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.

Impact of Clipped Node as a Sentinel Lymph Node on Axillary Staging Following Neoadjuvant Chemotherapy in Clinically Node-Positive Breast Cancer.

BACKGROUND: Residual disease after neoadjuvant chemotherapy (NAC) is prognostic and informs adjuvant treatment. Targeted axillary dissection (TAD) following NAC has low false-negative rates, facilitating accurate axillary staging. This study evaluates the clipped node status in axillary staging utilizing TAD. METHODS: Retrospective review identified cN1 breast cancer patients treated with NAC and TAD from July 2013 to June 2023. Nodal ultrasound and biopsy defined cN1 status. Patient, tumor, and treatment characteristics were compared based on clipped node status (sentinel lymph node [SLN] or non-SLN). Multivariate analysis of factors associated with the clipped node as a non-SLN was performed. RESULTS: A total of 680 patients underwent TAD, 94.6% with dual-tracer mapping. In three patients (0.4%), no SLN was identified. The clipped node was a SLN in 610 patients (90%) and non-SLN in 70 (10.3%). When the clipped node was a non-SLN, 42 (60%) were positive for metastasis. In 22 of 42 patients (52%), the clipped non-SLN was the only positive node. The clipped non-SLN cohort had a higher proportion with >3 suspicious nodes at presentation (p = 0.003), fewer SLNs excised (mean 2.2 vs. 3.5, p ≤ 0.001), and fewer positive SLNs (p ≤ 0.001). On multivariate analysis, > 3 suspicious nodes on ultrasound (odds ratio 3.0, p = 0.001) and tumor size at presentation (odds ratio 0.9, p = 0.02) were significantly associated with the clipped node as a non-SLN. CONCLUSIONS: When the clipped node was a non-SLN, half of the time it was the only positive node and only residual disease on TAD. Given implications for adjuvant therapy, selective clipped node excision is recommended for precise identification of residual disease after NAC.

Significance of Residual Nodal Disease in Clinically Node-Negative Breast Cancer After Neoadjuvant Chemotherapy.

BACKGROUND: Trials evaluating omission of axillary dissection (ALND) in patients with cN0 breast cancer with positive sentinel lymph nodes (SLNs) have excluded neoadjuvant chemotherapy (NACT). It remains unclear whether the data can be extrapolated to cN0 patients undergoing NACT. This study sought to identify factors associated with positive SLNs and additional disease on ALND in cT1-2N0 disease after NACT. METHODS: The authors queried their database for cT1-2N0 patients treated with NACT followed by SLN biopsy from 1996 to 2022. Physical examination and ultrasound determined clinical nodal status. Multivariable logistic regression identified factors associated with positive SLNs and disease on ALND. RESULTS: Of 1930 patients, 234 (12.1%) had positive SLNs. Positive SLNs were predicted by hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) status (odds ratio [OR] 2.5; p < 0.0001), lobular histology (OR 1.8; p = 0.007), multifocality (OR 2; p = 0.001), grade 1 tumors (OR 2.5; p = 0.002), and cT2 category (OR 1.9; p = 0.004). Of the 234 patients with positive SLNs and known SLN metastasis size, 148 (63.2%) underwent ALND, and 39 (26.4%) had additional positive nodes. Increasing patient age predicted disease on ALND (OR 1.03; p = 0.02). No additional positive nodes on ALND were identified in patients with only isolated tumor cells compared with 12.3% who had micrometastases and 37.6% who had macrometastases (p = 0.01). During a 5-year median follow-up period of the SLN-positive patients, three (1.3%) experienced axillary recurrence and two of the three underwent ALND at the initial surgery with no additional positive nodes. CONCLUSIONS: In cT1-2N0 breast cancer, HR+/HER2- status, lobular histology, multifocality and cT2 category predicted positive SLNs after NACT. Older age predicted positive nodes on ALND. Patients with positive SLNs had low axillary recurrence rates. These findings support investigation into omission of ALND in cN0 breast cancer and a low volume of SLN disease after NACT.

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.

Internal Mammary Lymphadenopathy Does Not Impact Oncologic Outcomes in Patients Treated with Neoadjuvant Chemotherapy: Results from the I-SPY2 Clinical Trial.

