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Background: Sentinel lymph node biopsy (SLNB) for axillary staging in patients with ductal carcinoma in situ (DCIS) undergoing mastectomy is debated due to low nodal positivity rate and risk of morbidity. Standard SLNB entails removing all lymph nodes (LN) that have a radioactive count > 10% of the most radioactive node, contain blue dye or are palpably suspicious. In this study, we hypothesize that judicious SLNB with attempt to remove only the node with the highest radioactive count provides sufficient pathologic information while minimizing morbidity., Method: A single institution prospective database was retrospectively reviewed to identify women with DCIS who underwent mastectomy and SLNB between 2010 and 2022. Patient characteristics, number of SLNs retrieved, pathologic results and long-term upper extremity complications were analyzed., Results: A total of 743 LNs were removed in 324 pts. Median (IQR) age was 62 (51-70) years. Dual tracer technique, with technetium-99m labeled radiocolloid and blue dye, was used in 311 (96%) pts, whereas single agent (radioisotope or blue dye alone) was utilized in 9 (2.8%) and 4 (1.2%) patients, respectively. Median (IQR) number of SLN removed was 2 (1-3) (range 1-9). In 99% of cases, the SLN with the highest radioactive count was identified among the first 3 dissected LNs. Final pathology revealed upstaging to invasive cancer in 27.5% (n = 89) of the breasts and nodal positivity in 1.9% (n = 6) of the patients. In all 6 cases, metastatic disease was identified in the LN with highest radioactive count among the LNs retrieved. No additional metastatic nodes were identified after > 3 SLN had been removed. At median follow-up of 57 (range 28-87) months, 8.3% (n = 27) of pts complained of long-term upper extremity symptoms. 7.1% (23 pts) were referred to physical therapy for symptoms such as swelling, fullness, heaviness, stiffness, or sensory discomfort in the upper extremity and/or axillary cording. Long-term upper extremity complications were higher when > 3 SLNs compared to ≤ 3 SLNs were removed (10.4% vs. 6.5%, P = .005)., Conclusion: In this cohort of patients with DCIS undergoing mastectomy who were upstaged on final pathology to node positive invasive cancers, the SLN with the highest radioactive count provided sufficient information for axillary staging. Acknowledging that the "hottest" LN is not always the first 1 removed, these data support an increased likelihood of developing long-term complications when more than 3 SLNs are removed. Rather than comprehensive removal of all SLNs meeting the standard "10% rule," prioritizing the sequence of removal to the highest count provides the same prognostic information with reduced morbidity., Competing Interests: Disclosures The authors have stated that they have no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Importance: Choosing Wisely recommendations advocate against routine use of axillary staging in older women with early-stage, clinically node-negative (cN0), hormone receptor-positive (HR+), and HER2-negative breast cancer. However, rates of sentinel lymph node biopsy (SLNB) in this population remain persistently high., Objective: To evaluate whether an electronic health record (EHR)-based nudge intervention targeting surgeons in their first outpatient visit with patients meeting Choosing Wisely criteria decreases rates of SLNB., Design, Setting, and Participants: This nonrandomized controlled trial was a hybrid type 1 effectiveness-implementation study with subsequent postintervention semistructured interviews and lasted from October 2021 to October 2023. Data came from EHRs at 8 outpatient clinics within an integrated health care system; participants included 7 breast surgical oncologists. Data were collected for female patients meeting Choosing Wisely criteria for omission of SLNB (aged ≥70 years with cT1 and cT2, cN0, HR+/HER2- breast cancer). The study included a 12-month preintervention control period; baseline surveys assessing perceived acceptability, appropriateness, and feasibility of the designed intervention; and a 12-month intervention period., Intervention: A column nudge was embedded into the surgeon's schedule in the EHR identifying patients meeting Choosing Wisely criteria for potential SLNB omission., Main Outcomes and Measures: The primary outcome was rate of SLNB following nudge deployment into the EHR., Results: Similar baseline demographic and tumor characteristics were observed before (control period, n = 194) and after (intervention period, n = 193) nudge deployment. Patients in both the control and intervention period had a median (IQR) age of 75 (72-79) years. Compared with the control period, unadjusted rates of SLNB decreased by 23.1 percentage points (46.9% SLNB rate prenudge to 23.8% after; 95% CI, -32.9 to -13.8) in the intervention period. An interrupted time series model showed a reduction in the rate of SLNB following nudge deployment (adjusted odds ratio, 0.26; 95% CI, 0.07 to 0.90; P = .03). The participating surgeons scored the intervention highly on acceptability, appropriateness, and feasibility. Dominant themes from semistructured interviews indicated that the intervention helped remind the surgeons of potential Choosing Wisely applicability without the need for additional clicks or actions on the day of the patient visit, which facilitated use., Conclusions and Relevance: This study showed that a nudge intervention in the EHR significantly decreased low-value axillary surgery in older women with early-stage, cN0, HR+/HER2- breast cancer. This user-friendly and easily implementable EHR-based intervention could be a beneficial approach for decreasing low-value care in other practice settings or patient populations., Trial Registration: ClinicalTrials.gov Identifier: NCT06006910.

