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Background: Immediate lymphatic reconstruction (ILR) via lymphovenous anastomosis is performed in patients undergoing axillary lymph node dissection (ALND) to minimize the risk of lymphedema. Following ALND, drains are placed to prevent seromas, while prolonged drain days are associated with increased risk of infection. The study aim was to determine the impact of ILR on the number of drain days following ALND in patients with breast cancer. Methods: We report a post-hoc analysis of a prospective trial (April 2018-January 2023) comparing patients with breast cancer who underwent ALND with ILR (intervention arm) vs ALND without ILR (control arm). Wilcoxon rank sum test and chi-squared or Fisher’s exact tests compared continuous and categorical variables, respectively. Multivariable quantile regression models evaluated the difference in drain days and days until drain removal criteria were met with covariates adjusted. Results: Data from 214 patients were analyzed (n = 115 interventional arm, n = 99 control arm). The intervention arm had a median of 15 axillary drain days compared to 11 days in the control arm ( P = .001). There was no significant difference between groups when measuring drain days based on the date the drain met removal criteria, rather than actual drain removal date. Seroma incidence was lower in the intervention arm (3.5%) vs the control arm (12.1%) ( P = .017) without a statistical difference in incidence of infection. Conclusion: ALND with ILR does not decrease the number of drain days compared to ALND without ILR in patients with breast cancer, although we found the incidence of seromas to be lower without increase in incidence of infection.

PURPOSE Adjuvant endocrine therapy (ET) improves overall survival (OS) in estrogen receptor (ER)–positive early-stage breast cancer (BC). However, the benefit of ET for those with ER-low BC (ER 1%-10%) is unclear. METHODS Using the National Cancer Database, we studied patients with high-risk stage I to III, ER-low BC (defined as immunohistochemistry 1%-10%) who received (neo)adjuvant chemotherapy and did or did not initiate ET. OS was analyzed with ET initiation as a time-dependent covariate using Cox proportional hazards regression. RESULTS Of 10,362 patients with stage I to III ER-low BC, 7,018 received chemotherapy and met inclusion criteria. ET omission was 42% at 12 months and more common in patients with tumors that were progesterone receptor–negative, human epidermal growth factor receptor 2–negative, higher-grade (grade 2/3) and higher Ki-67 (≥20%; all P < .001) and those who received neoadjuvant chemotherapy (NAC; P < .001). With a median follow-up of 3 years, 586 deaths were observed. In a multivariable analysis, ET omission was associated with a higher risk of death (hazard ratio [HR], 1.23 [95% CI, 1.04 to 1.46]; P = .02), with a greater impact in those with higher ER levels: ER 1%-5% (HR, 1.15 [95% CI, 0.91 to 1.45]; P = .24) versus ER 6%-10% (HR, 1.42 [95% CI, 1.00 to 2.02]; P = .048). Among patients treated with NAC (n = 4,377, 62%), ET omission was associated with worse OS in those with residual disease (RD; HR, 1.26 [95% CI, 1.00 to 1.57]; P = .046) but not in those who achieved a pathologic complete response (HR, 1.06 [95% CI, 0.62 to 1.80]; P = .84). CONCLUSION In ER-low, early-stage BC, ET omission is associated with significantly worse OS, especially in patients with RD after NAC and those with higher (6%-10%) ER levels. Until prospective data are available, patients with ER-low BC should be counseled regarding the potential benefit of ET.

Importance Neoadjuvant systemic therapy (NST) has been associated with pathologic complete response (pCR) in up to 60% of breast cancers (BCs). The findings of this trial question the necessity of surgery. Objective To report preplanned 5-year efficacy outcomes evaluating radiotherapy alone without breast surgery in patients selected with image-guided vacuum assisted biopsy (VAB). Design, Setting, and Participants This single-arm, prospective, phase 2 nonrandomized clinical trial was conducted at 7 US medical centers and included women 40 years or older with cT1-2N0-1M0 ERBB2 -positive (formerly HER2 -positive) or triple-negative invasive BC who showed residual breast lesions after NST of less than 2 cm on imaging. Enrollment was from March 6, 2017, to November 9, 2021. Data analysis was from October to December 2024. Intervention Image-guided VAB of the tumor bed (9G with a minimum of 12 cores) was performed after standard NST. Patients with clinically node-negative disease at diagnosis and no residual cancer in the breast on post-NST VAB underwent whole-breast radiotherapy with a boost without breast or axillary surgery. Patients with initial documented nodal disease and a breast pCR on VAB underwent targeted axillary dissection, while those with residual cancer when undergoing VAB had standard breast and axillary surgery. Patients were monitored with physical examinations and mammography every 6 months. Main Outcome Measures The primary outcome was ipsilateral breast tumor recurrence. Results Fifty patients (median [IQR] age, 62 [55-77] years) were enrolled and underwent post-NST VAB. Twenty-nine (58%) and 21 (42%) patients had ERBB2 -positive and triple-negative invasive BC, respectively. Breast pCR on VAB was identified in 31 patients (62%; 95% CI, 47.2%-75.34%), and axillary pCR was identified among all 8 patients with initial nodal metastases and breast pCR on VAB who underwent targeted axillary dissection. At a median follow-up of 55.4 (IQR, 44.0-63.5) months, the ipsilateral breast tumor recurrence rate was 0%, and disease-free and overall survival rates were 100% for patients without breast surgery. Conclusions and Relevance The results of this nonrandomized clinical trial that reported preplanned 5-year outcomes suggest that omission of breast surgery in select patients after NST may be feasible, with no recurrences seen. More confirmatory studies are necessary before this new approach alters surgical practice. Trial Registration ClinicalTrials.gov Identifier: NCT02945579

