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.

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.

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.

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.

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.

Predicting Complications in Breast Reconstruction: Development and Prospective Validation of a Machine Learning Model.

IMPORTANCE: Necrosis of the nipple-areolar complex (NAC) is the Achilles heel of nipple-sparing mastectomy (NSM), and it can be difficult to assess which patients are at risk of this complication (Ann Surg Oncol 2014;21(1):100-106). OBJECTIVE: To develop and validate a model that accurately predicts NAC necrosis in a prospective cohort. DESIGN: Data were collected from a retrospectively reviewed cohort of patients who underwent NSM and immediate breast reconstruction between January 2015 and July 2019 at our institution, a high -volume, tertiary academic center. Preoperative clinical characteristics, operative variables, and postoperative complications were collected and linked to NAC outcomes. These results were utilized to train a random-forest classification model to predict necrosis. Our model was then validated in a prospective cohort of patients undergoing NSM with immediate breast reconstruction between June 2020 and June 2021. RESULTS: Model predictions of NAC necrosis in the prospective cohort achieved an accuracy of 97% (95% confidence interval [CI], 0.89-0.99; P = 0.009). This was consistent with the accuracy of predictions in the retrospective cohort (0.97; 95% CI, 0.95-0.99). A high degree of specificity (0.98; 95% CI, 0.90-1.0) and negative predictive value (0.98; 95% CI, 0.90-1.0) were also achieved prospectively. Implant weight was the most predictive of increased risk, with weights greater than 400 g most strongly associated with NAC ischemia. CONCLUSIONS AND RELEVANCE: Our machine learning model prospectively predicted cases of NAC necrosis with a high degree of accuracy. An important predictor was implant weight, a modifiable risk factor that could be adjusted to mitigate the risk of NAC necrosis and associated postoperative complications.

Changes in Surgical Management of the Axilla Over 11 Years - Report on More Than 1500 Breast Cancer Patients Treated with Neoadjuvant Chemotherapy on the Prospective I-SPY2 Trial.

BACKGROUND: Axillary surgery after neoadjuvant chemotherapy (NAC) is becoming less extensive. We evaluated the evolution of axillary surgery after NAC on the multi-institutional I-SPY2 prospective trial. METHODS: We examined annual rates of sentinel lymph node (SLN) surgery with resection of clipped node, if present), axillary lymph node dissection (ALND), and SLN and ALND in patients enrolled in I-SPY2 from January 1, 2011 to December 31, 2021 by clinical N status at diagnosis and pathologic N status at surgery. Cochran-Armitage trend tests were calculated to evaluate patterns over time. RESULTS: Of 1578 patients, 973 patients (61.7%) had SLN-only, 136 (8.6%) had SLN and ALND, and 469 (29.7%) had ALND-only. In the cN0 group, ALND-only decreased from 20% in 2011 to 6.25% in 2021 (p = 0.0078) and SLN-only increased from 70.0% to 87.5% (p = 0.0020). This was even more striking in patients with clinically node-positive (cN+) disease at diagnosis, where ALND-only decreased from 70.7% to 29.4% (p < 0.0001) and SLN-only significantly increased from 14.6% to 56.5% (p < 0.0001). This change was significant across subtypes (HR-/HER2-, HR+/HER2-, and HER2+). Among pathologically node-positive (pN+) patients after NAC (n = 525) ALND-only decreased from 69.0% to 39.2% (p < 0.0001) and SLN-only increased from 6.9% to 39.2% (p < 0.0001). CONCLUSIONS: Use of ALND after NAC has significantly decreased over the past decade. This is most pronounced in cN+ disease at diagnosis with an increase in the use of SLN surgery after NAC. Additionally, in pN+ disease after NAC, there has been a decrease in use of completion ALND, a practice pattern change that precedes results from clinical trials.