Importance: Data on oncological outcomes after omission of axillary lymph node dissection (ALND) in patients with breast cancer that downstages from node positive to negative with neoadjuvant chemotherapy are sparse. Additionally, the best axillary surgical staging technique in this scenario is unknown., Objective: To investigate oncological outcomes after sentinel lymph node biopsy (SLNB) with dual-tracer mapping or targeted axillary dissection (TAD), which combines SLNB with localization and retrieval of the clipped lymph node., Design, Setting, and Participants: In this multicenter retrospective cohort study that was conducted at 25 centers in 11 countries, 1144 patients with consecutive stage II to III biopsy-proven node-positive breast cancer were included between April 2013 and December 2020. The cumulative incidence rates of axillary, locoregional, and any invasive (locoregional or distant) recurrence were determined by competing risk analysis., Exposure: Omission of ALND after SLNB or TAD., Main Outcomes and Measures: The primary end points were the 3-year and 5-year rates of any axillary recurrence. Secondary end points included locoregional recurrence, any invasive (locoregional and distant) recurrence, and the number of lymph nodes removed., Results: A total of 1144 patients (median [IQR] age, 50 [41-59] years; 78 [6.8%] Asian, 105 [9.2%] Black, 102 [8.9%] Hispanic, and 816 [71.0%] White individuals; 666 SLNB [58.2%] and 478 TAD [41.8%]) were included. A total of 1060 patients (93%) had N1 disease, 619 (54%) had ERBB2 (formerly HER2)-positive illness, and 758 (66%) had a breast pathologic complete response. TAD patients were more likely to receive nodal radiation therapy (85% vs 78%; P = .01). The clipped node was successfully retrieved in 97% of TAD cases and 86% of SLNB cases (without localization). The mean (SD) number of sentinel lymph nodes retrieved was 3 (2) vs 4 (2) (P < .001), and the mean (SD) number of total lymph nodes removed was 3.95 (1.97) vs 4.44 (2.04) (P < .001) in the TAD and SLNB groups, respectively. The 5-year rates of any axillary, locoregional, and any invasive recurrence in the entire cohort were 1.0% (95% CI, 0.49%-2.0%), 2.7% (95% CI, 1.6%-4.1%), and 10% (95% CI, 8.3%-13%), respectively. The 3-year cumulative incidence of axillary recurrence did not differ between TAD and SLNB (0.5% vs 0.8%; P = .55)., Conclusions and Relevance: The results of this cohort study showed that axillary recurrence was rare in this setting and was not significantly lower after TAD vs SLNB. These results support omission of ALND in this population.

Purpose: Natural language understanding (NLU) may be particularly well equipped for enhanced data capture from the electronic health record given its examination of both content-driven and context-driven extraction., Methods: We developed and applied a NLU model to examine rates of pathological node positivity (pN+) and rates of lymphedema to determine whether omission of routine axillary staging could be extended to younger patients with estrogen receptor-positive (ER+)/cN0 disease., Results: We found that rates of pN+ and arm lymphedema were similar between patients age 55-69 years and ≥70 years, with rates of lymphedema exceeding rates of pN+ for clinical stage T1c and smaller disease., Conclusion: Data from our NLU model suggest that omission of sentinel lymph node biopsy might be extended beyond Choosing Wisely recommendations, limited to those older than 70 years and to all postmenopausal women with early-stage ER+/cN0 disease. These data support the recently reported SOUND trial results and provide additional granularity to facilitate surgical de-escalation.

Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest or other items to disclose.

Objective: The Exercise Program in Cancer and Cognition (EPICC) Study was a randomized controlled trial (RCT) designed to determine whether six months of moderate-intensity aerobic exercise improves neurocognitive function in women with breast cancer (BC) receiving endocrine therapy (ET)., Methods: Postmenopausal women with hormone receptor+, early-stage BC, within two years post-primary therapy were randomized to the exercise intervention (six months, ≥150 minutes of moderate-intensity aerobic exercise/week) or usual care control condition. Outcomes were assessed at pre-randomization and after intervention completion. Groups were compared using linear mixed-effects modeling., Results: Participants (N=153) were X ¯ = 62.09 ± 8.27 years old, with stage I BC (64.1%) and a median of 4.7 months post-diagnosis. We found a group-by-time interaction (p=0.041) and a trend for the main effect of time (p=0.11) for processing speed with improved performance in the exercise group and no change in the controls. Similar main effects of time were observed for learning and memory (p=0.024) and working memory (p=0.01). Better intervention adherence was associated with improved processing speed (p=0.017)., Conclusions: Six months of moderate-intensity aerobic exercise improves processing speed in postmenopausal women with BC receiving ET who initiate exercise within two years of completing primary therapy (surgery +/- chemotherapy). This is the first large-scale study to examine the effects of aerobic exercise on neurocognitive function in women with BC. Additional research is needed to address the long-term effects of aerobic exercise on cognitive function.

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.