PURPOSE Over 50% of households in the United States have at least one musician—many musicians are also breast cancer survivors. This group has not been well studied, and given the level of fine sensory-motor skill required for musicianship, we hypothesized that musicians experience unique manifestations of breast cancer treatment toxicities. METHODS A nine-item Musical Toxicity Questionnaire (MTQ) was distributed to patients who had consented to participate in the Mayo Clinic Breast Cancer Registry. The MTQ screened participants by asking if they played a musical instrument or sang in the last 10 years: questions populated for those who answered yes. Respondents were asked if they noticed difficulty with their musical endeavor during or after breast cancer treatment, defined as acute musical toxicity (AMT). The questionnaire asked which side effect and cancer-directed therapy most influenced musical ability, what musical attributes were affected, and the timeline of resolution. Multivariable and classification tree analyses assessed relationships between AMT and treatment characteristics. RESULTS Of 1,871 survey respondents, 29% (535/1,871) self-identified as musicians. Over a quarter (27%, 144/535) reported AMT, and for 57% (82/144), AMT had not resolved at the time of survey. Of the treatments each participant received, chemotherapy was most often reported as most negatively impactful (63/89 who received chemotherapy, 71%). Decreased endurance was the most common musical difficulty (64% of those with AMT, 92/144), followed by decreased accuracy, trouble playing/singing quickly, and difficulty using proper technique. Multivariable and classification tree analyses revealed that receipt of chemotherapy was most strongly correlated with AMT. CONCLUSION These results will help oncology care teams counsel musicians, answer questions about impacts on musicality, and provide a timeline for resolution of musical symptoms.

Abstract Chemotherapy regimens for triple-negative breast cancer (TNBC) combine agents without knowing which agents drive response. Consequently, predictors derived from multi-agent regimens cannot be assumed to generalize to individual drugs or other regimens, motivating development of treatment-matched predictors. Here, we used TNBC patient-derived xenografts (PDXs) treated with carboplatin, docetaxel, or the combination to deconvolute drug-specific responses and identify associated molecular features. Combination treatment rarely improved upon the best single agent, with enhanced responses in only 13% of PDXs and antagonism in a comparable fraction. Proteogenomic analyses identified high cytokeratin-5 (KRT5) as a general marker of chemotherapy responsiveness and KRT5 immunohistochemistry discriminated responsive PDXs (AUROC, 0.83). To train treatment-specific predictors, we integrated these data with independent PDX and clinical cohorts with responses assessed after anthracycline-free platinum, taxane, or platinum-taxane therapy, ensuring response corresponded to the modeled treatment. Four feature selection strategies yielded largely nonoverlapping biomarker panels converging on treatment-relevant pathways. On independent test data, RNA-based predictors of complete response (CR) to platinum-based (carboplatin or cisplatin) and taxane-based (docetaxel or paclitaxel) chemotherapy achieved AUROCs of 0.80 and 0.86, respectively. For platinum-taxane regimens (carboplatin plus docetaxel or paclitaxel), proteomic-guided feature selection generated a 10-biomarker, protein- informed RNA predictor of pathologic complete response (pCR) that outperformed RNA-only feature selection and achieved an AUROC of 0.85 in an independent clinical cohort, while retaining practicality as an RNA-based assay. Treatment-matched integration of multi-omic PDX and clinical datasets provides a framework for chemotherapy-specific predictors with clinically relevant performance, supporting biomarker-guided precision selection and treatment optimization for patients with TNBC. Statement of significance Integration of multi-omic data from patient-derived xenografts with treatment-matched clinical cohorts yielded three retrospectively validated predictors of platinum, taxane, and platinum+taxane response, enabling biomarker-guided chemotherapy selection for patients with triple-negative breast cancer.