Breast Conservation Surgery and Mastectomy Have Similar Locoregional Recurrence After Neoadjuvant Chemotherapy: Results From 1462 Patients on the Prospective, Randomized I-SPY2 Trial.

Neoadjuvant chemotherapy (NAC) increases rates of successful breast-conserving surgery (BCS) in patients with breast cancer. However, some studies suggest that BCS after NAC may confer an increased risk of locoregional recurrence (LRR). We assessed LRR rates and locoregional recurrence-free survival (LRFS) in patients enrolled on I-SPY2 (NCT01042379), a prospective NAC trial for patients with clinical stage II to III, molecularly high-risk breast cancer. Cox proportional hazards models were used to evaluate associations between surgical procedure (BCS vs mastectomy) and LRFS adjusted for age, tumor receptor subtype, clinical T category, clinical nodal status, and residual cancer burden (RCB). In 1462 patients, surgical procedure was not associated with LRR or LRFS on either univariate or multivariate analysis. The unadjusted incidence of LRR was 5.4% after BCS and 7.0% after mastectomy, at a median follow-up time of 3.5 years. The strongest predictor of LRR was RCB class, with each increasing RCB class having a significantly higher hazard ratio for LRR compared with RCB 0 on multivariate analysis. Triple-negative receptor subtype was also associated with an increased risk of LRR (hazard ratio: 2.91, 95% CI: 1.8-4.6, P < 0.0001), regardless of the type of operation. In this large multi-institutional prospective trial of patients completing NAC, we found no increased risk of LRR or differences in LRFS after BCS compared with mastectomy. Tumor receptor subtype and extent of residual disease after NAC were significantly associated with recurrence. These data demonstrate that BCS can be an excellent surgical option after NAC for appropriately selected patients.

Improving Medical Student Anatomy Knowledge and Confidence for the Breast Surgical Oncology Rotation.

BACKGROUND: The anatomy curriculum has undergone considerable reductions in class time, resulting in decreased student anatomical knowledge retention and confidence during their surgical rotations. To counter this deficit in anatomy knowledge, a clinical anatomy mentorship program (CAMP) was developed by fourth-year medical student leaders and staff mentors in a near-peer teaching fashion prior to the surgical clerkship. This study analyzed the impact this program had on third-year medical students (MS3s) self-assessed anatomical knowledge and confidence in the operating room on the Breast Surgical Oncology rotation after this near-peer program. METHODS: A single-center prospective survey study was performed at an academic medical center. Pre- and post-program surveys were administered to all students who participated in the CAMP and rotated on the breast surgical oncology (BSO) service during the surgery clerkship rotation. A control group of individuals who did not rotate on the CAMP was established, and this group was administered a retrospective survey. A 5-point Likert scale was used to assess surgical anatomy knowledge, confidence in the operating room, and comfort in assisting in the operating room. Control group versus post-CAMP intervention group and pre- versus post-CAMP intervention groups survey results were compared using the Student's t-test with a p-value of <0.05 statistically significant. RESULTS: All CAMP students rated their surgical anatomy knowledge (p < 0.01), confidence in the operating room (p < 0.01), and comfort in assisting in the operating room (p < 0.01) as greater than those who did not participate in the program. Additionally, the program improved the ability of third-year medical students to prepare for operating room cases going into their third-year breast surgical oncology clerkship (p < 0.03). CONCLUSIONS: This near-peer surgical education model appears to be an effective way to prepare third-year medical students for the breast surgical oncology rotation during the surgery clerkship by improving anatomic knowledge and student confidence. The program can serve as a template for medical students, surgical clerkship directors, and other faculty interested in efficiently expanding surgical anatomy at their institution.

Use of Ultrasound and Ki-67 Proliferation Index to Predict Breast Cancer Tumor Response to Neoadjuvant Endocrine Therapy.