BACKGROUND: Internal mammary lymphadenopathy (IML) plays a role in breast cancer stage and prognosis. We aimed to evaluate method of IML detection, how IML impacts response to neoadjuvant chemotherapy (NAC), and oncologic outcomes. METHODS: We evaluated patients enrolled in the I-SPY-2 clinical trial from 2010 to 2022. We captured the radiographic method of IML detection (magnetic resonance imaging [MRI], positron emission tomography/computed tomography [PET/CT], or both) and compared patients with IML with those without. Rates of locoregional recurrence (LRR), distant recurrence (DR) and event-free survival (EFS) were compared by bivariate analysis. RESULTS: Of 2095 patients, 198 (9.5%) had IML reported on pretreatment imaging. The method of IML detection was 154 (77.8%) MRI only, 11 (5.6%) PET/CT only, and 33 (16.7%) both. Factors associated with IML were younger age (p = 0.001), larger tumors (p < 0.001), and higher tumor grade (p = 0.027). Pathologic complete response (pCR) was slightly higher in the IML group (41.4% vs. 34.0%; p = 0.03). There was no difference in breast or axillary surgery (p = 0.41 and p = 0.16), however IML patients were more likely to undergo radiation (68.2% vs. 54.1%; p < 0.001). With a median follow up of 3.72 years (range 0.4-10.2), there was no difference between IM+ versus IM- in LRR (5.6% vs. 3.8%; p = 0.25), DR (9.1% vs. 7.9%; p = 0.58), or EFS (61.6% vs. 57.2%; p = 0.48). This was true for patients with and without pCR. CONCLUSIONS: In this large cohort of patients treated with NAC, outcomes were not negatively impacted by IML. We demonstrated that IML influences treatment selection but is not a poor prognostic indicator when treated with modern NAC and multidisciplinary disease management.

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

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

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

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

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.

Eliminating breast surgery for invasive breast cancer in exceptional responders to neoadjuvant systemic therapy: a multicentre, single-arm, phase 2 trial.

BACKGROUND: Neoadjuvant systemic therapy (NST) for triple-negative breast cancer and HER2-positive breast cancer yields a pathological complete response in approximately 60% of patients. A pathological complete response to NST predicts an excellent prognosis and can be accurately determined by percutaneous image-guided vacuum-assisted core biopsy (VACB). We evaluated radiotherapy alone, without breast surgery, in patients with early-stage triple-negative breast cancer or HER2-positive breast cancer treated with NST who had an image-guided VACB-determined pathological complete response. METHODS: This multicentre, single-arm, phase 2 trial was done in seven centres in the USA. Women aged 40 years or older who were not pregnant with unicentric cT1-2N0-1M0 triple-negative breast cancer or HER2-positive breast cancer and a residual breast lesion less than 2 cm on imaging after clinically standard NST were eligible for inclusion. Patients had one biopsy (minimum of 12 cores) obtained by 9G image-guided VACB of the tumour bed. If no invasive or in-situ disease was identified, breast surgery was omitted, and patients underwent standard whole-breast radiotherapy (40 Gy in 15 fractions or 50 Gy in 25 fractions) plus a boost (14 Gy in seven fractions). The primary outcome was the biopsy-confirmed ipsilateral breast tumour recurrence rate determined using the Kaplan-Meier method assessed in the per-protocol population. Safety was assessed in all patients who received VACB. This study has completed accrual and is registered with ClinicalTrials.gov, NCT02945579. FINDINGS: Between March 6, 2017, and Nov 9, 2021, 58 patients consented to participate; however, four (7%) did not meet final inclusion criteria and four (7%) withdrew consent. 50 patients were enrolled and underwent VACB following NST. The median age of the enrolled patients was 62 years (IQR 55-77); 21 (42%) patients had triple-negative breast cancer and 29 (58%) had HER2-positive breast cancer. VACB identified a pathological complete response in 31 patients (62% [95% CI 47·2-75·4). At a median follow-up of 26·4 months (IQR 15·2-39·6), no ipsilateral breast tumour recurrences occurred in these 31 patients. No serious biopsy-related adverse events or treatment-related deaths occurred. INTERPRETATION: Eliminating breast surgery in highly selected patients with an image-guided VACB-determined pathological complete response following NST is feasible with promising early results; however, additional prospective clinical trials evaluating this approach are needed. FUNDING: US National Cancer Institute (National Institutes of Health).

