Patient-Reported Outcomes of Omission of Breast Surgery Following Neoadjuvant Systemic Therapy: A Nonrandomized Clinical Trial.

Importance: Patients should have an active role in decisions about pursuing or forgoing specific therapies in treatment de-escalation trials. Objective: To evaluate longitudinal patient-reported outcomes (PROs) encompassing decisional comfort and health-related quality of life (HRQOL) among patients who elected to enroll in a clinical trial evaluating radiotherapy alone, without breast surgery, for invasive breast cancers with exceptional response to neoadjuvant systemic therapy (NST). Design, Setting, and Participants: Prospective, single-group, phase 2 clinical trial at 7 US medical centers. Women aged 40 years or older with invasive cT1-2 N0-1 M0 triple-negative or human epidermal growth factor receptor 2 (ERBB2)-positive breast cancer with no pathologic evidence of residual disease following standard NST enrolled from March 6, 2017, to November 9, 2021. Validated PRO measures were administered at baseline and 6, 12, and 36 months post-radiotherapy. Data were analyzed from January to February 2023. Interventions: PRO measures included the Decision Regret Scale (DRS), Functional Assessment of Cancer Therapy-Lymphedema (FACT-B+4), and Breast Cancer Treatment Outcomes Scale (BCTOS). Main Outcomes and Measures: Changes in PRO measure scores and subscores over time. Results: Among 31 patients, the median (IQR) age was 61 (56-66) years, 26 (84%) were White, and 26 (84%) were non-Hispanic. A total of 15 (48%) had triple-negative disease and 16 (52%) had ERBB2-positive disease. Decisional comfort was high at baseline (median [IQR] DRS score 10 [0-25] on a 0-100 scale, with higher scores indicating higher decisional regret) and significantly increased over time (median [IQR] DRS score at 36 months, 0 [0-20]; P < .001). HRQOL was relatively high at baseline (median [IQR] FACT-B composite score 121 [111-134] on a 0-148 scale, with higher scores indicating higher HRQOL) and significantly increased over time (median [IQR] FACT-B score at 36 months, 128 [116-137]; P = .04). Perceived differences between the affected breast and contralateral breast were minimal at baseline (median [IQR] BCTOS score 1.05 [1.00-1.23] on a 1-4 scale, with higher scores indicating greater differences) and increased significantly over time (median [IQR] BCTOS score at 36 months, 1.36 [1.18-1.64]; P < .001). At 36 months postradiotherapy, the cosmetic subscore was 0.45 points higher than baseline (95% CI, 0.16-0.74; P = .001), whereas function, pain, and edema subscores were not significantly different than baseline. Conclusions and Relevance: In this nonrandomized phase 2 clinical trial, analysis of PROs demonstrated an overall positive experience for trial participants, with longitudinal improvements in decisional comfort and overall HRQOL over time and minimal lasting adverse effects of therapy. Trial Registration: ClinicalTrials.gov Identifier: NCT02945579.

Lactation Education for Surgeons: American Society of Breast Surgeons (ASBrS) Survey Demonstrates Strong Member Interest in Expanded Training.

BACKGROUND: The availability and extent of breastfeeding-specific surgical training has not been previously described. We aimed to survey breast surgeons on their lactation education and desire for additional knowledge. METHODS: Members of the American Society of Breast Surgeons were invited via email to anonymously complete an electronic survey from 27 October 2021 to 23 January 2022. The survey content included demographic information, sources of lactation education, and desired topics and methods for further training. Descriptive statistics were used to analyze the data. RESULTS: A total of 2698 surveys were delivered and 542 (20.1%) completed. While nearly all respondents (99%) reported treating lactating patients at least once or twice per year, 78% reported that their training was inadequate. The most frequently cited sources of lactation information were peer-to-peer informal knowledge sharing (50%) and personal experience with breastfeeding (44%). Nearly all respondents (99%) agreed that formal lactation education would benefit breast surgeons. Specific topics of interest included management of patients with complications of lactation (48%), management of lactating patients with a new diagnosis of breast cancer (47%), and counseling patients with pregnancy-associated breast cancer who desire to breastfeed (46%). The most frequently recommended educational formats included presentation at a national conference (60%), evidence-based management guidelines (58%), webinar (55%), and workshop/course (47%). CONCLUSION: Breast surgeons self-report minimal formal training in the management of benign and malignant breast disease in lactating patients and strong desire for expanded education. Development of clinical practice guidelines and additional educational content for surgeons should be considered to meet the needs of this patient population.

