Breast Cancer-Related Lymphedema (BCRL) and Bioimpedance Spectroscopy: Long-Term Follow-Up, Surveillance Recommendations, and Multidisciplinary Risk Factors.

BACKGROUND: Early detection and intervention for breast cancer-related lymphedema (BCRL) significantly decreases progression to persistent BCRL (pBCRL). We aimed to provide long-term follow-up on our early detection with bioimpedance spectroscopy (BIS) and early home intervention demonstrating reduced pBCRL to guide surveillance recommendations. PATIENTS AND METHODS: In total, 148 female patients with breast cancer who had axillary lymph node dissection (ALND) from November 2014 to December 2017 were analyzed. Baseline BIS measurements and postoperative follow-up occurred every 3 months for 1 year, biannual for 1 year, and then annually. An elevated BIS triggered evaluation and initiation of at-home interventions with reassessment for resolution versus persistent BCRL (pBCRL). High-risk factors and timing were analyzed. RESULTS: Mean follow-up was 55 months, and 65 (44%) patients had an abnormal BIS. Of these, 54 (82%) resolved with home intervention. The overall pBCRL rate was 8%. Average time to first abnormal BIS was 11.7 months. None of the stage 0 patients (0/34) and only 5/25 (20%) of stage 1 patients had pBCRL. All of stage 2 and stage 3 patients (7/7) had pBCRL. pBCRL correlated with number of positive nodes, percentage of positive nodes, stage of lymphedema at diagnosis, and recurring abnormal BIS measurements (p < 0.05). CONCLUSIONS: We have shown that patients undergoing ALND with early BCRL identified by BIS who performed home interventions had an 8% pBCRL rate. Patients at high risk for pBCRL should have routine surveillance starting at 9 months postoperatively to identify an opportunity for early intervention.

Mouse-INtraDuctal (MIND): an in vivo model for studying the underlying mechanisms of DCIS malignancy.

Due to widespread adoption of screening mammography, there has been a significant increase in new diagnoses of ductal carcinoma in situ (DCIS). However, DCIS prognosis remains unclear. To address this gap, we developed an in vivo model, Mouse-INtraDuctal (MIND), in which patient-derived DCIS epithelial cells are injected intraductally and allowed to progress naturally in mice. Similar to human DCIS, the cancer cells formed in situ lesions inside the mouse mammary ducts and mimicked all histologic subtypes including micropapillary, papillary, cribriform, solid, and comedo. Among 37 patient samples injected into 202 xenografts, at median duration of 9 months, 20 samples (54%) injected into 95 xenografts showed in vivo invasive progression, while 17 (46%) samples injected into 107 xenografts remained non-invasive. Among the 20 samples that showed invasive progression, nine samples injected into 54 xenografts exhibited a mixed pattern in which some xenografts showed invasive progression while others remained non-invasive. Among the clinically relevant biomarkers, only elevated progesterone receptor expression in patient DCIS and the extent of in vivo growth in xenografts predicted an invasive outcome. The Tempus XT assay was used on 16 patient DCIS formalin-fixed, paraffin-embedded sections including eight DCISs that showed invasive progression, five DCISs that remained non-invasive, and three DCISs that showed a mixed pattern in the xenografts. Analysis of the frequency of cancer-related pathogenic mutations among the groups showed no significant differences (KW: p > 0.05). There were also no differences in the frequency of high, moderate, or low severity mutations (KW; p > 0.05). These results suggest that genetic changes in the DCIS are not the primary driver for the development of invasive disease. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Oncoplastic Breast Reconstruction for Large Pediatric Breast Tumors: A Case Series.

