there remained no association between yoga and difficulty falling or staying asleep among breast cancer survivors., Conclusion: There is no direct association between yoga and sleep quality in breast cancer survivors.

Purpose: To compare the impact of exercise and mind-body prehabilitation interventions on changes in quality of life and cancer treatment-related symptoms in women with newly diagnosed breast cancer., Methods: The following describes a secondary analysis of a randomized window of opportunity trial (The Pre-Operative Health and Body Study). Forty-nine women were randomized to participate in either an exercise prehabilitation intervention or a mind-body prehabilitation intervention from the time of enrollment to surgery. Participants (N = 47) completed measures of quality of life, anxiety, depression, and stress at the time of enrollment (T1), post-intervention/surgery (T2), and one-month post-surgery (T3). Changes in outcome measures between groups were compared over time using longitudinal models., Results: Mind-body group participants experienced significant improvements in cognitive functioning in comparison to exercise group participants between T1 and T3 (difference in average change: -9.61, p = 0.04, d = 0.31), otherwise, there were no significant differences between groups. Within group comparisons demonstrated that both groups experienced improvements in anxiety (exercise: average change = -1.18, p = 0.03, d = 0.34; mind-body: average change = -1.69, p = 0.006, d = 0.43) and stress (exercise: average change = -2.33, p = 0.04, d = 0.30; mind-body: average change = -2.59, p = 0.05, d = 0.29), while mind-body group participants experienced improvements in insomnia (average change = -10.03, p = 0.04, d = 0.30) and cognitive functioning (average change = 13.16, p = 0.0003, d = 0.67)., Conclusions: Both prehabilitation interventions impacted cancer treatment-related symptoms. Further work in larger groups of patients is needed to evaluate the efficacy of prehabilitation interventions on quality of life in women with breast cancer. Pre-operative exercise and mind-body interventions may impact physical and/or psychological effects of cancer diagnosis and treatment in women with breast cancer., Trial Registration: ClinicalTrials.gov Identifier: NCT01516190. Registered January 24, 2012., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Mammography remains the only validated screening tool for breast cancer, however, there are limitations to mammography. One of the limitations of mammography is the variable sensitivity based on breast density. Supplemental screening may be considered based on the patient's risk level and breast density. For average-risk women with nondense breasts, the sensitivity of digital breast tomosynthesis (DBT) screening is high; additional supplemental screening is not warranted in this population. For average-risk women with dense breasts, given the decreased sensitivity of mammography/DBT, this population may benefit from additional supplemental screening with contrast-enhanced mammography, screening ultrasound (US), breast MRI, or abbreviated breast MRI. In intermediate-risk women, there is emerging evidence suggesting that women in this population may benefit from breast MRI or abbreviated breast MRI. In intermediate-risk women with dense breasts, given the decreased sensitivity of mammography/DBT, this population may benefit from additional supplemental screening with contrast-enhancedmammography or screening US. There is strong evidence supporting screening high-risk women with breast MRI regardless of breast density. Contrast-enhanced mammography, whole breast screening US, or abbreviated breast MRI may be also considered. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment., (Copyright © 2021 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Although postmastectomy radiation therapy is known to reduce local recurrence in patients with T1/2N1 breast cancer, some have postulated that not all patients require this treatment. In this era of genomic analyses and personalized therapy, clinicians have debated whether the toxicity of post-mastectomy radiation therapy (PMRT) can be avoided for some subsets of patients. However, the data in this regard remain controversial, particularly as surgeons de-escalate the surgical management of the axilla. Several ongoing clinical trials may provide a glimpse into optimal management in this scenario. However, the "right" answer to this debate currently remains unclear., (© 2021. Society of Surgical Oncology.)

