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Background: Most patients with breast cancer treated with neoadjuvant chemotherapy (NAC) experience clinical benefit, however, a small proportion progress. We aimed to characterize factors predicting in-breast tumor progression and impact on distant recurrence. Patients and Methods: We reviewed all patients with clinical stage I–III breast cancer treated with NAC in 2006–2021 at our institution. We compared in-breast progressive disease (PD), defined as ≥ 20% increase in tumor size, with stable disease (SD) or response. Distant recurrence-free survival (DRFS) was analyzed using the Kaplan–Meier method and Cox proportional hazards regression. Results: Of 1403 patients, 70 (5%) experienced in-breast PD, 243 (17%) SD, 560 (40%) partial response (PR), and 530 (38%) breast pathologic complete response (breast pCR, ypT0/Tis). The rate of PD varied by tumor subtype (8% in HR+/HER2−, 5% TNBC, 2% HER2+, p < 0.001). With median 48 months follow-up, the rates of DRFS were significantly different according to clinical breast response as follows: PD 56%, SD 68%, PR 82%, or breast pCR 93%, p < 0.001. In patients with PD on multivariable analysis, post-NAC grade (adjusted HR 2.9, p = 0.002) and ypT3–4 category (adjusted HR 2.4, p = 0.03) were the strongest predictors of DRFS. Combining these factors, 23% had neither, 44% had one, and 33% had both, which stratified outcome in PD with 3-year DRFS of 100%, 77%, and 30%, respectively (p < 0.001). Conclusions: While in-breast PD during NAC is uncommon (5%), it predicts poor survival. Among patients with in-breast PD, post-NAC tumor grade and T category predict outcomes and may be useful to guide treatment escalation. [ABSTRACT FROM AUTHOR]

Background: Rates of pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) for breast cancer have improved, especially among human epidermal growth factor 2-positive (HER2+) and triple-negative subtypes. The frequency and significance of biomarker profile change in residual disease are unclear. This study aimed to determine the rate of biomarker profile changes after NAC and the impact on clinical outcomes in a contemporary cohort. Methods: Upon institutional review board approval, the study identified 634 consecutive patients treated with NAC between 2010 and 2022 at two academic institutions. The study cohort was focused on patients with residual disease who underwent biomarker profile retesting. Biomarker profile change for each subtype was compared across groups using Fisher-Irwin tests. Cox Proportional Hazards Model and Kaplan-Meier plots were performed to evaluate the association of changed versus unchanged biomarker profile with event-free survival. Results: Biomarker retesting was performed for 259 (61.4 %) of 422 patients with residual disease. Biomarker profile change occurred in 18.1 % overall and was significantly higher among those with pre-NAC HER2+ disease (32.7 %, 17/52) than among those with HER2–disease (14.5 %, 30/207) (p = 0.004). Conversion of pre-NAC biomarker profiles of HR+HER2– and HR+HER2+ to triple-negative breast cancer (TNBC) post-NAC may be associated with worse event-free survival, hazard ratios of 2.23 (95 % confidence interval [CI], 0.90–5.53; p = 0.08), trending toward significance, and 36.7 (95 % CI, 2.2–610.8; p = 0.01), respectively. Conclusions: The results from one of the largest contemporary cohorts demonstrated that biomarker profile change in patients with residual disease after NAC was common. Furthermore, specific biomarker profile change in residual disease may have prognostic value. These findings strengthen the rationale for routine re-testing of biomarkers in residual disease after NAC. [ABSTRACT FROM AUTHOR]

Background: Efforts to define the key technical elements of breast cancer surgery, the foundation of curative treatment, have been recognized recently by the Commission on Cancer (CoC). Effective 1 January 2023, surgeon documentation in synoptic format of specific technical elements of axillary surgery for breast cancer became a CoC accreditation requirement (standards 5.3 and 5.4). Methods: After Institutional Review Board approval, the study identified patients from the authors' prospective breast surgery database granting research consent who underwent axillary surgery for breast cancer from 1 January 2023 to 31 December 2023. Operative reports, which since 2017 have been standardized templates, were reviewed for compliance. Results: The study identified 592 eligible patients who had 623 axillary operations (76 % cN0, 24 % cN+). Full compliance with standard 5.3 was met in 71 % of cases and with standard 5.4 in 97 % of cases. Regarding standard 5.3, a mid-year internal review and subsequent individual surgeon-level communication significantly increased full synoptic documentation compliance to 98 % in quarter 4 (p < 0.001). The most common reasons for non-compliance were failure to record a response as "not applicable" regarding tracer use to identify sentinel lymph nodes in the neoadjuvant setting (the most deficient element, 81 % deficient) and failure to record "not applicable" for elements conditional on setting (upfront vs neoadjuvant surgery). Regarding standard 5.4, which has fewer elements overall, none of which are conditional, compliance was high throughout 2023. Conclusions: Mid-year audit and individual surgeon-level communication successfully improved compliance with standard 5.3 to meet the required threshold for accreditation. Prior practice adoption of templated operative notes likely facilitated integration of the synoptic standards into surgeon workflow. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Axillary lymph node dissection is the current standard for management of the axilla in inflammatory breast cancer (IBC). The present study aims to determine whether the initially positive node identified by clip placement accurately represents the overall nodal status of axilla after neoadjuvant chemotherapy (NAC) in IBC. Patients and Methods: A retrospective study was conducted on patients with IBC who underwent operation (2014–2023). For patients with IBC who had clip placement in a positive axillary node at diagnosis, operative notes, specimen radiographs, and pathology reports were reviewed to confirm final pathologic status of clipped nodes. Results: In total, 92 patients with IBC (90 cN+) were identified (median age 54 years, 78% invasive ductal, 10% invasive lobular, and 12% mixed); 81 (90%) were biopsy-proven cN+, with a clip placed in the positive node for 62/81 (77%). All patients were treated with NAC and axillary surgery with median 19 (range 4–49) nodes removed. Among 28 (out of 56) patients with retrieved clipped nodes that were pathologically negative (ypN0), only 1 had an additional positive node with micrometastasis for a false negative rate of 4% (95% CI 1–19%). Conversely, 3/3 patients with isolated tumor cells (ITCs) only in the clipped node had additional axillary disease (ITCs in 1, macrometastasis in 2), and 20/23 (87%) of patients with pathologically positive clipped node (micrometastasis or greater) had additional positive nodes [19/20 (95%) with macrometastasis]. Conclusions: The clipped biopsy-positive axillary node in IBC accurately represented the post-NAC overall axillary nodal status. ITCs post-NAC should be considered positive as an indicator of additional nodes with metastasis. [ABSTRACT FROM AUTHOR]