Purpose: Although published data have supported the use of hypofractionated regional nodal irradiation (HF-RNI) for breast cancer, limited dosimetric data exist to evaluate predictors of lung toxicity. The ongoing RT CHARM trial limits the percentage of ipsilateral lung volume that receives ≥18 Gy to 35 to 40%. We assessed dosimetry, toxicity, and disease outcomes in patients with breast cancer treated with HF-RNI with a particular focus on pneumonitis., Methods and Materials: We retrospectively reviewed all patients with breast cancer treated with HF-RNI (40-43 Gy in 15-16 fractions) after either lumpectomy or mastectomy at The University of Pittsburgh Medical Center from September 2018 to December 2021 to collect dosimetric and outcomes data. All post-radiation therapy chest computed tomography (CT) scans were manually reviewed for evidence of acute (≤6 months postradiation) or chronic (>6 months postradiation) pneumonitis., Results: One-hundred-ninety-one patients qualified with a median follow-up of 20.3 months (range, 5.1-42.2). Acute grade 1 (G1) pneumonitis was observed in 6.8% of the overall cohort (13 of 191 patients) and 39.4% of the patients (13 of 33) who received a chest CT ≤6 months postradiation therapy. Only 1 patient developed acute G2 pneumonitis. Chronic G1 pneumonitis was observed in 29.8% of the overall cohort (57 of 191 patients) and 77% of patients (57 of 74 patients) who received a chest CT >6 months postradiation therapy. No patients developed acute G3+ or chronic G2+ pneumonitis., Conclusions: Rates of symptomatic pneumonitis were low in this cohort of patients treated with HF-RNI, even with integration of HER2/neu-directed therapy, chemotherapy, hormone therapy, and internal mammary nodal irradiation. Lung V20Gy <26% appeared safe in this cohort to limit symptomatic pneumonitis, though this is not meant to represent the safe upper limit. Given the low event rate of symptomatic pneumonitis, data from larger cohorts will be needed to assess dosimetric predictors and the safe upper limit of lung dose., (Copyright © 2022 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Purpose: Benign phyllodes tumors (BPT) are rare breast neoplasms with clinical behavior that poses low recurrence risk. Guidelines regarding appropriate margins recommend surgical excision to negative margins, sometimes requiring re-excision surgery. Contemporary experience suggests that re-excision in the face of positive margins may not be needed., Methods: This is a retrospective review of a single-institution experience with BPT from 2010 to 2019 with 102 patients. Demographics, outcomes and follow-up were analyzed., Results: The median age was 37 years. 95% had a pre-operative biopsy and only 6% were confirmed BPT before surgery.56% had positive margins and were more likely to be younger and have a pre-operative diagnosis of fibroadenoma. The median follow-up was 33 months. Between the positive and negative margin groups, recurrence rates were not significantly different (p = 0.87)., Conclusion: Positive margins on excision of BPT poses a low recurrence risk and re-excision surgery is not necessary., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Neoadjuvant systemic therapy (NST) for triple-negative breast cancer and HER2-positive breast cancer yields a pathological complete response in approximately 60% of patients. A pathological complete response to NST predicts an excellent prognosis and can be accurately determined by percutaneous image-guided vacuum-assisted core biopsy (VACB). We evaluated radiotherapy alone, without breast surgery, in patients with early-stage triple-negative breast cancer or HER2-positive breast cancer treated with NST who had an image-guided VACB-determined pathological complete response., Methods: This multicentre, single-arm, phase 2 trial was done in seven centres in the USA. Women aged 40 years or older who were not pregnant with unicentric cT1-2N0-1M0 triple-negative breast cancer or HER2-positive breast cancer and a residual breast lesion less than 2 cm on imaging after clinically standard NST were eligible for inclusion. Patients had one biopsy (minimum of 12 cores) obtained by 9G image-guided VACB of the tumour bed. If no invasive or in-situ disease was identified, breast surgery was omitted, and patients underwent standard whole-breast radiotherapy (40 Gy in 15 fractions or 50 Gy in 25 fractions) plus a boost (14 Gy in seven fractions). The primary outcome was the biopsy-confirmed ipsilateral breast tumour recurrence rate determined using the Kaplan-Meier method assessed in the per-protocol population. Safety was assessed in all patients who received VACB. This study has completed accrual and is registered with ClinicalTrials.gov, NCT02945579., Findings: Between March 6, 2017, and Nov 9, 2021, 58 patients consented to participate; however, four (7%) did not meet final inclusion criteria and four (7%) withdrew consent. 50 patients were enrolled and underwent VACB following NST. The median age of the enrolled patients was 62 years (IQR 55-77); 21 (42%) patients had triple-negative breast cancer and 29 (58%) had HER2-positive breast cancer. VACB identified a pathological complete response in 31 patients (62% [95% CI 47·2-75·4). At a median follow-up of 26·4 months (IQR 15·2-39·6), no ipsilateral breast tumour recurrences occurred in these 31 patients. No serious biopsy-related adverse events or treatment-related deaths occurred., Interpretation: Eliminating breast surgery in highly selected patients with an image-guided VACB-determined pathological complete response following NST is feasible with promising early results; however, additional prospective clinical trials evaluating this approach are needed., Funding: US National Cancer Institute (National Institutes of Health)., Competing Interests: Declaration of interests HMK reports consulting fees from Merck; honorarium from Physicians Education Resources; payment as an Editor from the New England Journal of Medicine Group; royalties from McGraw-Hill Professional and Elsevier Publishing; and leadership role in National Surgical Adjuvant Breast and Bowel Project, the Radiation Therapy Oncology Group, and the Gynecologic Oncology Group oncology Clinical Trials Cooperative Group, Breast Cancer Committee, local-regional member. BDS reports salary support from Varian Medical Systems and a royalty and equity interest in Oncora Medical. SK reports consulting fees from AstraZeneca, and royalties from Elsevier Publishing. WTY reports royalties from Elsevier Publishing. VV reports a grant from Zymeworks, consulting and honoraria from Genentech/Roche, Novartis, and AstraZeneca; and leadership roles in the NRG Breast Committee and Trio Health Scientific Steering. JCB reports research funding from MD Anderson Cancer Center and SymBioSis paid to their institution. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Phyllodes tumors (PTs) are rare breast neoplasms with variable clinical behavior by histologic type: benign, borderline, or malignant. Until recently, management guidelines recommended one approach for all subtypes., Methods: A 21-question survey was sent to American Society of Breast Surgeon members to evaluate management patterns by subtype. Surgeon demographics, decisions regarding management of margins, re-excision, surveillance, and synoptic reporting were collected. Chi-square or analysis of variance (ANOVA) were used as appropriate, with significance set at p < 0.05., Results: A total of 493 of 2969 surveys were completed for a response rate of 18.3%. Among the survey takers, 55% were fellowship trained, 72% were in practice > 10 years, and 82% performed > 100 breast cases per year. Although 25% of respondents enucleate a mass with clinical suspicion of a PT alone, this decreased to 18% if a preoperative core biopsy performed was suggestive of PT. For margin management, 47% do not re-excise positive margins for benign PTs, but 96% would for a borderline or malignant PTs (p < 0.001). Only 2% perform axillary staging for malignant PTs, and 90% refer borderline or malignant PTs for radiation. Two-year surveillance was performed by about half of respondents for benign PT. However, two-thirds of respondents would increase surveillance to 5 years for borderline or malignant PTs. Only 38% report a templated synoptic pathology report at their institution., Conclusion: PT management patterns are evolving but still variable when looking at initial margin intent, decision for re-excision, radiation referral, pathologic reporting, and surveillance. This suggests the need for more specific management guidelines by subtype given differences in clinical behavior., (© 2022. Society of Surgical Oncology.)