ABSTRACT: Large breast fibroadenomas in pediatric females may cause discomfort, asymmetry, and psychological stress, and patients may elect for surgical excision. There are no criteria for reconstruction after the excision of these masses, and the research is limited in describing oncoplastic techniques in pediatric fibroadenoma excision. Nononcoplastic techniques, such as mastectomy with implant or flap reconstruction, have been used for pediatric fibroadenoma excision reconstruction. Oncoplastic techniques using Wise pattern or circumareolar incisions have shown to have efficacious outcomes. In addition, pediatric females undergoing breast surgery risk long-term complications such as continued breast asymmetry due to further breast growth, nipple and breast hypoesthesia, and future breastfeeding difficulty. This case series describes the oncoplastic techniques used for large benign mass excision and reconstruction of 3 pediatric females. A Wise pattern technique was used for all 3 patients, and 2 underwent a free-nipple graft. Oncoplastic techniques for pediatric breast mass excision provide satisfactory aesthetic outcomes with minimal surgical morbidity. Further research assessing the long-term effects of pediatric breast mass excision and reconstruction would be beneficial.

The clinical impact of MRI on surgical planning for patients with in-breast tumor recurrence.

OBJECTIVE: The objective of this study was to evaluate the clinical utility of breast MRI for patients with known in-breast tumor recurrence (IBTR). The aim was to determine if the addition of breast MRI altered surgical approach or multidisciplinary management. Previous studies have focused on using breast MRI for surgical planning for index breast cancers (BC) or detecting IBTR. However, the clinical impact of obtaining MRI in the setting of known IBTR has not been evaluated. METHODS: A single-institution retrospective chart review was performed to compare surgical approach and multidisciplinary management for patients diagnosed with isolated IBTR who did and did not undergo breast MRI following IBTR diagnosis. RESULTS: IBTR was identified in 69 patients, 46% of whom underwent MRI. There was no difference in the operative approach (p = 0.14) for IBTR patients who did and did not undergo breast MRI Additionally, there was no difference in multidisciplinary care, treatment order, metastatic disease identification, or mortality between cohorts. A relatively small subgroup of patients (n = 3) required change in surgical plan based on MRI results. Patients proceeding with surgery first who also underwent breast MRI experienced a significantly longer time to surgical intervention (p = 0.03). CONCLUSION: Breast MRI following IBTR diagnosis infrequently impacted clinical management, including surgical approach and multidisciplinary care. MRI for local disease assessment at the time of IBTR should be used selectively based on clinical concern.

Rethinking Routine Surgical Excision for all Radial Sclerosing Lesions of the Breast.

INTRODUCTION: The need for routine surgical excision of a radial sclerosing lesions (RSL) of the breast identified on percutaneous biopsy remains controversial, as contemporary upgrade rates are lower than historically cited. MATERIALS AND METHODS: A prospectively-maintained database of high-risk breast biopsies undergoing multidisciplinary review at a single institution was queried to identify cases of RSL from 2/2015 to 11/2020. Demographic, radiologic, and pathologic variables were summarized using frequencies and analyzed in association with RSL excision status using mixed-effects logistic regression or Fisher's exact tests. RESULTS: 217 RSL were identified, diagnosed at a mean age of 57 y. The median imaging size was 1.3 cm and the majority had estimated >50% of the target removed by core needle biopsy. 32.3% underwent surgical excision of the RSL biopsy site and 2/70 (2.9%) upgraded to ductal carcinoma in situ (DCIS) on final surgical pathology. Upgrade was significantly higher for atypical RSL (P = 0.02). None of the RSL (n = 60) without atypia who had undergone excision were upgraded. For those omitting surgical excision, there was no subsequent breast cancer diagnosis at the RSL site over a mean follow-up of 23 mo. CONCLUSIONS: Surgical excision may be omitted for RSL without atypia as this group has 0% risk of upgrade after multidisciplinary review.

Is bioimpedance spectroscopy a useful tool for objectively assessing lymphovenous bypass surgical outcomes in breast cancer-related lymphedema?