Background: For patients with clinically node-positive (cN+) breast cancer undergoing neoadjuvant chemotherapy (NAC), retrieving previously clipped, biopsy-proven positive lymph nodes during sentinel lymph node biopsy [i.e., targeted axillary dissection (TAD)] may reduce false negative rates. However, the overall utilization and impact of clipping positive nodes remains uncertain. Patients and Methods: We retrospectively analyzed cN+ ISPY-2 patients (2011–2022) undergoing axillary surgery after NAC. We evaluated trends in node clipping and associations with type of axillary surgery [sentinel lymph node (SLN) only, SLN and axillary lymph node dissection (ALND), or ALND only] and event-free survival (EFS) in patients that were cN+ on a NAC trial. Results: Among 801 cN+ patients, 161 (20.1%) had pre-NAC clip placement in the positive node. The proportion of patients that were cN+ undergoing clip placement increased from 2.4 to 36.2% between 2011 and 2021. Multivariable logistic regression showed nodal clipping was independently associated with higher odds of SLN-only surgery [odds ratio (OR) 4.3, 95% confidence interval (CI) 2.8–6.8, p < 0.001]. This was also true among patients with residual pathologically node-positive (pN+) disease. Completion ALND rate did not differ based on clip retrieval success. No significant differences in EFS were observed in those with or without clip placement, both with or without successful clip retrieval [hazard ratio (HR) 0.85, 95% CI 0.4–1.7, p = 0.7; HR 1.8, 95% CI 0.5–6.0, p = 0.3, respectively]. Conclusion: Clip placement in the positive lymph node before NAC is increasingly common. The significant association between clip placement and omission of axillary dissection, even among patients with pN+ disease, suggests a paradigm shift toward TAD as a definitive surgical management strategy in patients with pN+ disease after NAC. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

This is an executive summary of the most recent American Society for Radiation Oncology (ASTRO) guidelines on use of partial breast irradiation in early-stage breast cancer. In the conscientious pursuit of "right-sizing" the management of patients with early-stage breast cancer, there has been an emphasis on judicious de-escalation of therapy. A component of this paradigm shift is partial breast irradiation (PBI), an approach characterized by targeted radiation therapy (RT) to lumpectomy cavity margins rather than to the whole breast (i.e., whole breast irradiation [WBI]) after breast conservation surgery (BCS). The American Society for Radiation Oncology (ASTRO) recently completed a revision of its evidence-based guidelines for the application of PBI.1 To accomplish this, recent PBI data were reviewed by panel members, including representatives of the American Society for Radiation Oncology (ASTRO), in collaboration with the American Society of Clinical Oncology (ASCO), and the Society of Surgical Oncology (SSO), which provided representatives and peer reviewers. The guideline was approved by the ASTRO Board of Directors and endorsed by the Canadian Association of Radiation Oncology, European Society for Radiotherapy and Oncology, Royal Australian and New Zealand College of Radiologists, and the Society of Surgical Oncology. The recommendations focused on indications for PBI as an alternative to WBI and technical considerations specific to PBI. This editorial provides a summary and comments on the updated ASTRO PBI guidelines, offering insights into the implications of these findings for clinical practice and multidisciplinary decision-making while underscoring technical considerations for optimal incorporation of PBI into patient care. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: A 3-biomarker homologous recombination deficiency (HRD) score is a key component of a currently FDA-approved companion diagnostic assay to identify HRD in patients with ovarian cancer using a threshold score of ≥ 42, though recent studies have explored the utility of a lower threshold (GIS ≥ 33). The present study evaluated whether the ovarian cancer thresholds may also be appropriate for major breast cancer subtypes by comparing the genomic instability score (GIS) distributions of BRCA1/2-deficient estrogen receptor–positive breast cancer (ER + BC) and triple-negative breast cancer (TNBC) to the GIS distribution of BRCA1/2-deficient ovarian cancer. Methods: Ovarian cancer and breast cancer (ER + BC and TNBC) tumors from ten study cohorts were sequenced to identify pathogenic BRCA1/2 mutations, and GIS was calculated using a previously described algorithm. Pathologic complete response (pCR) to platinum therapy was evaluated in a subset of TNBC samples. For TNBC, a threshold was set and threshold validity was assessed relative to clinical outcomes. Results: A total of 560 ovarian cancer, 805 ER + BC, and 443 TNBC tumors were included. Compared to ovarian cancer, the GIS distribution of BRCA1/2-deficient samples was shifted lower for ER + BC (p = 0.015), but not TNBC (p = 0.35). In the subset of TNBC samples, univariable logistic regression models revealed that GIS status using thresholds of ≥ 42 and ≥ 33 were significant predictors of response to platinum therapy. Conclusions: This study demonstrated that the GIS thresholds used for ovarian cancer may also be appropriate for TNBC, but not ER + BC. GIS thresholds in TNBC were validated using clinical response data to platinum therapy. [ABSTRACT FROM AUTHOR]

