Subcutaneous vs Intravenous Trastuzumab/Pertuzumab: A Time and Motion Substudy of a Phase II Trial of Adjuvant Trastuzumab/Pertuzumab for Stage I HER2+ Breast Cancer (ADEPT trial).

PURPOSE: The time required for in-clinic drug administration can substantially affect breast cancer patients' quality of life. Subcutaneous (SC) drug administration, as opposed to intravenous (IV), may reduce this time commitment. This study sought to estimate the difference in time burden between IV and SC administration of trastuzumab and pertuzumab (HP). METHODS: We prospectively enrolled a subcohort of patients participating in the ADEPT trial (ClinicalTrials.gov identifier: NCT04569747, investigating adjuvant HP plus endocrine therapy for stage I human epidermal growth factor receptor 2-positive breast cancer) to this single-arm crossover time and motion substudy. Patients received two cycles of IV HP followed by two cycles of SC HP. During each cycle, time points in drug preparation and administration were captured. The primary end point was total patient time in the treatment chair. Additional end points included total patient treatment experience time and total pharmacy workflow time. A sample size of 22 patients was estimated to provide 90.7% power with two-sided alpha .05 to detect a difference of 70 minutes in the primary end point by treatment arm (IV v SC). RESULTS: Twenty-two patients were enrolled. The mean total patient time in the treatment chair was 61.8 minutes shorter with SC versus IV HP (22.5 v 84.3 minutes; P < .0001). The mean total patient treatment experience time (incorporating time spent waiting for treatment initiation and time spent in the treatment chair) was 81.8 minutes shorter for SC administration (96 v 177.8 minutes; P < .0001). The pharmacy workflow time was 78.2 minutes shorter for SC versus IV formulation (41 v 119.2 minutes; P < .0001). CONCLUSION: SC administration of HP shortened patient time burden by approximately 1 hour. SC drug administration can facilitate faster workflows for health care professionals and improve patients' breast cancer treatment experience.

The role of breast cancer-related arm lymphedema in physical functioning and physical activity participation among long-term African American breast cancer survivors.

PURPOSE: Breast cancer-related arm lymphedema (BCRL) is a common chronic and debilitating condition that involves accumulation of lymphatic fluid in the arm or hand. Limited data are available on BCRL in African American women. Lack of physical activity (PA) and poor physical functioning (PF) are both associated with increased morbidity and mortality among breast cancer survivors. We examined the association of BCRL with PA and PF among African American breast cancer survivors. METHODS: 323 African American women who previously participated in a case-only study in three states (TN, GA, SC) completed a survivorship-focused questionnaire (mean: 4.2 years post-diagnosis) in 2015-2016. Validated measures were used to determine BCRL, PF, and PA. Adjusted binary logistic regression models estimated ORs and 95% CIs for the association of BCRL and meeting PA guidelines (≥ 150 min/week), while multinomial logistic regression was used for PF and PA (minutes/week) categorized based on tertiles. RESULTS: Approximately 32% reported BCRL since diagnosis; 25.4% reported BCRL in the last 12-months. About 26% and 50% reported that BCRL interfered with exercise and ability to do daily activities, respectively. The mean PF among those with BCRL was 51.0(SD:29.0) vs. 68.5(SD:30.1) among those without BCRL. BCRL was associated with lower PF (adjusted-OR for tertile 2: 2.12(95% CI:1.03-4.36) and adjusted-OR for tertile 1: 2.93(95% CI:1.44-5.96)). CONCLUSIONS: BCRL was associated with lower PF among long-term African American breast cancer survivors. Continued monitoring by health care professionals and increased education and behavioral interventions to support PA and improved PF among survivors living with BCRL are warranted.

Aspirin vs Placebo as Adjuvant Therapy for Breast Cancer: The Alliance A011502 Randomized Trial.

