A spatially resolved single-cell genomic atlas of the adult human breast.

The adult human breast is comprised of an intricate network of epithelial ducts and lobules that are embedded in connective and adipose tissue1-3. Although most previous studies have focused on the breast epithelial system4-6, many of the non-epithelial cell types remain understudied. Here we constructed the comprehensive Human Breast Cell Atlas (HBCA) at single-cell and spatial resolution. Our single-cell transcriptomics study profiled 714,331 cells from 126 women, and 117,346 nuclei from 20 women, identifying 12 major cell types and 58 biological cell states. These data reveal abundant perivascular, endothelial and immune cell populations, and highly diverse luminal epithelial cell states. Spatial mapping using four different technologies revealed an unexpectedly rich ecosystem of tissue-resident immune cells, as well as distinct molecular differences between ductal and lobular regions. Collectively, these data provide a reference of the adult normal breast tissue for studying mammary biology and diseases such as breast cancer.

National trends in neoadjuvant chemotherapy utilization in patients with early-stage node-negative triple-negative breast cancer: the impact of the CREATE-X trial.

PURPOSE: Neoadjuvant chemotherapy (NAC) for triple-negative breast cancer (TNBC) allows for assessment of tumor pathological response and has survival implications. In 2017, the CREATE-X trial demonstrated survival benefit with adjuvant capecitabine in patients TNBC and residual disease after NAC. We aimed to assess national rates of NAC for cT1-2N0M0 TNBC before and after CREATE-X and examine factors associated with receiving NAC vs adjuvant chemotherapy (AC). METHODS: A retrospective cohort study of women with cT1-2N0M0 TNBC diagnosed from 2014 to 2019 in the National Cancer Database (NCDB) was performed. Variables were analyzed via ANOVA, Chi-squared, Fisher Exact tests, and a multivariate linear regression model was created. RESULTS: 55,633 women were included: 26.9% received NAC, 52.4% AC, and 20.7% received no chemotherapy (median ages 53, 59, and 71 years, p < 0.01). NAC utilization significantly increased over time: 19.5% in 2014-15 (n = 3,465 of 17,777), 27.1% in 2016-17 (n = 5,140 of 18,985), and 33.6% in 2018-19 (n = 6,337 of 18,871, p < 0.001). On multivariate analysis, increased NAC was associated with younger age (< 50), non-Hispanic white race/ethnicity, lack of comorbidities, cT2 tumors, care at an academic or integrated-network cancer program, and diagnosis post-2017 (p < 0.05 for all). Patients with government-provided insurance were less likely to receive NAC (p < 0.01). Women who traveled > 60 miles for treatment were more likely to receive NAC (p < 0.01). CONCLUSION: From 2014 to 2019, NAC utilization increased for patients with cT1-2N0M0 TNBC. Racial, socioeconomic, and access disparities were observed in who received NAC vs AC and warrants interventions to ensure equitable care.

Clinical outcomes after 1 versus 2-3 lines of neoadjuvant therapy in stage III inflammatory breast cancer.

PURPOSE: Many stage III inflammatory breast cancer (IBC) patients experience a sufficient response to first-line (1L) neoadjuvant chemotherapy (NAC) to allow surgery, while some require additional NAC. We evaluated the pathologic complete response (pCR), breast cancer-free survival (BCFS) and overall survival (OS) among patients requiring 1 vs. 2-3 lines (L) of NAC prior to surgery. METHODS: Stage III IBC patients from 2 institutions who received 1L or 2-3L of NAC prior to surgery were identified. Hormone receptor and HER2 status, grade, and pCR were evaluated. BCFS and OS were evaluated by the Kaplan-Meier method. Multivariable Cox models were utilized to estimate the hazard ratio (HR). RESULTS: 808 eligible patients (1997-2020) were identified (median age 51 years, median follow-up 69 months). 733 (91%) had 1L and 75 (9%) had 2-3L of NAC. Grade III, triple-negative and HER2-positive disease were more prevalent in 2-3L patients. 178 (24%) 1L and 14 (19%) 2-3L patients had pCR. 376 1L patients and 41 2-3L patients had recurrences. The 5-year BCFS was worse for the 2-3L group (33 vs. 46%, HR = 1.37; 95% CI 0.99-1.91). However, in 192 patients with a pCR, BCFS was similar (76 vs. 83% in 1L vs. 2-3L, respectively). There were 308 deaths (276 among 1L and 32 among 2-3L patients). The 5-year OS in 1L vs. 2-3L was 60 vs. 53% (HR = 1.32, 95% CI 0.91-1.93). CONCLUSIONS: Among stage III IBC patients, pCR rates were similar, irrespective of the NAC lines number, and BCFS and OS were comparable with pCR after 1L and 2-3L.