PURPOSE: We sought to determine if bioimpedance spectroscopy (BIS) measurements can accurately assess changes in breast cancer-related lymphedema (BCRL) in patients undergoing lymphovenous bypass (LVB). METHODS: Patients undergoing LVB for BCRL refractory to conservative treatment from 1/2015 to 12/2018 were identified from an IRB-approved prospectively maintained database at a single institution. All breast cancer patients were assessed with baseline BIS measurements prior to any oncologic surgery and serial BIS during follow-up office visits including before and after LVB. Clinicopathologic information, LVB operative details, and pre- and post-LVB operative BIS measurements were collected. Analysis focused on clinically significant BIS change, defined as two standard deviations (SD), and comparing LVB anastomosis to BIS changes. RESULTS: During the study timeframe, nine patients underwent LVB for treatment of BCRL. The majority (78%) received radiation, taxane chemotherapy, and underwent axillary dissection. An average of 5.6 LVB anastomoses were performed per patient. The average change in BIS following LVB was a 3SD reduction, indicating a clinically significant change. This improvement was stable over time, with persistent 2SD reduction at 22 months postoperatively. The number of LVB anastomoses performed did not significantly correlate with the degree of BIS change. CONCLUSIONS: This is the first study to utilize BIS measurements to assess response to LVB surgical intervention for BCRL. BIS measurements demonstrated clinically significant improvement after LVB, providing objective evidence in support of this surgical treatment for BCRL. BIS changes should be reported as key objective data in future studies assessing BCRL interventions, including response to LVB.

Is axillary imaging for invasive lobular carcinoma accurate in determining clinical node staging?

PURPOSE: Preoperative evaluation of clinical N-stage (cN) is difficult in breast cancer patients with invasive lobular carcinoma (ILC). Our goal was to assess the predictive value of axillary imaging in ILC by comparing imaging cN and pathologic N-stage (pN). METHODS: A single-institution retrospective review was performed for newly diagnosed stage I-III ILC patients undergoing preoperative breast imaging from 2011 to 2016. Clinicopathologic factors; mammogram, MRI, and ultrasound findings; and surgical pathology data were reviewed. Sub-analysis for pN2-N3 patients was performed to determine imaging sensitivity for patients with a larger nodal disease burden. Statistical analysis included sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of each imaging modality. RESULTS: Of the total 349 patients included, 70.5% were cN0, and 62% were pN0 (p = 0.03). For all patients, mammogram sensitivity was 7%, specificity 97%, PPV 50%, NPV 72%; ultrasound sensitivity was 26%, specificity 86%, PPV 52%, NPV 67%; MRI sensitivity was 7%, specificity 98%, PPV 80%, NPV 51%. For pN2/N3 patients, 38% were identified as cN0. Mammogram sensitivity was 10%; ultrasound 42%; MRI 65%. Pathology evaluation of N2/N3 patients indicated LN were replaced with ILC but maintained normal architecture. The average largest pathologic tumor deposit (1.5 ± 0.8 cm) correlated with average largest imaging LN size (1.4 ± 0.6 cm) (p = 0.58). CONCLUSION: A statistically significant difference between clinical and pathologic N-stage exists for ILC patients. MRI was most sensitive for identification of pN2-N3 patients and should be considered part of routine axillary imaging evaluation for ILC patients.

Multidisciplinary Review of Intraductal Papilloma of the Breast can Identify Patients who may Omit Surgical Excision.

BACKGROUND: The purpose of this study was to define contemporary management recommendations regarding who would benefit from surgical excision of intraductal papilloma (IDP). METHODS: A prospective database from a single institution identified patients with IDP on percutaneous biopsy from February 2015 to September 2020. Categorical patient demographic, biopsy, and pathologic variables were analyzed using Fisher's exact test and continuous demographic and imaging variables using the Mann-Whitney U test. RESULTS: IDP was present in 416 biopsies, at a median age of 56 years. The median size was 0.9 cm, and the majority had greater than 50% of the target excised by biopsy. Surgical excision was performed for 124 of 416 biopsies (29.8%). Upgrade to malignancy was identified in 14 (11.3%): 8 to ductal carcinoma in situ (DCIS) and 6 to invasive cancer. Upgrade was significantly associated with concurrent ipsilateral breast cancer (p = 0.027), larger imaging size (p = 0.045), <50% excised with biopsy (p = 0.02), and atypia involving IDP (p = 0.045). Age, clinical presentation, and concurrent contralateral cancer were not significantly associated with upgrade. Lowest upgrade risk (0%) was in pure IDP ≤1 cm with >50% removed by biopsy. Of 401 biopsies that either did not upgrade or undergo excision, 7 (1.7%) developed subsequent breast cancer over a median follow-up of 23.5 months (interquartile range [IQR] 11,41), none at IDP site. CONCLUSIONS: After multidisciplinary review, the management of IDP can be stratified into low- and high-risk for upgrade groups using key criteria. Low-risk group may omit surgical excision, because those patients have 0% risk of upgrade over the limited short-term follow-up.

