Preoperative MRI and Its Impact on Surgical Outcomes in Patients with Triple Negative Breast Cancer Treated with Primary Surgery: Did New Margin Guidelines or Cavity Shave Margins Practice Diminish the Role of Preoperative MRI?

BACKGROUND: Results of an earlier retrospective study from our institution suggested that patients with triple negative breast cancer (TNBC) who had preoperative MRI may have had an improved local recurrence rate (LRR) after breast conserving surgery (BCS). We aimed to clarify the impact of preoperative MRI on surgical outcomes in an expanded TNBC cohort treated by BCS in a contemporary era. METHODS: Our study cohort comprised 648 patients with TNBC who underwent BCS between 2009 and 2018. Demographic and clinical characteristics were compared between those with (n = 292, 45.1%) and without (n = 356, 54.9%) preoperative MRI. Multivariable logistic regression was performed to assess the association of preoperative MRI with surgical outcomes. RESULTS: The crude LRR of 3.5% was lower than previously reported. Univariable analyses demonstrated that the LRR and re-excision rates in the MRI and no-MRI groups were 3.4 and 3.7%, 21.6% and 27.2%, p = 0.876 and p = 0.10, respectively. Multivariable logistic regression analyses demonstrated that preoperative MRI was not associated with a lower LRR: odds ratio (OR) = 1.42 (p = 0.5). During our study period, new margin guidelines and shave margins practice were adopted in 2014 and 2015. To account for their effects, the year of diagnosis/surgery and other clinical variables were adjusted in multivariable logistic regression and inverse probability weighting models to demonstrate that preoperative MRI remained associated with a lower re-excision risk, OR 0.56, p = 0.04l; and a lower re-excision rate, 23.15% versus 36.0%, p < 0.01, respectively. CONCLUSIONS: Our findings suggested that patients with TNBC anticipating BCS may benefit from preoperative MRI.

Immediate Breast Reconstruction for Inflammatory Breast Cancer: Trends in Use and Clinical Outcomes 2004-2016.

INTRODUCTION: National guidelines specify against immediate breast reconstruction (IBR) among inflammatory breast cancer (IBC) patients. However, limited data exist regarding this practice. We report practice patterns and oncologic outcomes among nonmetastatic IBC patients receiving trimodality therapy, with or without IBR. METHODS: Using the National Cancer Database, we identified nonmetastatic IBC patients treated with trimodality therapy from 2004 to 2016. Primary outcome was overall survival (OS), assessed on unadjusted analysis using Kaplan-Meier estimates and on adjusted analysis using multivariable Cox proportional hazards and inverse probability weighting (IPW) models. OS analysis was also conducted with propensity score matched (PSM) cohorts. Secondary outcomes included IBR utilization rates, time to postmastectomy radiotherapy (PMRT), and surgical outcomes. RESULTS: 6589 women were included, including 5954 (90.4%) non-reconstructed and 635 (9.6%) IBR. Among IBR recipients, 250 (39.4%) underwent autologous reconstruction, 171 (26.9%) underwent implant-based reconstruction, and 214 (33.7%) unspecified. IBR utilization increased from 6.3% to 10.1% from 2004 to 2016 at a 4% average annual growth rate (P < 0.001). Median follow-up was 43 and 45 months for IBR and non-reconstructed patients, respectively (P = 0.29). On Cox multivariable analysis, IBR was associated with improved OS (HR 0.63, 95% CI 0.44-0.90, P = 0.01), but this association was not significant on IPW analysis (P = 0.06). In PSM cohorts, this association remained significant (HR 0.60, 95% CI 0.40-0.92, P = 0.02). Margin status, time to PMRT, 30-day readmission, and 30-/90-day mortality did not differ between groups (all P > 0.05). CONCLUSION: Although not endorsed by national guidelines, IBR is increasing among IBC patients; however, more granular data are needed to determine oncologic safety.

CDH2/N-cadherin and early diagnosis of invasion in patients with ductal carcinoma in situ.

