Quality-of-Life Outcomes from NRG/NSABP B-39/RTOG 0413: Whole-breast Irradiation vs Accelerated Partial-breast Irradiation after Breast Conserving Surgery.

PURPOSE: NRG Oncology (NRG)/NSABP B-39/RTOG 0413 compared whole-breast irradiation (WBI) to accelerated partial-breast irradiation (APBI). APBI was not equivalent to WBI in local tumor control. Secondary outcome was Quality-of-life (QOL). METHODS: The QOL sub-study used validated self-report questionnaires including the Breast Cancer Treatment Outcome Scale (BCTOS) and SF-36 vitality scale. Assessments occurred: before randomization, at treatment completion (chemotherapy or radiotherapy), 4-weeks later, at 6-, 12-, 24-, and 36-months. Primary aims: cosmesis change equivalency (baseline to 3 years; a priori margin of equivalence 0.4 standard deviations) and fatigue change superiority (baseline to end-of-treatment (EOT)) for APBI vs WBI, by patient groups treated with or without chemotherapy when appropriate. RESULTS: From 3/21/05-5/25/09, 975 patients enrolled in this sub-study; 950 had follow-up data. APBI had 3-year cosmesis equivalent to WBI (95%CI,-0.0001-0.16; equivalence margin -0.22-0.22) in all patients. The APBI group without chemotherapy had less EOT fatigue (p = .011; mean score APBI 63 vs WBI 59); APBI group receiving chemotherapy had worse EOT fatigue (p = .011; APBI 43 vs WBI 49). The APBI group reported less pain (BCTOS) at EOT (WBI 2.29 vs APBI 1.97), but worse pain at 3-years (WBI 1.62 vs APBI 1.71). APBI patients reported greater convenience of care than with WBI and reported less symptom severity at EOT and 4-weeks later. CONCLUSION: Cosmetic outcomes were similar for APBI and WBI groups, with small statistically significant differences in other outcomes that varied over time. Differences in fatigue and other symptoms appeared to resolve by ≥ 6 months. APBI may be preferred by some patients, for whom extended treatment is burdensome.

Feasibility of breast conserving surgery alone in HER2-positive exceptional responders to neoadjuvant systemic therapy.

It is unknown if radiation therapy provides additional benefit among patients who achieve pathologic complete response (pCR) following neoadjuvant systemic therapy (NST). We sought to assess feasibility of radiation omission after breast conserving surgery in early-stage, node-negative, HER2+ breast cancer patients with pCR after NST. This was a single-arm study of women 30 years and older with cT2N0 disease based on imaging. Six patients were followed with mammography or MRI every 6 months following surgery. The median age of patients was 58 years (IQR: 46-66). At a median follow-up of 31.6 months (range: 21-40 months), no Ipsilateral Breast Tumor Recurrences (IBTR) were identified. This approach was found to be feasible, warranting further study in larger prospective trials.

Defining Breast Cryoablation Treatment Success: A Guide for the Curative and Palliative Treatment of Breast Cancer.

RATIONALE AND OBJECTIVES: Recent ICE3 trial of breast cryoablation for breast cancer demonstrated 98% success rate, similar to breast-conserving surgery. However, ICE3 and other published studies did not differentiate curative from palliative treatment nor define patient-specific treatment objectives. We sought to define treatment success of curative and palliative breast cryoablation for breast cancer in meeting procedure objectives and patient-specific treatment objectives. MATERIALS AND METHODS: We conducted a retrospective analysis of breast cancer patients who underwent breast cryoablation during 2021-2024. Breast radiologists performed outpatient cryoablation using local anesthesia and argon gas cryoprobes under ultrasound or MRI guidance. Patient demographics, referral indications, tumor characteristics, procedure details, and imaging follow-up findings were analyzed. Cryoablation was categorized as curative or palliative. Treatment success was defined as achievement of both procedure and patient-specific treatment objectives. RESULTS: Breast cryoablation was performed for 34 lesions in 29 patients with N0M0 (n = 25), N1M0 (n = 2), N2M0 (n = 1), and N0M1 (n = 1) disease. Most tumors were invasive ductal carcinoma (IDC), low to intermediate grade, estrogen receptor (ER) and progesterone receptor (PR) positive and HER2 negative (23 tumors, 68%). Tumor size ranged from 0.4-1.9 (median 0.8) cm for curative cryoablation and 0.6-6.0 (median 1.3) cm for palliative cryoablation. For 27 patients with follow-up imaging, ablation was curative in 14 patients, 14 tumors and palliative in 13 patients, 18 lesions. Imaging follow-up time ranged from 3 to 26 (median 16) months, > 12 months in 22 of 27 patients and 25 of 32 tumors. Complications were limited to 2 cases of skin frost injury, 1 mild and 1 moderate. Treatment success was achieved in 13 of 14 patients with curative and all 13 patients with palliative cryoablation. CONCLUSION: Our study defines treatment success for curative and palliative breast cryoablation, demonstrates breast cryoablation achieves not only procedure (technical) but also patient-specific treatment objectives without significant complications, and may serve as guide for integrating breast cryoablation in the treatment of breast cancer patients.