Importance: Observational studies of survivors of breast cancer and prospective trials of aspirin for cardiovascular disease suggest improved breast cancer survival among aspirin users, but prospective studies of aspirin to prevent breast cancer recurrence are lacking. Objective: To determine whether aspirin decreases the risk of invasive cancer events among survivors of breast cancer. Design, Setting, and Participants: A011502, a phase 3, randomized, placebo-controlled, double-blind trial conducted in the United States and Canada with 3020 participants who had high-risk nonmetastatic breast cancer, enrolled participants from 534 sites from January 6, 2017, through December 4, 2020, with follow-up to March 4, 2023. Interventions: Participants were randomized (stratified for hormone receptor status [positive vs negative], body mass index [≤30 vs >30], stage II vs III, and time since diagnosis [<18 vs ≥18 months]) to receive 300 mg of aspirin (n = 1510) or placebo once daily (n = 1510) for 5 years. Main Outcomes and Measures: The primary outcome was invasive disease-free survival. Overall survival was a key secondary outcome. Results: A total of 3020 participants were randomized when the data and safety monitoring committee recommended suspending the study at the first interim analysis because the hazard ratio had crossed the prespecified futility bound. By median follow-up of 33.8 months (range, 0.1-72.6 months), 253 invasive disease-free survival events were observed (141 in the aspirin group and 112 in the placebo group), yielding a hazard ratio of 1.27 (95% CI, 0.99-1.63; P = .06). All invasive disease-free survival events, including death, invasive progression (both distant and locoregional), and new primary events, were numerically higher in the aspirin group, although the differences were not statistically significant. There was no difference in overall survival (hazard ratio, 1.19; 95% CI, 0.82-1.72). Rates of grades 3 and 4 adverse events were similar in both groups. Conclusion and Relevance: Among participants with high-risk nonmetastatic breast cancer, daily aspirin therapy did not improve risk of breast cancer recurrence or survival in early follow-up. Despite its promise and wide availability, aspirin should not be recommended as an adjuvant breast cancer treatment. Trial Registration: ClinicalTrials.gov Identifier: NCT02927249.

Microwave hyperthermia enhances radiosensitization by decreasing DNA repair efficiency and inducing oxidative stress in PC3 prostatic adenocarcinoma cells.

PURPOSE: Radiotherapy (RT) is the primary treatment for prostate cancer (PCa); however, the emergence of castration-resistant prostate cancer (CRPC) often leads to treatment failure and cancer-related deaths. In this study, we aimed to explore the use of microwave hyperthermia (MW-HT) to sensitize PCa to RT and investigate the underlying molecular mechanisms. METHODS: We developed a dedicated MW-HT heating setup, created an in vitro and in vivo MW-HT + RT treatment model for CRPC. We evaluated PC3 cell proliferation using CCK-8, colony experiments, DAPI staining, comet assay and ROS detection method. We also monitored nude mouse models of PCa during treatment, measured tumor weight, and calculated the tumor inhibition rate. Western blotting was used to detect DNA damage repair protein expression in PC3 cells and transplanted tumors. RESULTS: Compared to control, PC3 cell survival and clone formation rates decreased in RT + MW-HT group, demonstrating significant increase in apoptosis, ROS levels, and DNA damage. Lower tumor volumes and weights were observed in treatment groups. Ki-67 expression level was reduced in all treatment groups, with significant decrease in RT + MW-HT groups. The most significant apoptosis induction was confirmed in RT + MW-HT group by TUNEL staining. Protein expression levels of DNA-PKcs, ATM, ATR, and P53/P21 signaling pathways significantly decreased in RT + MW-HT groups. CONCLUSION: MW-HT + RT treatment significantly inhibited DNA damage repair by downregulating DNA-PKcs, ATM, ATR, and P53/P21 signaling pathways, leading to increased ROS levels, aggravate DNA damage, apoptosis, and necrosis in PC3 cells, a well-established model of CRPC.

Gynecomastia Surgery Patient Education: An Information Quality Assessment of YouTube Videos.

BACKGROUND: YouTube is a platform for many topics, including plastic surgery. Previous studies have shown poor educational value in YouTube videos of plastic surgery procedures. The purpose of this study was to evaluate the quality and accuracy of YouTube videos concerning gynecomastia surgery (GS). METHODS: The phrases "gynecomastia surgery" (GS) and "man boobs surgery" (MB) were queried on YouTube. The first 50 videos for each search term were examined. The videos were rated using our novel Gynecomastia Surgery Specific Score to measure gynecomastia-specific information, the Patient Education Materials Assessment Tool (PEMAT) to measure understandability and actionability, and the Global Quality Scale to measure general quality. RESULTS: The most common upload source was a board-certified plastic surgeon (35%), and content category was surgery techniques and consultations (51%). Average scores for the Global Quality Scale (x̄ = 2.25), Gynecomastia Surgery Specific Score (x̄ = 3.50), and PEMAT Actionability (x̄ = 44.8%) were low, whereas PEMAT Understandability (x̄ = 77.4%) was moderate to high. There was no difference in all scoring modalities between the GS and MB groups. Internationally uploaded MB videos tended to originate from Asian countries, whereas GS videos tended to originate from non-US Western countries. Patient uploaders had higher PEMAT Actionability scores than plastic surgeon uploaders. CONCLUSIONS: The quality and amount of gynecomastia-specific information in GS videos on YouTube are low and contain few practical, take-home points for patients. However, understandability is adequate. Plastic surgeons and professional societies should strive to create high-quality medical media on platforms such as YouTube.