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

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

Lobular Neoplasia Diagnosed by MRI-Guided Breast Biopsy: Identifying Upgrade Rate to Malignancy and Outcomes of Clinical and Surgical Management.

OBJECTIVE: The aim of this study was to determine surgical and clinical outcomes of lobular neoplasia (LN) diagnosed by magnetic resonance imaging (MRI) biopsy, including upgrade to malignancy, and to assess for characteristics associated with upgrade. METHOD: A single-institution retrospective study, between 2013 and 2022, of patients with histopathological findings of LN via MRI-guided biopsy was performed using an institutional database and review of the electronic medical records. Decision for excision or surveillance was made by a multidisciplinary team per institutional practice. Patient demographics and imaging characteristics were summarized using descriptive analyses. Upgrade was defined as upgrade to cancer on surgical pathology for patients treated with excision or the development of cancer at the biopsy site during surveillance. The Wilcoxon rank-sum test and Fisher's exact test were used to compare features of the upgraded cohort with the remainder of the group. RESULTS: Ninety-four MRI biopsies diagnosing LN were included. Median age was 57 years (range 37-78 years). Forty-six lesions underwent excision while 48 lesions were surveilled. The upgrade rate was 7.4% (7/94). Upgrades in the excised cohort consisted of pleomorphic lobular carcinoma in situ (LCIS; n = 1), ductal carcinoma in situ (DCIS; n = 3) and invasive lobular carcinoma (ILC; n = 2), while one interval development of DCIS was observed at the site of biopsy in the surveillance cohort. No MRI or patient variables were associated with upgrade. CONCLUSIONS: In this contemporary cohort of MRI-detected LNs, the upgrade rate was low. Omission of surgery for MRI-detected LNs in carefully selected patients may be considered in a shared decision-making capacity between the patient and the treatment team. Larger cohorts are needed to determine factors predictive of upgrade risk.

Assessing Surgeon Familiarity with the Commission on Cancer Operative Standards for Cancer Surgery.

BACKGROUND: In response to growing evidence that proper performance of operative techniques during cancer surgery is associated with improved patient outcomes, the American College of Surgeons (ACS) implemented six operative standards as part of Commission on Cancer (CoC) accreditation. This study aimed to assess surgeon familiarity with these standards when first introduced and 2 years after their adoption. METHODS: The ACS Cancer Surgery Standards Program distributed an anonymous 36-question survey to CoC-accredited cancer programs in 2021 and 2023. Questions specific to operative techniques determined the Surgery Score, and those specific to the accreditation standards determined the Standards Score. Mean scores were compared using one-way analysis of variance (ANOVA) and t tests. RESULTS: The survey was completed by 376 surgeons in 2021 and 380 surgeons in 2023. The Surgery Scores were higher than the Standards Scores in 2021 and 2023. The surgeons who practiced at institutions with CoC accreditation had significantly higher Standards Scores than the surgeons at non-accredited institutions in 2021 (p = 0.005) and 2023 (p = 0.004), but not significantly different Surgery Scores. CONCLUSIONS: The baseline survey in 2021 demonstrated significant knowledge of technical aspects of cancer surgery among a broad surgeon base, but a need for greater understanding of the accreditation standards. The repeat survey distribution 2 years after rollout of the operative standards and associated educational programing showed increased awareness surrounding the operative standards in 2023 and a trend toward improvement in knowledge of the accreditation standards across all specialties. Further evaluation will be directed toward compliance with the accreditation standards.

Clinical Outcomes in Patients with Early Stage Node-Negative HER2-Positive Breast Cancer Receiving Upfront Surgery or Neoadjuvant Systemic Therapy.