Monitoring response to neoadjuvant chemotherapy in triple negative breast cancer using circulating tumor DNA.

BACKGROUND: Triple negative breast cancer (TNBC) is an aggressive subtype with poor prognosis. We aimed to determine whether circulating tumor DNA (ctDNA) and circulating tumor cell (CTC) could predict response and long-term outcomes to neoadjuvant chemotherapy (NAC). METHODS: Patients with TNBC were enrolled between 2017-2021 at The University of Texas MD Anderson Cancer Center (Houston, TX). Serial plasma samples were collected at four timepoints: pre-NAC (baseline), 12-weeks after NAC (mid-NAC), after NAC/prior to surgery (post-NAC), and one-year after surgery. ctDNA was quantified using a tumor-informed ctDNA assay (SignateraTM, Natera, Inc.) and CTC enumeration using CellSearch. Wilcoxon and Fisher's exact tests were used for comparisons between groups and Kaplan-Meier analysis used for survival outcomes. RESULTS: In total, 37 patients were enrolled. The mean age was 50 and majority of patients had invasive ductal carcinoma (34, 91.9%) with clinical T2, (25, 67.6%) node-negative disease (21, 56.8%). Baseline ctDNA was detected in 90% (27/30) of patients, of whom 70.4% (19/27) achieved ctDNA clearance by mid-NAC. ctDNA clearance at mid-NAC was significantly associated with pathologic complete response (p = 0.02), whereas CTC clearance was not (p = 0.52). There were no differences in overall survival (OS) and recurrence-free survival (RFS) with positive baseline ctDNA and CTC. However, positive ctDNA at mid-NAC was significantly associated with worse OS and RFS (p = 0.0002 and p = 0.0034, respectively). CONCLUSIONS: Early clearance of ctDNA served as a predictive and prognostic marker in TNBC. Personalized ctDNA monitoring during NAC may help predict response and guide treatment.

Residual Nodal Burden After Neoadjuvant Chemotherapy in cN1 Breast Cancer Patients with Positive Nodes at Targeted Axillary Dissection.

BACKGROUND: Targeted axillary dissection (TAD) facilitates nodal staging in cN1 breast cancer after neoadjuvant chemotherapy (NAC). Completion axillary node dissection (cALND) remains the standard of care for TAD-positive patients. This study investigated factors associated with additional positive nodes at cALND (cALND+) and the impact on the residual cancer burden (RCB). METHODS: Retrospective review of cN1 breast cancer patients treated with NAC and TAD was conducted from July 2013 to June 2023. The review defined cN1 status by ultrasound (US) and biopsy. Patient, tumor, and treatment characteristics were evaluated. Multivariate analysis was performed to identify factors associated with cALND+, and RCB was calculated. RESULTS: Of 902 patients who underwent TAD, 554 (61.4%) were TAD-positive. 457 underwent cALND, and 124 (27%) were cALND+ (average 4.1 additional +nodes). The cALND+ patients had larger primary tumors at diagnosis (4 vs 3.5 cm; p = 0.04), more than three suspicious nodes on initial US (30% vs 13%; p ≤ 0.0001), larger residual primary tumors on pathology (median, 3 vs 2.1 cm; p = 0.0004), and more positive TAD nodes (median, 2 vs 1; p ≤ 0.0001). In the multivariate analysis, the factors associated with cALND+ were more than three suspicious nodes on initial US (odds ratio [OR], 2.9; p ≤ 0.0001), more positive TAD nodes (OR, 1.1; p ≤ 0.0001), larger clipped node metastasis (OR, 1.1; p ≤ 0.0001), and larger residual tumor on pathology (OR, 1.1; p = 0.006). Of 65 cALND+ patients with RCB class I or II, 29 (45%) had an increase in RCB based on cALND. CONCLUSION: Of cN1 breast cancer patients treated with NAC who are TAD-positive, approximately 25% will have additional nodal disease on cALND. In these patients, positive cALND is associated with greater disease burden, which has potential implications for RCB status and prognosis.

