Factors influencing prophylactic surgical intervention in women with genetic predisposition for breast cancer.

INTRODUCTION: In the United States, 5%-10% of breast cancer cases are due to genetic predisposition. Among this population, prophylactic mastectomy is viable risk-reducing option. OBJECTIVE: The objective of this study is to understand the timing to prophylactic mastectomy in patients with genetic predisposition to breast cancer and uncover factors influencing this decision. METHODS: This study is a retrospective review of patients diagnosed with genetic predisposition for breast cancer from 2010 to 2020. RESULTS: In a cohort of 506 patients with genetic predisposition for breast cancer, 154 (30.4%) underwent prophylactic mastectomy, the remainder opted for surveillance alone. The median time from diagnosis to mastectomy was 1.1 years (IQR, 0.5-3.1 years). During the surveillance period, 118 patients (33.5%) underwent breast biopsy. Of the patients with benign or atypical findings, 35 (36.8%) pursued prophylactic mastectomy, a median of 0.5 years (IQR, 0.2-1.6 years) after their gene diagnosis. The most common factor impacting the decision to undergo prophylactic mastectomy was having a family member with cancer (54.7%) followed by a personal diagnosis of other cancer(s) (27.5%). CONCLUSION: Understanding the factors influencing the decision to undergo prophylactic surgery will allow for more effective shared decision-making for primary care providers, breast surgeons, and reconstructive surgeons.

De-Escalating the Extent of Sentinel Lymph Node Biopsy in Patients With Ductal Carcinoma in Situ Undergoing Mastectomy.

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.

Lifetime Pain Management Experiences of Female Breast Cancer Survivors Aged 65+ Years.

PURPOSE: Explore factors influencing pain management among female breast cancer survivors aged 65+ years with moderate to severe pain based on a score of 4 or greater on the 0-10 numeric rating scale. DESIGN: Qualitative descriptive study. METHODS: We interviewed 21 purposefully sampled women aged 65+ years who experienced moderate to severe pain. Researchers coded interview transcripts for factors affecting study participants' pain management experiences. RESULTS: Pain management facilitators included patient-centered interactions with care teams and reliance on psychosocial assets. Challenges included ineffective care team interactions and participants' negative perceptions of opioid analgesia. Other factors included pain attributed to cancer treatment, pain management plan adherence, and psychosocial influencers. CONCLUSIONS: With regard to this sample, patient-centered communication and pain management education help female breast cancer survivors aged 65+ years manage their pain. Mitigation of opioid stigma and undermanaged painful comorbid conditions could further optimize pain management. Further research on the effects of breast cancer treatment, level of adherence to pain management recommendations, and psychosocial influences on pain management is needed. CLINICAL IMPLICATIONS: Providing contact information for care team members during and after clinic hours facilitates open communication, including timely reporting of new and undertreated pain. Collaborating with the patient and care team on a clear pain management plan and establishing parameters for when to notify the care team empower patients to optimize management of their pain. Verifying patients' understanding of prescribed analgesia and management of side effects and providing education as needed may reduce negative perceptions of opioid analgesia.

Genomic landscape of malignant phyllodes tumors reveals multiple targetable opportunities.

BACKGROUND: Malignant phyllodes tumors (MPT) are rare fibroepithelial breast cancers with no known effective systemic therapy; metastatic progression portends a dismal prognosis. We sought to describe the genomic landscape of MPTs through genomic profiling and immunotherapeutic biomarker analysis. MATERIALS AND METHODS: Cases of sequenced MPT were identified from a Clinical Laboratory Improvement Amendments-certified, College of American Pathologists-accredited laboratory (Foundation Medicine). All cases underwent genomic profiling using adaptor ligation-based, next-generation sequencing assay of 324 genes. Tumor agnostic immunotherapy biomarkers, microsatellite instability, tumor mutational burden (TMB), and programmed death-ligand 1 (PD-L1) expression were evaluated. Fisher's Exact Tests and analysis of variance were used to test for differences between groups and for continuous variables as appropriate. RESULTS: Of 135 MPT cases identified; 94 (69.6%) were localized/locally recurrent and 41 (30.4%) were metastatic. Median age was 54 years (range 14-86). The median TMB was 2.5 mut/Mb and 3 were TMB-high (≥10 mut/Mb). 21.4% were PD-L1+ via Dako 22C3 assay (CPS ≥1). Most commonly altered genes included TERT-promoter (69.7%), CDKN2A (45.9%), TP53 (37.8%), NF1 (35.6%), CDKN2B (33.3%), MED12 (28.9%), MTAP (27.7%), KMT2D (22.2%), PIK3CA (20.0%), PTEN (18.5%), and RB1 (18.5%). Several tumors harboring genomic alterations with US Food and Drug Administration-approved indications in other tumor types were found including NF1, PIK3CA, EGFR Exon 19/20 insertions, and BRAF V600E mutations. CONCLUSIONS: In the largest genomic evaluation of MPT to date, multiple clinically actionable mutations were found. Routine sequencing of metastatic MPT may provide additional information to guide treatment decisions and clinical trial enrollment.