BACKGROUND: HER2-positive breast cancer is traditionally treated with neoadjuvant systemic therapy (NST), but optimal treatment sequencing is less clear in patients with small tumors. We investigated clinicopathologic and oncologic outcomes in early stage HER2-positive breast cancer. PATIENTS AND METHODS: An institutional database was queried to identify patients with cT1-2 (≤ 3 cm) N0M0, HER2-positive breast cancer treated from 2015 to 2020 and compared upfront surgery and NST cohorts. Logistic regression was performed to identify factors predicting upstaging. Survival outcomes by group were compared using log-rank tests. RESULTS: Of 256 patients identified, 170 (66.4%) received upfront surgery and 86 (33.6%) NST. The NST cohort was younger and had more cT2 and grade 3 tumors and negative sentinel nodes. There was no significant difference in type of breast surgery or receipt of axillary lymphadenectomy. After upfront surgery, 4 (2.4%) patients had upstaging to pT > 3 cm and 18 (10.6%) to pN1-3. No factors predicted upstaging. After NST, 47 (54.7%) achieved pathologic complete response and 3 (3.5%) had upstaging to ypN1-3 with older age (OR 1.08, p = 0.004) and hormone receptor-positive status (OR 7.07, p = 0.002) identified as predictors. At median follow-up of 3.55 years, 10 (3.9%) patients had recurrence and 5 (2.0%) patients died. There were no significant differences in oncologic outcomes between groups. CONCLUSIONS: Patients with cT1-2 (≤ 3 cm)N0 HER2-positive breast cancer selected for NST have higher-risk disease. Low rates of pathologic upstaging were observed with no difference in surgical treatments and overall excellent oncologic outcomes in both groups. These findings may guide decision-making regarding treatment sequencing for patients with early stage HER2-positive disease.

Standardization of Colon Resection for Cancer: An Overview of the American College of Surgeons Commission on Cancer Standard 5.6.

The purpose of this editorial is to review the American College of Surgeons Commission on Cancer Standard 5.6, which pertains to curative intent colon resections performed for cancer. We first provide a broad overview of the Operative Standard, followed by the underlying rationale, technical components, and documentation requirements.

Does Neoadjuvant Chemotherapy in Clinical T1-T2 N0 Triple-Negative Breast Cancer Increase the Extent of Axillary Surgery?

BACKGROUND: Current management strategies for early-stage triple-negative breast cancer (TNBC) include upfront surgery to determine pathologic stage to guide chemotherapy recommendations, or neoadjuvant chemotherapy (NAC) to de-escalate surgery, elucidate tumor response, and determine the role of adjuvant chemotherapy. However, patients who receive NAC with residual pathological nodal (pN) involvement require axillary lymph node dissection (ALND) as they are Z11/AMAROS ineligible. We aimed to evaluate the impact of NAC compared with upfront surgery on pN status and ALND rates in cT1-2N0 TNBC. METHODS: The National Cancer Database (NCDB) was queried for women with operable cT1-2N0 TNBC from 2014 to 2019. Demographic, clinicopathologic, and treatment data were collected. Multivariable linear regression analysis was performed to assess the odds of pN+ disease and undergoing ALND. RESULTS: Overall, 55,624 women were included: 26.9% (n = 14,942) underwent NAC and 73.1% (n = 40,682) underwent upfront surgery. The NAC cohort was younger (mean age 52.9 vs. 61.3 years; p < 0.001) with more cT2 tumors (71.6% vs. 31.0%; p < 0.001), and had lower ALND rates (4.3% vs. 5.5%; p < 0.001). The upfront surgery cohort was more likely to have one to three pathologically positive nodes (12.1% vs. 6.5%; odds ratio [OR] 2.37, 95% confidence interval (CI) 2.17-2.58; p < 0.001) but there was no difference in the likelihood of ALND (OR 1.1, 95% CI 0.99-1.24; p = 0.08). CONCLUSION: Patients who underwent upfront surgery were more likely to be pN+; however, ALND rates were similar between the two cohorts. Thus, the use of NAC does not result in a higher odds of ALND and the decision for NAC should be individualized and based on modern guidelines and systemic therapy benefits.

