Faculty Bibliography

BACKGROUND:The SOUND randomized controlled trial demonstrated that omitting sentinel lymph node biopsy (SLNB) is noninferior to performing SLNB in early-stage breast cancer. Lymphovascular invasion (LVI), however, is an adverse pathologic feature associated with axillary nodal metastasis. In this study, we evaluated the association of LVI with occult axillary nodal metastasis in early-stage, SOUND-eligible breast cancer. PATIENTS AND METHODS/METHODS:We retrospectively reviewed patients with cT1N0 breast cancer from 2011 to 2025 who underwent upfront breast-conserving surgery and lymph node surgery who met SOUND trial eligibility criteria. Clinicopathologic variables were collected, and Pearson's chi-square test, unpaired t-test, and logistic regression were used to analyze the cohort. RESULTS:We identified 364 cT1N0 breast tumors, of which 63 (17.3%) were LVI-present. The overall nodal upstaging rate (pN+) was 11.3%. However, pN+ among LVI-present patients was 33.3% compared with 6.6% among LVI-absent patients (OR 7.03; 95%CI 3.51, 14.05; p < 0.001). Only 1 case (0.3%) had extensive nodal disease (pN2) in which LVI was present. On multivariate analysis for predictors of LVI-present, premenopausal (OR 4.23, 95%CI 2.31, 7.76; p < 0.001) was significantly associated with LVI-present, and well differentiated was significantly associated with LVI-absent (OR 0.060, 95%CI 0.010, 0.47; p = 0.0071). On multivariate analysis for predictors of pN+, only LVI-present (OR 6.47, 95%CI 3.14, 13.34 p < 0.001) was significantly associated with pN+. CONCLUSIONS:Pathologic-confirmed LVI was present in one-third of patients with SOUND-eligible breast cancer with axillary nodal metastasis. LVI-present was independently predictive of axillary nodal metastasis and may have implications for decision-making regarding SLNB-omission.

Treatment selection in breast cancer is guided by risk assessment using molecular subtypes and clinicopathological characteristics. However, current approaches lack the precision required for optimal clinical decision-making. To address this, we use data from 8161 patients to develop and evaluate an AI test integrating digital pathology with clinical data. The AI test provides a robust method for predicting disease-free interval (C-index: 0.71 [0.68-0.75], HR: 3.63 [3.02-4.37, p < 0.001]). In a direct comparison, the AI test displays numerically higher discrimination (C-index: 0.67 [0.61-0.74]) than the standard-of-care 21-gene assay (C-index: 0.61 [0.49-0.73]). Across molecular subtypes, the AI test demonstrates robust prognostic performance, including in triple negative breast cancer (C-index: 0.71 [0.62-0.81], HR: 3.81 [2.35-6.17, p=0.02]), where no guideline-recommended assays currently exist. These findings highlight the potential of AI-based pathology tests as a promising tool for improved risk stratification across all major subtypes, with implications for clinical decision-making.

BACKGROUND:Clinical trials suggest that adjuvant radiotherapy (RT) may be omitted in women aged 65 or older with early-stage, hormone-receptor (HR) positive breast cancer provided completion of 5 years of endocrine therapy (ET). However, at the time of RT consult, it is often unknown whether the patient will start ET or will start but not complete 5 years, either of which, if known in advance, would alter RT recommendations. We studied a cohort of patients who would have been eligible for RT omission to examine factors associated with declining or discontinuing ET. METHODS:Using a prospectively maintained institutional database, we identified patients age ≥65 who underwent surgery from 2010 to 2017 with stage I HR-positive breast cancer. Patients were classified as having osteopenia or osteoporosis based on the lowest T-score on DEXA. Missing data were replaced using multiple imputation. Recurrence and survival statistics were calculated using Kaplan-Meier analysis. Univariate and multivariate logistic regression was used to assess factors associated with not starting or discontinuing ET. RESULTS:We identified 590 eligible patients. Of these, 453 (76.8%) started ET. Patients who did not start ET were older (mean age 77.02 vs. 72.46, p < 0.001), had lower BMI (mean 25.36 vs. 26.78, p = 0.008), and lower DEXA scores (mean score -1.92 vs. -1.58, p = 0.056), and were less likely to undergo axillary surgery (64.2% vs. 86.8%, p < 0.001). Of the 453 patients who started ET, 315 (69.5%) completed at least 5 years. Discontinuation of ET was associated with older age (HR 1.082, 95% CI 1.033-1.133, p = 0.001), not undergoing axillary surgery (HR 0.365, 95% CI 0.146-0.915, p = 0.032) and smoking (HR 1.636, 95% CI 1.001-2.676, p = 0.05). Patients who were single or never married were less likely to discontinue ET (HR 0.281, 95% CI 0.096-0.821, p = 0.020). Patients who completed 5 years ET had significantly better local recurrence-free survival (96.8%) compared to those who stopped early (87.7%, p=0.01) or did not start ET (88.7%, p < 0.001). CONCLUSIONS:Older age, osteopenia, and lower BMI were associated with not starting ET, while older age, marital status, axillary surgery, and smoking history predicted discontinuation of ET. These factors may guide discussions regarding the omission of adjuvant radiotherapy.