Purpose: Genetic testing (GT) can identify individuals with pathogenic/likely pathogenic variants (PV/LPVs) in breast cancer (BC) predisposition genes, who may consider contralateral risk-reducing mastectomy (CRRM). We report on CRRM rates in young women newly diagnosed with BC who received GT through a multidisciplinary clinic., Methods: Clinical data were reviewed for patients seen between November 2014 and June 2019. Patients with non-metastatic, unilateral BC diagnosed at age ≤ 45 and completed GT prior to surgery were included. Associations between surgical intervention and age, BC stage, family history, and GT results were evaluated., Results: Of the 194 patients, 30 (15.5%) had a PV/LPV in a BC predisposition gene (ATM, BRCA1, BRCA2, CHEK2, NBN, NF1), with 66.7% in BRCA1 or BRCA2. Of 164 (84.5%) uninformative results, 132 (68%) were negative and 32 (16.5%) were variants of uncertain significance (VUS). Overall, 67 (34.5%) had CRRM, including 25/30 (83.3%) PV/LPV carriers and 42/164 (25.6%) non-carriers. A positive test result (p < 0.01) and significant family history were associated with CRRM (p = 0.02). For the 164 with uninformative results, multivariate analysis showed that CRRM was not associated with age (p = 0.23), a VUS, (p = 0.08), family history (p = 0.10), or BC stage (p = 0.11)., Conclusion: In this cohort of young women with BC, the identification of a PV/LPV in a BC predisposition gene and a significant family history were associated with the decision to pursue CRRM. Thus, incorporation of genetic services in the initial evaluation of young patients with a new BC could contribute to the surgical decision-making process., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The Society for Surgical Oncology's Choosing Wisely guidelines recommend against sentinel lymph node biopsy (SLNB) in favor of observation in this population. Recent analyses reveal that this has not been widely adopted. The purpose of this cost-effectiveness analysis is to compare the costs and benefits associated with observation or SLNB in women >70 years old with hormone receptor-positive, clinically node-negative, operable breast cancer., Methods: A decision tree with Markov modeling was created to compare treatment strategies using long-term follow-up data from clinical trials in this population. Costs were estimated from published literature and publicly available databases. Breast cancer-specific health-state utilities were derived from the literature and expert opinion. One-way, 2-way, and probabilistic sensitivity analyses were conducted. A structural sensitivity analysis was performed to assess the effect of functional status and anxiety from nonevaluation of the axilla on cost-effectiveness. Costs and benefits, measured in life-years (LYs) and quality-adjusted life-years (QALYs), were tabulated across 10, 15, and 20 years and compared using incremental cost-effectiveness ratios (ICERs)., Results: SLNB is not cost-effective from the payer or societal perspectives with ICERs of $138,374/LY and $131,900/LY, respectively. When QALYs were considered, SLNB provided fewer QALYs (SLNB, 10.33 QALYs; observation, 10.53 QALYs) at a higher cost (SLNB, $15,845; observation, $4020). Structural sensitivity analysis revealed that SLNB was cost-effective in certain patients with significant anxiety related to axillary observation (ICER, $39,417/QALY)., Conclusions: Routine SLNB in this population is not cost-effective. The cost-effectiveness of SLNB, however, is dependent on individual patient factors, including functional status as well as patient preference., (© 2022 American Cancer Society.)