Eliminating Breast Surgery for Invasive Cancer with Exceptional Response to Neoadjuvant Systemic Therapy: Prospective Multicenter Clinical Trial Planned Initial Feasibility Endpoint.

BACKGROUND: Response to neoadjuvant systemic therapy (NST) for breast cancer enables tailoring of subsequent therapy. Image-guided breast biopsy after NST can accurately predict a pathologic complete response (pCR). The feasibility phase of the clinical trial reported here assesses omission of breast surgery followed by radiotherapy in terms of local recurrence before trial expansion. STUDY DESIGN: Women with unicentric, cT1-2 N0-1 M0 triple-negative (TNBC) or human epidermal growth factor receptor 2-positive breast cancer (HER2+BC) cancer with <2 cm residual disease on post-NST imaging were eligible to enroll. If no residual invasive or in situ disease was identified by image-guided, vacuum-assisted core biopsy (VACB), breast surgery was omitted, and radiotherapy delivered. The primary endpoint for the feasibility phase was ipsilateral breast tumor recurrence at 6 months. If any recurrence occurred during the feasibility phase the trial would halt. RESULTS: Thirteen patients were enrolled from March 2017 to October 2018. The mean age was 60.8 years (range 51 to 75) and most patients were White (69.2%) and non-Hispanic/Latino (84.6%). All patients had invasive ductal carcinoma (6 TNBC, 7 HER2+BC). Mean tumor size was 2.4 cm (range 0.9 to 5.0) before NST and 0.7 cm (range 0 to 1.8) after NST. Seven patients (53.8%) had residual disease identified on VACB; the remaining 6 (46.2%) comprised the feasibility cohort. At a median follow-up of 44.3 months (range 41.3 to 51.3) there was no ipsilateral breast tumor recurrence in this cohort. CONCLUSIONS: These early data suggest that omission of breast surgery in patients with invasive TNBC and HER2+BC with no evidence of residual disease on standardized VACB after NST is potentially feasible. Results from the expansion phase of this clinical trial will be reported per protocol prespecified analyses.

Association of Women Surgeons' Comprehensive Initiative for Healthy Surgical Families During Residency and Fellowship Training.

Importance: The lack of family-friendly policies continues to contribute to the underrepresentation and attrition of surgical trainees. Women in surgery face unique challenges in balancing surgical education with personal and family needs. Observations: The Association of Women Surgeons is committed to supporting surgical families and developing equitable family-friendly guidelines. Herein we detail recommendations for adequate paid parental leave, access to childcare, breastfeeding support, and insurance coverage of fertility preservation and assisted reproductive technology. Conclusions and Relevance: The specific recommendations outlined in this document form the basis of a comprehensive initiative for supporting surgical families.

Race-Related Differences in the Clinical Presentation and Histopathologic Features of Phyllodes Tumor.

BACKGROUND: Phyllodes tumor (PT) is a rare fibroepithelial lesion of the breast with variable malignant potential. Black women have a higher incidence of a related benign tumor, fibroadenoma, but there are limited epidemiological data on PT. The aim of our study was to evaluate race-related differences in the clinicopathologic features and outcomes of PT. METHODS: Our institutional pathology database was queried for breast specimen reports from 01/2009 to 10/2019 to identify patients with a pathologic diagnosis of PT. Chart review and detailed slide review were performed to obtain clinical and histopathologic variables, respectively. RESULTS: Among twelve patients, two had malignant PT, three had borderline PT, and seven had benign PT. All patients with malignant and borderline PT were black, compared with 29% of those with benign PT. There were no apparent race-related differences in specific histopathologic features among black vs. non-black women with benign PT. Malignant and borderline PT were relatively larger than benign PT, with mean tumor sizes of 9.0 cm (standard deviation [SD] 4.7 cm), 12.2 cm (SD 9.4 cm), and 5.4 cm (SD 5.8 cm), respectively. Two women had a local recurrence, both of whom were black. DISCUSSION: In this single-institution retrospective study, we observed disproportionate rates of aggressive histopathologic features and disparate outcomes among black women with PT. A multi-institutional PT registry would facilitate improved knowledge about race-related differences in the presentation and outcomes of this rare tumor.

Management of Common Complications of Lactation: The Breast Surgeon's Role in Examining the Science and Debunking Old Myths.