Does the Addition of Breast MRI Add Value to the Diagnostic Workup of Invasive Lobular Carcinoma?

BACKGROUND: Invasive lobular carcinoma (ILC) has unique histologic growth pattern. Few studies have focused on the value of breast magnetic resonance imaging (MRI) specifically for ILC. We hypothesized that MRI adds value to the diagnostic workup in ILC by better defining the extent of disease and identifying additional foci of malignancy, which can change the surgical plan. MATERIALS AND METHODS: This was a single-institution retrospective review of women diagnosed with ILC from 1/2012 to 7/2019 who underwent preoperative MRI. Patient, tumor characteristics, and initial surgical plan were reviewed. MRI had added value if ILC size correlated best to final pathologic size or if additional malignancy was identified. MRI was considered harmful if additional biopsies were benign or if the size was overestimated. RESULTS: ILC was identified in 166 breasts in 165 women. Original surgical plan was for lumpectomy in 86 (52%), mastectomy in 49 (30%), and undecided in 31 (18%). MRI changed the plan in 25 (19%) with 24 (96%) changing from lumpectomy to mastectomy. Additional biopsy was performed in 28% after MRI, the majority (n = 41, 72%) were benign or high risk and 16 (28%) identified additional malignancy. MRI was not a better size estimate than mammogram/ultrasound. Re-excision rate after lumpectomy was 6.8% (5/73). MRI added value in 48 (28.9%) and was harmful in 48 (28.9%). CONCLUSIONS: Using breast MRI in the diagnostic workup of ILC has both positive and negative implications on surgical treatment planning. A shared decision-making conversation is warranted before proceeding with MRI to maximize value and minimize harms associated with this diagnostic tool.

Secondary angiosarcoma following catheter-based brachytherapy.

Secondary angiosarcoma of the breast following catheter-based brachytherapy after lumpectomy is rare. We describe a case of a patient with breast cancer treated with partial mastectomy and sentinel node biopsy followed by accelerated partial breast irradiation (APBI), who developed skin changes 6 years after completion of therapy. Punch biopsy confirmed the diagnosis of secondary angiosarcoma. This case is even more unique in that the location of the skin changes was remote to the lumpectomy site. There is a critical need to recognize secondary angiosarcoma presentation after APBI and determine the rate of occurrence compared with traditional external beam irradiation.

Primary tumor resection in de novo stage IV breast cancer patients.

Breast and axillary surgery in Stage IV disease is outside current national guidelines but has been a topic of ongoing debate. A single institution retrospective study identified women with de novo stage IV BC from 2011-2016 to evaluate the rate and goals of primary site surgery. Only 10.2% (n = 27/265patients) had primary site surgery. The goal of surgery was most often treatment intent (n = 23, 85.1%) not palliation (n = 4, 14.8%). There was no 30-day mortality and low (n = 1, 3.7%) 30-day morbidity. Multi-disciplinary patient care pathways based on modern evidence may help identify patients potentially suitable for primary site surgery.

Reducing Breast Cancer-Related Lymphedema (BCRL) Through Prospective Surveillance Monitoring Using Bioimpedance Spectroscopy (BIS) and Patient Directed Self-Interventions.