PACE: A Randomized Phase II Study of Fulvestrant, Palbociclib, and Avelumab After Progression on Cyclin-Dependent Kinase 4/6 Inhibitor and Aromatase Inhibitor for Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor-Negative Metastatic Breast Cancer.

PURPOSE: Cyclin-dependent kinase (CDK) 4/6 inhibitors (CDK4/6is) are an important component of treatment for hormone receptor-positive/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC), but it is not known if patients might derive benefit from continuation of CDK4/6i with endocrine therapy beyond initial tumor progression or if the addition of checkpoint inhibitor therapy has value in this setting. METHODS: The randomized multicenter phase II PACE trial enrolled patients with hormone receptor-positive/HER2- MBC whose disease had progressed on previous CDK4/6i and aromatase inhibitor (AI) therapy. Patients were randomly assigned 1:2:1 to receive fulvestrant (F), fulvestrant plus palbociclib (F + P), or fulvestrant plus palbociclib and avelumab (F + P + A). The primary end point was investigator-assessed progression-free survival (PFS) in patients treated with F versus F + P. RESULTS: Overall, 220 patients were randomly assigned between September 2017 and February 2022. The median age was 57 years (range, 25-83 years). Most patients were postmenopausal (80.9%), and 40% were originally diagnosed with de novo MBC. Palbociclib was the most common previous CDK4/6i (90.9%). The median PFS was 4.8 months on F and 4.6 months on F + P (hazard ratio [HR], 1.11 [90% CI, 0.79 to 1.55]; P = .62). The median PFS on F + P + A was 8.1 months (HR v F, 0.75 [90% CI, 0.50 to 1.12]; P = .23). The difference in PFS with F + P and F + P + A versus F was greater among patients with baseline ESR1 and PIK3CA alterations. CONCLUSION: The addition of palbociclib to fulvestrant did not improve PFS versus fulvestrant alone among patients with hormone receptor-positive/HER2- MBC whose disease had progressed on a previous CDK4/6i plus AI. The increased PFS seen with the addition of avelumab warrants further investigation in this patient population.

A Subpopulation of Luminal Progenitors Secretes Pleiotrophin to Promote Angiogenesis and Metastasis in Inflammatory Breast Cancer.

Inflammatory breast cancer (IBC) is a highly aggressive subtype of breast cancer characterized by rapidly arising diffuse erythema and edema. Genomic studies have not identified consistent alterations and mechanisms that differentiate IBC from non-IBC tumors, suggesting that the microenvironment could be a potential driver of IBC phenotypes. Here, using single-cell RNA sequencing, multiplex staining, and serum analysis in patients with IBC, we identified enrichment of a subgroup of luminal progenitor (LP) cells containing high expression of the neurotropic cytokine pleiotrophin (PTN) in IBC tumors. PTN secreted by the LP cells promoted angiogenesis by directly interacting with the NRP1 receptor on endothelial tip cells located in both IBC tumors and the affected skin. NRP1 activation in tip cells led to recruitment of immature perivascular cells in the affected skin of IBC, which are correlated with increased angiogenesis and IBC metastasis. Together, these findings reveal a role for cross-talk between LPs, endothelial tip cells, and immature perivascular cells via PTN-NRP1 axis in the pathogenesis of IBC, which could lead to improved strategies for treating IBC. SIGNIFICANCE: Nonmalignant luminal progenitor cells expressing pleiotrophin promote angiogenesis by activating NRP1 and induce a prometastatic tumor microenvironment in inflammatory breast cancer, providing potential therapeutic targets for this aggressive breast cancer subtype.

Metformin and other anti-diabetic medication use and breast cancer incidence in the Nurses' Health Studies.