Breast surgeons are well poised to promote evidence-based recommendations for lactation-related breast disorders and clarify existing misconceptions in traditional care. Surgeons can resolve lactational fluid collections and avoid milk fistula development during drainage and/or other procedures on the breast. Using principles of surgical wound management, they can provide effective care of nipple trauma. They can distinguish between inflammatory and infectious mastitis and promote delicate tissue handling to prevent breast injury and phlegmon. Finally, breast surgeons can debunk the myth of fungal infections occurring on the highly vascularized nipple and recognize common presentations of conditions such as dermatitis.

Academy of Breastfeeding Medicine Clinical Protocol #36: The Mastitis Spectrum, Revised 2022.

A central goal of the Academy of Breastfeeding Medicine is the development of clinical protocols for managing common medical problems that may impact breastfeeding success. These protocols serve only as guidelines for the care of breastfeeding mothers and infants and do not delineate an exclusive course of treatment or serve as standards of medical care. Variations in treatment may be appropriate according to the needs of an individual patient. The Academy of Breastfeeding Medicine recognizes that not all lactating individuals identify as women. Using gender-inclusive language, however, is not possible in all languages and all countries and for all readers. The position of the Academy of Breastfeeding Medicine (https://doi.org/10.1089/bfm.2021.29188.abm) is to interpret clinical protocols within the framework of inclusivity of all breastfeeding, chestfeeding, and human milk-feeding individuals.

Heterogeneity in Survival with Immune Checkpoint Inhibitors and Its Implications for Survival Extrapolations: A Case Study in Advanced Melanoma.

Background: Survival heterogeneity and limited trial follow-up present challenges for estimating lifetime benefits of oncology therapies. This study used CheckMate 067 (NCT01844505) extended follow-up data to assess the predictive accuracy of standard parametric and flexible models in estimating the long-term overall survival benefit of nivolumab plus ipilimumab (an immune checkpoint inhibitor combination) in advanced melanoma. Methods: Six sets of survival models (standard parametric, piecewise, cubic spline, mixture cure, parametric mixture, and landmark response models) were independently fitted to overall survival data for treatments in CheckMate 067 (nivolumab plus ipilimumab, nivolumab, and ipilimumab) using successive data cuts (28, 40, 52, and 60 mo). Standard parametric models allow survival extrapolation in the absence of a complex hazard. Piecewise and cubic spline models allow additional flexibility in fitting the hazard function. Mixture cure, parametric mixture, and landmark response models provide flexibility by explicitly incorporating survival heterogeneity. Sixty-month follow-up data, external ipilimumab data, and clinical expert opinion were used to evaluate model estimation accuracy. Lifetime survival projections were compared using a 5% discount rate. Results: Standard parametric, piecewise, and cubic spline models underestimated overall survival at 60 mo for the 28-mo data cut. Compared with other models, mixture cure, parametric mixture, and landmark response models provided more accurate long-term overall survival estimates versus external data, higher mean survival benefit over 20 y for the 28-mo data cut, and more consistent 20-y mean overall survival estimates across data cuts. Conclusion: This case study demonstrates that survival models explicitly incorporating survival heterogeneity showed greater accuracy for early data cuts than standard parametric models did, consistent with similar immune checkpoint inhibitor survival validation studies in advanced melanoma. Research is required to assess generalizability to other tumors and disease stages. Highlights: Given that short clinical trial follow-up periods and survival heterogeneity introduce uncertainty in the health technology assessment of oncology therapies, this study evaluated the suitability of conventional parametric survival modeling approaches as compared with more flexible models in the context of immune checkpoint inhibitors that have the potential to provide lasting survival benefits.This study used extended follow-up data from the phase III CheckMate 067 trial (NCT01844505) to assess the predictive accuracy of standard parametric models in comparison with more flexible methods for estimating the long-term survival benefit of the immune checkpoint inhibitor combination of nivolumab plus ipilimumab in advanced melanoma.Mixture cure, parametric mixture, and landmark response models provided more accurate estimates of long-term overall survival versus external data than other models tested.In this case study with immune checkpoint inhibitor therapies in advanced melanoma, extrapolation models that explicitly incorporate differences in cancer survival between observed or latent subgroups showed greater accuracy with both early and later data cuts than other approaches did.

Challenges in the Management of Breast Conditions During Lactation.