Self-Reported Management of Inflammatory Breast Cancer Among the American Society of Breast Surgeons Membership: Consensus and Opportunities.

BACKGROUND: Inflammatory breast cancer (IBC) is rare and biologically aggressive. We sought to assess diagnostic and management strategies among the American Society of Breast Surgeons (ASBrS) membership. PATIENTS AND METHODS: An anonymous survey was distributed to ASBrS members from March to May 2023. The survey included questions about respondents' demographics and information related to stage III and IV IBC management. Agreement was defined as a shared response by >80% of respondents. In areas of disagreement, responses were stratified by years in practice, fellowship training, and annual IBC patient volume. RESULTS: The survey was administered to 2337 members with 399 (17.1%) completing all questions and defining the study cohort. Distribution of years in practice was 26.0% 0-10 years, 26.6% 11-20 years and 47.4% > 20 years. Overall, 51.2% reported surgical oncology or breast fellowship training, 69.2% maintain a breast-only practice, and 73.5% treat < 5 IBC cases/year. Agreement was identified in diagnostic imaging, trimodal therapy, and mastectomy with wide skin excision for stage III IBC. Lack of agreement was identified in surgical management of the axilla; respondents with < 10 years in practice or fellowship training were more likely to perform axillary dissection for cN0-N2 stage III IBC. Locoregional management of stage IV IBC was variable. CONCLUSIONS: Among ASBrS members, there is consensus in diagnostic evaluation, treatment sequencing and surgical approach to the breast in stage III IBC. Differences exist in surgical management of the cN0-2 axilla with uptake of de-escalation strategies. Clinical trials are needed to evaluate oncologic safety of de-escalation in this high-risk population.

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

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

The Prevalence of Sentinel Lymph Node Positivity and Implications for the Utility of Frozen Section Diagnosis Following Neoadjuvant Systemic Therapy in Patients with Clinically Node-Negative HER2-Positive or Triple-Negative Breast Cancer.

BACKGROUND: Axillary dissection is the standard of care for patients with positive sentinel lymph nodes (SLNs) following neoadjuvant systemic therapy. Frozen section can provide intraoperative information regarding the need for axillary dissection during the index operation. However, there are limited data on the utility of frozen section in patients with clinically node-negative (cN0) HER2-positive or triple-negative breast cancer. METHODS: We conducted a single-institution observational cohort study including patients with non-inflammatory, cN0, HER2-positive or triple-negative breast cancer treated with neoadjuvant systemic therapy between 2015 and 2019. We estimated the prevalence of SLN positivity and the diagnostic test characteristics of SLN frozen section. RESULTS: Overall, 662 patients were eligible for inclusion, and 44 patients had one or more positive SLNs (prevalence: 6.6%, 95% confidence interval [CI] 4.9-8.8). There were 490 (74.0%) patients who had intraoperative frozen section, and 19 (3.9%) tested positive among 33 (6.7%) with positive final pathology. Frozen section sensitivity was 57.6% (95% CI 39.2-74.5), specificity was 100% (95% CI 99.2-100), positive predictive value was 100% (95% CI 82.4-100), and negative predictive value was 97.0% (95% CI 95.1-98.4). The sensitivity of frozen section for detection of micrometastases or isolated tumor cells was 35.3% (95% CI 14.2-61.7). CONCLUSION: In patients with cN0 HER2-positive or triple-negative breast cancer who have been treated with neoadjuvant therapy, positive SLNs are uncommon and frozen section sensitivity is modest. Decisions to defer SLN evaluation to final pathology, which may be reasonable in many settings, can be informed, in part, by these findings.

Lactation Education for Surgeons: American Society of Breast Surgeons (ASBrS) Survey Demonstrates Strong Member Interest in Expanded Training.