BACKGROUND: Prediction of tumor shrinkage and pattern of treatment response following neoadjuvant endocrine therapy (NET) for estrogen receptor positive (ER+), Her2 negative (Her2-) breast cancers have had limited assessment. We examined if ultrasound (US) and Ki-67 could predict the pathologic response to treatment with NET and how the pattern of response may impact surgical planning. METHODS: A total of 103 postmenopausal women with ER+, HER2- breast cancer enrolled on the FELINE trial had Ki-67 obtained at baseline, day 14, and surgical pathology. A total of 70 patients had an US at baseline and at the end of treatment (EOT). A total of 48 patients had residual tumor bed cellularity (RTBC) assessed. The US response was defined as complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD). CR or PR on imaging and ≤70% residual tumor bed cellularity (RTBC) defined a contracted response pattern. RESULTS: A decrease in Ki-67 at day 14 was not predictive of EOT US response or RTBC. A contracted response pattern was identified in one patient with CR and in sixteen patients (33%) with PR on US. Although 26 patients (54%) had SD on imaging, 22 (85%) had RTBC ≤70%, suggesting a non-contracted response pattern of the tumor bed. The remaining four (15%) with SD and five with PD had no response. CONCLUSION: Ki-67 does not predict a change in tumor size or RTBC. NET does not uniformly result in a contracted response pattern of the tumor bed. Caution should be taken when using NET for the purpose of downstaging tumor size or converting borderline mastectomy/lumpectomy patients.

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.

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.

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.

Prognostic Significance of Lobular Carcinoma In-Situ (LCIS) Diagnosed Alongside Invasive Breast Cancer.

Purpose: Women with lobular carcinoma in-situ (LCIS) have an increased risk for developing breast cancer (BC) compared with the general population. However, little is known about the clinical implication of diagnosing LCIS concurrently with an invasive breast cancer. We aimed to define the rate of LCIS diagnosed concurrently with an invasive breast cancer and investigate the risk of contralateral breast cancer (CBC) during survivorship care. Materials and methods: A single center retrospective review over 6 years identified women with stage I-III BC who underwent lumpectomy or unilateral mastectomy. Patients with or without concurrent LCIS were compared using Chi-squared analyses to assess for differences in clinicopathologic factors and risk of future CBC (including invasive and in-situ disease). Results: Of 1808 patients, 16.6% (n = 301) had LCIS concurrent with their index breast cancer. Patients with LCIS had a higher rate of subsequent CBC development than those without LCIS (3.3% versus 1.0%, P = .004). The risk ratio for patients with LCIS developing subsequent CBC compared with those without LCIS was 3.3 (95% confidence interval [CI]: 1.5-7.3). Conclusions: Patients with LCIS diagnosed concurrently with their index breast cancer at surgery are at higher risk for subsequent CBC than those without LCIS. The evidence from this study suggest that it may be appropriate for women with LCIS diagnosed alongside an index breast cancer to consider on-going high-risk screening during survivorship care.

Is image-guided core needle biopsy of borderline axillary lymph nodes in breast cancer patients clinically helpful?

BACKGROUND: When borderline axillary lymph nodes (bALN) are identified on ultrasound (US) for breast cancer (BC) patients, preoperative management is unclear. We aimed to evaluate if core needle biopsy (CNB) for bALN is clinically helpful or disruptive. METHODS: Retrospective review of BC patients with bALN from 2014 to 2019 was performed. Clinicopathologic data were compared for those who did and did not have CNB. RESULTS: CNB (n = 34) and no CNB (n = 31) were similar with respect to clinicopathologic factors. Surgical LN-positive rate was the same between cohorts (p = 0.26). CNB was disruptive in 58.8 %; all had CNB for pN0 disease. CNB was helpful in 34.2 %: 14.7 % proceeded directly to axillary dissection; 17.6 % had positive LN localized after neoadjuvant chemotherapy. CONCLUSIONS: CNB for bALN is more likely clinically disruptive and did not impact surgical LN positive rate. BC patients with bALN should undergo CNB only if it will change clinical management.

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.

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.

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.