Lymphedema Rates Following Axillary Lymph Node Dissection With and Without Immediate Lymphatic Reconstruction: A Prospective Trial.

BACKGROUND: Immediate lymphatic reconstruction (ILR) has been proposed to decrease lymphedema rates. The primary aim of our study was to determine whether ILR decreased the incidence of lymphedema in patients undergoing axillary lymph node dissection (ALND). METHODS: We conducted a two-site pragmatic study of ALND with or without ILR, employing surgeon-level cohort assignment, based on breast surgeons' preferred standard practice. Lymphedema was assessed by limb volume measurements, patient self-reporting, provider documentation, and International Classification of Diseases, Tenth Revision (ICD-10) codes. RESULTS: Overall, 230 patients with breast cancer were enrolled; on an intention-to-treat basis, 99 underwent ALND and 131 underwent ALND with ILR. Of the 131 patients preoperatively planned for ILR, 115 (87.8%) underwent ILR; 72 (62.6%) were performed by one breast surgical oncologist and 43 (37.4%) by fellowship-trained microvascular plastic surgeons. ILR was associated with an increased risk of lymphedema when defined as ≥10% limb volume change on univariable analysis, but not on multivariable analysis, after propensity score adjustment. We did not find a statistically significant difference in limb volume measurements between the two cohorts when including subclinical lymphedema (≥5% inter-limb volume change), nor did we see a difference in grade between the two cohorts on an intent-to-treat or treatment received basis. For all patients, considering ascertainment strategies of patient self-reporting, provider documentation, and ICD-10 codes, as a single binary outcome measure, there was no significant difference in lymphedema rates between those undergoing ILR or not. CONCLUSION: We found no significant difference in lymphedema rates between patients undergoing ALND with or without ILR.

Cancer Survivorship Care in the United States at Facilities Accredited by the Commission on Cancer.

Importance: Since 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. Objective: To determine the prevalence, types, and outcomes of cancer survivorship services at CoC-accredited facilities. Design, Setting, and Participants: This 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. Exposure: CoC 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 Measures: Questions 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. Results: There 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 Relevance: These 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.

Contemporary Axillary Surgical Management in Patients with Pathologically Node Positive Disease After Neoadjuvant Chemotherapy: A Survey of Members of the American Society of Breast Surgeons.

BACKGROUND: Axillary lymph node dissection (ALND) is increasingly omitted for breast cancer patients with pathologic nodal disease after neoadjuvant chemotherapy (NAC). This study aimed to understand when and why surgeons consider omitting ALND after NAC. METHODS: The American Society of Breast Surgeons membership was surveyed, and responses were tabulated. To identify patterns, multiple correspondence analyses followed by cluster analysis on coordinates provided by the former were performed. Chi-squared analyses determined whether cluster characteristics were significantly (P < 0.05) associated with omission of ALND. RESULTS: Of members, 328/2172 (15.1%) completed the survey. Most (60.7%) always offer sentinel lymph node surgery to cN1 patients who respond to NAC, and many (43.9%) sometimes omit ALND in the setting of residual nodal disease. Respondents less often consider omitting ALND with increasing volume of pathologic nodal disease after NAC and are less likely to omit ALND among patients with cN1 disease at presentation than cN0 (P < 0.05 across all volumes). Respondents cited radiation administration (74.1%) and belief that ALND would not improve locoregional (48.2%), distant recurrence or survival (47.6%) outcomes when axillary radiation is administered as reasons to omit ALND. The respondent group comprising male private practice surgeons, practicing ≥ 21 years, consider omitting ALND significantly more frequently. CONCLUSIONS: Surgeons sometimes consider ALND omission for patients with pathologic nodal disease after NAC but are more likely to do so in cN0 patients and patients with smaller volumes of nodal disease. These decisions are largely based on perceived lack of oncologic benefit despite absence of prospective data supporting this deescalation.

Locoregional Management of Multiple Ipsilateral Breast Cancers: A Review.

