Schrup, Sarah E.

Abstract Objective To evaluate the clinical value of breast MRI in radiation-associated angiosarcoma of the breast (RAASB) for assessing disease extent at diagnosis and after neoadjuvant therapy compared with clinical examination and surgical pathology. Methods This IRB-approved retrospective study included 25 patients with breast MRIs between1995 and 2020. MRI estimated disease extent was compared to clinical exam and surgical pathology. MRI findings were evaluated for additional disease and impact on clinical management. Agreement between MRI and clinical assessment of disease was evaluated using Cohen’s kappa statistic. Results Baseline MRI demonstrated moderate agreement with clinical disease extent (Cohen’s κ = 0.44; 95% CI, 0.14-0.75). Thirteen of 24 (54%) of MRIs reflected clinical exam, 4/24 (17%) MRIs underestimated disease, and 5/24 (21%) MRIs overestimated disease. Baseline MRI changed surgical management in 4/24 (17%). In 8 patients who proceeded directly to surgery, MRI reflected pathology in 6/8 (75%). In 10 patients with post-neoadjuvant MRI, 4/10 (40%) pathology and MRI extent were similar, 5/10 (50%) MRI overestimated disease, and 1/10 (10%) MRI underestimated disease. Conclusion MRI has clinical value in assessing RAASB with the potential for significantly altering surgical management. In this small cohort, post-neoadjuvant MRI demonstrated limited additional clinical value. Larger studies are needed to define the optimal role and timing of post-neoadjuvant MRI. Advances in knowledge Baseline MRI detected additional disease not identified on initial clinical exam in 5/24 (21%) and changed surgical management in 4/24 (17%). Although baseline MRI demonstrated moderate agreement with clinical examination, post-neoadjuvant MRI frequently overestimated residual disease when compared with final pathology.

Abstract Background While the rate of physician burnout has been characterized as relatively high among urologists compared to other specialties, a specific examination of burnout and predictors of burnout among urologists specializing in sexual medicine has not been conducted. Aim The aim of this study was to collect demographic characteristics of urologists specializing in sexual medicine, assess the occurrence of and risk factors for burnout, and characterize satisfaction with career, compensation and work-life balance. Methods We surveyed 96 urologists specializing in sexual medicine to characterize demographic and practice characteristics and assess their satisfaction with career aspects and levels of burnout. Univariable and multivariable modeling with stepwise variable selection was utilized to identify predictive variables of burnout. Outcomes The Copenhagen Burnout Inventory was used to assess personal burnout, work-related burnout, patient-related burnout, and overall burnout. Results Twenty-four percent (n = 23) of participants reported burnout with 35.4% (n = 34) reporting personal burnout, 38.5% (n = 37) reporting work-related burnout, and 24.0% (n = 23) reporting patient-related burnout. Younger age (P = 0.051), Black/African American or multiracial race compared to white race (P < 0.0001), Latino or Hispanic background (P = 0.034), female sex (P = 0.059), being unmarried (P = 0.047), and increased educational debt (0.030) were identified as predictive of overall burnout in adjusted analysis. Dissatisfaction with work-life balance was significantly related to an increase in all categories of burnout (P < 0.01). Clinical implications These findings may guide practice patterns and initiatives to support groups identified at increased risk of burnout, as well as function as a benchmark for future studies of burnout in the sexual medicine urology community. Strengths and limitations While this is the first study of burnout specifically among sexual medicine urologists and findings are consistent with the overall urology community, the small sample size may lead to a biased sample. Conclusion Several demographic and personal characteristics were identified to be predictive of burnout among the sexual medicine urology community, indicating opportunities for additional support.

Abstract Background Most breast biopsies are diagnosed as benign breast disease, with 1.5- to 4-fold increased breast cancer risk. Apart from pathologic diagnoses of atypical hyperplasia, few factors aid in breast cancer risk assessment of these patients. We assessed whether a 313–single nucleotide variation (formerly single-nucleotide polymorphism) polygenic risk score stratifies risk of benign breast disease patients. Methods We pooled data from 5 Breast Cancer Association Consortium case-control studies (mean age = 59.9 years), including 6706 participants with breast cancer and 8488 participants without breast cancer. Using logistic regression, we estimated breast cancer risk associations by self-reported benign breast disease history and strata of polygenic risk score, with median polygenic risk score category among women without benign breast disease as the referent. We assessed interactions and mediation of benign breast disease and polygenic risk score with breast cancer risk. Results Benign breast disease history was associated with increased breast cancer risk (odds ratio [OR] = 1.48, 95% confidence interval [CI] = 1.37 to 1.60; P < .001). Polygenic risk score increased breast cancer risk, irrespective of benign breast disease history (Pinteraction = .48), with minimal evidence of mediation of either factor by the other. Women with benign breast disease and polygenic risk score in the highest tertile had more than twofold increased odds of breast cancer (OR = 2.73, 95% CI = 2.41 to 3.09), and those with benign breast disease and polygenic risk score in the lowest tertile experienced reduced breast cancer risk (OR = 0.79, 95% CI = 0.70 to 0.91) compared with the referent group. Women with benign breast disease and polygenic risk score in the highest decile had a 3.7-fold increase (95% CI = 3.00 to 4.61) compared with those with median polygenic risk score without benign breast disease. Conclusion Breast cancer risks are elevated among women with benign breast disease and increase progressively with polygenic risk score, suggesting that optimal combinations of these factors may improve risk stratification.