The promising results of the robotic approach for multiple cancer operations has led to interest in the potential of robotic nipple-sparing mastectomy (R-NSM); however, further studies are required to compare the benefits and complications of this approach with those of conventional open nipple-sparing mastectomy (C-NSM). We performed a meta-analysis to compare surgical complications of R-NSM versus C-NSM. We performed a review of literature through June 2022 in PubMed, Scopus, and EMBASE. We included randomized controlled trials (RCTs), cohorts, case–control studies, and case series with > 50 patients comparing the two techniques. Separate meta-analyses were conducted according to study design. From 80 publications, we identified six studies. The sample size ranged from 63 to 311 mastectomies from 63 to 275 patients. The tumor size and disease stage were similar between groups. The positive margin rate was 0–4.6% in the R-NSM arm and 0–2.9% in the C-NSM arm. Four studies reported early recurrence data, which were similar between groups (R-NSM: 0%, C-NSM: 0–8%). The R-NSM group had a lower rate of overall complications compared to the C-NSM group in cohorts/RCTs (RR = 0.68, 95%CI 0.49–0.96). In case–control studies, rate of necrosis was lower with R-NSM. Operative time was significantly longer in the R-NSM group in cohort/RCTs. In early experience with R-NSM, R-NSM had a lower overall complication rate compared to C-NSM in cohorts/RCTs. While these data are promising, our results show variability and heterogeneity limiting definitive conclusions. Additional trials are needed to guide the role of R-NSM and its oncologic outcomes. [ABSTRACT FROM AUTHOR]

Purpose: Triple-negative invasive lobular carcinoma (TN-ILC) of breast cancer is a rare disease and the clinical outcomes and prognostic factors are not well-defined. Methods: Women with stage I–III TN-ILC or triple-negative invasive ductal carcinoma (TN-IDC) of the breast undergoing mastectomy or breast-conserving surgery between 2010 and 2018 in the National Cancer Database were included. Kaplan–Meier curves and multivariate Cox proportional hazard regression were used to compare overall survival (OS) and evaluate prognostic factors. Multivariate logistic regression was performed to analyze the factors associated with pathological response to neoadjuvant chemotherapy. Results: The median age at diagnosis for women with TN-ILC was 67 years compared to 58 years in TN-IDC (p < 0.001). There was no significant difference in the OS between TN-ILC and TN-IDC in multivariate analysis (HR 0.96, p = 0.44). Black race and higher TNM stage were associated with worse OS, whereas receipt of chemotherapy or radiation was associated with better OS in TN-ILC. Among women with TN-ILC receiving neoadjuvant chemotherapy, the 5-year OS was 77.3% in women with a complete pathological response (pCR) compared to 39.8% in women without any response. The odds of achieving pCR following neoadjuvant chemotherapy were significantly lower in women with TN-ILC compared to TN-IDC (OR 0.53, p < 0.001). Conclusion: Women with TN-ILC are older at diagnosis but have similar OS compared to TN-IDC after adjusting for tumor and demographic characteristics. Administration of chemotherapy was associated with improved OS in TN-ILC, but women with TN-ILC were less likely to achieve complete response to neoadjuvant therapy compared to TN-IDC. [ABSTRACT FROM AUTHOR]

In inflammatory breast cancer (IBC), obstructed lymphatics present a barrier to sentinel node biopsy. In theory this challenge could be overcome by clipping the clinically positive node at presentation and surgically retrieving it after neoadjuvant chemotherapy (NAC). If the clipped node accurately reflects the axillary status, then deescalation of axillary nodal dissection could be a possibility in IBC with complete pathological nodal response post-NAC. [ABSTRACT FROM AUTHOR]

The utility of spatial immunobiomarker quantitation in prognostication and therapeutic prediction is actively being investigated in triple-negative breast cancer (TNBC). Here, with high-plex quantitative digital spatial profiling, we map and quantitate intraepithelial and adjacent stromal tumor immune protein microenvironments in systemic treatment-naïve (female only) TNBC to assess the spatial context in immunobiomarker-based prediction of outcome. Immune protein profiles of CD45-rich and CD68-rich stromal microenvironments differ significantly. While they typically mirror adjacent, intraepithelial microenvironments, this is not uniformly true. In two TNBC cohorts, intraepithelial CD40 or HLA-DR enrichment associates with better outcomes, independently of stromal immune protein profiles or stromal TILs and other established prognostic variables. In contrast, intraepithelial or stromal microenvironment enrichment with IDO1 associates with improved survival irrespective of its spatial location. Antigen-presenting and T-cell activation states are inferred from eigenprotein scores. Such scores within the intraepithelial compartment interact with PD-L1 and IDO1 in ways that suggest prognostic and/or therapeutic potential. This characterization of the intrinsic spatial immunobiology of treatment-naïve TNBC highlights the importance of spatial microenvironments for biomarker quantitation to resolve intrinsic prognostic and predictive immune features and ultimately inform therapeutic strategies for clinically actionable immune biomarkers. The tumor immune microenvironment is an important determinant of clinical outcomes and therapeutic responses in patients with triple-negative breast cancer (TNBC). Here the authors perform digital spatial profiling of tumor tissues to characterize the spatial immunobiology of treatment-naïve TNBC. [ABSTRACT FROM AUTHOR]

Purpose: Disseminated tumor cells (DTCs) expressing epithelial markers in the bone marrow are associated with recurrence and death, but little is known about risk factors predicting their occurrence. We detected EPCAM+/CD45− cells in bone marrow from early stage breast cancer patients after neoadjuvant chemotherapy (NAC) in the I-SPY 2 Trial and examined clinicopathologic factors and outcomes. Methods: Patients who signed consent for SURMOUNT, a sub-study of the I-SPY 2 Trial (NCT01042379), had bone marrow collected after NAC at the time of surgery. EPCAM+CD45− cells in 4 mLs of bone marrow aspirate were enumerated using immunomagnetic enrichment/flow cytometry (IE/FC). Patients with > 4.16 EPCAM+CD45− cells per mL of bone marrow were classified as DTC-positive. Tumor response was assessed using the residual cancer burden (RCB), a standardized approach to quantitate the extent of residual invasive cancer present in the breast and the axillary lymph nodes after NAC. Association of DTC-positivity with clinicopathologic variables and survival was examined. Results: A total of 73 patients were enrolled, 51 of whom had successful EPCAM+CD45− cell enumeration. Twenty-four of 51 (47.1%) were DTC-positive. The DTC-positivity rate was similar across receptor subtypes, but DTC-positive patients were significantly younger (p = 0.0239) and had larger pretreatment tumors compared to DTC-negative patients (p = 0.0319). Twenty of 51 (39.2%) achieved a pathologic complete response (pCR). While DTC-positivity was not associated with achieving pCR, it was significantly associated with higher RCB class (RCB-II/III, 62.5% vs. RCB-0/I; 33.3%; Chi-squared p = 0.0373). No significant correlation was observed between DTC-positivity and distant recurrence-free survival (p = 0.38, median follow-up = 3.2 years). Conclusion: DTC-positivity at surgery after NAC was higher in younger patients, those with larger tumors, and those with residual disease at surgery. [ABSTRACT FROM AUTHOR]