BACKGROUND: The availability and extent of breastfeeding-specific surgical training has not been previously described. We aimed to survey breast surgeons on their lactation education and desire for additional knowledge. METHODS: Members of the American Society of Breast Surgeons were invited via email to anonymously complete an electronic survey from 27 October 2021 to 23 January 2022. The survey content included demographic information, sources of lactation education, and desired topics and methods for further training. Descriptive statistics were used to analyze the data. RESULTS: A total of 2698 surveys were delivered and 542 (20.1%) completed. While nearly all respondents (99%) reported treating lactating patients at least once or twice per year, 78% reported that their training was inadequate. The most frequently cited sources of lactation information were peer-to-peer informal knowledge sharing (50%) and personal experience with breastfeeding (44%). Nearly all respondents (99%) agreed that formal lactation education would benefit breast surgeons. Specific topics of interest included management of patients with complications of lactation (48%), management of lactating patients with a new diagnosis of breast cancer (47%), and counseling patients with pregnancy-associated breast cancer who desire to breastfeed (46%). The most frequently recommended educational formats included presentation at a national conference (60%), evidence-based management guidelines (58%), webinar (55%), and workshop/course (47%). CONCLUSION: Breast surgeons self-report minimal formal training in the management of benign and malignant breast disease in lactating patients and strong desire for expanded education. Development of clinical practice guidelines and additional educational content for surgeons should be considered to meet the needs of this patient population.

Low Rates of Local-Regional Recurrence Among Inflammatory Breast Cancer Patients After Contemporary Trimodal Therapy.

BACKGROUND: Inflammatory breast cancer (IBC) represents a rare (2-3 %) but aggressive subset of breast cancer with a historically reported 5-year overall survival rate of 50 % and a 3-year local-regional recurrence (LRR) rate of 20 %. This study aimed to evaluate long-term LRR in a contemporary cohort of non-metastatic IBC patients undergoing trimodal therapy at a single institution and identify factors associated with local and distant failure. METHODS: The study identified 262 patients with non-metastatic IBC who received trimodal therapy (neoadjuvant chemotherapy, modified radical mastectomy, adjuvant radiation) from an institutional prospective database (2007-2019). Long-term outcomes of local-regional and distant metastasis were reported. Survival outcomes were analyzed using the Cox proportional hazards regression model. RESULTS: The median age at diagnosis was 52 years, and the median follow-up period was 5.1 years. In this cohort, 82 (31.3 %) patients achieved a pathologic complete response (pCR) in the breast and axilla. Local-regional recurrence was observed in 18 (6.9 %) patients (11 isolated to the chest wall, 4 isolated to regional nodes, and 3 involving chest wall and ipsilateral axillary nodes). Distant metastasis was observed in 92 (35.1 %) patients. During the follow-up period, 90 deaths occurred. In the multivariate analysis, pCR was associated with improved disease-free survival (hazard ratio [HR], 0.26; 95 % confidence interval [CI], 0.13-0.51; p = 0.001) and overall survival (HR, 0.31; 95 % CI, 0.15-0.65; p = 002). CONCLUSIONS: During a median follow-up period longer than 5 years, the local-regional relapse rate for the IBC patients treated with contemporary trimodal therapy was 6.9%, similar to that for the non-IBC patients. After chemotherapy, surgical resection with modified radical mastectomy to negative margins and postmastectomy radiation therapy resulted in excellent long-term local-regional control.

To Dissect or Not to Dissect: Can We Predict the Presence of Four or More Axillary Lymph Node Metastases in Postmenopausal Women with Clinically Node-Negative Breast Cancer?

BACKGROUND: Axillary lymph node (ALN) involvement is important for prognosis and guidance of multidisciplinary treatment of breast cancer patients. This study sought to identify preoperative clinicopathologic factors predictive of four or more pathologically positive ALNs in patients with cN0 disease and to develop a predictive nomogram to inform therapy recommendations. METHODS: Using an institutional prospective database, the study identified postmenopausal women with cN0 invasive breast cancer undergoing upfront sentinel lymph node biopsy (SLNB) with or without completion ALND (cALND) between 1993 and 2007. Logistic regression analyses identified factors predictive of four or more positive nodes in the cN0 population and patients with one, two, or more SLNs. RESULTS: The study identified 2532 postmenopausal women, 615 (24.3%) of whom underwent cALND. In the univariate analysis, tumor size, lymphovascular (LVI), histology, estrogen receptor (ER)-positive status, and multifocality/multicentricity were predictive of four or more positive nodes (n = 63; p < 0.05), and all except ER status were significant in the multivariate analysis. Of the 2532 patients, 1263 (49.2%) had hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative disease, and 30 (2.4%) were found to have four or more positive nodes. Of the 130 patients with exactly one positive SLN who underwent cALND (n = 130, 5.4%), 7 had four or more positive nodes, with grade as the only predictive factor (p = 0.01). Of the 33 patients with two or more positive SLNs who underwent cALND, 9 (27.3%) had four or more positive nodes after cALND, but no factors were predictive in this subset. CONCLUSION: Postmenopausal women with early-stage cN0 HR-positive, HER2-negative breast cancer with a single positive SLN had a very low risk (5%) of having four or more positive nodes on final pathology. With such a low risk of N2 disease, limited staging with SLNB may be sufficient to guide therapy decisions for this subset of patients.