The National Cancer Database (NCDB) collects data from approximately 1,500 Commission on Cancer (CoC) facilities and represent 73.7% of newly diagnosed cancers nationwide. The American College of Surgeons Cancer Program developed it first annual report from the NCDB 2021 participant user file reporting new observations and recent trends of cancer diagnoses, patient demographics, and treatments as well as an in-depth report on treatment and outcomes in breast, pancreas, and colon cancers. Of the 1,328,131 cancers diagnosed in 2021 at 1,281 reporting CoC hospitals, one-fifth continue to be female breast cancer. In 2021, the NCDB’s 5 most common adult cancers were breast, prostate, lung, colon, and melanoma and varied by patient sex. Use of neoadjuvant systemic therapy increased in recent years in pancreas, breast, and urinary bladder cancer, although a slight decrease in pancreas and breast cancer was observed in 2021. Breast cancer has high survival rates, especially in lower-stage disease and estrogen receptor-positive/human epidermal growth factor receptor 2-negative disease. There is increase in neoadjuvant systemic therapy use, especially in human epidermal growth factor receptor 2-positive disease and estrogen receptor-negative disease. Colon cancer presents most commonly as stage III or II with a primary in the cecum or ascending colon in 38.9%. The majority are microsatellite instability stable, Kirsten rat sarcoma viral oncogene homologue normal, and CEA positive. Survival is most dependent on stage but also associated with microsatellite instability stability, abnormal Kirsten rat sarcoma viral oncogene homologue, and positive CEA. Pancreatic cancer presents with stage IV disease in nearly half, although an increase in stage I disease is seen. The most common location is pancreatic head. Survival is relatively low and most dependent on stage.

ImportanceThe American College of Surgeons (ACS) operative standards were established to detail critical elements of cancer surgery, reduce technical variation, and improve outcomes. Two of the 6 operative standards target adequate axillary surgery for breast cancer. The potential association of the operative standards with short-term oncologic outcomes, such as nodal yield and nodal positivity rates, is currently unknown.ObjectiveTo evaluate the potential association of the ACS operative standards with short-term oncologic outcomes in breast cancer.Design, Setting, and ParticipantsA cohort study was performed using data on 1 201 317 women 18 years or older who underwent sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND) for invasive breast cancer from January 1, 2012, to December 31, 2020. Patients were identified using the National Cancer Database (NCDB), a clinical oncology database encompassing approximately 70% of new cancer diagnoses, sourced from hospital registry data from 1317 facilities. Statistical analysis was performed from October 2023 to June 2024.ExposureSentinel lymph node biopsy or ALND.Main Outcomes and MeasuresReliability-adjusted facility-level lymph node yield and nodal positivity rate for each procedure were calculated using generalized linear mixed models, Poisson regression, and logistic regression with facility-level random intercepts.ResultsThe cohort included 1 201 317 women with a median age of 62 years (IQR, 53-70 years). Facility-level nodal yield ranged from 1 to 6 for SLNB and from 6 to 22 for ALND. Median facility-level nodal yield for SLNB was 2.6 (IQR, 2.3-3.0) and the nodal positivity rate for SLNB was 12.2% (IQR, 11.0%-13.7%), with rates ranging from 6% to 21%. A weak correlation between facility-level lymph node yield and nodal positivity was observed (Spearman correlation coefficient, 0.17). Median nodal upstaging rate (≥4 positive nodes) for ALND was 30.5% (IQR, 26.5%-35.0%), with rates ranging from 11% to 54%; median nodal yield was 12.2 (IQR, 10.9-13.6). A strong correlation between nodal yield and nodal upstaging rates was observed (Spearman correlation coefficient, 0.53).Conclusions and RelevanceIn this cohort study of women undergoing axillary surgery for invasive breast cancer, facility-level variation in lymph node yield was present for both SLNB and ALND, which could potentially be improved through the ACS operative standards. However, this variation had mixed associations with nodal positivity and upstaging rates, suggesting the association of the ACS operative standards with oncologic outcomes may be mixed.