The lactating breast can develop a wide range of conditions that require surgical management, from abscess drainage to the evaluation of nipple-areolar complex (NAC) lesions. In addition, both benign and malignant masses can present in the lactating population. Patients should undergo routine diagnostic workup including core needle biopsy if indicated. Ultrasound, mammogram, and magnetic resonance imaging (MRI) with gadolinium contrast are safe in lactation and do not require interruption of breastfeeding.

Low incidence of milk fistula with continued breastfeeding following radiologic and surgical interventions on the lactating breast.

BACKGROUND: Milk fistula is a potential complication of radiologic and surgical procedures on the lactating breast, though its incidence is unknown. Some postulate that larger defects and/or closer proximity to the nipple increase the risk of fistula. OBJECTIVE: This study aimed to estimate the incidence of milk fistula and characterize risk factors in patients who continued breastfeeding after surgical or radiological procedures. METHODS: A retrospective cohort analysis of pregnant or lactating women treated at a multidisciplinary breast clinic from July 2016 through August 2019 was performed. Demographic and clinical variables were analyzed using ANOVA and Pearson's Chi-square. RESULTS: Two pregnant and 43 lactating patients underwent 71 interventions. The incidence of milk fistula within one week of intervention was 1.4%. One fistula was diagnosed six days after retroareolar abscess drainage. The fistula closed successfully with continued breastfeeding. When categorized by the caliber of the most invasive intervention (large-caliber: mass excision, n = 7; medium-caliber: percutaneous drain insertion, n = 18; small-caliber: stab incision, aspiration, core needle biopsy, n = 20), patients were similar in age, race/ethnicity, weeks postpartum, and frequency of central versus peripheral interventions. The low incidence of fistula prevented quantitative evaluation of potential risk factors. CONCLUSIONS: Milk fistula is a rare occurrence following radiologic or surgical breast interventions performed during pregnancy or lactation. Indicated procedures should not be deferred, but periareolar approaches should be avoided when possible. Cessation of lactation is not mandatory for fistula closure, and continued breastfeeding should be recommended.

Refining breast cancer prognosis by incorporating age at diagnosis into clinical prognostic staging: introduction of a novel online calculator.

PURPOSE: American Joint Committee on Cancer (AJCC) clinical staging is used to estimate breast cancer prognosis, but individual patient survival within each stage varies considerably by age at diagnosis. We hypothesized that the addition of age at diagnosis to the staging schema will enable more refined risk stratification. METHODS: We performed a retrospective population analysis of adult women diagnosed with invasive breast cancer between 2010 and 2015 registered in SEER. Multivariable Cox hazards models were used to evaluate the association of AJCC 8th edition clinical prognostic stage (CPS) and age with risk of overall mortality. Separate hierarchical models were fit to the data: Model 1: CPS alone; Model 2: CPS + age + age2; and Model 3: CPS + age + age2 + CPS x age + CPS x age2. Models were compared by the Akaike information criterion (AIC), the c-statistic for time-dependent receiver operator characteristic curves, and category-free net reclassification improvement (NRI). Internal validation was performed using bootstrapping samples. RESULTS: Among 86,637 women, the median follow-up was 36 months and 3-year overall survival was 91.9% ± 0.1%. Age significantly modified the effect of CPS on survival (p < 0.0001). Model 3 was the most precise, with the lowest AIC (126,619.63), the highest c-statistic (0.8212, standard error 0.0187), and superior NRI indices. CONCLUSION: Age at diagnosis is a highly prognostic variable that warrants consideration for inclusion in future editions of the AJCC Breast Cancer Staging Manual.

It's Not Yeast: Retrospective Cohort Study of Lactating Women with Persistent Nipple and Breast Pain.

Introduction: Health care providers treating lactating women for nipple and breast pain often attribute symptoms to Candida albicans infection. However, multiple other conditions may present with pain, erythema, and pruritis. We explored the experience of a breastfeeding medicine practice that received referrals for patients failing antifungal therapy and who desired further evaluation for alternative diagnoses. Materials and Methods: We conducted a retrospective chart review of breastfeeding women referred for evaluation of "yeast" to a breast surgery/breastfeeding medicine practice from July 2016 to August 2019. Results: Twenty-five women met inclusion criteria. Median age was 33 (range 24-43) and median months postpartum was 4 (range 0.5-18). All 25 women reported minimal to no improvement on oral and/or topical antifungal therapy. In addition to history and examination, milk culture was obtained in four women, punch biopsy in one, and core needle biopsy in one. No woman was confirmed to have a diagnosis of Candida. Diagnoses were changed to the following: subacute mastitis/mammary dysbiosis (n = 8), nipple bleb (n = 6), dermatitis (n = 6), vasospasm (n = 2), milk crust (n = 1), hyperlactation (n = 1), and postpartum depression (n = 1). Treatment included discontinuation of antifungal medication, as well as the following per individual diagnoses: antibiotics and probiotics; 0.1% triamcinolone cream; heat therapy; discontinuation of exclusive pumping; and antidepressant medication and counseling referral. All women experienced resolution of symptoms following revision of diagnosis and change in management (range 2-42 days). Conclusion: While persistent nipple and breast pain in breastfeeding is often attributed to Candida, this cohort demonstrates that providers should consider multiple other conditions in their differential diagnosis. Accurate, timely diagnosis is crucial, as pain is a risk factor for premature cessation of breastfeeding. Symptomatic resolution occurs on appropriate therapy.