A multi-institutional prediction model to estimate the risk of recurrence and mortality after mastectomy for T1-2N1 breast cancer.

BACKGROUND: Post-mastectomy radiation therapy (PMRT) in women with pathologic stage T1-2N1M0 breast cancer is controversial. METHODS: Data from five North American institutions including women undergoing mastectomy without neoadjuvant therapy with pT1-2N1M0 breast cancer treated from 2006 to 2015 were pooled for analysis. Competing-risks regression was performed to identify factors associated with locoregional recurrence (LRR), distant metastasis (DM), overall recurrence (OR), and breast cancer mortality (BCM). RESULTS: A total of 3532 patients were included for analysis with a median follow-up time among survivors of 6.8 years (interquartile range [IQR], 4.5-9.5 years). The 2154 (61%) patients who received PMRT had significantly more adverse risk factors than those patients not receiving PMRT: younger age, larger tumors, more positive lymph nodes, lymphovascular invasion, extracapsular extension, and positive margins (p < .05 for all). On competing risk regression analysis, receipt of PMRT was significantly associated with a decreased risk of LRR (hazard ratio [HR], 0.21; 95% confidence interval [CI], 0.14-0.31; p < .001) and OR (HR, 0.76; 95% CI, 0.62-0.94; p = .011). Model performance metrics for each end point showed good discrimination and calibration. An online prediction model to estimate predicted risks for each outcome based on individual patient and tumor characteristics was created from the model. CONCLUSIONS: In a large multi-institutional cohort of patients, PMRT for T1-2N1 breast cancer was associated with a significant reduction in locoregional and overall recurrence after accounting for known prognostic factors. An online calculator was developed to aid in personalized decision-making regarding PMRT in this 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.

Breast conservation and axillary management after primary systemic therapy in patients with early-stage breast cancer: the Lucerne toolbox.

Primary systemic therapy is increasingly used in the treatment of patients with early-stage breast cancer, but few guidelines specifically address optimal locoregional therapies. Therefore, we established an international consortium to discuss clinical evidence and to provide expert advice on technical management of patients with early-stage breast cancer. The steering committee prepared six working packages to address all major clinical questions from diagnosis to surgery. During a consensus meeting that included members from European scientific oncology societies, clinical trial groups, and patient advocates, statements were discussed and voted on. A consensus was reached in 42% of statements, a majority in 38%, and no decision in 21%. Based on these findings, the panel developed clinical guidance recommendations and a toolbox to overcome many clinical and technical requirements associated with the diagnosis, response assessment, surgical planning, and surgery of patients with early-stage breast cancer. This guidance could convince clinicians and patients of the major clinical advancements purported by primary systemic therapy, the use of less extensive and more targeted surgery to improve the lives of patients with breast cancer.

Clinical Course of Breast Cancer Patients with Local-Regional Progression During Neoadjuvant Systemic Therapy.

BACKGROUND: Neoadjuvant systemic therapy (NST) is standard for locally advanced breast cancer and is now frequently considered for those with early-stage and node-positive disease. We aimed to evaluate the treatment course and outcomes in patients with disease progression during NST. METHODS: Patients diagnosed with unilateral stage I-III breast cancer between 2005 and 2015 with documented local-regional progression while receiving NST, by clinical examination and/or imaging after two or more cycles of chemotherapy, were identified from a prospective database, stratified by receipt of surgery and outcomes analyzed. RESULTS: Of 6362 patients treated with NST during the study period, 124 (1.9%) developed disease progression. At a median live follow-up of 71 months, 23.4% were alive without disease and 70.2% had died from breast cancer. Median overall survival (OS) time for patients with progression was 26 months and median distant disease-free survival (DFS) was 14 months. Triple-negative breast cancer was associated with a higher likelihood of death (p < 0.001) and development of distant metastasis (p = 0.002). Among patients who had surgery (104, 89.3%), 40 (38.5%) developed local-regional recurrence, 67 (64.4%) developed distant metastasis, and 69 (66.3%) died from breast cancer. Median OS and median distant DFS in this subgroup was 31 and 16 months, respectively. CONCLUSIONS: High rates of local-regional and distant failure were seen following disease progression while receiving NST. This suggests aggressive tumor biology and the need to study novel systemic therapies. Poor survival outcomes despite surgical management highlight the importance of careful patient selection when considering operative intervention after progression while receiving NST.