The incidence of preoperatively diagnosed multiple ipsilateral breast cancer (MIBC) is increasing due to improved sensitivity of screening and preoperative staging modalities including digital breast tomosynthesis (3D breast mammography) and magnetic resonance imaging (MRI). The surgical management of MIBC remains controversial. Many surgeons continue to recommend mastectomy due to high local recurrence rates in patients with MIBC undergoing breast conservation therapy reported in historic, retrospective studies. More recent retrospective studies report acceptable rates of local recurrence. Yet concerns persist due to a paucity of prospective data regarding recurrence as well as concerns for margin positivity, cosmetic outcomes and the feasibility of adequate and safe delivery of radiation following breast conserving surgery. Breast conservation has emerged as the preferred surgical strategy for eligible patients with unifocal disease. Benefits include improved quality of life, body image and sexual function and lower surgical complication rates. A recent prospective clinical trial has corroborated a large body of retrospective data confirming the safety of breast conserving therapy and adjuvant radiation in women with MIBC with good oncologic control, low rates of conversion to mastectomy and satisfactory patient-reported cosmetic outcomes. With the current rise in MIBC diagnoses, it is imperative that surgeons understand the existent evidence in order to guide shared decision-making conversations with patients diagnosed with MIBC. This comprehensive review synthesizes the best available data and offers current recommendations for management of both the primary sites of disease as well as management of the axilla in patients with MIBC.

Pre-treatment peripheral blood immunophenotyping and response to neoadjuvant chemotherapy in operable breast cancer.

BACKGROUND: Tumor immune infiltration and peripheral blood immune signatures have prognostic and predictive value in breast cancer. Whether distinct peripheral blood immune phenotypes are associated with response to neoadjuvant chemotherapy (NAC) remains understudied. METHODS: Peripheral blood mononuclear cells from 126 breast cancer patients enrolled in a prospective clinical trial (NCT02022202) were analyzed using Cytometry by time-of-flight with a panel of 29 immune cell surface protein markers. Kruskal-Wallis tests or Wilcoxon rank-sum tests were used to evaluate differences in immune cell subpopulations according to breast cancer subtype and response to NAC. RESULTS: There were 122 evaluable samples: 47 (38.5%) from patients with hormone receptor-positive, 39 (32%) triple-negative (TNBC), and 36 (29.5%) HER2-positive breast cancer. The relative abundances of pre-treatment peripheral blood T, B, myeloid, NK, and unclassified cells did not differ according to breast cancer subtype. In TNBC, higher pre-treatment myeloid cells were associated with lower pathologic complete response (pCR) rates. In hormone receptor-positive breast cancer, lower pre-treatment CD8 + naïve and CD4 + effector memory cells re-expressing CD45RA (TEMRA) T cells were associated with more extensive residual disease after NAC. In HER2 + breast cancer, the peripheral blood immune phenotype did not differ according to NAC response. CONCLUSIONS: Pre-treatment peripheral blood immune cell populations (myeloid in TNBC; CD8 + naïve T cells and CD4 + TEMRA cells in luminal breast cancer) were associated with response to NAC in early-stage TNBC and hormone receptor-positive breast cancers, but not in HER2 + breast cancer. TRIAL REGISTRATION: NCT02022202 . Registered 20 December 2013.

Impact of Presenting Stage on Overall Survival in Patients Treated with Neoadjuvant Chemotherapy for Triple Negative Breast Cancer.