Background: Postmastectomy breast reconstruction (BR) has been shown to provide long-term quality of life and psychosocial benefits. Despite the policies initiated to improve access to BR, its delivery continues to be inequitable, suggesting that barriers to access have not been fully identified and/or addressed. The purpose of this study was to assess the influence of geographic location, socioeconomic status, and race in access to immediate BR (IBR)., Methods: An institutional review board-approved observational study was conducted. All patients who underwent breast cancer surgery from 2014 to 2019 were queried from our institutional Breast Cancer Registry. A geographical analysis was conducted using demographic characteristics and patient's ZIP codes. Euclidean distance from patient home ZIP code to UPMC Magee Women's Hospital was calculated, and χ2, Student t test, Mann-Whitney, and Kruskal-Wallis tests was used to evaluate differences between groups, as appropriate. Statistical significance was set at P < 0.05., Results: Overall, 5835 patients underwent breast cancer surgery. A total of 56.7% underwent lumpectomy or segmental mastectomy, and 43.3% underwent modified, total, or radical mastectomy. From the latter group, 33.5% patients pursued BR at the time of mastectomy: 28.6% autologous, 48.1% implant-based, 19.4% a combination of autologous and implant-based, and 3.9% unspecified reconstruction. Rates of IBR varied among races: White or European (34.1%), Black or African American (27.7%), and other races (17.8%), P = 0.022. However, no difference was found between type of BR among races (P = 0.38). Moreover, patients who underwent IBR were significantly younger than those who did not pursue reconstruction (P < 0.0001). Patients who underwent reconstruction resided in ZIP codes that had approximately US $2000 more annual income, a higher percentage of White population (8% vs 11% non-White) and lower percentage of Black or African American population (1.8% vs 2.9%) than the patients who did not undergo reconstruction., Conclusions: While the use of postmastectomy BR has been steadily rising in the United States, racial and socioeconomic status disparities persist. Further efforts are needed to reduce this gap and expand the benefits of IBR to the entire population without distinction., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Age is one of the most important risk factors for the development of breast cancer. Nearly a third of all breast cancer cases occur in older women (aged ≥70 years), with most cases being oestrogen receptor-positive (ER+). Such tumours are often indolent and unlikely to be the ultimate cause of death for older women, particularly when considering other comorbidities. This Review focuses on unique clinical considerations for screening, detection, and treatment regimens for older women who develop ER+ breast cancers-specifically, we focus on recent trends for de-implementation of screening, staging, surgery, and adjuvant therapies along the continuum of care. Additionally, we also review emerging basic and translational research that will further uncover the unique underlying biology of these tumours, which develop in the context of systemic age-related inflammation and changing hormone profiles. With prevailing trends of clinical de-implementation, new insights into mechanistic biology might provide an opportunity for precision medicine approaches to treat patients with well tolerated, low-toxicity agents to extend patients' lives with a higher quality of life, prevent tumour recurrences, and reduce cancer-related burdens.

Background: A substantial expense in surgical care is incurred in the operating room (OR). We evaluated the financial impact of a systematic reduction in instrument tray contents on charges for breast surgery procedures., Methods: A catalog of OR trays historically used for breast procedures (excisional biopsy, segmental and total mastectomy with or without axillary staging) was reviewed by four dedicated breast surgeons and downsized to a single tray accommodating all surgeon preferences. A matched-case comparison was performed pre- and post-downsizing. Cost analysis for salary and benefits (S&B) and unit supply cost (USC) pre- and post-downsizing were carried out. Instrument number, OR tray weights, set-up, and breakdown times were also compared., Results: Post-downsizing, OR tray counts were reduced from 132 to 67 instruments (49%) and tray weight decreased from 30 to 20 pounds (33%). Scrub technician set-up and breakdown times were shorter by 22% and 25%, respectively. Comparing 449 matched cases (239 pre- and 210 post-downsizing), S&B and USC post-downsizing were decreased collectively for all procedures (p < 0.0001). With an average variance of S&B and USC (pre- to post-intervention) of $354, and an annualized case load of 813 operations, this could translate into S&B and USC savings of $287,802 per year., Conclusion: Simply downsizing OR breast trays resulted in decreased combined S&B and USC per procedure, leading to a substantial cost savings for the healthcare system. This measure aligns with a value and quality-based approach to patient care and could be easily replicated across institutions and specialties., (© 2021. Society of Surgical Oncology.)