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.

Prospective Registry Trial Assessing the Use of Magnetic Seeds to Locate Clipped Nodes After Neoadjuvant Chemotherapy for Breast Cancer Patients.

BACKGROUND: Targeted axillary dissection (TAD) involves locating and removing both clipped nodes and sentinel nodes for assessment of the axillary response to neoadjuvant chemotherapy (NAC) by clinically node-positive breast cancer patients. Initial reports described radioactive seeds used for localization, which makes the technique difficult to implement in some settings. This trial was performed to determine whether magnetic seeds can be used to locate clipped axillary lymph nodes for removal. METHODS: This prospective registry trial enrolled patients who had biopsy-proven node-positive disease with a clip placed in the node and treatment with NAC. A magnetic seed was placed under ultrasound guidance in the clipped node after NAC. All the patients underwent TAD. RESULTS: Magnetic seeds were placed in 50 patients by 17 breast radiologists. All the patients had successful seed placement at the first attempt (mean time for localization was 6.1 min; range 1-30 min). The final position of the magnetic seed was within the node (n = 44, 88%), in the cortex (n = 3, 6%), less than 3 mm from the node (n = 2, 4%), or by the clip when the node could not be adequately visualized (n = 1, 2%). The magnetic seed was retrieved at surgery from all the patients. In 49 (98%) of the 50 cases, the clip and magnetic seed were retrieved from the same node. Surgeons rated the transcutaneous and intraoperative localization as easy for 43 (86%) of the 50 cases. No device-related adverse events occurred. CONCLUSIONS: Localization and selective removal of clipped nodes can be accomplished safely and effectively using magnetic seeds.

Contralateral Axillary Metastasis in Patients with Inflammatory Breast Cancer.

BACKGROUND: Nearly one-third of patients with inflammatory breast cancer (IBC) present with de novo stage IV disease. There are limited data on frequency and clinical outcomes of contralateral axillary metastasis (CAM) in IBC with no consensus diagnostic and treatment guidelines. PATIENTS AND METHODS: Frequency of synchronous CAM was calculated in unilateral IBC patients at a single center (10/2004-6/2019). Clinicopathologic variables, diagnostic evaluation, treatment received, and overall survival (OS) were assessed and compared. RESULTS: Of 588 unilateral IBC patients, 49 (8.3%) had synchronous CAM. Of these, 32 (65.3%) also presented with metastatic disease at another distant site. CAM was not associated with age, tumor laterality, breast cancer subtype, grade, or cN stage (p > 0.05). The sensitivity/specificity to detect CAM was as follows: mammography (18.2%/99.2%), ultrasound (92.3%/95.5%), PET (90.1/99.1%), and MRI (76.0%/98.6%). Following systemic therapy, 22 patients had contralateral axillary surgery, and 18 received adjuvant contralateral nodal radiation. On multivariable analysis including tumor receptor subtypes, patients with stage IV-isolated CAM has statistically similar survival to stage III patients (HR 1.37, 95% CI 0.70-2.69, p = 0.36). Patients with Stage IV non-CAM (HR 2.18, 95% CI 1.66-2.85, p < 0.001) and stage IV-CAM plus other distant metastasis (HR 2.57, 95% CI 1.59-4.16, p < 0.001) had higher risk of death (reference: stage III disease). CONCLUSIONS: CAM in IBC was diagnosed in 8.3% of patients at presentation and was best identified by ultrasound and PET. We recommend routine contralateral axillary ultrasound as part of staging for all IBC patients. Diagnosis of CAM is a key first step toward much-needed prospective clinical trials evaluating management and outcomes of CAM in IBC.

Anatomy and physiology of the sentinel lymph nodes of the upper extremity: Implications for axillary reverse mapping in breast cancer.