Clinical Outcomes for BRCA Pathogenic Variant Carriers With Breast Cancer Undergoing Breast Conservation.

Importance: Although most women with BRCA-associated breast cancer choose bilateral mastectomy, current guidelines support breast-conserving therapy as an option. As the indications for genetic testing expand and targeted therapies emerge, understanding the outcomes of breast-conserving therapy in the population of patients choosing breast conservation is important. Objective: To describe the clinical outcomes of women with BRCA-associated breast cancer who were treated with breast-conserving therapy, including the risks of ipsilateral and contralateral cancer events and bilateral mastectomy-free survival. Design, Setting, and Participants: This cohort study conducted at a single-institution academic national comprehensive cancer center included 172 women identified from a prospectively maintained database who had pathogenic BRCA1/2 variants and were treated with breast-conserving therapy from January 1, 1977, to December 31, 2021. Main Outcomes and Measures: Clinical and pathologic characteristics for patients with BRCA1 and BRCA2 were compared, and estimates of overall survival, bilateral mastectomy-free survival, distant disease-free survival, risk of ipsilateral breast cancer, and risk of contralateral cancer were computed. Results: The cohort included 172 women (mean [SD] age, 47.1 [11.7] years), with 42 (24.4%) receiving a diagnosis of breast cancer prior to 40 years of age. Compared with BRCA2 variant carriers (80 [46.5%]), women with BRCA1 variants (92 [53.5%]) were younger at breast cancer diagnosis and tended to have more advanced tumors, which were more likely to be hormone receptor negative and higher grade. At a median follow-up of 11.8 years (IQR, 5.7-18.2 years), estimates of 10-year survival and risk were: overall survival, 88.5% (95% CI, 83.1%-94.2%); bilateral mastectomy-free survival, 70.7% (95% CI, 63.3%-78.9%); risk of an ipsilateral breast cancer event, 12.2% (95% CI, 5.8%-18.2%); and risk of contralateral cancer, 21.3% (95% CI, 13.3%-28.6%). Risks continued to increase after 10 years of follow-up. Conclusions and Relevance: In this cohort study, although women with breast cancer and pathogenic BRCA1/2 variants treated with breast-conserving therapy had above-average risks of ipsilateral and contralateral breast cancer events, most did not have another cancer event and remained bilateral mastectomy free. These findings may be useful for informing patients with BRCA variants choosing breast conservation.

Premastectomy Radiotherapy and Immediate Breast Reconstruction: A Randomized Clinical Trial.