BACKGROUND: Breast cancer-related lymphedema (BCRL) is a chronic progressive disease that results from breast cancer treatment and nodal surgery. NCCN guidelines support baseline measurements with prospective assessment for early diagnosis and treatment. We sought to determine if baseline measurement with bioimpedance spectroscopy (BIS) and serial postoperative evaluations provide early detection amenable to conservative interventions that reduce BCRL. METHODS: Breast cancer patients with unilateral disease high-risk for BCRL from a single institution were evaluated from November 2014 to December 2017. High risk was defined as axillary lymph node dissection with radiation and/or taxane chemotherapy. Patients received preoperative baseline BIS measurements followed by postoperative measurements with at least two follow-ups. Patients with BIS results that were 2 standard deviations above baseline (10 + points) started home conservative interventions for 4-6 weeks. Postintervention measurements were taken to assess improvement. RESULT: A total of 146 patients high-risk for BCRL were included. Forty-nine patients (34%) developed early BCRL and started self-directed treatment. Forty patients (82%) had elevated BIS measurements return to normal baseline range. Nine (6%) patients had persistent BCRL requiring referral for advanced therapy. Patients with persistent BCRL had significant nodal burden on surgical pathology; eight (89%) had N2/N3 disease. Six (76%) with BCRL refractory to conservative measures died of their breast cancer. CONCLUSION: Our results demonstrated that early conservative intervention for breast cancer patients high risk for BCRL who were prospectively monitored by utilizing BIS significantly lowers rates of BCRL. These findings support early prospective screening and intervention for BCRL. Early detection with patient-directed interventions improves patient outcomes and decreases the risk of persistent BCRL.

Advanced degrees, gender, and professional rank in surgery, disparities in academic medicine.

INTRODUCTION: Women comprise nearly half of all residents in training, yet there is a significant disparity of women in academic leadership. Surgical subspecialties are dominated by men in both percentages of physicians and leadership positions. We sought to examine the association of advanced non-medical degrees with academic rank and gender in academic surgery departments. METHODS: Faculty from 126 ACGME-accredited academic medical centers were analyzed to identify faculty gender as described in online biographical information, advanced non-medical degrees, academic rank, and additional leadership positions held. Descriptive statistics and logistic regression models were used for statistical analyses. RESULTS: 4536 surgeons were identified, 69.3% men, 27.3% female, and 3.3% unlisted. Female surgeons were more likely to hold advanced non-doctoral degrees than men (18.2% vs. 13.8%, p â€‹< â€‹0.002). Among those with advanced degrees, PhDs were held by 3.3% of women and 5.7% of men (p â€‹< â€‹0.001). Female surgeons were less likely to hold the rank of Professor than male surgeons (15.8% vs 30.3%, p â€‹< â€‹0.001), and more likely to hold the rank of Assistant Professor than male surgeons (51.9% vs 36.1%, p â€‹< â€‹0.001). This likelihood remained true when analyzing only surgeons with one or more advanced non-medical degrees. Men were more likely to be Chair of Surgery (3.0%), Division Chief (9.6%), and Research Chair (0.5%); compared to women (1.3%; 4.8%; 0.2%; p â€‹= â€‹0.001, <0.001, 0.21 respectively). CONCLUSIONS: There continues to be a significant male predominance in general surgery. Gender discrepancy is also seen in professional rank and academic title despite women holding more advanced degrees. Advanced degrees are currently considered academic qualifications, but this does not reflect surgical academic leadership roles or rank.

Evaluation of learning curve with Indocyanine Green (IcG) versus blue dye for sentinel lymph node biopsy in breast cancer.

BACKGROUND: Indocyanine green (IcG) is an alternative to isosulfan blue (IB) for sentinel lymph node (SLN) mapping in breast cancer (BC). IcG carries improved cost and safety, but oncologic data upon implementation in practice is limited. We evaluated the learning curve defined as oncologic yield and operative (OR) time for IcG in SLN mapping in BC. METHODS: Retrospective review of patients >18 years with cTis-2 cN0 BC undergoing surgery first with SLN biopsy using IB or IcG. Analysis compared IB versus IcG across three time cohorts. RESULTS: Of 278 patients, 77 received IB and 201 received IcG. OR time was longer for IcG (p â€‹= â€‹0.022). There was no difference in oncologic yield between groups (p â€‹= â€‹0.35, p â€‹= â€‹0.61). CONCLUSIONS: Surgeons may be able to safely transition from IB to IcG for patients with early-stage breast cancer undergoing surgery first. Individuals should track their own data to confirm safety of the technique.