We aimed to examine the association between the use of metformin and other anti-diabetic medications and breast cancer incidence within two large prospective cohort studies. We followed 185,181 women who participated in the Nurses' Health Study (NHS; 1994-2016) and the NHSII (1995-2017), with baseline corresponding to the date metformin was approved for type 2 diabetes (T2D) treatment in the US Information on T2D diagnosis, anti-diabetes medications, and other covariates was self-reported at baseline and repeatedly assessed by follow-up questionnaires every 2 years. Breast cancer cases were self-reported and confirmed by medical record review. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between medication use and breast cancer were estimated using Cox proportional hazards regression models, adjusting for breast cancer risk factors. During 3,324,881 person-years of follow-up, we ascertained 9,192 incident invasive breast cancer cases, of which 451 were among women with T2D. Compared with women without T2D (n = 169,263), neither metformin use (HR = 0.97; 95% CI = 0.81-1.15) nor other anti-diabetic medications use (HR = 1.11; 95% CI = 0.90-1.36) associated with significantly lower breast cancer incidence. Among women with T2D (n = 15,918), compared with metformin never users, metformin ever use was not significantly inversely associated with breast cancer (HR = 0.92; 95% CI = 0.74-1.15). Although we observed that past use of metformin was inversely associated with breast cancer in the T2D population (HR = 0.67; 95% CI = 0.48-0.94), current use (HR = 1.01; 95% CI = 0.80-1.27) and longer duration of metformin use were not associated with breast cancer (each 2-year interval: HR = 1.01; 95% CI = 0.95-1.07). Overall, metformin use was not associated with the risk of developing breast cancer among the overall cohort population or among women with T2D.

A novel body composition risk score (B-Score) and overall survival among patients with nonmetastatic breast cancer.

BACKGROUND & AIMS: Measurements (amount, distribution, and radiodensity) of muscle and adipose tissue were reported to be individually associated with overall survival in patients with breast cancer. However, they were not typically combined to develop an overall risk score, which can identify patients at high risk of death and prioritize patients in need of dietary and lifestyle interventions. Thus, we aimed to develop a novel composite body composition risk score (B-Score). METHODS: We included 3105 patients with stage II or III breast cancer at Kaiser Permanente Northern California and Dana Farber Cancer Institute. From CT scans at diagnosis, we assessed areas and radiodensity of muscle and adipose tissue at the third lumber vertebrae. We considered skeletal muscle index (SMI), subcutaneous adipose tissue index (SATI) and SAT radiodensity as they were independent prognostic factors for overall survival. Each measurement was dichotomized using optimal stratification, with low SMI (<40.1 cm2/m2), high SATI (≥75.7 cm2/m2), and high SAT radiodensity (≥-97.2HU) considered risk factors. We calculated B-Score as the sum of these factors and estimated its association with overall survival using Cox proportional hazards regression with adjustment for clinicopathologic factors. RESULTS: Mean (standard deviation) age was 53.9 (11.8) years, 70.3% were Non-Hispanic White, and 60.5% were stage II. Most patients (60.6%) had only one body composition risk factor (B-Score = 1). Compared to those with no risk factors (B-Score = 0), the risk of death increased with more body composition risk factors: the adjusted hazard ratios were 1.10 (95% CI: 0.85, 1.42), 1.47 (95% CI: 1.12, 1.92), and 2.11 (95% CI: 1.26, 3.53) for B-Scores of 1, 2, and 3, respectively (Ptrend < 0.001). CONCLUSIONS: More unfavorable body composition characteristics were associated with increased risks of overall mortality in a dose-response manner. Considering body composition measurements together as a composite score (B-Score) may improve risk stratification and inform dietary and lifestyle interventions following breast cancer diagnosis.

Assessing the Readability of Online English and Spanish Language Patient Education Resources Provided by the American Society of Plastic Surgeons, American Society of Aesthetic Plastic Surgeons, and American Society of Reconstructive Microsurgeons.