PURPOSE: For operable triple-negative breast cancer (TNBC) treated with neoadjuvant chemotherapy (NAC), clinical prognostication and postoperative decision-making relies exclusively on whether a pathologic complete response (pCR) is achieved or not. We evaluated whether extent of disease at presentation further influenced overall survival (OS) among patients with pCR or with residual disease (RD) following NAC. METHODS: Patients with stage I-III TNBC who underwent NAC were identified from the National Cancer Database from 2010 to 2019. Overall survival was assessed by disease extent using the Kaplan-Meier method and Cox proportional hazards regression for univariate and multivariable analysis. RESULTS: A total of 35,598 patients met inclusion criteria, and 11,967 achieved pCR. Ten-year OS was 88.5% and varied by cT and cN category at presentation. Best 10-year OS was seen in patients with cT1-2, cN0 (90.9%) and was worst in those with cT3-4, cN2-3 disease (72.0%). A total of 23,631 patients had RD. Ten-year OS was 60.1% and varied by cT and cN category at presentation. Best 10-year OS was seen in patients with cT1-2, cN0 (73.0%) and was worst in those with cT3-4, cN2-3 disease (36.3%). Notably, OS was significantly poorer for patients with cT3-4, cN2-3 disease at diagnosis and pCR versus those with cT1-2 cN0 and RD (aHR 1.30, 95% confidence interval 1.03-1.63, p = 0.03). CONCLUSIONS: Among patients with TNBC, extent of disease at presentation was prognostic for OS independently of response to NAC. Patients with advanced stage at presentation had poorer OS even in the context of pCR. Further investigation is needed to evaluate whether additional adjuvant therapy strategies should be considered for these patients.

Internal mammary lymphadenopathy in breast cancer: a narrative review and update.

Background and Objective: While the axillary nodal basin is the most common lymphatic drainage pathway of the breast, the internal mammary (IM) lymph node chain plays a significant role in breast cancer staging and treatment. It has been identified as sentinel nodal drainage in approximately 13-37% of patients. Despite this, the data is still limited with regard to diagnosis and management when there is suspicion or confirmation of IM lymph node (IMLN) involvement by metastatic breast cancer. The objective of this publication is to provide a comprehensive assessment of the current body of literature surrounding the diagnosis, management and prognostic value of IMLNs in breast cancer treatment. Methods: Review of the literature published regarding IMLN diagnosis, significance, and management was completed in PubMed. Additional focus was placed on reviewing articles published within the past 10 years as foundation for an update regarding the current practice and future directions in this space. Key Content and Findings: Improved imaging techniques, with positron emission tomography-computed tomography and magnetic resonance imaging, have led to increase in the identification of IM lymphadenopathy, yielding surgical staging of the IM nodes nearly obsolete. While IM nodal metastases may play a role in overall survival (OS), it has not been demonstrated to be an independent risk factor for increased locoregional recurrence. IM nodal irradiation (IMNI) therapy has been a mainstay in the treatment of IM disease in the context of breast cancer. IMNI has demonstrated improvement in OS and risk of distant recurrence. Wide variations in radiation practices for patients with IM lymphadenopathy exist internationally, highlighting the lack of clear data driven consensus guidelines. Conclusions: Herein, we provide an updated assessment of the current diagnosis, clinical significance, and management of IM lymphadenopathy for breast cancer patients.

OmicsFootPrint: a framework to integrate and interpret multi-omics data using circular images and deep neural networks.

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 (SHAP) algorithm, the framework enhances model interpretability. Tested with The Cancer Genome Atlas (TCGA) data, OmicsFootPrint effectively classified lung and breast cancer subtypes, achieving high Area Under Curve (AUC) scores - 0.98±0.02 for lung cancer subtype differentiation, 0.83±0.07 for breast cancer PAM50 subtypes, and successfully distinguishe 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 existing algorithms. 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.

Automated mitotic spindle hotspot counts are highly associated with clinical outcomes in systemically untreated early-stage triple-negative breast cancer.