Background: The ACOSOG Z1031 trial addressed the ability of three neoadjuvant aromatase inhibitors (NAIs) to reduce residual disease (cohort A) and to assess whether switching to neoadjuvant chemotherapy (NCT) after 4 weeks of receiving NAI with Ki67 greater than 10% increases pathologic complete response (pCR) in postmenopausal women with estrogen receptor-enriched (Allred score 6–8) breast cancer (BC). Methods: The study enrolled 622 women with clinical stage 2 or 3 estrogen receptor-positive (ER+) BC. Cohort A comprised 377 patients, and cohort B had 245 patients. The analysis cohort consisted of 509 patients after exclusion of patients who did not meet the trial eligibility criteria, switched to NCT or surgery due to 4-week Ki67 greater than 10%, or withdrew before surgery. Distribution of time to local-regional recurrence (LRR) was estimated using the competing-risk approach, in which distant recurrence and second primaries were considered to be competing-risk events. Patients who died without LRR, distant recurrence, or a second primary were censored at the last evaluation. Results: Of the 509 patients, 342 (67.2%) had breast-conserving surgery (BCS). Of 221 patients thought to require mastectomy at presentation, 50% were able to have BCS. Five (1%) patients had no residual disease in the breast or nodes at surgery. Among 382 women alive at this writing, 90% have been followed longer than 5 years. The 5-year cumulative incidence rate for LRR is estimated to be 1.53% (95% confidence interval 0.7–3.0%). Conclusions: Rarely does NAI result in pCR for patients with stage 2 or 3 ER+ BC. However, a significant proportion will have downstaged to allow for BCS. Local-regional recurrence after surgery is uncommon (1.5% at 5 years), supporting the use of BCS after NAI. [ABSTRACT FROM AUTHOR]

Background: Ductal carcinoma in situ (DCIS) is noninvasive breast cancer and therefore nodal staging is not routinely recommended. We evaluated the use of and factors associated with axillary surgery in DCIS in the National Cancer Database (NCDB). Methods: DCIS cases were identified from the NCDB 2012–2018. Use of axillary surgery was evaluated over time, and factors associated with axillary surgery were assessed for breast-conserving surgery (BCS) and mastectomy groups. Results: We identified 178,762 patients, median age of 60 years. Majority of DCIS (87%) was ER-positive, and 14% low, 43% intermediate, and 44% high grade. Median DCIS size was 1.1 cm. BCS was performed in 72%, whereas 28% had mastectomy. Overall axillary surgery was performed in 38% and was higher in patients undergoing mastectomy compared with patients undergoing BCS (88% vs. 19%, p < 0.001). At axillary surgery, the vast majority (92%) had 1–5 nodes examined, whereas 8% had >5 nodes examined. Over time, axillary surgery decreased in BCS patients (21% in 2012 to 17% in 2018, p < 0.001) but increased slightly in mastectomy patients (86% in 2012 to 90% in 2018, p < 0.001). On multivariable analysis, factors significantly associated with axillary surgery were younger patient age, larger tumor size, higher grade, and ER-negative status. Conclusions: Factors associated with axillary surgery reflect higher risk disease for upstage to invasive cancer, indicating surgeon judgment. However, despite axillary surgery being overtreatment of DCIS, it is common in mastectomy and is performed for one in five patients undergoing BCS. This provides opportunity for improvement in breast cancer care delivery. [ABSTRACT FROM AUTHOR]

Background: When a positive sentinel lymph node (SLN) is identified after neoadjuvant chemotherapy (NAC), completion axillary lymph node dissection (cALND) is generally recommended. We sought to evaluate the rate of non-SLN positivity and factors influencing this in patients with a positive SLN following NAC. Methods: We identified all patients at our hospital between 2006 and 2021 with a positive SLN (> 0.2 mm) following NAC who underwent cALND. Rates of positive non-SLN (NSLN) on cALND were compared by nodal status. Chi-square tests and multivariable logistic regression were used to assess factors predictive of positive NSLN and overall nodal burden. Results: Overall, 229 cases (177 cN+, 52 cN0 prior to NAC) with positive SLN(s) after NAC underwent cALND. Additional NSLN involvement was found in 129/229 (56.3%) patients, including 24/52 (46.2%) cN0 and 105/177 (59.3%) cN+ patients (p = 0.09). There was a trend for patients with SLN micrometastases to be less likely to have positive NSLN(s) than those with SLN macrometastases (38.5% vs. 58.6%; p = 0.05). Subgroup analyses showed no clinicopathologic factors significantly associated with additional axillary involvement for initially cN0 patients. Factors found to significantly influence NSLN positivity in the initially cN+ subgroup were HER2 status, multicentricity/multifocality, number of positive SLNs, and size of SLN metastasis. SLN metastasis size > 5 mm and three or more positive SLNs exerted the greatest influence on NSLN positivity. Conclusion: Rates of nodal positivity on cALND in the setting of positive SLN after NAC are high, supporting the current standard of routine cALND. In cN+ disease, NSLN positivity varies by tumor biology, multicentricity/multifocality, number of positive SLNs, and SLN metastasis size. [ABSTRACT FROM AUTHOR]