INTRODUCTION: The National Institutes of Health recommends that patient education materials (PEMs) be written at the sixth grade level. However, PEMs online are still generally difficult to read. The usefulness of online PEMs depends on their comprehensibility. OBJECTIVES: This study assessed the readability of PEMs from national Plastic and Reconstructive Surgery (PRS) organization websites. METHODS: Patient education materials were collected from 3 prominent PRS organizations-the American Society of Plastic Surgeons (ASPS), American Society of Aesthetic Plastic Surgeons (ASAPS), and the American Society of Reconstructive Microsurgeons (ASRM). ASPS PEMs were organized into reconstructive and cosmetic groups, and then further subdivided into English and Spanish subgroups. ASAPS and ASRM PEMs provided cosmetic and reconstructive comparison groups to ASPS, respectively. Readability scores were generated using the Simple Measure of Gobbledygook (SMOG) and the Spanish SMOG scales. RESULTS: Overall, all PEMs failed to meet readability guidelines. Within ASPS, Spanish PEMs were easier to read than English PEMs ( P < 0.001), and cosmetic PEMs were easier to read than reconstructive PEMs ( P < 0.05). There was no significant difference between ASPS cosmetic and ASAPS PEMs ( P = 0.36), nor between ASPS reconstructive and ASRM PEMs ( P = 0.65). ASAPS and ASRM did not have any Spanish PEMs, and 92% of all ASPS PEMs were in English. CONCLUSION: Although PRS societies strive to better educate the public on the scope of PRS, PRS ranks lowly in public understanding of its role in patient care. In addition, Spanish language PEMs from the 3 PRS organizations are severely lacking. Addressing these concerns will make online patient resources more equitable for various patient populations.

TimesUpPRS: A Social Media Movement for Promoting Diversity, Equity, and Inclusion in Plastic Surgery.

OBJECTIVE: Minority representation and promotion in medicine is lacking. Social media can facilitate change by raising awareness of biases, empowering others, and cultivating connections. The TimesUpPRS Instagram account was created in March 2020 to foster diversity, equity, and inclusion (DEI) in plastic surgery by celebrating surgeons of diverse identities and emphasizing the need to create safe, fair, and equitable workplaces. We aim to characterize its content, audience demographics, engagement, and impact. METHODS: All TimesUpPRS posts published until March 2022 were reviewed for content analysis. Audience demographics were assessed through Instagram Insights. Engagement was assessed through likes, comments, and posts tagging @TimesUpPRS. RESULTS: Three hundred fifty-five posts have been published, with 45.9% original content. These posts discuss representation or treatment of women (39.7%), Black (24.2%), Asian and Pacific Islander (14.4%), LGBTQ+ (12.7%), LatinX (6.5%), people of color overall (4.8%), first generation-low income (1.7%), and Native American (1.1%) individuals. 45.1% aimed to raise social awareness, 19.4% spotlighted plastic surgery figures, 16.3% highlighted research, and 5.6% advertised opportunities for community involvement. The mean (SE) number of hashtags utilized was 10.9 (0.6), with #ilooklikeasurgeon used most. There were 2052 followers, but 10,025 accounts reached. Of reached accounts, 66.8% were women, 71.8% were from the U.S., and 55% were aged 25 to 34. The mean (SE) number of likes and comments per post was 62.2 (3.4) and 2.6 (0.2). 85.0% of comments were supportive. Three hundred sixty-six posts tagged @TimesUpPRS. TimesUpPRS has also garnered industry and private sponsorship, inspired DEI programming, and collaborated with multiple other organizations. CONCLUSIONS: In 2 years, TimesUpPRS has generated 350+ posts and reached 10,000+ accounts. Content highlighted figures of diverse identities and cultivated high, positive engagement. Now with 20 content creators, TimesUpPRS will continue increasing content, expanding its audience, and fostering impactful discussion that helps shift the existing culture to one of inclusivity and equity.

Assessing the Readability of Online Patient Education Resources Related to Neophallus Reconstruction.

INTRODUCTION: Online patient education materials (PEMs) often exceed the recommended 6th grade reading level. This can negatively affect transmasculine patients' understanding of treatment plans, increasing barriers to care and worsening health outcomes and patient satisfaction. This study assessed the readability of online English and Spanish PEMs regarding phalloplasty and urethroplasty. METHODS: The English and Spanish terms for phalloplasty and urethroplasty were queried on Google. The first fifty results were grouped into institutional (government, medical school, teaching hospital), noninstitutional (private practice, news channel, blog, etc.), and academic (journal articles, book chapters) categories. Readability scores were generated using the Simple Measure of Gobbledygook and Spanish Simple Measure of Gobbledygook scales. RESULTS: All PEMs exceeded recommended reading levels. For both procedures, English PEMs had an average reading level approximately of a university sophomore and Spanish PEMs had an average reading level approximately of a high school junior. For both procedures, English PEMs were harder to read than Spanish PEMs overall (P < 0.001) and when compared across the three categories between the two languages (P < 0.001). For Spanish urethroplasty PEMs, noninstitutional PEMs were more difficult to read than institutional PEMs (P < 0.05). CONCLUSIONS: Online information for phalloplasty and urethroplasty should be revised and/or standardized materials should be created by trans-affirming health-care providers and national organizations in order to more fully educate the public and prospective patients prior to intervention. A well-informed patient population will improve patient decision-making and surgeon-patient communication, ultimately leading to better health outcomes.