PURPOSE: This proof-of-concept study investigates gene expression in core needle biopsies (CNB) to predict whether individuals diagnosed with ductal carcinoma in situ (DCIS) on CNB were affected by invasion at the time of diagnosis. METHODS: Using a QuantiGene Plex 2.0 assay, 14 gene expression profiling was performed in 303 breast tissue samples. Preoperative diagnostic performance of a gene was measured by area under receiver-operating characteristic curve (AUC) with 95% confidence interval (CI). The gene mRNA positivity cutoff was computed using Gaussian mixture model (GMM); protein expression was measured by immunohistochemistry; DNA methylation was evaluated by targeted bisulfite sequencing. RESULTS: mRNA from 69% (34/49) mammoplasties, 72% (75/104) CNB DCIS, and 89% (133/150) invasive breast cancers (IBC) were analyzed. Based on pre-and post-surgery DCIS chart reviews, 21 cases were categorized as DCIS synchronous with invasion and 54 DCIS were pure DCIS without pathologic evidence of invasive disease. The ectopic expression of neuronal cadherin CDH2 was probable in 0% mammoplasties, 6% pure DCIS, 29% synchronous DCIS, and 26% IBC. The CDH2 mRNA positivity in preoperative biopsies showing pure DCIS was predictive of a final diagnosis of invasion (AUC = 0.67; 95% CI 0.53-0.80; P = 0.029). Site-specific methylation of the CDH2 promoter (AUC = 0.76; 95% CI 0.54-0.97; P = 0.04) and measurements of N-cadherin, a pro-invasive cell-cell adhesion receptor encoded by CDH2 (AUC = 0.8; 95% CI 0.66-0.99; P < 0.005) had a discriminating power allowing for discernment of CDH2-positive biopsy. CONCLUSIONS: Evidence of CDH2/N-cadherin expression, predictive of invasion synchronous with DCIS, may help to clarify a diagnosis and direct the course of therapy earlier in a patient's care.

Negative prognostic impact of epidermal growth factor receptor copy number gain in young adults with isocitrate dehydrogenase wild-type glioblastoma.

PURPOSE: Young adults with isocitrate-dehydrogenase wild-type (IDH-WT) glioblastoma (GBM) represent a rare, understudied population compared to pediatric high-grade glioma, IDH-mutant GBM, or IDH-WT GBM in older patients. We aimed to explore the prognostic impact of epidermal growth factor receptor copy number gain (EGFR CN gain), one of the most common genetic alterations in IDH-WT glioma, in young adults with IDH-WT GBM. METHODS: We performed a retrospective cohort study of patients 18-45 years old with newly diagnosed, IDH-WT GBM whose tumors underwent next-generation sequencing at our institution between 2014 and 2018. The impact of EGFR CN gain on time to tumor progression (TTP) and overall survival (OS) was assessed. A validation cohort of patients 18-45 years old with IDH-WT GBM was analyzed from The Cancer Genome Atlas (TCGA). RESULTS: Ten of 28 patients (36%) from our institution had EGFR CN gain, which was associated with shorter TTP (median 6.5 vs. 11.9 months; p = 0.06) and OS (median 16.3 vs. 23.5 months; p = 0.047). The negative prognostic impact of EGFR CN gain on OS persisted in a multivariate model (HR 6.40, 95% CI 1.3-31.0, p = 0.02). In the TCGA cohort (N = 43), EGFR CN gain was associated with shorter TTP and worse OS, although these did not reach statistical significance (TTP, median 11.5 vs. 14.4 months, p = 0.18; OS, median 23.6 vs. 27.8 months; p = 0.18). CONCLUSIONS: EGFR CN gain may be associated with inferior outcomes in young adults with newly diagnosed, IDH-WT GBM, suggesting a potential role for targeting EGFR in this population.

Treatment Patterns and Clinical Outcomes of Adenoid Cystic Breast Carcinoma: A Single-Institution Experience.

BACKGROUND: Adenoid cystic breast carcinoma (ACC) is a rare subtype of triple-negative breast cancer. We aim to characterize the treatment patterns and clinical outcomes of women diagnosed with ACC at a large medical center. METHODS: Female patients diagnosed with ACC at our institution between 2009 and 2019 were retrospectively identified. Patients with limited clinicopathologic data were excluded. RESULTS: In our final study cohort (n = 9), the majority of ACCs (6/9, 66.7%) were hormone receptor (-) (HR-) and HER-2/neu (-) (HER2-), while 3 ACCs were HR+ HER2-. Two patients received adjuvant chemotherapy, and 4 patients received adjuvant radiotherapy. The crude local and distant recurrence rate of our cohort was 22.2% and 11.1% (median follow-up of 36 months). CONCLUSIONS: The majority of ACCs were triple negative but some ACCs were HR+. The unadjusted local and distant recurrence rates were not negligible, suggesting that adjuvant chemotherapy and radiotherapy may be warranted in select cases.

Clinical characteristics and outcomes of benign, atypical, and malignant breast adenomyoepithelioma: a single institution's experience.

BACKGROUND: Breast adenomyoepithelioma (AME) is rare. We sought to evaluate clinical characteristics, treatment, and outcomes of a contemporary patient cohort stratified by histology. METHODS: We queried health records containing "adenomyoepithelioma" between 2000 and 2018. Histology was confirmed with centralized review and classified into benign, atypical, and malignant. Clinical characteristics, demographics, treatment, and oncologic outcomes were compared. RESULTS: Our query yielded 24 patients with adenomyoethelioma. Histologic diagnosis was confirmed in 12 (benign n = 6, atypical n = 3, malignant n = 3). Excision (n = 11) was the usual initial treatment, with margin status available in 10 patients. Mean follow up was 44 months (range 1-138 months) with no local recurrence observed. Two patients with benign AME presented with concurrent contralateral breast cancer, and one with malignant AME died of metastatic AME. CONCLUSION: Wide excision of atypical and malignant AME is recommended as local recurrence when excised completely was not observed. Given metastatic potential of malignant AME, multimodal therapy may be warranted.