Importance: Overtreatment of early-stage breast cancer with favorable tumor biology in older patients may be harmful without affecting recurrence and survival. Guidelines that recommend deimplementation of sentinel lymph node biopsy (SLNB) (Choosing Wisely) and radiotherapy (RT) (National Comprehensive Cancer Network) have been published., Objective: To describe the use rates and association with disease recurrence of SLNB and RT in older women with breast cancer., Design, Setting, and Participants: This cohort study obtained patient and clinical data from an integrated cancer registry and electronic health record of a single health care system in Pennsylvania. The cohort was composed of consecutive female patients 70 years or older who were diagnosed with early-stage, estrogen receptor-positive, ERBB2 (formerly HER2)-negative, clinically node-negative breast cancer from January 1, 2010, to December 31, 2018, who were treated at 15 community and academic hospitals within the health system., Exposures: Sentinel lymph node biopsy and adjuvant RT., Main Outcomes and Measures: Primary outcomes were 5-year locoregional recurrence-free survival (LRFS) rate and disease-free survival (DFS) rate after SLNB and after RT. Secondary outcomes included recurrence rate, subgroups that may benefit from SLNB or RT, and use rate of SLNB and RT over time. Propensity scores were used to create 2 cohorts to separately evaluate the association of SLNB and RT with recurrence outcomes. Cox proportional hazards regression model was used to estimate hazard ratios (HRs)., Results: From 2010 to 2018, a total of 3361 women 70 years or older (median [interquartile range {IQR}] age, 77.0 [73.0-82.0] years) with estrogen receptor-positive, ERBB2-negative, clinically node-negative breast cancer were included in the study. Of these women, 2195 (65.3%) received SLNB and 1828 (54.4%) received adjuvant RT. Rates of SLNB steadily increased (1.0% per year), a trend that persisted after the 2016 adoption of the Choosing Wisely guideline. Rates of RT decreased slightly (3.4% per year). To examine patient outcomes and maximize follow-up time, the analysis was limited to cases from 2010 to 2014, identifying 2109 patients with a median (IQR) follow-up time of 4.1 (2.5-5.7) years. In the propensity score-matched cohorts, no association was found between SLNB and either LRFS (HR, 1.26; 95% CI, 0.37-4.30; P = .71) or DFS (HR, 1.92; 95% CI, 0.86-4.32; P = .11). In addition, RT was not associated with LRFS (HR, 0.33; 95% CI, 0.09-1.24; P = .10) or DFS (HR, 0.99; 95% CI, 0.46-2.10; P = .97). Subgroup analysis showed that stratification by tumor grade or comorbidity was not associated with LRFS or DFS. Low absolute rates of recurrence were observed when comparing the groups that received SLNB (3.5%) and those that did not (4.5%) as well as the groups that received RT (2.7%) and those that did not (5.5%)., Conclusions and Relevance: This study found that receipt of SLNB or RT was not associated with improved LRFS or DFS in older patients with ER-positive, clinically node-negative breast cancer. Despite limited follow-up time and wide 95% CIs, this study supports the continued deimplementation of both SLNB and RT in accordance with the Choosing Wisely and National Comprehensive Cancer Network guidelines.

Background: Enhanced Recovery Protocols (ERPs) provide a multimodal approach to perioperative care, with the aims of improving patient outcomes while decreasing perioperative antiemetic and narcotic requirements. With high rates of post-operative nausea or vomiting (PONV) following total mastectomy (TM), we hypothesized that our institutional designed ERP would reduce PONV while improving pain control and decrease opioid use., Methods: An ERP was implemented at a single institution for patients undergoing TM with or without implant-based reconstruction. Patients from the first two months of implementation (ERP group, N = 72) were compared with a retrospective usual-care cohort from a three-month period before implementation (UC group, N = 83). Outcomes included PONV incidence, measured with antiemetic use; patient-reported pain scores; perioperative opioid consumption, measured by oral morphine equivalents (OME); and length of stay (LOS)., Results: The characteristics of the two groups were similar. PONV incidence and perioperative opioid consumption were lower in the ERP than the UC group (21% vs. 40%, p 0.011 and mean 44.1 OME vs. 104.3 OME, p < 0.001), respectively. These differences in opioid consumption were observed in the operating room and post-anesthesia care unit (PACU); opioid consumption on the floor was similar between the two groups. Patient-reported pain scores were lower in the ERP than the UC group (mean highest pain score 6.4 vs. 7.4, p 0.003). PACU and hospital LOS were similar between the two groups., Conclusion: ERP implementation was successful in decreasing PONV following TM with and without reconstruction, while simultaneously decreasing overall opioid consumption without compromising patient comfort.

Purpose: Multifocal pattern of regression after neoadjuvant chemotherapy has been identified as a risk factor for ipsilateral breast tumor recurrence (IBTR). We aimed to determine the significance of multifocal regression as a predictor of IBTR after neoadjuvant chemotherapy and breast conservation therapy in the modern era., Methods and Materials: We retrospectively reviewed 346 patients treated between November 2009 and June 2017. Pattern of regression was categorized as pathologic complete response (pCR), unifocal (tumor present as a cohesive mass), limited multifocal (single cells or clusters of cells concentrated in 1 portion of the fibrotic area), or diffuse multifocal (cells spread over entire fibrotic area). IBTR was defined as new ipsilateral invasive or noninvasive breast tumor after breast conservation therapy. Predictive factors were analyzed using Cox regression., Results: Incidence of multifocal regression was 25.7% for the overall cohort and 12.2% for estrogen receptor (ER) negative/progesterone receptor (PR) negative/human epidermal growth factor receptor 2 (HER2) positive, 17.5% for triple-negative, 36.9% for ER+ or PR+/HER2-, and 38.5% for triple-positive (P < .001). With a median follow-up of 41.1 months, 4-year IBTR-free survival after pCR or unifocal regression versus multifocal regression was 94.1% versus 90.9% (P = .411). Pattern of regression (P = .010; compared to pCR, hazard ratio [HR] of 11.2 for diffuse multifocal regression, 1.65 for limited multifocal regression, and 3.81 for unifocal regression), phenotype (P = .001; compared to ER+ or PR+/HER2-, HR of 30.67 for ER-/PR-/HER2+, 25.30 for triple-negative, and 1.60 for triple-positive), and lack of nodal pCR (P = .004; HR of 3.78) predicted for IBTR on multivariate Cox regression. On multivariate subset analysis, pattern of regression and lymphovascular space invasion predicted for IBTR in hormone receptor-negative patients, but pattern of regression was not associated with IBTR for hormone receptor-positive patients., Conclusions: Multifocal regression, hormone receptor-negative phenotype, and lack of nodal pCR predict for increased risk of IBTR after neoadjuvant chemotherapy. Although more common in hormone receptor-positive disease, multifocal regression was associated with worse outcome only in hormone receptor-negative patients., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Metaplastic breast carcinoma is a rare heterogeneous category of breast cancer, often associated with a poor prognosis. Clinical-pathologic studies with respect to varied morphologic subtypes are lacking. There is also a dearth of studies assessing the response of metaplastic breast carcinoma to neoadjuvant chemotherapy. Cases of metaplastic breast carcinoma diagnosed between 2007 and 2017 were identified. Various clinical-pathologic variables were tested for association with survival. Patients who underwent neoadjuvant chemotherapy were assessed for pathologic response. Median age at diagnosis with metaplastic breast carcinoma was 64 years. With a median follow-up of 39 months, 26 patients (27%) recurred (24 distant and 2 loco-regional). The overall survival rate of the cohort was 66% (64/97). A number of variables were associated with survival in univariable analysis; however, in multivariable analysis, only lymph node status and tumor size (pT3 vs. pT1/2) were significantly associated with all survival endpoints: recurrence-free survival, distant recurrence-free survival, overall survival and breast cancer-specific survival. Twenty-nine of 97 (30%) patients with metaplastic breast carcinoma received neoadjuvant chemotherapy. Five (17%) patients achieved pathologic complete response. Matrix-producing morphology was associated with higher probability of achieving pathologic complete response (p = 0.027). Similar to other breast cancer subtypes, tumor size and lymph node status are prognostic in metaplastic carcinomas. The pathologic complete response rate of metaplastic breast carcinoma in our cohort was 17%, higher than previously reported. Although the matrix-producing subtype was associated with pathologic complete response, there was no survival difference with respect to tumor subtypes.