Operable triple-negative breast cancer (TNBC) has a higher risk of recurrence and death compared to other subtypes. Tumor size and nodal status are the primary clinical factors used to guide systemic treatment, while biomarkers of proliferation have not demonstrated value. Recent studies suggest that subsets of TNBC have a favorable prognosis, even without systemic therapy. We evaluated the association of fully automated mitotic spindle hotspot (AMSH) counts with recurrence-free (RFS) and overall survival (OS) in two separate cohorts of patients with early-stage TNBC who did not receive systemic therapy. AMSH counts were obtained from areas with the highest mitotic density in digitized whole slide images processed with a convolutional neural network trained to detect mitoses. In 140 patients from the Mayo Clinic TNBC cohort, AMSH counts were significantly associated with RFS and OS in a multivariable model controlling for nodal status, tumor size, and tumor-infiltrating lymphocytes (TILs) (p < 0.0001). For every 10-point increase in AMSH counts, there was a 16% increase in the risk of an RFS event (HR 1.16, 95% CI 1.08-1.25), and a 7% increase in the risk of death (HR 1.07, 95% CI 1.00-1.14). We corroborated these findings in a separate cohort of systemically untreated TNBC patients from Radboud UMC in the Netherlands. Our findings suggest that AMSH counts offer valuable prognostic information in patients with early-stage TNBC who did not receive systemic therapy, independent of tumor size, nodal status, and TILs. If further validated, AMSH counts could help inform future systemic therapy de-escalation strategies.

Patient-specific signaling signatures predict optimal therapeutic combinations for triple negative breast cancer.

Triple negative breast cancer (TNBC) is a heterogeneous group of tumors which lack estrogen receptor, progesterone receptor, and HER2 expression. Targeted therapies have limited success in treating TNBC, thus a strategy enabling effective targeted combinations is an unmet need. To tackle these challenges and discover individualized targeted combination therapies for TNBC, we integrated phosphoproteomic analysis of altered signaling networks with patient-specific signaling signature (PaSSS) analysis using an information-theoretic, thermodynamic-based approach. Using this method on a large number of TNBC patient-derived tumors (PDX), we were able to thoroughly characterize each PDX by computing a patient-specific set of unbalanced signaling processes and assigning a personalized therapy based on them. We discovered that each tumor has an average of two separate processes, and that, consistent with prior research, EGFR is a major core target in at least one of them in half of the tumors analyzed. However, anti-EGFR monotherapies were predicted to be ineffective, thus we developed personalized combination treatments based on PaSSS. These were predicted to induce anti-EGFR responses or to be used to develop an alternative therapy if EGFR was not present.In-vivo experimental validation of the predicted therapy showed that PaSSS predictions were more accurate than other therapies. Thus, we suggest that a detailed identification of molecular imbalances is necessary to tailor therapy for each TNBC. In summary, we propose a new strategy to design personalized therapy for TNBC using pY proteomics and PaSSS analysis. This method can be applied to different cancer types to improve response to the biomarker-based treatment.

Identification of a Notch transcriptomic signature for breast cancer.

BACKGROUND: Dysregulated Notch signalling contributes to breast cancer development and progression, but validated tools to measure the level of Notch signalling in breast cancer subtypes and in response to systemic therapy are largely lacking. A transcriptomic signature of Notch signalling would be warranted, for example to monitor the effects of future Notch-targeting therapies and to learn whether altered Notch signalling is an off-target effect of current breast cancer therapies. In this report, we have established such a classifier. METHODS: To generate the signature, we first identified Notch-regulated genes from six basal-like breast cancer cell lines subjected to elevated or reduced Notch signalling by culturing on immobilized Notch ligand Jagged1 or blockade of Notch by γ-secretase inhibitors, respectively. From this cadre of Notch-regulated genes, we developed candidate transcriptomic signatures that were trained on a breast cancer patient dataset (the TCGA-BRCA cohort) and a broader breast cancer cell line cohort and sought to validate in independent datasets. RESULTS: An optimal 20-gene transcriptomic signature was selected. We validated the signature on two independent patient datasets (METABRIC and Oslo2), and it showed an improved coherence score and tumour specificity compared with previously published signatures. Furthermore, the signature score was particularly high for basal-like breast cancer, indicating an enhanced level of Notch signalling in this subtype. The signature score was increased after neoadjuvant treatment in the PROMIX and BEAUTY patient cohorts, and a lower signature score generally correlated with better clinical outcome. CONCLUSIONS: The 20-gene transcriptional signature will be a valuable tool to evaluate the response of future Notch-targeting therapies for breast cancer, to learn about potential effects on Notch signalling from conventional breast cancer therapies and to better stratify patients for therapy considerations.