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

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

Lymphedema in Inflammatory Breast Cancer Patients Following Trimodal Treatment.

BACKGROUND: Breast cancer-related lymphedema (BCRL) is a debilitating sequela of breast cancer treatment and is becoming a greater concern in light of improved long-term survival. Inflammatory breast cancer (IBC) is a rare and aggressive malignancy for which systemic therapy, surgery, and radiotherapy remain the standard of care, thereby making IBC patients highly susceptible to developing BCRL. This study evaluated BCRL in IBC following trimodal therapy. METHODS: IBC patients treated from 2016 to 2019 were identified from an institutional database. Patients were excluded if they presented with recurrent disease, underwent bilateral axillary surgery, did not complete trimodal therapy, or were lost to follow-up. Demographic, clinicopathologic factors, oncologic outcomes, and perometer measurements were recorded. BCRL was defined by clinician diagnosis and/or objective perometer measurements when available. Time to development of BCRL and treatment received were captured. RESULTS: Eighty-three patients were included. Median follow-up was 33 months. The incidence of BCRL was 50.6% (n = 42). Mean time to BCRL from surgery was 13 (range 2-24) months. Demographic and clinicopathologic features were similar between patients with and without BCRL with exception of higher proportion receiving delayed reconstruction in the BCRL group (38.1% vs. 14.6%, p = 0.03). Forty patients (95.2%) underwent BCRL treatment, which included physical therapy (n = 39), compression (n = 38), therapeutic lymphovenous bypass (n = 13), and/or vascularized lymph node transfer (n = 12). CONCLUSIONS: IBC patients are at high-risk for BCRL after treatment, impacting 51% of patients in this cohort. Strategies to reduce or prevent BCRL and improve real-time diagnosis should be implemented to better direct early management in this patient population.

Long-term Oncologic Outcomes in Patients with Inflammatory Breast Cancer with Supraclavicular Nodal Involvement.

BACKGROUND: Inflammatory breast cancer (IBC) is a rare and aggressive subtype of breast cancer characterized by rapid progression and early metastasis, often with advanced nodal locations, including the supraclavicular (SCV) nodal basin. Previously considered M1 disease, ipsilateral clinical supraclavicular node involvement (N3c) disease is now considered locally advanced disease and warrants treatment with intent to cure. The objective of this study was to evaluate the long-term outcomes of patients with IBC and N3c disease. PATIENTS AND METHODS: This study was conducted using a prospectively collected database of all patients with IBC treated at a dedicated cancer center from 2007 to 2019. Surgical patients with SCV nodal involvement and complete follow-up were identified. Our primary outcome was 5-year overall survival (OS). Multivariate Cox proportional hazards models were used to determine predictors for survival. Event-free survival (EFS) and OS were calculated using the Kaplan-Meier method. RESULTS: There were 70 patients who met inclusion criteria. All patients underwent comprehensive trimodality therapy. The majority of patients had complete (66.2%) radiologic response in the SCV nodal basins following neoadjuvant therapy. Six patients (8.6%) had a locoregional recurrence, with two (2.9%) occurring in the supraclavicular fossa. The 5-year OS was 60.2% [95% confidence interval (CI) 47.7-72.7%]. Increasing age (hazard ratio 2.7; p = 0.03) and triple-negative subtype (hazard ratio 4.9; p = 0.03) were associated with poor OS. The 5-year EFS was 56.1% (95% CI 40.9-68.8%). The presence of more than ten positive axillary nodes on final surgical pathology (hazard ratio 5.5; p = 0.01) predicted poor EFS. CONCLUSIONS: With comprehensive trimodality therapy and multidisciplinary team approach, patients with IBC with supraclavicular nodal involvement experience excellent locoregional control and favorable survival.