Objectives: Pathologic complete response (pCR) rate after neoadjuvant chemotherapy was compared between 141 estrogen receptor (ER)-negative (43%), 41 low ER+ (13%), 47 moderate ER+ (14%), and 98 high ER+ (30%) tumors., Methods: Human epidermal growth factor receptor 2-positive cases, cases without semiquantitative ER score, and patients treated with neoadjuvant endocrine therapy alone were excluded., Results: The pCR rate of low ER+ tumors was similar to the pCR rate of ER- tumors (37% and 26% for low ER and ER- respectively, P = .1722) but significantly different from the pCR rate of moderately ER+ (11%, P = .0049) and high ER+ tumors (4%, P < .0001). Patients with pCR had an excellent prognosis regardless of the ER status. In patients with residual disease (no pCR), the recurrence and death rate were higher in ER- and low ER+ cases compared with moderate and high ER+ cases., Conclusions: Low ER+ breast cancers are biologically similar to ER- tumors. Semiquantitative ER H-score is an important determinant of response to neoadjuvant chemotherapy.

Objectives: We hypothesized that prognostic accuracy of the residual disease in breast and lymph nodes (RDBN) method, which is calculated using residual tumor size, nodal involvement, and tumor grade, may be improved by incorporating residual tumor cellularity., Methods: Cases included 614 patients who underwent neoadjuvant therapy for breast cancer. Tumor size was adjusted for residual cellularity of invasive carcinoma and used to calculate modified RDBN (mRDBN) and compared with unmodified gross tumor size (gRDBN)., Results: RDBN could be calculated in 428 cases. Relative risks of recurrence and death were significantly higher for RDBN-3 and RDBN-4 compared with RDBN-1. Kaplan-Meier analysis showed significant differences in disease-free survival and overall survival for estrogen receptor (ER)-negative/human epidermal growth factor receptor 2 (HER2)-negative and ER-positive/HER2-negative subgroups (P < .0001)., Conclusions: Both mRDBN and gRDBN provide prognostic information, particularly in HER2-negative carcinoma; however, mRDBN showed better stratification of RDBN-3 and RDBN-4 patients.

Magee Equations were derived as an inexpensive, rapid alternative to Oncotype DX. The Magee Equation 3 utilizes immunohistochemical and FISH data for estrogen receptor (ER), progesterone receptor (PR), HER2 and Ki-67 for its calculation (24.30812+ERIHC × (-0.02177)+PRIHC × (-0.02884)+(0 for HER2 negative, 1.46495 for equivocal, 12.75525 for HER2 positive)+Ki-67 × 0.18649). We hypothesize that Magee Equation 3 scores from pre-therapy core biopsy can predict response to neoadjuvant systemic chemotherapy. A prospectively-maintained database of patients who received neoadjuvant systemic therapy from 2010 to 2014 at a single institution was retrospectively reviewed. Pathologic complete response was defined as absence of invasive tumor in the breast and regional lymph nodes. Of the 614 cases, tumors with missing immunohistochemical results and those that were ER negative or HER2 positive were excluded. This resulted in 237 ER positive, HER2 negative/equivocal tumors that formed the basis of this study. Magee Equation 3 scores were divided into 3 categories similar to Oncotype DX, ie, 0 to <18 (low), 18 to <31 (intermediate), and 31 or higher (high) scores. The pathologic complete response rate for low, intermediate and high Magee Equation 3 scores was 0%, 4%, and 36%, respectively. Patients with high Magee Equation 3 scores were 13 times more likely to achieve pathologic complete response compared to those with Magee Equation 3 scores less than 31 (95% CI 5.09-32.87, P<0.0001). For patients that did not achieve pathologic complete response, high Magee Equation 3 correlated with higher recurrence rate, with the majority occurring in patients with positive lymph nodes in the resection specimen. Magee Equation 3 score ≥31 predicts pathologic complete response in the neoadjuvant setting and for tumor recurrence, when pathologic complete response is not achieved. These results show the utility of Magee Equation 3 in predicting patients who will benefit from chemotherapy but warrant prospective multi-institutional validation.