Germline Testing in Patients With Breast Cancer: ASCO-Society of Surgical Oncology Guideline.

PURPOSE: To develop recommendations for germline mutation testing for patients with breast cancer. METHODS: An ASCO-Society of Surgical Oncology (SSO) panel convened to develop recommendations based on a systematic review and formal consensus process. RESULTS: Forty-seven articles met eligibility criteria for the germline mutation testing recommendations; 18 for the genetic counseling recommendations. RECOMMENDATIONS: BRCA1/2 mutation testing should be offered to all newly diagnosed patients with breast cancer ≤65 years and select patients >65 years based on personal history, family history, ancestry, or eligibility for poly(ADP-ribose) polymerase (PARP) inhibitor therapy. All patients with recurrent breast cancer who are candidates for PARP inhibitor therapy should be offered BRCA1/2 testing, regardless of family history. BRCA1/2 testing should be offered to women who develop a second primary cancer in the ipsilateral or contralateral breast. For patients with prior history of breast cancer and without active disease, testing should be offered to patients diagnosed ≤65 years and selectively in patients diagnosed after 65 years, if it will inform personal and family risk. Testing for high-penetrance cancer susceptibility genes beyond BRCA1/2 should be offered to those with supportive family histories; testing for moderate-penetrance genes may be offered if necessary to inform personal and family cancer risk. Patients should be provided enough pretest information for informed consent; those with pathogenic variants should receive individualized post-test counseling. Variants of uncertain significance should not impact management, and patients with such variants should be followed for reclassification. Referral to providers experienced in clinical cancer genetics may help facilitate patient selection and interpretation of expanded testing, and provide counseling of individuals without pathogenic germline variants but with significant family history.Additional information is available at www.asco.org/breast-cancer-guidelines.

Society of Surgical Oncology Breast Disease Site Working Group Statement on Contralateral Mastectomy: Indications, Outcomes, and Risks.

Rates of contralateral mastectomy (CM) among patients with unilateral breast cancer have been increasing in the United States. In this Society of Surgical Oncology position statement, we review the literature addressing the indications, risks, and benefits of CM since the society's 2017 statement. We held a virtual meeting to outline key topics and then conducted a literature search using PubMed to identify relevant articles. We reviewed the articles and made recommendations based on group consensus. Patients consider CM for many reasons, including concerns regarding the risk of contralateral breast cancer (CBC), desire for improved cosmesis and symmetry, and preferences to avoid ongoing screening, whereas surgeons primarily consider CBC risk when making a recommendation for CM. For patients with a high risk of CBC, CM reduces the risk of new breast cancer, however it is not known to convey an overall survival benefit. Studies evaluating patient satisfaction with CM and reconstruction have yielded mixed results. Imaging with mammography within 12 months before CM is recommended, but routine preoperative breast magnetic resonance imaging is not; there is also no evidence to support routine postmastectomy imaging surveillance. Because the likelihood of identifying an occult malignancy during CM is low, routine sentinel lymph node surgery is not recommended. Data on the rates of postoperative complications are conflicting, and such complications may not be directly related to CM. Adjuvant therapy delays due to complications have not been reported. Surgeons can reduce CM rates by encouraging shared decision making and informed discussions incorporating patient preferences.

ASO Author Reflections: Toward Individualized Management of Heterogenous Mixed Invasive Ductolobular Breast Cancers.

Mixed invasive ductolobular breast cancer (MIDLC) is a rare breast cancer with varying lobular and ductal components. Characteristics, management, and outcomes of MIDLC are not well understood due to the rarity of the cancer and the lack of uniform diagnostic criteria and reporting. There is a need for better understanding and individualized management of this heterogeneous spectrum of breast cancers.

Lobular-Like Features and Outcomes of Mixed Invasive Ductolobular Breast Cancer (MIDLC): Insights from 54,403 Stage I-III MIDLC Patients.