Background: Inter-rater reliability between breast surgical oncologists and reconstructive surgeons using cosmesis scales, and the correlation between their observations and patients' own subjective assessments, is poorly understood., Methods: Patients undergoing BCS in a prospective trial rated their cosmetic outcome on a Likert scale (poor/fair/good/excellent) at the postoperative and 1-year time points; photographs were also taken. Three breast surgical oncologists (not involved in these cases) and two reconstructive surgeons were asked to independently rate cosmesis using the Harvard/NSABP/RTOG scale., Results: Overall, 55 and 17 patients had photographs and Likert self-evaluations at the postoperative and 1-year time points, respectively. There was poor agreement between surgeon and patient ratings postoperatively [kappas - 0.042 (p = 0.659), 0.069 (p = 0.226), and 0.076 (p = 0.090) for the breast surgical oncologists; and 0.018 (p = 0.689) and 0.112 (p = 0.145) for the reconstructive surgeons], and poor interobserver agreement between surgeons of the same specialty (kappa - 0.087, 95% confidence interval [CI] - 0.091 to - 0.082, p = 0.223 for breast surgical oncologists; and kappa - 0.150, 95% CI - 0.157 to - 0.144, p = 0.150, for reconstructive surgeons). At 1 year, the interobserver agreement between breast surgical oncologists was better (kappa 0.507, 95% CI 0.501-0.512, p < 0.001); however, there was still poor correlation between the reconstructive surgeons (kappa - 0.040, 95% CI - 0.049 to - 0.031, p = 0.772). Agreement between surgeon and patient ratings remained poor at this time point [kappas - 0.115 (p = 0.477), 0.177 (p = 0.245), and 0.101 (p = 0.475) for breast surgical oncologists; and 0.335 (p = 0.037) and -0.118 (p = 0.221) for reconstructive surgeons]., Conclusion: Despite gradation scales for measuring cosmesis after BCS, high levels of agreement between surgeons is lacking and these do not always reflect patients' subjective assessments., (© 2021. Society of Surgical Oncology.)

Background: While the optimal time interval between mastectomy and postmastectomy radiation therapy (PMRT) has not been well-elucidated, a delay in PMRT has been associated with increased local recurrence. We sought to determine factors associated with a delay in PMRT beyond 12 weeks in patients not undergoing adjuvant chemotherapy., Methods: Medical records of breast cancer patients who underwent mastectomy at our institution between January 2010 and December 2017 who subsequently received PMRT were retrospectively reviewed. As adjuvant chemotherapy can delay PMRT, patients receiving adjuvant chemotherapy were excluded. Factors associated with a delay in PMRT (defined as > 12 weeks from the time of mastectomy) were analyzed., Results: Among the 89 patients who met our inclusion criteria, the mean time from mastectomy to PMRT was 11.4 weeks. 24 patients (27.0%) had PMRT > 12 weeks after mastectomy. Factors associated with a delay in PMRT included black race ( P = 0.031), younger age ( P = 0.047), higher body mass index ( P = 0.015), contralateral prophylactic mastectomy ( P = 0.033), longer initial hospital length of stay ( P = 0.001), and more complications ( P = 0.025). On multivariable analysis controlling for all of these factors, only initial hospital length of stay (OR 1.63; 95% CI: 1.07-2.49; P = 0.024) was associated with a delay in PMRT., Conclusion: Over a quarter of patients not undergoing adjuvant chemotherapy have a delay in PMRT beyond 12 weeks from the time of mastectomy. Length of initial hospital stay is the key driver in delaying PMRT.