Objectives: To overcome the limitations of power Doppler in imaging angiogenesis, we sought to develop and investigate new quantitative biomarkers of a contrast-free ultrasound microvasculature imaging technique for differentiation of benign from malignant pathologies of breast lesion. Methods: In this prospective study, a new high-definition microvasculature imaging (HDMI) was tested on 521 patients with 527 ultrasound-identified suspicious breast masses indicated for biopsy. Four new morphological features of tumor microvessels, microvessel fractal dimension (mvFD), Murray's deviation (MD), bifurcation angle (BA), and spatial vascularity pattern (SVP) as well as initial biomarkers were extracted and analyzed, and the results correlated with pathology. Multivariable logistic regression analysis was used to study the performance of different prediction models, initial biomarkers, new biomarkers, and combined new and initial biomarkers in differentiating benign from malignant lesions. Results: The new HDMI biomarkers, mvFD, BA, MD, and SVP, were statistically significantly different in malignant and benign lesions, regardless of tumor size. Sensitivity and specificity of the new biomarkers in lesions > 20 mm were 95.6% and 100%, respectively. Combining the new and initial biomarkers together showed an AUC, sensitivity, and specificity of 97% (95% CI: 95–98%), 93.8%, and 89.2%, respectively, for all lesions regardless of mass size. The classification was further improved by adding the Breast Imaging Reporting and Data System (BI-RADS) score to the prediction model, showing an AUC, sensitivity, and specificity of 97% (95% CI: 95–98%), 93.8%, and 89.2%, respectively. Conclusion: The addition of new quantitative HDMI biomarkers significantly improved the accuracy in breast lesion characterization when used as a complementary imaging tool to the conventional ultrasound. Key Points: • Novel quantitative biomarkers extracted from tumor microvessel images increase the sensitivity and specificity in discriminating malignant from benign breast masses. • New HDMI biomarkers Murray's deviation, bifurcation angles, microvessel fractal dimension, and spatial vascularity pattern outperformed the initial biomarkers. • The addition of BI-RADS scores based on US descriptors to the multivariable analysis using all biomarkers remarkably increased the sensitivity, specificity, and AUC in all size groups. [ABSTRACT FROM AUTHOR]

Background: Although an advantage of neoadjuvant chemotherapy (NAC) is eradication of axillary disease, nodal pCR rates are much lower for ER+/HER2− breast cancer than other subtypes. We sought to evaluate the association of genomic risk with nodal pCR in ER+/HER2− disease. Methods: Patients with ER+/HER2− clinically-node-positive (cT0-cT4d/cN1-cN3/cM0) breast cancer treated with NAC and surgery 2010–2018 in the National Cancer Database were identified. Low genomic risk was classified as Oncotype Dx Recurrence Score (RS) 0–25, or Mammaprint 70-gene or RS coded as "Low." High genomic risk included RS >25, or 70-gene or RS coded as "High." Nodal pCR was compared between patients with high versus low genomic risk by using chi-square tests and multivariable logistic regression. Results: Of 15,698 patients, genomic risk was available for 692 of 15,698 (4.4%). High genomic risk was similar between patients aged <50 years versus 50+ (50.8% vs. 57.3%, p = 0.10). Nodal pCR was higher in high genomic risk (25.0%) than low genomic risk (10.4%, p < 0.001). This difference was observed both for patients aged <50 years (29.9% vs. 9.8%) and aged ≥50 years (22.7% vs. 10.8%). On multivariable analysis adjusted for potential confounding variables, including age, grade, and PR status, genomic risk was independently associated with decreased odds of residual nodal disease (odds ratio 0.49, p = 0.002). Conclusions: For patients with node-positive ER+/HER2− breast cancer treated with NAC, nodal pCR was highest in patients aged <50 years with high genomic risk tumors. In contrast, nodal pCR rates were low in patients with low genomic risk tumors, regardless of age. This information may help when counseling patients regarding axillary management. [ABSTRACT FROM AUTHOR]

Background: The distinct histologic appearance of invasive lobular carcinoma (ILC) may pose diagnostic challenges for sentinel lymph node (SLN) analysis. We evaluated the impact of cytokeratin immunohistochemistry (IHC) on SLN assessment in ILC and its contribution to pathologic nodal upstaging. Methods: We identified ILC patients treated with SLN surgery at our institution between September 2008 and August 2021. IHC for SLN assessment was employed at the discretion of the pathologist. Differences between groups evaluated with and without IHC were compared using Chi-square tests. Results: Overall, 608 cases of ILC were identified in patients who underwent SLN surgery. IHC was used in 301 cases (49.5%) and was not associated with cT category, pT category, or tumor grade. Use of IHC increased detection of SLN+ disease when isolated tumor cells (ITCs) were included in the analysis (35.9% with IHC vs. 21.2% without IHC; p < 0.001). There was no effect on nodal upstaging to micrometastatic disease (pN1mi) or greater (21.9% with IHC vs. 21.2% without IHC; p = 0.82). IHC did not increase the number of positive SLNs detected (median 1 with and without IHC) nor did it increase axillary lymph node dissection (ALND) rates (11.6% with IHC vs. 15.3% without IHC; p = 0.18). Conclusion: IHC improved detection of pN0(i+) disease among ILC patients undergoing SLN surgery. IHC did not increase upstaging to pN1mi or higher categories of nodal disease, detection of a greater number of positive SLNs, or ALND rates. Our data suggest routine use of IHC for SLN assessment in ILC patients does not add clinical utility. [ABSTRACT FROM AUTHOR]