BACKGROUND: Mixed invasive ductolobular breast cancer (MIDLC) is a rare histological subtype of breast cancer (BC), with components of both invasive ductal cancer (IDC) and invasive lobular cancer (ILC). Its clinicopathological features and outcomes have not been well characterized. METHOD: The National Cancer Database 2010-2017 was reviewed to identify women with stage I-III BCs. Univariate analysis was performed using Chi-square or Wilcoxon rank-sum tests and multivariable analysis with logistic regression to predict surgical decisions. Survival was assessed using multivariable Cox proportional hazards regression analysis. RESULTS: We identified 955,828 women with stage I-III BCs (5.7% MIDLC, 10.3% ILC, and 84.0% IDC). MIDLC was more like ILC than IDC in terms of multicentricity (14.2% MIDLC, 13.0% ILC, 10.0% IDC), hormone receptor positivity (96.6% MIDLC, 98.2% ILC, 81.2% IDC), and use of neoadjuvant chemotherapy (NAC; 5.8% MIDLC, 5.2% ILC, 10.8% IDC). 744,607 women underwent upfront surgery. The mastectomy rates were 42.3% for MIDLC, 46.5% for ILC, and 33.3% for IDC (all p < 0.001). With 5.5 years of median follow-up, the adjusted overall survival in the upfront surgery hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) biological subgroup was better in MIDLC (hazard ratio 0.88, p < 0.001) and ILC (hazard ratio 0.91, p < 0.001) than in IDC. Like ILC, MIDLC also had a lower pathological complete response to NAC than IDC (12.3% MIDLC, 7.3% ILC, 28.6% IDC). CONCLUSIONS: MIDLC displays a mixed pattern of characteristics favoring features of ILC compared with IDC, with favorable 5-year overall survival compared with IDC within the HR+/HER2- subtype who underwent upfront surgery.

Nodal pCR and overall survival following neoadjuvant chemotherapy for node positive ER+/Her2- breast cancer.

PURPOSE: The role of neoadjuvant chemotherapy (NAC) in node-positive (N+) ER+/HER2- breast cancer (BC) is debated, given low total pathologic complete response (pCR) rates. However, the rate and impact of nodal pCR is unknown. We sought to evaluate nodal pCR rates and the impact on overall survival (OS). Further, we sought to validate the association between nodal pCR with age and Ki67. METHODS: We queried the National Cancer Database for cN + ER+/HER2- BC patients treated with NAC and surgery. Data from 2010 to 2018 were used to evaluate nodal pCR and OS, with multivariable Cox proportional hazards modeling for OS, as well as Ki67 for the years 2018-2019. RESULTS: From 2010 to 2018, we identified 19,611 cN + ER+/HER2- BC patients treated with NAC. While total pCR occurred in only 7.4%, nodal pCR rates were nearly double (14.3%). Nodal pCR (+/- breast pCR) was seen in 21.7% and associated with 5-year OS rate of 86.1% (95% CI: 84.9-87.4%) versus 77.1% (95% CI: 76.3-77.9%) in patients without nodal pCR (p < 0.001). On multivariable analysis, nodal pCR had better OS (adjusted HR 0.57, 95% CI 0.52-0.63, p < 0.001) across all age groups. Of 2,444 patients with available Ki67, those with age < 50 and Ki67 ≥ 20% had the highest nodal pCR at 31.6%. CONCLUSION: In cN + ER+/HER2- BC treated with NAC, nodal pCR is common, associated with age and Ki67, and prognostic for OS. These data strongly suggest that for cN + patients, eradication of nodal disease is critical for OS, and total pCR may not be the optimal measure of NAC benefit.

Tumor Characteristics of Bilateral Breast Cancer Compared with Unilateral Breast Cancer.