Atypia Involving Fibroadenomas: Outcomes and Upgrade Rates.

OBJECTIVE: Fibroadenomas (FAs) involved by atypia are rare. Consensus guidelines for management of FAs involved by atypia when diagnosed on image-guided biopsy do not exist because of limited data reporting surgical upgrade rates to ductal carcinoma in situ (DCIS) or invasive malignancy. Therefore, these lesions commonly undergo surgical excision. METHODS: This single-institution retrospective study identified cases of FAs involved by atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), and/or lobular carcinoma in situ (LCIS) diagnosed on image-guided biopsy between January 2014 and April 2023 to determine upgrade rates. Cases with incidental atypia adjacent to but not involving FAs were excluded. RESULTS: Among 1736 FAs diagnosed on image-guided biopsy, 32 cases (1.8%) were FAs involved by atypia including 43.8% (14/32) ALH, 28.1% (9/32) ADH, 18.8% (6/32) LCIS, 6.3% (2/32) LCIS + ALH, and 3.1% (1/32) unspecified atypia. The most common imaging finding was a mass. Most cases, 81.3% (26/32), underwent subsequent surgical excisional biopsy. A single case of ADH involving and adjacent to an FA was upgraded to FA involved by low-grade DCIS on excision for an overall surgical upgrade rate of 3.8%. There were no cases upgraded to invasive malignancy. For those omitting surgical excision, there was no subsequent malignancy diagnosis at the FA biopsy site over a mean follow-up of 73 months. CONCLUSION: Cases of radiologic-pathologic concordant FAs involved by atypia have a low upgrade rate of 3.8% and should undergo multidisciplinary review. Larger multi-institutional analysis is needed to determine whether guidelines for excision of atypia should apply to atypia involving FAs.

Interactive multidisciplinary pilot workshop to improve medical student perception of and interest in breast surgical oncology.

BACKGROUND: Exposure to breast surgical oncology (BSO) and the multidisciplinary management of patients with breast cancer is limited in medical school. The purpose of this study was to assess changes in student perceptions of BSO as a career following an interactive multidisciplinary workshop. METHODS: Pre-clinical medical students participated in a multidisciplinary, hands-on workshop, composed of breast radiology (BR), breast surgical oncology (BSO) and breast plastic reconstructive surgery (B-PRS). BR presented students screening and diagnostic breast imaging followed by hands-on ultrasound-guided biopsy on phantom simulators. BSO demonstrated lumpectomy, mastectomy, sentinel lymph node biopsy, and axillary lymph node dissections while B-PRS demonstrated oncoplastic techniques and autologous flap reconstruction with cadavers. Pre-and post-workshop surveys assessed student opinions on surgery and BSO. Results were compared using Wilcoxon Signed Rank, Wilcoxon Rank Sum, and Fisher's Exact. RESULTS: The workshop was attended by twenty-four students. There was a statistically significant increase in interest in BSO from 52% to 86% after the workshop (p = 0.003). The event improved understanding of the work and lifestyle in BSO for 79% (19/24). All students (100%) expressed interest to further explore BSO. The most common attractors to a career in BSO were impacts on patients' lives (N = 23), intellectual stimulation (N = 22), and earnings (N = 20). The most reported deterrents were lack of personal time (N = 18) and stress (N = 15). CONCLUSION: An interactive, anatomically based exposure to multidisciplinary breast cancer surgery improves medical student perception and interest in BSO. Medical schools should consider incorporating similar events to foster interest in BSO and other surgical subspecialties.

Clinical and Biomarker Findings of Neoadjuvant Pembrolizumab and Carboplatin Plus Docetaxel in Triple-Negative Breast Cancer: NeoPACT Phase 2 Clinical Trial.