Electronic Health Record-Based Nudge Intervention and Axillary Surgery in Older Women With Breast Cancer: A Nonrandomized Controlled Trial.

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.

Effects of aerobic exercise on neurocognitive function in postmenopausal women receiving endocrine therapy for breast cancer: The Exercise Program in Cancer and Cognition randomized controlled trial.

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.

Use of Natural Language Understanding to Facilitate Surgical De-Escalation of Axillary Staging in Patients With Breast Cancer.

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.

Omission of Axillary Dissection Following Nodal Downstaging With Neoadjuvant Chemotherapy.

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.

Upgrade Rates of Variant Lobular Carcinoma In Situ Compared to Classic Lobular Carcinoma In Situ Diagnosed in Core Needle Biopsies: A 10-Year Single Institution Retrospective Study.

The primary aim of this study was to determine the upgrade rates of variant lobular carcinoma in situ (V-LCIS, ie, combined florid [F-LCIS] and pleomorphic [P-LCIS]) compared with classic LCIS (C-LCIS) when diagnosed on core needle biopsy (CNB). The secondary goal was to determine the rate of progression/development of invasive carcinoma on long-term follow-up after primary excision. After institutional review board approval, our institutional pathology database was searched for patients with "pure" LCIS diagnosed on CNB who underwent subsequent excision. Radiologic findings were reviewed, radiologic-pathologic (rad-path) correlation was performed, and follow-up patient outcome data were obtained. One hundred twenty cases of LCIS were identified on CNB (C-LCIS = 97, F-LCIS = 18, and P-LCIS = 5). Overall upgrade rates after excision for C-LCIS, F-LCIS, and P-LCIS were 14% (14/97), 44% (8/18), and 40% (2/5), respectively. Of the total cases, 79 (66%) were deemed rad-path concordant. Of these, the upgrade rate after excision for C-LCIS, F-LCIS, and P-LCIS was 7.5% (5 of 66), 40% (4 of 10), and 0% (0 of 3), respectively. The overall upgrade rate for V-LCIS was higher than for C-LCIS (P = .004), even for the cases deemed rad-path concordant (P value: .036). Most upgraded cases (23 of 24) showed pT1a disease or lower. With an average follow-up of 83 months, invasive carcinoma in the ipsilateral breast was identified in 8/120 (7%) cases. Six patients had died: 2 of (contralateral) breast cancer and 4 of other causes. Because of a high upgrade rate, V-LCIS diagnosed on CNB should always be excised. The upgrade rate for C-LCIS (even when rad-path concordant) is higher than reported in many other studies. Rad-path concordance read, surgical consultation, and individualized decision making are recommended for C-LCIS cases. The risk of developing invasive carcinoma after LCIS diagnosis is small (7% with ∼7-year follow-up), but active surveillance is required to diagnose early-stage disease.

Use of natural language understanding to facilitate surgical de-escalation of axillary staging in patients with breast cancer.

Natural language understanding (NLU) may be particularly well-equipped for enhanced data capture from the electronic health record (EHR) given its examination of both content- and context-driven extraction. We developed and applied a NLU model to examine rates of pathological node positivity (pN+) and rates of lymphedema to determine if omission of routine axillary staging could be extended to younger patients with ER+/cN0 disease. We found that rates of pN+ and arm lymphedema were similar between patients 55-69yo and ≥70yo, with rates of lymphedema exceeding rates of pN+ for clinical stage T1c and smaller disease. Data from our NLU model suggest that omission of SLNB might be extended beyond Choosing Wisely recommendations, limited to those over 70 years old, 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.

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.

Summary: Appropriate Use Criteria for Lymphoscintigraphy in Sentinel Node Mapping and Lymphedema/Lipedema.