BackgroundBreast conserving surgery represents the preferred surgical treatment option for patients with early-stage breast cancer. Reexcision rates are generally higher for patients undergoing lumpectomies for ductal carcinoma in situ (DCIS) compared to invasive breast cancer, as the microscopic extent of disease is difficult to assess during excision. This study investigated the clinicopathological characteristics of patients undergoing BCS for pure DCIS and reexcision rates over time, including the effect of the MarginProbe™ device.MethodsWe queried our prospectively maintained Institutional Breast Cancer Database for patients diagnosed with DCIS and treated with BCS as their primary procedure from 2010-2021. The primary endpoint was the rate of reexcision. Variables of interest included age at diagnosis, race/ethnicity, mode of diagnostic imaging, mammographic breast density, method of core biopsy, nuclear grade, size of DCIS, multifocality, DCIS subtype, and MarginProbe™ use.ResultsPapillary DCIS (P < 0.004) and larger size (P < 0.001) was associated with an increased reexcision rate. There were also differences in the method of core biopsy (P < 0.001), with stereotactic core biopsy predominating among patients who did not require reexcision (71.3% vs 49.5%). In an unadjusted estimate for the odds ratio for association, patients who had MarginProbe™ used were 81% less likely to require reexcision (OR = 0.19, 95% CI = 0.12, 0.31, P < 0.0001).ConclusionYounger age, papillary DCIS, larger DCIS size, and non-stereotactic core biopsy method were found to be associated with higher reexcision rates. Additionally, patients whose primary procedures included intraoperative margin assessment with the MarginProbe™ were significantly less likely to require reexcision.

PURPOSE/OBJECTIVE:With transition from supine to prone position, tenting of the pectoralis major occurs, displacing the muscle from the chest wall and shifting the level I and II axillary spaces. For patients for whom we aim to treat the level I and II axillae using the prone technique, accurate delineation of these nodal regions is necessary. Although different consensus guidelines exist for delineation of nodal anatomy in supine position, to our knowledge, there are no contouring guidelines in the prone position that account for this change in nodal anatomy. METHODS AND MATERIALS/METHODS:The level I and II nodal contours from the Radiation Therapy Oncology Group (RTOG) breast cancer supine atlas were adapted for prone position by 2 radiation oncologists and a breast radiologist based on anatomic changes observed from supine to prone positioning on preoperative diagnostic imaging. Forty-three patients from a single institution treated with prone high tangents from 2012 to 2018 were identified as representative cases to delineate the revised level I and II axillae on noncontrast computed tomography (CT) scans obtained during radiation simulation. The revised nodal contours were reviewed by an expanded expert multidisciplinary panel including breast radiologists, radiation oncologists, and surgical oncologists for consistency and reproducibility. RESULTS:Consensus was achieved among the panel in order to create modifications from the RTOG breast atlas for CT-based contouring of the level I and II axillae in prone position using bone, muscle, and skin as landmarks. This atlas provides representative examples and accompanying descriptions for the changes described to the caudal and anterior borders of level II and the anterior, posterior, medial, and lateral borders of level I. A step-by-step guide is provided for properly identifying the revised anterior border of the level I axilla. CONCLUSIONS:The adaptations to the RTOG breast cancer atlas for prone positioning will enable radiation oncologists to more accurately target the level I and II axillae when the axillae are targets in addition to the breast.