Background: Neoadjuvant chemotherapy (NAC) downstages axillary disease in 55 % of node-positive (N1) breast cancer. The feasibility and accuracy of sentinel lymph node biopsy (SLNB) after NAC for percutaneous biopsy-proven N1 patients who are clinically node negative (cN0) by physical examination after NAC is under investigation. ACOSOG Z1071 reported a false-negative rate of <10 % if ≥3 nodes are removed with dual tracer, including excision of the biopsy-proven positive lymph node (BxLN). We report our experience using radioactive seed localization (RSL) to retrieve the BxLN with SLNB (RSL/SLNB) for cN0 patients after NAC., Methods: We performed a retrospective review of a single-institution, prospectively maintained registry for the years 2013 to 2014. Patients with BxLN who received NAC and had RSL/SLNB were identified. All BxLNs were marked with a radiopaque clip before NAC to facilitate RSL., Results: Thirty patients with BxLN before NAC were cN0 after NAC and underwent RSL/SLNB. Median age was 55 years. Disease stage was IIA-IIIB. Twenty-nine of 30 had ductal cancer (12 triple negative and 16 HER-2 positive). One to 11 nodes were retrieved. Twenty-nine of 30 BxLN were successfully localized with RSL. Note was made of the BxLN-containing isotope and/or dye in 22 of 30. Nineteen patients had no residual axillary disease; 11 had persistent disease. All who remained node positive had disease in the BxLN., Conclusions: RSL/SLNB is a promising approach for axillary staging after NAC in patients whose disease becomes cN0. The status of the BxLN after NAC predicted nodal status, suggesting that localization of the BxLN may be more accurate than SLNB alone for staging the axilla in the cN0 patient after NAC.

Purpose: Early detection and timely intervention have potential to reduce late-stage lymphedema (LE) in patients with breast cancer undergoing axillary lymph node dissection (ALND). This study aims to determine if detection and early treatment of subclinical LE by using prospective monitoring with bioimpedance spectroscopy (BIS) can lead to reduced development of clinical LE., Methods and Results: Subclinical LE was prospectively detected using an L-Dex(®) U400 analyzer to measure BIS in 186 patients who underwent ALND between 2010 and 2013 through our LE monitoring program. Baseline measurements were obtained and at 3-6 month intervals for 5 years. Patients diagnosed with subclinical LE received short-term physical therapy, compression garments, and education about exercise, elevation, infection precautions, BMI, and hand usage. The control group had a preoperative baseline L-Dex(®) measurement, but had only clinical follow-ups with circumferential arm measurements. Mean age and BMI were 56 years and 28.3 kg/m(2), respectively. The majority of the women underwent mastectomy (61%) and received chemotherapy (89%) and radiotherapy (77%). Thirty-three percent patients who had repeated L-Dex measurements were diagnosed with subclinical LE and received early intervention. Progression to clinical lymphedema occurred in 4.4% over an average of 20 months follow-up. In the control group, the incidence of clinical LE was 36.4%., Conclusion: Periodic monitoring of women at high risk for LE with BIS allows early detection and timely intervention for LE, which reduces the incidence of clinical LE from 36.4% to 4.4%. This may have implications for quality of life and health care costs.

Background: Improved resolution and utilization of screening breast imaging has increased identification of nonpalpable high-risk lesions (HRL) and subsequent excisional breast biopsies (EBBs). Wire localization (WL), used most commonly for EBBs, may have shortcomings, including wire displacement, patient discomfort, limitations with incision planning and scheduling logistics. Radioactive seed localization (RSL) may overcome these drawbacks. The purpose of this study was to compare WL and RSL for EBBs for HRLs., Methods: All single-site EBBs for HRL performed by four breast surgeons were retrospectively reviewed over two consecutive 1-year periods. Patients with cancer on percutaneous core biopsy (CB) were excluded. Clinicopathologic information, operative time, targeted lesion retrieval rate, and upstage rate were collected., Results: A total of 324 EBBs for HRL were performed: 196 using WL and 128 using RSL. CB pathology was atypical hyperplasia in 56 % of WLs and 62 % of RSLs. The remaining pathologies were radial scar, papilloma, atypical papilloma or lobular carcinoma in situ. Mean age was 54 years. OR time was 27 ± 8 min for WL and 27 ± 7 min for RSL (p = 0.9). Upstage rate was 6 and 5 % for WLs and RSLs, respectively (p = 0.5). Targeted lesions were retrieved in 98 % of WL and 99 % of RSL (p = 0.5). SV was 37.2 ± 32.8 cm(3) and 25.7 ± 22.3 cm(3) for WL and RSL, respectively (p = 0.001)., Conclusions: RSL is comparable to WL for EBB of HRLs with similar OR times and upstage rates. SV is significantly decreased with RSL and may translate into improved cosmetic outcomes without sacrificing the diagnostic accuracy of the EBB.