BACKGROUND: Bilateral breast cancer (BC) has an incidence of 1 to 3 %. This study aimed to describe the clinicopathologic characteristics and management of bilateral BC, estimate disease-free survival (DFS), and compare DFS with unilateral BC. METHODS: A retrospective analysis was performed for patients who had bilateral invasive BC or unilateral invasive BC and contralateral ductal carcinoma in situ (DCIS) treated at Mayo Clinic Rochester from 2008 to 2022. A 4:1 matched cohort of patients with unilateral invasive BC was used for comparison. The groups were compared using Wilcoxon rank-sum or chi-square tests. Disease-free survival was analyzed using the Kaplan-Meier method and log-rank test, with Cox proportional hazards regression used for multivariable analysis. RESULTS: The study identified 278 cases of bilateral breast cancer (177 cases of bilateral invasive cancer and 101 cases of unilateral invasive cancer with contralateral DCIS), representing 4.1 % of invasive BCs. Biologic subtype was concordant between sides in 79.8 % of the patients. Initial surgery was bilateral mastectomy for 76.6 %, bilateral lumpectomy for 20.5 %, and unilateral mastectomy with unilateral lumpectomy for 2.9 % of the patients. Pathogenic variants in breast cancer predisposition genes were present in 21.7 % of those tested. The patients who had bilateral BC presented with a higher cT category than the patients who had unilateral BC (p = 0.02), and a higher proportion presented with ILC (17.3 % vs 10.9 %; p = 0.004), estrogen receptor-positive (ER+) disease (89.2 % vs 84.2 %; p = 0.04), multicentric/multifocal disease (37.1 % vs 24.3 %; p < 0.001), breast cancer pathogenic variant (21.7 % vs 12.4 %; p = 0.02), and palpable presentation (48.2 % vs 40.8 %; p = 0.03). The patients with bilateral BC showed DFS similar to that for the unilateral BC cohort (p = 0.71). CONCLUSIONS: Bilateral BCs most commonly are biologically concordant between sides. Bilateral BC presented more commonly with larger tumors, lobular histology, ER+ status, multicentricity or multifocality, pathogenic variant, and palpable disease. Bilateral BC is not associated with worse DFS than unilateral BC.

Assessment of the effect of the American Society of Breast Surgery guidelines on contralateral prophylactic mastectomy rates for unilateral breast cancer.

BACKGROUND: In July 2016, the American Society of Breast Surgeons published guidelines discouraging contralateral prophylactic mastectomy for average-risk women with unilateral breast cancer. We incorporated these into practice with structured patient counseling and aimed to assess the effect of this initiative on contralateral prophylactic mastectomy rates. METHODS: We evaluated female patients with unilateral breast cancer undergoing mastectomy at our institution from January 2011 to November 2022. Variables associated with contralateral prophylactic mastectomy and trends over time were analyzed using the Wilcoxon rank sum test or χ2 analysis as appropriate. RESULTS: Among 3,208 patients, (median age 54 years) 1,366 (43%) had a unilateral mastectomy, and 1,842 (57%) also had a concomitant contralateral prophylactic mastectomy. Across all patients, contralateral prophylactic mastectomy rates significantly decreased post-implementation from 2017 to 2019 (55%) vs 2015 to 2016 (62%) (P = .01) but increased from 2020 to 2022 (61%). Immediate breast reconstruction rate was 70% overall (81% with contralateral prophylactic mastectomy and 56% without contralateral prophylactic mastectomy, P < .001). Younger age, White race, mutation status, and earlier stage were also associated with contralateral prophylactic mastectomy. Genetic testing increased from 27% pre-guideline to 74% 2020 to 2022, as did the proportion of patients with a pathogenic variant (4% pre-guideline vs 11% from 2020-2022, P < .001), of whom 91% had a contralateral prophylactic mastectomy. Among tested patients without a pathogenic variant and patients not tested, contralateral prophylactic mastectomy rates declined from 78% to 67% and 48% to 38% pre -and post-guidelines, respectively, P < .001. CONCLUSION: Implementation of specific patient counseling was effective in decreasing contralateral prophylactic mastectomy rates. While recognizing that patient choice plays a significant role in the decision for contralateral prophylactic mastectomy, further educational efforts are warranted to affect contralateral prophylactic mastectomy rates, particularly in the setting of negative genetic testing.