PURPOSE/OBJECTIVE:Our institution was an early adopter of 5-fraction accelerated partial breast irradiation (ABPI) to treat women with early-stage breast cancer. This study reports long-term oncologic and cosmetic outcomes. METHODS:We included patients receiving APBI 600 cGy × 5 fx delivered every other day or every day between 2010 and 2022. Logistic regression models were used to identify factors associated with development of late toxicities, clinician, and patient-rated cosmesis. Kaplan-Meier methodology was used to calculate overall survival (OS), disease-free survival (DFS), and locoregional recurrence-free survival (LR-RFS). RESULTS:442 patients received APBI either daily (56%) or every other day (44%) in the prone position (92%). At a median follow-up of 48 months (range: 5.96-155 months), 12 (2.7%) patients developed a local recurrence (LR). Out of 258 patients with > 3-month toxicity data available, the most common late grade ≥ 2 adverse event was breast fibrosis (6.2%). On multivariate analysis, daily APBI treatment (vs every other day) did not correlate with an increased risk of any late grade ≥ 2 toxicity though it did correlate with a lower risk of any late grade ≥ 2 fibrosis. Overall, at a median follow-up of 80 months, the rates of good-excellent physician and patient-rated cosmesis were 95% and 85%, respectively, with no difference between patients treated on consecutive vs. every other day. On multivariate analysis, patients who did not receive any adjuvant therapy were at increased risk of developing a LR. Five-year OS, LRFS, and DFS were 97.2%, 97.7%, and 89.5%, respectively. CONCLUSIONS:Five-fraction APBI delivered primarily in the prone position either daily or every other day was effective with low rates of local recurrence, minimal toxicity, and excellent cosmesis at long-term follow-up.

BACKGROUND:Nipple-sparing mastectomy (NSM) has become widely available for breast cancer prophylaxis. There are limited data on its long-term oncologic safety. The objective of this study was to determine the incidence of breast cancer in patients who underwent prophylactic NSM. METHODS:All patients undergoing prophylactic NSM at a single institution from 2006 through 2019 were retrospectively reviewed. Patient demographic factors, genetic predispositions, mastectomy specimen pathology, and oncologic occurrences at follow-up were recorded. Descriptive statistics were performed where necessary to classify demographic factors and oncologic characteristics. RESULTS:A total of 871 prophylactic NSMs were performed on 641 patients, with median follow-up of 82.0 months (standard error 1.24). A total of 94.4% of patients ( n = 605) underwent bilateral NSMs, although only the prophylactic mastectomy was considered. The majority of mastectomy specimens (69.6%) had no identifiable pathology. A total of 38 specimens (4.4%) had cancer identified in mastectomy specimens, with ductal carcinoma in situ being the most common (92.1%; n = 35). Multifocal or multicentric disease was observed in seven cases (18.4%) and lymphovascular invasion was identified in two (5.3%). One patient (0.16%), who was a BRCA2 variant carrier, was found to have breast cancer 6.5 years after prophylactic mastectomy. CONCLUSIONS:Overall primary oncologic occurrence rates are very low in high-risk patients undergoing prophylactic NSM. In addition to reducing the risk of oncologic occurrence, prophylactic surgery itself may be therapeutic in a small proportion of patients. Continued surveillance for these patients remains important to assess at longer follow-up intervals. CLINICAL QUESTION/LEVEL OF EVIDENCE/METHODS:Risk, IV.

UNLABELLED:Prophylactic nipple-sparing mastectomies (NSM) have become increasingly common, although there is little long-term data on its efficacy in prevention of breast cancer. The objective of this study was to assess the incidence of breast cancer in a cohort of patients undergoing prophylactic NSM with a median follow-up of 10 years. METHODS/UNASSIGNED:Patients receiving prophylactic NSM at a single institution from 2006 to 2019 were included in a retrospective nature. Patient demographics, genetic mutations, operative details, and specimen pathology were recorded, and all postoperative patient visits and documentation were screened for cancer occurrence. Descriptive statics were performed where appropriate. RESULTS/UNASSIGNED:Two hundred eighty-four prophylactic NSMs were performed on 228 patients with a median follow-up of 120.5 ± 15.7 months. Roughly, a third of patients had a known genetic mutation, with 21% BRCA1 and 12% BRCA2. The majority (73%) of prophylactic specimens had no abnormal pathology. The most commonly observed pathologies were atypical lobular hyperplasia (10%) and ductal carcinoma in situ (7%). Cancer was identified in 10% of specimens, with only one case of lymphovascular invasion. Thus far, there have been no incidences of locoregional breast cancer occurrence in this cohort. CONCLUSIONS/UNASSIGNED:The long-term breast cancer occurrence rate in this cohort of prophylactic NSM patients at the time of this study is negligible. Despite this, continued surveillance of these patients is necessary until lifetime risk of occurrence following NSM has been established.