Financial Toxicity Following Surgical Treatment for Breast Cancer: A Cross-sectional Pilot Study.

BACKGROUND: Despite growing national attention, there is limited understanding of the patient- and treatment-level characteristics related to treatment cost-associated distress ("financial toxicity") in breast cancer patients. Our aim is to identify risk factors for financial toxicity amongst breast cancer patients undergoing surgical treatment. METHODS: This is a single-institution cross-sectional survey of adult female breast cancer patients who underwent lumpectomy or mastectomy between January 2018 and June 2019. Financial toxicity was measured via the 11-item comprehensive score for financial toxicity (COST) instrument. Responses were linked with data on patient demographics and clinical history abstracted from the corresponding medical record. Multivariate regression was used to identify patient- and treatment-level factors associated with worsening financial toxicity. Secondary outcome measures included self-reported coping strategies for high treatment costs. RESULTS: A total of 571 patients were included; overall, these individuals were mostly white (76.0%), in-state residents (72.3%), and married (73.0%). Following multivariate analysis, lower financial distress was associated with the use of supplemental insurance, increasing annual household income, and a higher credit score (score > 740). Conversely, work reduction or cessation, increased out-of-pocket spending, advanced tumor stage, and being employed at the time of diagnosis were associated with increased financial distress. Patients with higher reported financial distress were more likely to decrease their spending on food, clothing, and leisure activities. CONCLUSIONS: Financial toxicity was associated with baseline demographic, disease, and treatment characteristics in our cohort of insured patients. These characteristics may be critical opportunities for interventions related to financial navigation along the treatment continuum.

The Role of Mastectomy in De Novo Stage IV Inflammatory Breast Cancer.

INTRODUCTION: The role of modified radical mastectomy (MRM) in patients with de novo stage IV inflammatory breast cancer (IBC) remains controversial. We evaluated the impact of MRM on outcomes in this population. METHODS: Ninety-seven women presenting with stage IV IBC were identified in an institutional database (2007-2016) and were stratified by receipt of MRM or no surgery (non-MRM). Demographic, clinicopathologic, and treatment factors were compared. Local-regional recurrence patterns were described and survival analyses were conducted. RESULTS: All patients initially received chemotherapy. Fifty-two patients (53.6%) underwent MRM; 47 received post-mastectomy radiation. Differences between the non-MRM and MRM groups included tumor receptor subtypes (hormone receptor-positive [HR+]/human epidermal growth factor receptor 2-positive [HER2+]: 4.4% vs. 19.2%; HR+/HER2-negative [HER2-]: 31.1% vs. 44.2%; HR-negative [HR-]/HER2+: 24.4% vs. 15.4%; and HR-/HER2-: 40.0% vs. 21.2%; p = 0.03), number of metastatic sites (3 vs. 2; p = 0.01), and clinical partial/complete response to chemotherapy (13.3% vs. 75.0%; p < 0.001). Of the 47 patients who completed trimodality therapy, 6 (12.8%) had a local-regional recurrence. Median overall survival (OS) was 19 months in the non-MRM group and 58 months in the MRM group (p < 0.001). On multivariable analysis, clinical N3 disease (hazard ratio 2.16, 95% confidence interval [CI] 1.07-4.37; p = 0.03) as well as tumor subtypes HR+/HER2- (hazard ratio 4.98, 95% CI 1.15-21.47; p = 0.03) and HR-/HER2- (hazard ratio 7.18, 95% CI 1.66-31.07; p = 0.008) were associated with decreased OS. Partial/complete response of distant disease to chemotherapy (hazard ratio 0.43, 95% CI 0.24-0.77; p = 0.005) and receipt of MRM (hazard ratio 0.52, 95% CI 0.29-0.93; p = 0.03) were independently associated with improved OS. CONCLUSIONS: In our retrospective study, MRM in de novo stage IV IBC patients is an independent factor associated with improved OS. Our findings strongly support the need for prospective randomized trials evaluating possible survival benefits of MRM in de novo stage IV IBC patients.