BACKGROUND: This study characterizes the physiological drainage of the normal upper extremity using single-photon emission computed tomography/computed tomography (SPECT/CT) lymphoscintigraphy axillary reverse lymphatic mapping (ARM). METHODS: A consecutive series of patients assessed with SPECT/CT lymphoscintigraphy ARM of the upper extremity were included. Anatomical localization of the axillary sentinel lymph nodes (SLN) was completed in normal axillae in relation to consistent anatomic landmarks. Retrospective case note analysis was performed to collect patient demographic data. RESULTS: A total of 169 patients underwent SPECT/CT lymphoscintigraphy, and imaging of 182 normal axillae was obtained. All patients (100%) had an axillary SLN identified: 19% had a single contrast-enhanced SLN in the axilla and the remainder had multiple. The SLN(s) of the upper extremity was located in the upper outer quadrant (UOQ) of the axilla in 97% of cases (177 axillae). When the SLN(s) was found in the UOQ of the axilla, second-tier lymph nodes were found predominantly in the upper inner quadrant (50% of cases). CONCLUSIONS: The upper extremity SLN(s) is located in a constant region of the axilla. This study provides the most complete investigation to date and results can be directly applied clinically to ARM techniques and adjuvant radiation planning.

Impact of the early COVID-19 pandemic on Breast Surgical Oncology fellow education.

INTRODUCTION: The early COVID-19 pandemic rapidly transformed healthcare and medical education. We sought to evaluate the professional and personal impact of the pandemic on 2019-2020 Breast Surgical Oncology (BSO) fellows in Society of Surgical Oncology approved programs to capture the experience and direct future changes. METHODS: From July 15, 2020 to August 4, 2020 a survey was administered to the American Society of Breast Surgeons' fellow members. The survey assessed the impact of the pandemic on clinical experience, education/research opportunities, personal health/well-being, and future career. Responses were collected and aggregated to quantify the collective experience of respondents. RESULTS: Twenty-eight of fifty-seven (54%) eligible fellows responded. Twenty-one (75%) indicated the clinical experience changed. Twenty-seven (96%) reported less time spent caring for ambulatory breast patients and sixteen (57%) reported the same/more time spent in the operating room. Fourteen (50%) stated their future job was impacted and eight (29%) delayed general surgery board examinations. Stress was increased in 26 (93%). Personal health was unaffected in 20 (71%), and 3 (10%) quarantined for COVID-19 exposure/infection. CONCLUSION: The COVID-19 pandemic altered the clinical experience of BSO fellows; however, the operative experience was generally unaffected. The creation of frameworks and support mechanisms to mitigate potential challenges for fellows and fellowship programs in the ongoing pandemic and other times of national crisis should be considered.

Acceptability of 3D-printed breast models and their impact on the decisional conflict of breast cancer patients: A feasibility study.

PURPOSE: To evaluate the acceptability and impact of 3D-printed breast models (3D-BMs) on treatment-related decisional conflict (DC) of breast cancer patients. METHODS: Patients with breast cancer were accrued in a prospective institutional review board-approved trial. All patients underwent contrast-enhanced breast magnetic resonance imaging (MRI). A personalized 3D-BM was derived from MRI. DC was evaluated pre- and post-3D-BM review. 3D-BM acceptability was assessed post-3D-BM review. RESULTS: DC surveys before and after 3D-BM review and 3D-BM acceptability surveys were completed by 25 patients. 3D-BM were generated in two patients with bilateral breast cancer. The mean patient age was 48.8 years (28-72). The tumor stage was Tis (7), 1 (8), 2 (8), and 3 (4). The nodal staging was 0 (19), 1 (7), and 3 (1). Tumors were unifocal (15), multifocal (8), or multicentric (4). Patients underwent mastectomy (13) and segmental mastectomy (14) with (20) or without (7) oncoplastic intervention. Neoadjuvant therapy was given to seven patients. Patients rated the acceptability of the 3D-BM as good/excellent in understanding their condition (24/24), understanding disease size (25/25), 3D-BM detail (22/25), understanding their surgical options (24/25), encouraging to ask questions (23/25), 3D-BM size (24/25), and impartial to surgical options (17/24). There was a significant reduction in the overall DC post-3D-BM review, indicating patients became more assured of their treatment choice (p = 0.002). Reduction post-3D-BM review was also observed in the uncertainty (p = 0.012), feeling informed about options (p = 0.005), clarity about values (p = 0.032), and effective (p = 0.002) Decisional Conflict Scale subscales. CONCLUSIONS: 3D-BMs are an acceptable tool to decrease DC in breast cancer patients.