PURPOSE The nodal burden of patients with residual isolated tumor cells (ITCs) in the sentinel lymph nodes (SLNs) after neoadjuvant chemotherapy (NAC) (ypN0i+) is unknown, and axillary management is not standardized. We investigated rates of additional positive lymph nodes (LNs) at axillary lymph node dissection (ALND) and oncologic outcomes in patients with ypN0i+ treated with and without ALND. METHODS The Oncoplastic Breast Consortium-05/ICARO cohort study (ClinicalTrials.gov identifier: NCT06464341 ) retrospectively analyzed data from patients with stage I to III breast cancer with ITCs in SLNs after NAC from 62 centers in 18 countries. The primary end point was the 3-year rate of any axillary recurrence. The rate of any invasive recurrence was the secondary end point. RESULTS In total, 583 patients were included, of whom 182 (31%) had completion ALND and 401 (69%) did not. The median age was 48 years. Most patients (74%) were clinically node-positive at diagnosis and 41% had hormone receptor–positive/human epidermal growth factor receptor 2–negative tumors. The mean number of SLNs with ITCs was 1.2. Patients treated with ALND were more likely to present with cN2/3 disease (17% v 7%, P < .001), have ITCs detected on frozen section (62% v 8%, P < .001), have lymphovascular invasion (38% v 24%, P < .001), and receive adjuvant chest wall (89% v 78%, P = .024) and nodal radiation (82% v 75%, P = .038). Additional positive nodes were found at ALND in 30% of patients, but only 5% had macrometastases. The 3-year rates of any axillary and any invasive recurrence were 2% (95% CI, 0.95 to 3.6) and 11% (95% CI, 8 to 14), respectively, with no statistical difference by type of axillary surgery. CONCLUSION The nodal burden in patients with ypN0(i+) was low, and axillary recurrence after ALND omission was rare in patients selected for this approach. These results do not support routine ALND in all patients with ypN0(i+).

Abstract The OmicsFootPrint framework addresses the need for advanced multi-omics data analysis methodologies by transforming data into intuitive two-dimensional circular images and facilitating the interpretation of complex diseases. Utilizing deep neural networks and incorporating the SHapley Additive exPlanations algorithm, the framework enhances model interpretability. Tested with The Cancer Genome Atlas data, OmicsFootPrint effectively classified lung and breast cancer subtypes, achieving high area under the curve (AUC) scores—0.98 ± 0.02 for lung cancer subtype differentiation and 0.83 ± 0.07 for breast cancer PAM50 subtypes, and successfully distinguished between invasive lobular and ductal carcinomas in breast cancer, showcasing its robustness. It also demonstrated notable performance in predicting drug responses in cancer cell lines, with a median AUC of 0.74, surpassing nine existing methods. Furthermore, its effectiveness persists even with reduced training sample sizes. OmicsFootPrint marks an enhancement in multi-omics research, offering a novel, efficient and interpretable approach that contributes to a deeper understanding of disease mechanisms.

ImportanceSince 2021, American College of Surgeons Commission on Cancer (CoC) accreditation standards require providing a survivorship program for patients with adult-onset cancer treated with curative intent. Since more than 70% of all patients with cancer in the US are treated at CoC-accredited facilities, this presents an opportunity for a landscape analysis of survivorship care availability.ObjectiveTo determine the prevalence, types, and outcomes of cancer survivorship services at CoC-accredited facilities.Design, Setting, and ParticipantsThis survey study used an anonymous, online, cross-sectional survey conducted from May 4 to 25, 2023. Participants were CoC-accredited facilities in the US representing diverse CoC program categories, institutional characteristics, geographic regions, and practice types. Department of Veterans Affairs cancer programs were excluded due to data usage restrictions. Data were analyzed from July to October 2023.ExposureCoC Survivorship Standard 4.8 was released in October 2019 and programs were expected to adhere to the Standard beginning January 1, 2021.Main Outcomes and MeasuresQuestions included self-reported survivorship program characteristics, availability of services aligned to CoC Survivorship Standard 4.8, and perceived program impacts. Response frequencies and proportions were determined in aggregate and by CoC program category.ResultsThere were 1400 eligible programs, and 384 programs participated (27.4% response rate). All regions and eligible program categories were represented, and most had analytic caseloads of 500 to 4999 patients in 2021. Most survivorship program personnel included nurses (334 programs [87.0%]) and social workers (278 programs [72.4%]), while physical (180 programs [46.9%]) and occupational (87 programs [22.7%]) therapists were less common. Services most endorsed as available for all survivors were screening for new cancers (330 programs [87.5%]), nutritional counseling (325 programs [85.3%]), and referrals to specialists (320 programs [84.7%]), while treatment summaries (242 programs [64.7%]), and survivorship care plans (173 programs [43.0%]), sexual health (217 programs [57.3%]), and fertility (214 programs [56.9%]) were less common. Survivorship services were usually delivered by cancer treatment teams (243 programs [63.3%]) rather than specialized survivorship clinics (120 programs [31.3%]). For resources needed, additional advanced practice clinicians with dedicated survivorship effort (205 programs [53.4%]) and electronic health record enhancements (185 programs [48.2%]) were most endorsed. Lack of referrals and low patient awareness were endorsed as the primary barriers. A total of 335 programs (87.2%) agreed that Survivorship Standard 4.8 helped advance their programs.Conclusions and RelevanceThese findings of this survey study of CoC-accredited programs establish a benchmark for survivorship care delivery in the US, identify gaps in specific services and opportunities for intervention, contribute to longitudinal reevaluation for tracking progress nationally, and suggest the value of survivorship care standards.