Background: While obesity is thought to increase complication rates in general surgery procedures, its effect in mastectomy patients remains to be fully elucidated. We sought to determine if obesity is associated with a higher complication rate and length of stay after mastectomy, independent of clinicopathologic and treatment factors., Methods: Medical records of breast cancer patients undergoing mastectomy at our institution between January 2010 and December 2017 were retrospectively reviewed. Patients were separated into obese (body mass index [BMI] ≥ 30) and nonobese (BMI < 30) categories and compared using nonparametric statistical analyses., Results: Of 927 patients, 291 (31.2%) were obese. Obese patients had more complications (26.5% vs. 20.0%, P = 0.033) and a greater number of complications per patient ( P = 0.025) than nonobese patients. They were more likely to have infections (10.7% vs. 5.7%, P = .009), flap thrombosis/necrosis (5.5% vs. 2.4%, P = .018), and skin breakdown/wound complications (8.6% vs. 4.6%, P = .022). Additionally, obese patients had longer hospital length of stay (LOS; LOS > 2 days: 77.7% vs. 65.2%, P < .001). Controlling for potential confounders, obesity remained associated with a higher rate of thrombosis/necrosis of flap (odds ratio [OR] = 2.26; 95% confidence interval [CI] 1.01-5.08; P = .047) and LOS ≥ 2 days (OR = 1.82; 95% CI 1.23-2.69; P = .003)., Conclusion: Obese breast cancer patients undergoing mastectomy have more thrombosis/necrosis of flap and a longer hospital LOS than nonobese patients, regardless of other comorbidities and clinicopathologic/treatment factors.

Objective: Single-center studies have demonstrated that resection of cavity shave margins (CSM) halves the rate of positive margins and re-excision in breast cancer patients undergoing partial mastectomy (PM). We sought to determine if these findings were externally generalizable across practice settings., Methods: In this multicenter randomized controlled trial occurring in 9 centers across the United States, stage 0-III breast cancer patients undergoing PM were randomly assigned to either have resection of CSM ("shave" group) or not ("no shave" group). Randomization occurred intraoperatively, after the surgeon had completed their standard PM. Primary outcome measures were positive margin and re-excision rates., Results: Between July 28, 2016 and April 13, 2018, 400 patients were enrolled in this trial. Four patients (2 in each arm) did not meet inclusion criteria after randomization, leaving 396 patients for analysis: 196 in the "shave" group and 200 to the "no shave" group. Median patient age was 65 years (range; 29-94). Groups were well matched at baseline for demographic and clinicopathologic factors. Prior to randomization, positive margin rates were similar in the "shave" and "no shave" groups (76/196 (38.8%) vs. 72/200 (36.0%), respectively, P = 0.604). After randomization, those in the "shave" group were significantly less likely than those in the "no shave" group to have positive margins (19/196 (9.7%) vs. 72/200 (36.0%), P < 0.001), and to require re-excision or mastectomy for margin clearance (17/196 (8.7%) vs. 47/200 (23.5%), P < 0.001)., Conclusion: Resection of CSM significantly reduces positive margin and re-excision rates in patients undergoing PM., Competing Interests: The authors report no conflicts of interest., (Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.)

Background: We examined the impact of cavity shave margins (CSMs) on margin status in patients with pure ductal carcinoma in situ (DCIS) undergoing partial mastectomy (PM)., Methods: One hundred and nine patients from 2 multicenter, randomized controlled trials were identified with pure DCIS (no invasive cancer). Surgeons performed their best PM, with specimen radiography and resection of selective margins per surgeon discretion. Patients were then randomized to have CSM resected or not. A positive margin was defined as <2 mm from ink., Results: Median patient age was 63 years; median size of DCIS was 1.20 cm; 43.6% of patients had high-grade DCIS; and 58 (53.2%) patients were randomized to take CSM. The "shave" and "no-shave" groups were well-matched for age, race, ethnicity, palpability, grade, and size of DCIS. Although 33 (56.9%) of the patients in the shave group had a positive margin before randomization, only 12 (20.7%) had a positive margin after randomization to CSM (p < 0.001). In the no-shave group, 17 patients (33.3%) had a positive margin. Controlling for size and grade of DCIS, taking CSM resulted in a nearly 65% reduction in the positive-margin rate (odds ratio 0.366; 95% CI, 0.136 to 0.981; p = 0.046). Size of DCIS remained an independent predictor of positive margins in the model (odds ratio 1.646; 95% CI, 1.227 to 2.209; p = 0.001)., Conclusions: CSM reduces positive-margin rates in patients with pure DCIS, and can be a practical solution for DCIS patients who tend to have a high rate of margin positivity., (Copyright © 2020 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

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.