Importance: Premastectomy radiotherapy (PreMRT) is a new treatment sequence to avoid the adverse effects of radiotherapy on the final breast reconstruction while achieving the benefits of immediate breast reconstruction (IMBR). Objective: To evaluate outcomes among patients who received PreMRT and regional nodal irradiation (RNI) followed by mastectomy and IMBR. Design, Setting, and Participants: This was a phase 2 single-center randomized clinical trial conducted between August 3, 2018, and August 2, 2022, evaluating the feasibility and safety of PreMRT and RNI (including internal mammary lymph nodes). Patients with cT0-T3, N0-N3b breast cancer and a recommendation for radiotherapy were eligible. Intervention: This trial evaluated outcomes after PreMRT followed by mastectomy and IMBR. Patients were randomized to receive either hypofractionated (40.05 Gy/15 fractions) or conventionally fractionated (50 Gy/25 fractions) RNI. Main Outcome and Measures: The primary outcome was reconstructive failure, defined as complete autologous flap loss. Demographic, treatment, and outcomes data were collected, and associations between multiple variables and outcomes were evaluated. Analysis was performed on an intent-to-treat basis. Results: Fifty patients were enrolled. Among 49 evaluable patients, the median age was 48 years (range, 31-72 years), and 46 patients (94%) received neoadjuvant systemic therapy. Twenty-five patients received 50 Gy in 25 fractions to the breast and 45 Gy in 25 fractions to regional nodes, and 24 patients received 40.05 Gy in 15 fractions to the breast and 37.5 Gy in 15 fractions to regional nodes, including internal mammary lymph nodes. Forty-eight patients underwent mastectomy with IMBR, at a median of 23 days (IQR, 20-28.5 days) after radiotherapy. Forty-one patients had microvascular autologous flap reconstruction, 5 underwent latissimus dorsi pedicled flap reconstruction, and 2 had tissue expander placement. There were no complete autologous flap losses, and 1 patient underwent tissue expander explantation. Eight of 48 patients (17%) had mastectomy skin flap necrosis of the treated breast, of whom 1 underwent reoperation. During follow-up (median, 29.7 months [range, 10.1-65.2 months]), there were no locoregional recurrences or distant metastasis. Conclusions and Relevance: This randomized clinical trial found PreMRT and RNI followed by mastectomy and microvascular autologous flap IMBR to be feasible and safe. Based on these results, a larger randomized clinical trial of hypofractionated vs conventionally fractionated PreMRT has been started (NCT05774678). Trial Registration: ClinicalTrials.gov Identifier: NCT02912312.

Long-Term Outcomes and Predictors of Response in Breast Cancer Patients with Advanced Nodal Involvement.

BACKGROUND: Advanced nodal disease is associated with poor prognosis. However, modern neoadjuvant systemic therapy (NST) regimens have resulted in higher pathologic complete response (pCR) rates, which are associated with improved survival. We sought to assess contemporary outcomes in patients with advanced nodal involvement and response to NST. STUDY DESIGN: We conducted a single-institution, retrospective study of 521 patients with cN2-3 primary nonmetastatic breast cancer treated with NST followed by surgery and radiation from 2012 to 2018. Descriptive statistics, multivariate Cox regression, and Kaplan-Meier analyses were performed. RESULTS: The mean age was 50.5 years, and median follow-up was 61 (4.7 to 197) months. The majority of patients had hormone receptor-positive (HR+)/HER2-negative tumors (HER2-; n = 242, 47.8%). Most were cT2 (n = 243; 46.6%) or cT3 (n = 139; 26.7%) and 73.3% (n = 382) had cN3 disease. Rate of axillary pCR was 34.2%, and breast and axillary pCR was 19.4% (n = 101). Event-free survival (EFS) at 5 years was 75.1% (95% CI, 0.71 to 0.79). Rate of locoregional recurrence was 6.7%; distant metastatic rate was 29.4%. Axillary pCR with or without breast pCR was significantly associated with longer EFS (p = 0.001). Achieving breast/axillary pCR was an independent predictor of improved EFS (hazard ratio 0.22, p < 0.0001). Having triple-negative disease was associated with worse EFS (hazard ratio 1.74, p = 0.008). CONCLUSIONS: In a high-risk cohort of patients with cN2-3 disease, trimodality therapy was effective in achieving durable EFS. Approximately one-third of patients achieved axillary pCR, which was associated with improved survival. Further studies are needed to accurately determine axillary response in cN2-3 breast cancer after NST in order to develop de-escalation strategies to reduce morbidity associated with axillary surgery.

Axillary Nodal Metastases Conversion and Perioperative Complications with Neoadjuvant Pembrolizumab Therapy in Triple-Negative Breast Cancer.