Consumption of olive oil and risk of breast cancer in U.S. women: results from the Nurses' Health Studies.

BACKGROUND: Olive oil consumption may reduce breast cancer risk, but it is unclear whether olive oil is beneficial for breast cancer prevention in populations outside of Mediterranean regions, namely in the U.S., where the average consumption of olive oil is low compared with Mediterranean populations. We examined whether olive oil intake was associated with breast cancer risk in two prospective cohorts of U.S. women. METHODS: We used multivariable-adjusted time-varying Cox proportional hazards models to estimate hazard ratios (HR) and 95% confidence interval (CI) for breast cancer among 71,330 (Nurses' Health Study, 1990-2016) and 93,295 women (Nurses' Health Study II, 1991-2017) who were free of cancer at baseline. Diet was assessed by a validated semi-quantitative food frequency questionnaire every 4 years. RESULTS: During 3,744,068 person-years of follow-up, 9,638 women developed invasive breast cancer. The multivariable-adjusted HR (95% CI) for breast cancer among women who had the highest consumption of olive oil (>1/2 tablespoon/d or >7 g/d) compared with those who never or rarely consumed olive oil, was 1.01 (0.93, 1.09). Higher olive oil consumption was not associated with any subtype of breast cancer. CONCLUSION: We did not observe an association between higher olive oil intake and breast cancer risk in two large prospective cohorts of U.S. women, whose average olive oil consumption was low. Prospective studies are needed to confirm these findings and to further investigate whether different varieties of olive oil (e.g., virgin and extra virgin olive oil) may play a role in breast cancer risk.

Characterization of the Saddle Nose Deformity Following Endoscopic Endonasal Skull Base Surgery.

Objective The endoscopic endonasal approach (EEA) is commonly employed in skull base surgery for neoplasm resection. While nasal deformity following EEA is described, this study aimed to perform a detailed qualitative and quantitative assessment of the associated saddle nose deformity (SND) in particular. Setting/Participants This is a retrospective review of 20 adult patients with SND after EEA for resection of skull base tumors over a 5-year period at the University of Pittsburgh Medical Center. Main Outcome Measures Fifteen measurements related to SND were obtained on pre- and postoperative imaging. Statistical analyses were performed to evaluate differences between pre- and postoperative anatomies. Results The most common EEA was transsellar. Reconstruction techniques included nine free mucosal grafts alone, eight vascularized nasoseptal flaps (NSFs), one combined free mucosal graft/abdominal fat graft, and one combined NSF/fascia lata graft. Imaging analysis showed a trend toward loss of mean nasal height, nasal tip projection, and nasolabial angle postoperatively. Subgroup analysis showed that patients with NSF reconstruction had a significantly decreased nasal tip projection (1.2 mm, p = 0.039) and increased alar base width (1.2 mm, p = 0.046) postoperatively. Patients without functional pituitary microadenomas demonstrated significantly increased nasofrontal angle and decreased nasal tip projection on postoperative imaging, in contrast to those with functional adenomas who had no measurable significant changes. Conclusion Clinically evident SND does not always lead to significant radiographic changes. This analysis suggests that patients who undergo surgery for indications other than functional pituitary microadenomas or who receive NSF reconstruction develop more marked SND on standard imaging tests.

Clonal hematopoiesis in older patients with breast cancer receiving chemotherapy.