Background: Fine needle aspiration (FNA) of sonographically suspicious axillary lymph nodes is helpful to clinically stage patients and guide consideration of neoadjuvant therapy in breast cancer. However, data are limited for suspicious nodes that are FNA negative. Our goal is to compare the frequency of node positivity between patients with negative axillary ultrasound (AUSneg) versus suspicious AUS with negative FNA (FNAneg). Methods: With IRB approval, we identified all clinically node-negative (cN0) patients with invasive breast cancer treated with upfront surgery at our tertiary care center between 2016 and 2021. AUS is routinely performed with FNA of suspicious lymph node(s). We compared clinicopathologic characteristics and nodal positivity rates between AUSneg and FNAneg groups. Results: A total of 1580 cN0 patients with invasive breast cancer were analyzed, including 1240 AUSneg and 340 FNAneg patients. The FNAneg group was younger (median age 59.7 years versus 63.5 years, p < 0.001) and had higher clinical T (cT) category (29.1% versus 21.7% with cT2–cT4 disease, p = 0.005). Final axillary pathologic node positivity did not differ significantly between the AUSneg and FNAneg groups (16.5% versus 19.1%, p = 0.25). Among FNAneg patients, 58/340 (17.1%) had a clip placed, with retrieval confirmed in 28/58 (48.3%). Of the 28 retrieved clipped nodes, 27 were sentinel nodes. Final pathologic nodal status (pN+%) did not differ between patients in whom retrieval of the clipped node was confirmed versus not confirmed (28.6% versus 16.7%, p = 0.28). Conclusions: Both patients with sonographically suspicious node(s) and negative FNA and patients with negative AUS have a similarly low chance of positive nodes. Additionally, routine targeted excision of FNA-negative clipped nodes is not warranted. [ABSTRACT FROM AUTHOR]

Background: Neoadjuvant chemotherapy (NAC) is standard for most triple-negative and human epidermal growth factor receptor 2 (HER2)+ breast cancers, and frequently downstages node-positive (cN+) disease, permitting omission of axillary dissection. In estrogen receptor (ER)+/HER2– disease, response rates are lower. Whether Ki67 is associated with axillary downstaging in ER+/HER2– disease is unknown. Methods: With institutional review board approval, we queried our institutional database to identify all patients with primary ER+/HER2– biopsy-proven cN+ breast cancer treated with NAC followed by surgery from January 2012 to December 2021. Nodal pathologic complete response (pCR) rates were evaluated by pretreatment Ki67 and patient age. Results: 315 patients (median age 50 years) were included. Nodal pCR rate was 24.8% (78/315) and was higher in patients aged < 50 years than ≥ 50 years (31.8% versus 17.7%, p = 0.004). Ki67 was available on 236 patients (74.9%). Median Ki67 was 29.0% (range 1–98%) and did not differ by age category (p = 0.23). Patients with nodal pCR had higher Ki67 (median 40.3% versus 25.0%, p < 0.001). Nodal pCR rates were 28.4% (Ki67 ≥ 20%) versus 8.1% (Ki67 < 20%) (p < 0.001). On multivariable analysis, Ki67 and age category were predictive of nodal pCR. Combining these two parameters together, nodal pCR rates in age < 50 years were 35.8% when Ki67 ≥ 20% versus 14.3% with Ki67 < 20% (p = 0.02). In contrast, for age ≥ 50 years, nodal pCR was 21.0% for Ki67 ≥ 20% versus 2.6% with Ki67 < 20% (p = 0.008). Conclusions: In ER+/HER2– breast cancer, nodal downstaging with NAC is associated with age (< 50 years) and Ki67 (≥ 20%). Age and Ki67 should be considered for NAC decision-making and can identify patients with high rates of nodal downstaging (36%) who would benefit from NAC to enable axillary preservation. [ABSTRACT FROM AUTHOR]

Purpose: To identify the practice patterns related to use of surveillance mammography in male breast cancer (MaBC) survivors. Methods: Using administrative claims data from OptumLabs Data Warehouse, we identified men who underwent surgery for breast cancer during 2007–2017. We calculated the proportion of men who had at least one mammogram (a) within 13 months for all patients and (b) within 24 months amongst those who maintained their insurance coverage for at least that length of time after surgery. Multivariate logistic regression modeling was used to identify factors associated with mammography within each timeframe. Results: Out of 729 total MaBC survivors, 209 (29%) underwent mammography within 13 months after surgery. Among those who had lumpectomy, 41% underwent mammography, whereas among those who had mastectomy, 27% had mammography. Amongst 526 men who maintained consistent insurance coverage for 24 months after surgery, 215 (41%) underwent mammography at least once during that 24-month period. In this cohort, the proportion who had at least one mammogram during the 24-month period was 49% after lumpectomy and 40% after mastectomy. In a multivariate logistic regression model, more recent diagnosis (2015+) and older age at diagnosis were associated with lower odds of undergoing mammography, while receipt of radiation was associated with higher odds of undergoing mammography. Conclusions: Although recent ASCO guidelines recommend surveillance mammography after lumpectomy, a minority of MaBC survivors undergo surveillance mammography, even after lumpectomy. This is likely due to the paucity of data regarding the true benefits and harms of surveillance/screening mammography for MaBC. [ABSTRACT FROM AUTHOR]

Background: Management of the axilla in patients with cT1–2N0 breast cancer with one or two positive (+) sentinel lymph nodes (SLNs) is often debated, especially in patients undergoing mastectomy. In 2018, the National Cancer Database (NCDB) began collecting the number of +SLNs, enabling identification of patients with one or two +SLNs for the first time. Methods: From the 2018 NCDB participant user file (PUF), all cT1–2N0M0 patients with one or two +SLNs were identified. The rates of completion axillary lymph node dissection (cALND) after breast-conserving surgery (BCS) and mastectomy were determined, and logistic regression was used to assess factors associated with cALND. Results: Of 10,531 patients with one or two +SLNs, cALND was performed in 807/6498 (12.4%) BCS patients and 1845/4033 (45.7%) mastectomy patients (p < 0.001). Factors associated with cALND in BCS were cT2 versus cT1 (16.0% versus 11.1%, p < 0.001), two versus one positive SLN (20.7% versus 10.8%, p < 0.001), and higher tumor grade (grade 3: 15.4% versus grade 1–2: 11.7%, p = 0.002). Factors associated with cALND among mastectomy were cT2 versus cT1 (48.2% versus 43.7%, p = 0.004), two versus one positive SLN (56.6% versus 42.8%, p < 0.001), younger age (age < 50 years: 49.0%, age 50+ years: 44.1%, p = 0.004), and Hispanic ethnicity (55.7% versus 45.1%, p = 0.001). After adjusting for pN category, adjuvant radiation was significantly less likely after mastectomy if cALND was performed (odds ratio (OR) 0.51, p < 0.001). Conclusions: Omission of cALND with one or two +SLNs in BCS is common. Deescalation of axillary therapy in mastectomy is slower, with a cALND rate of 45.7% in 2018. With the recent updates to the National Cancer Care Network (NCCN) guidelines, we anticipate continued deescalation of axillary therapy in mastectomy patients. [ABSTRACT FROM AUTHOR]