Importance: Addition of pembrolizumab to anthracycline-based chemotherapy improves pathologic complete response (pCR) and event-free survival (EFS) in triple-negative breast cancer (TNBC). The efficacy of anthracycline-free chemoimmunotherapy in TNBC has not been assessed. Objective: To assess the efficacy of the anthracycline-free neoadjuvant regimen of carboplatin and docetaxel plus pembrolizumab in TNBC. Design, Setting, and Participants: This was an open-label phase 2 clinical trial including a single group of patients with stage I to III TNBC enrolled at 2 sites who received neoadjuvant carboplatin and docetaxel plus pembrolizumab every 21 days for 6 cycles. Participants were enrolled from 2018 to 2022. Intervention or Exposure: Carboplatin (with an area under the free carboplatin plasma concentration vs time curve of 6) and docetaxel (75 mg/m2) plus pembrolizumab (200 mg) every 21 days for 6 cycles. Myeloid growth factor support was administered with all cycles. Main Outcomes and Measures: Primary end point was pathologic complete response (pCR) defined as no evidence of invasive tumor in breast and axilla. The secondary end points were residual cancer burden, EFS, toxicity, and immune biomarkers. RNA isolated from pretreatment tumor tissue was subjected to next-generation sequencing. Specimens were classified as positive or negative for the 44-gene DNA damage immune response (DDIR) signature and for the 27-gene tumor immune microenvironment (TIM; DetermaIO) signature using predefined cutoffs. Stromal tumor-infiltrating lymphocytes (sTILs) were evaluated using standard criteria. Programmed cell death-ligand 1 (PD-L1) testing was performed using a standard immunohistochemical assay. Results: Among the eligible study population of 115 female patients (median [range] age, 50 [27-70] years) who enrolled from September 2018 to January 2022, 39% had node-positive disease. pCR and residual cancer burden 0 + 1 rates were 58% (95% CI, 48%-67%) and 69% (95% CI, 60%-78%), respectively. Grade 3 or higher immune-mediated adverse events were observed in 3.5% of patients. sTILs, PD-L1, DDIR, and TIM were each predictive of pCR in multivariable analyses. The areas under curve for pCR were 0.719, 0.740, 0.699, and 0.715 for sTILs, PD-L1, DDIR, and TIM, respectively. Estimated 3-year EFS was 86% in all patients; 98% in pCR group and 68% in no-pCR group. Conclusions and Relevance: The findings of the phase 2 clinical trial indicate that neoadjuvant carboplatin and docetaxel plus pembrolizumab shows encouraging pCR and 3-year EFS. The regimen was well tolerated, and immune enrichment as identified by various biomarkers was independently predictive of pCR. These results provide data on an alternative anthracycline-free chemoimmunotherapy regimen for patients who are not eligible for anthracycline-based regimens and support further evaluation of this regimen as a chemotherapy de-escalation strategy in randomized studies for TNBC. Trial Registration: ClinicalTrials.gov Identifier: NCT03639948.

Safety of de-escalation of surgical intervention for atypical ductal hyperplasia on percutaneous biopsy: One size does not fit all.

BACKGROUND: Oncologic safety of active monitoring (AM) for atypical ductal hyperplasia (ADH) on core-needle biopsy (CNB) is not well defined. We sought to define oncologic outcomes for AM to manage ADH meeting institutional predefined low-risk criteria (LOW). METHODS: ADH was diagnosed on CNB from 10/2015-03/2020. LOW (pure ADH, size <1 cm, >50% removed by CNB, <3 foci, and no necrosis) patients were offered AM; all others were recommended for surgical excision. Oncologic outcomes were compared for AM and surgery. RESULTS: 111 were included, 21 (19%) meeting LOW. AM occurred in 18 (86%) while 3 elected for excision (with 0% upgrade). Of the 18 LOW in AM, 2 required additional CNB (none at ADH site): 0% were diagnosed with cancer over median 23 month follow-up. CONCLUSIONS: There were no missed cancers at ADH site during AM for LOW, confirming the oncologic safety of AM in this select group.