Breast-conserving surgery for pure non-classic lobular carcinoma in situ: A single institution's experience.

BACKGROUND: Non-classic lobular carcinoma in situ (NC-LCIS) is a rare pre-cancer breast lesion that warrants excision to exclude invasive disease. In patients pursuing breast-conserving surgery (BCS) for NC-LCIS, the need for wide surgical margins is controversial. We characterized the outcomes of women diagnosed with NC-LCIS at a large, academic medical center. METHODS: Female patients seen at our institution from 2008 to 2018 with pure NC-LCIS were retrospectively identified. Patients were excluded if NC-LCIS was diagnosed in the background of invasive cancer or ductal carcinoma in situ. Clinicopathologic and follow-up data were collected. Rates of upstage, re-excision, and recurrence were calculated. RESULTS: We identified 26 patients with pure NC-LCIS diagnosed on biopsy. 80.8% of patients initially pursued breast conservation, while 19.2% underwent mastectomy. At definitive surgery, 11.5% were upstaged. Among 19 non-upstaged patients that underwent BCS, 47.4% had at least one re-excision and 26.3% converted to mastectomy. In patients receiving BCS without completion mastectomy, 64.3% had final surgical margins that were negative for NC-LCIS, while 35.7% had positive or close margins. No recurrences in patients with negative margins were observed. One patient with positive margins developed a recurrence 8.3 years post-surgery, and one patient with close margins did 2.2 years post-surgery. All non-upstaged patients were alive at time of analysis with no evidence of invasive disease. CONCLUSION: We presented the outcomes of one of the largest series of pure NC-LCIS. In patients with NC-LCIS pursuing breast conservation, re-excisions and completion mastectomies were common. However, when negative margins were achieved, prognosis was excellent.

Attitudes and Habits of Highly Humanistic Surgeons: A Single-Institution, Mixed-Methods Study.

PURPOSE: Humanism in medicine is associated with increased patient satisfaction, trust of patients in their doctors, and better outcomes. The authors sought to identify attitudes, habits, and other factors that sustain humanism in academic surgical faculty, and compare these with attributes determined from a previous study of internal medicine faculty. METHOD: A mixed-methods study design at University of Pennsylvania Health System was employed from 2016 to 2018 using a survey instrument and semistructured interviews. Surgical residents nominated faculty who exemplified humanism. In-depth interviews were then conducted with surgeons receiving the most nominations. The interviews were transcribed, and common themes were identified using the grounded theory method. These were compared with findings from a previous internal medicine study. RESULTS: Ten faculty described three strongly shared attitudes: humility, responsibility, and a desire to live up to a high standard of professional behavior. Five habits were found important to sustaining these attitudes and their practice: self-reflection, finding deep connections with patients, maintaining personal and professional relationships, "having fun" at work, and paying it forward to surgical trainees. Surgeons also cited the importance of past role models in developing humanistic attitudes and sustaining practice. Responses were compared with previously documented attitudes and habits of humanistic internal medicine faculty at the institution. CONCLUSIONS: This study identified recurring attitudes and habits that characterize humanistic behaviors in a cohort of academic surgeons. Learning from these exemplary humanistic surgeons may inform the development of future educational programs for residents and faculty in sustaining humanism.

Qualities and Methods of Highly Effective Surgical Educators: A Grounded Theory Model.

OBJECTIVE: To identify personal qualities and teaching methods of highly effective surgical educators using a novel research design. DESIGN: In this qualitative study, surgical residents were sent an electronic survey soliciting nominations for faculty perceived as highly effective surgical educators. In-depth, semistructured interviews were conducted with surgeons receiving the most nominations. Grounded theory methodology identified themes for analysis. SETTING: General, vascular, and plastic surgery residents and faculty at the University of Pennsylvania Health System. PARTICIPANTS: A total of 77 surgical residents were surveyed. Data saturation occurred after 12 semistructured interviews with attending surgeons, corresponding to the top 15% of faculty. RESULTS: Interviewees described both personal characteristics and specific teaching approaches that facilitated successful learning. These included providing exceptional surgical education as a mission, a strong influence from past mentors and role models, a love for the profession, and a low rate of self-professed burnout. Desirable teaching methods included promoting a culture of psychological safety (the perceived ability to take interpersonal risks within one's environment), progressive autonomy, accountability of trainees, and individualized teaching for the learner. Interviewees saw education as inseparable from clinical duties, and all surgeons believed providing exceptional patient care was the foundation of effective surgical teaching. The derived themes suggested that educators prefer "cognitive-based" approaches, focusing on learning processes rather than specific outcomes. CONCLUSIONS: This study identified characteristics and educational styles of highly effective educators in a cohort of academic surgeons. This framework may inform the development of educational programs for residents and faculty in effective teaching methods.