Introduction: The primary aim of this study was to evaluate patient-reported outcome measures in patients undergoing mastectomy with and without breast reconstruction (immediate or delayed) with and without nipple preservation. Methods: All female patients undergoing mastectomy between 2011 and 2015 at Mayo Clinic Rochester were identified and were mailed the BREAST-Q survey. Breast satisfaction, psychosocial well-being, and sexual well-being were evaluated and compared by surgery type using Wilcoxon rank-sum tests for univariate analysis and linear regression for multivariable analysis adjusting for potential confounders. Results: Of 1547 patients, 771 completed the BREAST-Q survey (response rate 50%). Of these 771 respondents, 237 (31%) did not have reconstruction, 198 (26%) had nipple-sparing mastectomy with reconstruction (NSM), and 336 (44%) had skin-sparing mastectomy with reconstruction (SSM) ± nipple–areolar complex (NAC) reconstruction (via surgery ± tattoo). Patients with breast reconstruction had consistently higher BREAST-Q scores versus those without. Comparing NSM with all SSMs, there was no difference in satisfaction with breasts (mean 71.8 vs. 70.2, p = 0.21) or psychosocial well-being (mean 81.9 vs. 81.3, p = 0.47); however, sexual well-being was significantly higher in the NSM group on univariate (mean 64.5 vs. 58.0, p = 0.002) and multivariable (β = −4.69, p = 0.03) analysis. Sexual well-being scores were similar for NSM and the SSM subgroups with any type of NAC reconstruction. Conclusions: This study demonstrates that NSM positively impacts patient sexual well-being after breast reconstruction compared with SSM, particularly SSM without nipple reconstruction or tattoo. SSM with any type of NAC reconstruction achieved similar satisfaction and sexual well-being to those undergoing NSM. [ABSTRACT FROM AUTHOR]

Introduction: The COVID-19 pandemic caused delays in breast cancer management forcing clinicians to potentially alter treatment recommendations. This study compared breast cancer stage at diagnosis and rates of neoadjuvant therapy among women presenting to our institution before and during COVID-19. Methods: Retrospective chart review of patients with a new breast cancer diagnosis from March 2020–August 2020 (during-COVID-19) were compared with March 2019–August 2019 (pre-COVID-19). We compared stage at diagnosis, clinical/demographic features, and neoadjuvant therapy use between the time periods. Results: A total of 573 patients included: 376 pre-COVID-19, 197 during-COVID-19. Method of cancer detection was by imaging in 66% versus 63% and by physical findings/symptoms in 34% versus 37% of patients comparing pre-COVID-19 to during-COVID-19, p = 0.47. Overall clinical prognostic stage did not differ significantly (p = 0.39) between the time periods, nor did cM1 disease (2% in each period); 23% pre-COVID-19 and 27% during-COVID-19 presented with cN+ disease (p = 0.38). Neoadjuvant therapy use was significantly higher during-COVID-19 (39%) versus pre-COVID-19 (29%, p = 0.02) driven by increased neoadjuvant endocrine therapy (NET) use (7% to 16%, p = 0.002), whereas neoadjuvant chemotherapy use did not change (22% vs. 23%, p = 0.72). In HR+/HER2− disease, NET use increased from 10% pre-COVID-19 to 23% during-COVID-19 (p = 0.001) with a significant increase in stage I patients (7 to 22%, p < 0.001) and nonsignificant increases in stage II (18 to 23%, p = 0.63) and stage III (9 to 29%, p = 0.29). Conclusions: Breast cancer stage at diagnosis did not differ significantly during-COVID-19 compared with pre-COVID-19. More patients during-COVID-19 were treated with NET, which was significantly increased in stage I HR+/HER2− disease. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: In 2016, SSO Choosing Wisely guidelines recommended against routine sentinel lymph node (SLN) surgery in women ≥ 70 with HR+ cN0 breast cancer. Following this, we identified a group of women at low-risk of nodal positivity where SLN may be omitted (grade 1, cT1mi-T1c, or grade 2, cT1mi-T1b). This study evaluates the impact of these changes on our practice. Methods: Retrospective chart review of women aged ≥ 70 years with HR+ cN0 breast cancer at our institution from 2010 to 2020. We compared SLN use before (2010–2016)/after (2017–2020) guideline release according to clinical risk and the association with adjuvant therapy. Results: A total of 1015 breast cancers in 987 women identified. SLN surgery rate significantly decreased from 90.6% (2010–2016) to 62.8% in 2020 (p < 0.001). This was driven by breast-conserving surgery (BCS) with SLN rates of 88.2% (2010–2016) and 46.7% in 2020. During 2017–2020, SLN use varied by risk within BCS patients: 52.2% low-risk, 81.9% higher-risk, p < 0.001. In contrast, in mastectomy patients SLN was performed in ≥ 98% regardless of risk level. SLN positivity was 13.4% overall: 7.4% in low-risk and 20.8% in higher-risk, p < 0.001. After adjusting for age and clinical risk, SLN use was not associated with adjuvant radiation [odds ratio (OR) 1.61, p = 0.11] or endocrine therapy (OR 1.12, p = 0.71). Conclusions: The Society of Surgical Oncology guideline release, followed by implementation of a clinical tool to stratify by nodal risk, was associated with decreased SLN use in women aged ≥ 70 years, in those with clinically low-risk HR+ disease surgically treated with BCS. Adjusting for confounders, omission of SLN surgery was not associated with use of subsequent adjuvant radiation or hormonal therapy. [ABSTRACT FROM AUTHOR]