ABM Clinical Protocol #34: Breast Cancer and Breastfeeding.

A central goal of The Academy of Breastfeeding Medicine is the development of clinical protocols for managing common medical problems that may impact breastfeeding success. These protocols serve only as guidelines for the care of breastfeeding mothers and infants and do not delineate an exclusive course of treatment or serve as standards of medical care. Variations in treatment may be appropriate according to the needs of an individual patient.

Breast Pathology That Contributes to Dysfunction of Human Lactation: a Spotlight on Nipple Blebs.

Nipple blebs are blister-like fibrinous lesions that form on the surface of the nipple during lactation, and can result in orifice obstruction and mastitis. They likely result from superficial extension of underlying ductal plugging, and can present concurrently with hyperlactation and mammary dysbiosis. Despite their prevalence, few formal reports on nipple blebs exist. In this perspective, we review the experience of a breastfeeding medicine practice that receives referrals for patients with nipple blebs, and provide preliminary insight into etiology, management, and outcomes of these lesions.

Associations Between Career Satisfaction, Personal Life Factors, and Work-Life Integration Practices Among US Surgeons by Gender.

Importance: Burnout among US surgeons is alarmingly high, particularly among women, and work-life integration conflicts contribute to career dissatisfaction. Objective: To evaluate associations between surgical career satisfaction and personal life factors such as time requirements for outside interests, household chores, and parenting responsibilities and to explore similarities and differences between men and women. Design, Setting, and Participants: This cross-sectional survey study of practicing US surgeons was conducted between June 4 and August 1, 2018. The 257-item online survey was sent to 25 748 fellows of the American College of Surgeons. A 31-item subanalysis was performed from August 13 to November 4, 2019. Main Outcomes and Measures: Degree of career satisfaction was measured on a 5-point Likert scale. Professional and personal life factors associated with career satisfaction were evaluated with gender-stratified multivariable proportional odds models. Results: Among 3807 respondents, 3166 self-identified as male (83%) and 639 (17%) as female. Fewer women reported career satisfaction (483 [77%] vs 2514 [82%]) and relatively more women reported problematic interruption of personal life owing to work (315 [50%] vs 1381 [45%]). A higher proportion of women reported being primarily responsible for meal preparation (282 [46%] vs 355 [12%]) and housekeeping (149 [24%] vs 161 [5%]). On multivariable analyses, factors independently associated with career satisfaction were generally similar between genders. Stronger collegial support of work-life integration efforts was significantly associated with higher career satisfaction for both genders (P < .001), although the odds ratio (OR) for women was higher than for men (OR, 4.52; 95% CI, 2.60-7.87 vs OR, 2.45; 95% CI, 1.88-3.21). For men and women, increasing age was significantly associated with higher career satisfaction (men: OR, 1.04; 95% CI, 1.03-1.05; P < .001; women: OR, 1.04; 95% CI, 1.02-1.06; P = .001), and insufficient time for family owing to work was associated with lower satisfaction (men: OR, 0.66; 95% CI, 0.49-0.90; P = 009; women: OR, 0.49; 95% CI, 0.30-0.81; P = .006). For women only, there was a significant association between primary responsibility for at least 1 household chore and lower career satisfaction (OR, 0.66; 95% CI, 0.45-0.98; P = .04). Conclusions and Relevance: In this study, although women had relatively lower surgical career satisfaction than men, the associations between career satisfaction and personal life factors were largely similar. Collegial support of work-life integration efforts appeared to be the most influential factor, particularly for women. Optimization of work-life integration may not only decrease physician burnout but also promote gender equity in surgery.