BACKGROUND: The expansion of hematopoietic stem cells carrying recurrent somatic mutations, termed clonal hematopoiesis (CH), is common in elderly individuals and is associated with increased risk of myeloid malignancy and all-cause mortality. Though chemotherapy is a known risk factor for developing CH, how myelosuppressive therapies affect the short-term dynamics of CH remains incompletely understood. Most studies have been limited by retrospective design, heterogeneous patient populations, varied techniques to identifying CH, and analysis of single timepoints. METHODS: We examined serial samples from 40 older women with triple-negative or hormone receptor-positive breast cancer treated on the prospective ADjuVANt Chemotherapy in the Elderly trial to evaluate the prevalence and dynamics of CH at baseline and throughout chemotherapy (6 and 12 weeks). RESULTS: CH was detected in 44% of patients at baseline and in 53% at any timepoint. Baseline patient characteristics were not associated with CH. Over the course of treatment, mutations exhibited a variety of dynamics, including emergence, expansion, contraction, and disappearance. All mutations in TP53 (n = 3) and PPM1D (n = 4), genes that regulate the DNA damage response, either became detectable or expanded over the course of treatment. Neutropenia was more common in patients with CH, particularly when the mutations became detectable during treatment, and CH was significantly associated with cyclophosphamide dose reductions and holds (P = .02). CONCLUSIONS: Our study shows that CH is common, dynamic, and of potential clinical significance in this population. Our results should stimulate larger efforts to understand the biological and clinical importance of CH in solid tumor malignancies. TRIAL REGISTRATION: ClinicalTrials.gov (https://clinicaltrials.gov/ct2/show/NCT03858322). Clinical trial registration number: NCT03858322.

Fertility and Childbearing Outcomes of Practicing Female Plastic Surgeons.

BACKGROUND: Women now represent approximately one-third of plastic surgery residents. The impact of a career in plastic surgery on family planning is unknown. The aim of this study was to report the current status of fertility and childbearing outcomes of practicing female plastic surgeons. METHODS: Following institutional review board approval, an anonymous online survey was distributed to all female active and candidate members of the American Society of Plastic Surgeons. Data collected included demographics, number and outcomes of pregnancies, obstetric complications, infertility, maternity leave, and breastfeeding. RESULTS: The response rate was 20%. Female plastic surgeons were less likely to have children and gave birth to their first child at an older age compared with the U.S. population. Plastic surgeons had seven times higher odds of having difficulty conceiving or carrying a pregnancy than American women. The rate of miscarriage was twice that of the U.S. population. Furthermore, the rates of obstetric complications and congenital malformations were higher than the U.S. population (47% versus 20%, and 8% versus 4%, respectively). Women took a mean of 6.6 weeks for maternity leave. Forty-three percent were dissatisfied with leave, and longer leave correlated with higher satisfaction. The mean length of breastfeeding was 7.6 months. Women who breastfed for a longer duration were more likely to feel satisfied with the amount of time they breastfed. CONCLUSIONS: Plastic surgeons are at high risk for infertility, miscarriage, congenital malformations, and obstetric complications. The data in this article provide a groundwork for identifying areas of concern and potential solutions.

Physical activity in association with mortality among Black women diagnosed with breast cancer in the Southern Community Cohort Study.

PURPOSE: Physical activity (PA) is associated with many health benefits. While PA has been associated with reduced mortality after breast cancer diagnosis in many studies, few studies have examined the role of PA in breast cancer survival among underserved and minority populations, including Black women. We investigated PA in association with mortality among Black predominantly low-income breast cancer survivors in the Southern Community Cohort Study (SCCS). METHODS: Study participants were women diagnosed with incident breast cancer (n = 949) in the SCCS, which is a prospective cohort study of predominantly low-income adults aged 40-79 years recruited from 12 Southeastern states between 2002 and 2009. Participants completed a detailed baseline questionnaire, with annual follow-up for mortality via registry linkages. Cox regression models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for associations of pre-diagnosis PA (measured via a validated questionnaire) with all-cause and breast cancer-specific mortality. RESULTS: Breast cancer survivors had a mean age of 61.1 years and most (79.3%) had a household income of < $25,000. In adjusted models, higher levels of total PA (MET-hours/day) were inversely associated with all-cause mortality with HRs (95% CIs): 0.79 (0.59-1.06), 0.66 (0.49-0.90), and 0.60 (0.43-0.84), for Q2, Q3, and Q4 (reference: Q1), respectively, ptrend ≤ 0.01. A similar inverse association was found for breast cancer-specific mortality. CONCLUSION: Higher levels of pre-diagnosis PA were associated with improved survival among low-income Black breast cancer survivors. Resources to reduce barriers to PA participation and increase support for education and intervention efforts to promote PA among Black women are needed.