Background: Randomized clinical trials support deescalation of axillary surgery in breast cancer patients with low-volume axillary disease treated with a surgery-first approach. However, few data exist to guide axillary surgery following neoadjuvant endocrine therapy (NET). Therefore, we evaluated the extent and outcomes of axillary surgery in a contemporary cohort of NET patients, a treatment approach that has become particularly relevant during the coronavirus disease-19 (COVID-19) pandemic. Patients and Methods: We identified invasive breast cancer patients treated with NET between October 2008 and November 2019. Patients presenting with stage IV disease or recurrent disease were excluded. Statistical analyses were performed using chi-square, Fisher's exact, and Wilcoxon rank-sum tests. Results: 194 invasive breast cancers in 186 patients (median age 66 years) were evaluated; 81 patients had breast-conserving surgery (BCS), while 113 underwent mastectomy. Eighty-four patients (43.3%) were biopsy-proven cN+ with 4/84 (4.8%) ypN0 following NET. Among cN+ patients, 14 (16.7%) had sentinel lymph node biopsy (SLNB) only, 27 (32.1%) had SLNB + axillary lymph node dissection (ALND), and 43 (51.2%) had ALND. Among 110 cN0 patients, 99 had axillary surgery with 28/99 (28.3%) ypN+: SLNB in 83 (75.5%), SLNB+ALND in 14 (12.7%), and ALND in 2 (1.8%). Among all ypN+ patients, 23/108 (21.3%) had SLNB alone: 18/43 (41.9%) of BCS and 5/65 (7.7%) mastectomy patients (p < 0.001). After median follow-up of 35 months, no regional recurrences were observed. Conclusions: Among biopsy-proven cN+ NET patients, we observed deescalation of axillary surgery in selected patients, despite a low nodal pathologic complete response (pCR) rate, without nodal recurrences. These data suggest that patients with low-volume axillary disease treated with NET may be managed similarly to patients treated with a surgery-first approach. [ABSTRACT FROM AUTHOR]

HER2-targeted therapy dramatically improves outcomes in early breast cancer. Here we report the results of two HER2-targeted combinations in the neoadjuvant I-SPY2 phase 2 adaptive platform trial for early breast cancer at high risk of recurrence: ado-trastuzumab emtansine plus pertuzumab (T-DM1/P) and paclitaxel, trastuzumab and pertuzumab (THP). Eligible women have >2.5 cm clinical stage II/III HER2+ breast cancer, adaptively randomized to T-DM1/P, THP, or a common control arm of paclitaxel/trastuzumab (TH), followed by doxorubicin/cyclophosphamide, then surgery. Both T-DM1/P and THP arms 'graduate' in all subtypes: predicted pCR rates are 63%, 72% and 33% for T-DM1/P (n = 52), THP (n = 45) and TH (n = 31) respectively. Toxicity burden is similar between arms. Degree of HER2 pathway signaling and phosphorylation in pretreatment biopsy specimens are associated with response to both T-DM1/P and THP and can further identify highly responsive HER2+ tumors to HER2-directed therapy. This may help identify patients who can safely de-escalate cytotoxic chemotherapy without compromising excellent outcome. HER2-targeted therapy improves patient's outcome in early breast cancer. Here, the authors present the efficacy and biomarker analysis of two HER2-targeted combinations (ado-trastuzumab emtansine plus pertuzumab and paclitaxel, trastuzumab and pertuzumab) in the context of the neoadjuvant I-SPY2 phase 2 adaptive platform trial for early breast cancer at high risk of recurrence. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has had widespread impact on healthcare, resulting in modifications to how we perform cancer research, including clinical trials for cancer. The impact of some healthcare workers and study coordinators working remotely and patients minimizing visits to medical facilities impacted clinical trial participation. Clinical trial accrual dropped at the onset of the pandemic, with improvement over time. Adjustments were made to some trial protocols, allowing telephone or video-enabled consent. Certain study activities were permitted to be performed by local healthcare providers or at local laboratories to maximize patients' ability to continue on study during these challenging times. We discuss the impact of COVID-19 on cancer clinical trials and changes at the local, cooperative group, and national level. [ABSTRACT FROM AUTHOR]

Background: Given reports of low response rates to neoadjuvant chemotherapy (NAC) in invasive lobular carcinoma (ILC), we evaluated whether use of alternative strategies such as neoadjuvant endocrine therapy (NET) is increasing. Additionally, we investigated whether NET is associated with more breast conservation surgery (BCS) and less extensive axillary surgery in those with ILC. Patients and Methods: We queried the NCDB from 2010 to 2016 and identified all women with stage I–III hormone receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2−) ILC who underwent surgery. We used Cochrane–Armitage tests to evaluate trends in utilization of the following treatment strategies: NAC, short-course NET, long-course NET, and primary surgery. We compared rates of BCS and extent of axillary surgery stratified by clinical stage and tumor receptor subtype for each treatment strategy. Results: Among 69,312 cases of HR+/HER2− ILC, NAC use decreased slightly (from 4.7 to 4.2%, p = 0.007), while there was a small but significant increase in long-course NET (from 1.6 to 2.7%, p < 0.001). Long-course NET was significantly associated with increased BCS in patients with cT2–cT4 disease and less extensive axillary surgery in clinically node positive patients with HR+/HER2− tumors. Conclusions: Primary surgery remains the most common treatment strategy in patients with ILC. However, NAC use decreased slightly over the study period, while the use of long-course NET had a small increase and was associated with more BCS and less extensive axillary surgery. [ABSTRACT FROM AUTHOR]