BACKGROUND: Triple-negative breast cancer (TNBC) is known to portend a worse prognosis compared with same-stage, hormone receptor-positive disease. However, with the recent change in practice to include pembrolizumab in neoadjuvant chemotherapy (NAC) for TNBC, an increase in pathologic complete responses (pCRs) has been reported. The perioperative repercussions of adding pembrolizumab to standard NAC regimens for TNBC are currently unknown. We aimed to explore the perioperative implications of adding pembrolizumab to standard NAC regimens for non-metastatic TNBC. METHODS: This was a retrospective review of the perioperative outcomes in patients with non-metastatic TNBC treated with pembrolizumab-NAC from January 2018 to October 2022 conducted at a high-volume cancer center. Patient demographics, comorbidities, clinical and pathological staging, NAC treatment regimen, initiation, and completion, as well as date of surgery and postoperative complications were analyzed. RESULTS: Of 87 patients, 67.8% had an overall pCR and 86% had an axillary pCR; 37.2% of cN+ patients were spared from axillary lymph node dissection. However, 24.1% of patients experienced surgical complications, 9% of patients were receiving steroids at the time of breast surgery secondary to adverse effects of pembrolizumab-NAC, and 7% underwent a change in the initial surgical plan such as omission of reconstruction. CONCLUSION: Pembrolizumab-NAC has not only significant oncologic benefit but also noteworthy perioperative implications in the surgical management of TNBC.

Patient Interest in Exploring Nonsurgical Treatment Approaches for Early-Stage Breast Cancer: A Qualitative Study.

PURPOSE: Advances in radiation therapy have enabled the ability to deliver ablative treatments, but there has been limited application of these treatments to early-stage breast cancers with a goal of omitting surgery. The purpose of this study was to explore patient interest in pursuing nonsurgical treatment approaches for their early-stage breast cancer. METHODS AND MATERIALS: We conducted a qualitative study involving interviews with 21 patients with early-stage breast cancer who were eligible for participation in a phase 2 clinical trial offering omission of definitive surgery. Interviews were transcribed and an inductive, thematic analysis was performed by 3 independent reviewers to generate themes and subthemes. RESULTS: Data analysis revealed the following factors that affected patient willingness and desire to explore nonsurgical treatment options: (1) perceptions and feelings about their cancer; (2) current quality of life and the level of support available in their daily life; (3) external conversations focusing on family members' and friends' experiences with cancer and/or cancer treatments; (4) personal health care experiences, including their current breast cancer diagnosis; (5) perceptions and feelings about their physicians; (6) conversations with their physicians about their treatment options; and (7) self-identified desire to direct care decisions. Specifically, patients verbalized fearing surgery and surgical recovery; wanting to preserve their breast(s); the prior negative surgical experiences of friends, family, and themselves; a desire to receive treatment per the latest research; wanting to match the level of treatment with the severity of their cancer; and other comorbidities as reasons for wanting to explore omitting surgery. CONCLUSIONS: Our findings demonstrate an unmet need directed by patient interest to explore nonsurgical options for early-stage, biologically favorable breast cancer. These results may shape conversations around shared decision-making and clinical trial design, and result in more personalized treatment options for women with early-stage breast cancer.

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.

Extremely Low Incidence of Local-Regional Recurrences Observed Among T1-2 N1 (1 or 2 Positive SLNs) Breast Cancer Patients Receiving Upfront Mastectomy Without Completion Axillary Node Dissection.