Expert representatives from 11 professional societies, as part of an autonomous work group, researched and developed appropriate use criteria (AUC) for lymphoscintigraphy in sentinel lymph node mapping and lymphedema. The complete findings and discussions of the work group, including example clinical scenarios, were published on October 8, 2022, and are available at https://www.snmmi.org/ClinicalPractice/content.aspx?ItemNumber=42021 The complete AUC document includes clinical scenarios for scintigraphy in patients with breast, cutaneous, and other cancers, as well as for mapping lymphatic flow in lymphedema. Pediatric considerations are addressed. These AUC are intended to assist health care practitioners considering lymphoscintigraphy. Presented here is a brief overview of the AUC, including the rationale and methodology behind development of the document. For detailed findings of the work group, the reader should refer to the complete AUC document online.

Single-institution outcomes after excision of benign phyllodes tumors: low recurrence risk even with positive margins.

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.

Postdischarge Nausea and Vomiting and Co-occurring Symptoms in Women Following Breast Cancer Surgery.

PURPOSE: The purpose of this study was to investigate the influence of potential co-occurring symptoms, including fatigue, sleep disturbance, anxiety, depressive symptoms, and pain, on the incidence of postdischarge nausea (PDN) measured two days following discharge to home after surgery for breast cancer. DESIGN: This study used a prospective, cross-sectional, observational design. METHODS: The sample was 334 women aged 27 to 88 years of age. Demographic data were collected from the patient and the medical record before surgery. Symptom data were collected 48 hours following surgery using the Patient Reported Outcome Measurement System (PROMIS) and numerical nausea and pain scales. FINDINGS: Eighty-five (25.4%) of study participants reported some nausea two days after discharge. Study participants who experienced PDN frequently described that it occurred after they left the hospital to drive home following their surgery. Unadjusted odds ratios showed the presence of co-occurring symptoms of anxiety, fatigue, sleep disturbance, and pain were all significantly associated with the presence of nausea 48 hours following surgery. Other significant factors associated with (PDN) were history of motion sickness, history of pregnancy-induced nausea, use of opioids, and type of surgery. CONCLUSIONS: Same-day surgery nurses providing postoperative education for women following surgery for breast cancer should explain to patients that nausea may occur after they are discharged, especially those with known motion sickness. In addition, patients should be informed that other symptoms, especially fatigue, sleep disturbance, and anxiety, may co-occur.

Surgical Nipple Delay and its Expanded Indications for Nipple-sparing Mastectomy.

Necrosis of the nipple-areolar complex (NAC) or surrounding skin has been reported in 6%-30% of nipple-sparing mastectomy (NSM) patients, with higher rates associated with larger breasts, previous breast surgery, previous radiation, and active smoking. The nipple delay (ND) procedure is known to improve viability of the NAC in NSM patients with high-risk factors. Methods: A single-institution retrospective review was done of patients who underwent ND and NSM or NSM alone from 2012 to 2022. Patient demographics, risk factors, and outcomes were compared. Results: Forty-two breasts received ND-NSM and 302 breasts received NSM alone. The ND-NSM group had significantly more high-risk factors, including elevated BMI (26.3 versus 22.9; P < 0.001), elevated prior breast surgery (50% versus 25%; P < 0.001), and greater mastectomy specimen weight (646.6 versus 303.2 g; P < 0.001). ND-NSM was more likely to have undergone preparatory mammoplasty before NSM (27% versus 1%; P < 0.001). There was no delay in NSM treatment from decision to pursue NSM (P = 0.483) or difference in skin necrosis (P = 0.256), NAC necrosis (P = 0.510), hematoma (P = 0.094), seroma (P = 0.137), or infection (P = 0.437) between groups. ND-NSM and NSM patients differed in total NAC necrosis (0% versus 3%) and implant loss (0% vs 13%), but not significantly. Conclusions: We demonstrated no NAC necrosis and no significant delay of treatment in higher risk ND-NSM patients. ND may allow higher risk patients to undergo NSM with similar morbidity as lower risk patients.

Dosimetry and Toxicity Outcomes in Patients Treated with Hypofractionated Regional Nodal Irradiation for Breast Cancer: What is the Best Dose-Volume Limit to Minimize Risks of Radiation Pneumonitis?

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.

Eliminating breast surgery for invasive breast cancer in exceptional responders to neoadjuvant systemic therapy: a multicentre, single-arm, phase 2 trial.

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).