BACKGROUND: Completion axillary node dissection (CLND) is routinely omitted in cT1-2 N0 breast cancer treated with upfront, breast-conserving therapy and sentinel node biopsy (SLNB) showing one to two positive sentinel nodes (SLNs). The purpose of this study was to determine the incidence and impact of axillary treatment among patients treated with mastectomy in a contemporary cohort. METHODS: A prospective, institutional database was reviewed from 2006 to 2015 to identify patients with T1-2 breast cancer treated with upfront mastectomy and SLNB found to have one to two positive SLNs. Patients were stratified by axillary therapy [including CLND and/or post-mastectomy radiation therapy (PMRT)], and clinicopathologic factors and incidence rates of local-regional and distant recurrence were analyzed. RESULTS: A total of 548 patients were identified, including 126 (23%) without CLND. Rates of PMRT were similar between those with and without CLND (35.3% vs. 28.6%, p = 0.16). On multivariate analysis, two rather than one positive SLN, larger SLN metastasis size, frozen-section analysis of the SLNB, and adjuvant chemotherapy were significantly associated with receipt of CLND. At a median follow-up of 7 years, there were only two local-regional recurrences in the no-CLND group, of which only one was an axillary recurrence. The 5-years incidence rate of LRR was not significantly different for those with and without CLND (1.3% vs. 1.8%, p = 0.93). CONCLUSIONS: We found extremely low rates of local-regional recurrence among those with T1-2 breast cancer undergoing upfront mastectomy with 1-2 positive SLNs. Further axillary surgery may not be indicated in selected patients treated with a multidisciplinary approach, including adjuvant therapies.

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.

Effectiveness Without Efficacy: Cautionary Tale from a Landmark Breast Cancer Randomized Controlled Trial.

Background: "Old" randomized controlled trials established breast conserving therapy (BCT) and total mastectomy (TM) equivalence for treating early breast cancer, whereas recent literature report improved survival with BCT. To reconcile this, we performed a simulation study and re-analyzed B-06 trial data. Methods: We estimated the distributions for overall survival (OS), cumulative incidence functions for breast-cancer-specific death (BCSD) and other causes-specific death (OCSD) by BCT and TM. The restricted mean survival time (RMST) difference and hazard ratio between the two arms were estimated. Given the estimated distributions, we simulated cause-specific death times from each arm, evaluating the power to test treatment difference in OS, BCSD, and OCSD with different sample sizes, follow-up times, and a modified setting by simulating BCT-arm OCSD times from the distribution of patients not receiving radiation. Results: With 200 months follow-up, the average BCT-over-TM gain measured by RMST was 3.7 months for OS and 4.5 months for BCSD. Increasing the trial size to 5,000 per arm, there is a 79.2% chance to detect the OS benefit with RMST and 92.4% for BCSD. A nonproportional increase of OCSD in BCT compared to TM was observed after 144 months, and particularly after 200 months post treatments. When OCSD times of BCT were simulated using patients not receiving radiation, the estimated OS gain increased to 4.4 months, and the power increased to 92.2%. Conclusions: The late excess other-cause-death, likely due to radiation, in the BCT arm and sample size constraints limited the power to report BCT superiority. Given radiation delivered in the era of B-06 trial, BCT and TM remain largely equivalent.

Predictors of Emergency Room Visits After Ambulatory Breast Cancer Surgery in the Medicare Population.

BACKGROUND: Emergency department (ED) overuse is a large contributor to healthcare spending in the USA. We examined the rate of and risk factors for ED visits following outpatient breast cancer surgery. PATIENTS AND METHODS: Using linked data from the Surveillance, Epidemiology, and End Results (SEER) program and Medicare, we identified women who underwent curative breast cancer surgery between 2003 and 2015. Our outcome of interest was ED visits within 30 days of surgery. Multivariate regression was used to evaluate the odds of ED visit while controlling for clinical and socioeconomic variables. Secondary analyses assessed admission from the ED as well as costs. RESULTS: Of the 78,060 included patients, 5.1% returned to the ED, of which only 29.8% required hospital admission. Rate of ED visits increased with patient age. A higher percentage of Black patients returned to the ED compared with white patients (7.0% versus 5.0%, p < 0.001). Patients with higher income were less likely to visit the ED compared with those with lower income (OR 0.76, p < 0.001). Predictors of ED visits included: being unmarried (OR 1.18, p < 0.001), having stage 2 (OR 1.20, p < 0.001) or stage 3 cancer (OR 1.38, p < 0.001), and those with Charlson comorbidity score of 1 (OR 1.39, p < 0.001) or ≥ 2 (OR 2.29, p < 0.001). CONCLUSION: While a substantial number of patients return to the ED following outpatient breast surgery, most do not require hospital admission, which indicates that a large proportion of these visits could have been avoided. We identified several clinical and socioeconomic predictors of postoperative ED visits, which will aid in the development of patient risk profiling tools.

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).