Abstract Objectives: Mammographic microcalcifications (calcs) are a sentinel marker of in-situ and invasive breast cancer (BC) but most calcs reflect benign breast disease (BBD). BBD comprises a diverse set of lesions, variably associated with increased BC risk. While calc frequency data for the modern era are limited, historically, calcs were reported in 11% of BBD biopsies. Some studies suggest that calcs in BBD impact BC risks; however, the frequency and BC risks associated with calcs during the percutaneous biopsy era have not been clearly established. Accordingly, we assessed the association of calcs with specific BBD lesions and BC risk in a large contemporaneous BBD cohort including detailed pathology review. Methods: A cohort of 4,819 patients with percutaneously diagnosed BBD from 2002-2013 at Mayo Clinic, were identified. The cohort was followed from 6 months after biopsy until censoring, BC diagnosis, or December 2021. Mean follow-up was 11.3 (SD=5.1) years for BBD patients who remained cancer-free in follow-up compared with 7.4 (SD=4.3) years for cases. Histology of all biopsies were reviewed microscopically to record pathologic findings. A natural language processing algorithm (NLPA) was developed and utilized to identify the presence of calcs based on pathology reports. NLPA results were compared to 300 matched biopsy reports, taken as ground truth. We performed age-adjusted Cox proportional hazards regression to assess hazard ratios (HRs) with 95% confidence intervals (CIs) for specific BBD lesions, stratified by the presence (calc+) or absence of calcs (calcs-), with estimation of an interaction term to test for differences in risks by calc strata. Standardized incidence ratios (SIRs) estimated risks for calc+ and calc- BBD lesions versus matched strata for Iowa SEER population-based BC incidence rates. Results: The NLPA achieved sensitivity=0.993 and specificity=0.986. Overall, 42.8% of BBD biopsies were calc+, including 49.1% of biopsies preceding BC and 42.4% of biopsies not preceding BC (Chi-square p=0.02). Overall, risks of BC among women with BBD calc+ biopsies did not differ significantly from those of women with calc- BBD: HR=1.13 (95% CI: 0.90,1.41), p=0.290. SIRs were also similar for the two groups; women with BBD calc+ biopsies had an SIR =2.00 (95% CI: 1.72, 2.33) and BBD calc- biopsies yielded an SIR= 1.91 (95% CI: 1.64,2.22) (Table 1). HRs were similar for specific calc+ and calc- BBD lesions, with progressively higher risks for non-proliferative disease (NP), proliferative disease without atypia (PDWA) and atypical hyperplasia (AH) (pinteraction=0.55). Interaction terms were not significant for any specific lesion, apart from a marginally significant result for dilated ducts, wherein risks were marginally higher for calc- lesions (pInteraction =0.048), perhaps representing a chance finding. SIRs for calc+ versus calc- BBD lesions were also similar. Overall, 77.3% of AH was calc+; for AH calc+, SIR=3.76 (95%CI: 2.74-5.17) and for AH calc-, SIR=4.41 (95%CI: 2.56-7.59). Conclusion: In this recent, larger percutaneous BBD cohort, calcs were present in 42.8% of all specimens, representing a marked increase compared with historical BBD data, particularly those dominated by surgical biopsy for diagnosis and preceding implementation of full-field digital mammography. In this study, calcs in percutaneously diagnosed BBD were not associated with increased BC risk. Table 1: Comparison of standard incidence ratio of subsequent breast cancer with and without microcalcifications in benign breast disease by histologic impression (NP = non-proliferative disease, PDWA = proliferative disease without atypia, and AH = atypical hyperplasia). (1) compared to Iowa SEER population Citation Format: Sarah Schrup, Robert Vierkant, Stacey Winham, Celine Vachon, Derek Radisky, Jodi Carter, Laura Pacheco-Spann, Matthew Jensen, Amy Degnim, Mark Sherman. Benign breast disease and microcalcifications in percutaneous biopsies and breast cancer risk [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS07-02.

Abstract Introduction: We used micro-computed tomography (microCT), a high-resolution imaging option, to detect and characterize microcalcifications (MCs) in three dimensions within pathology blocks of benign and malignant breast tissues. Methods: A set of 44 formalin-fixed, paraffin-embedded breast tissue blocks were assessed from n=22 women at two time points: benign breast biopsy and subsequent DCIS or DCIS with invasive disease breast cancer. Blocks were scanned using the Bruker Skyscan 1276 microCT at a resolution of 10 µm. SkyScan analysis CTAn software was utilized to prepare and analyze morphological parameters and multiple MCs contained within each block were averaged. Paired morphological parameters were compared between the benign and subsequent cancer samples within women using Wilcoxon signed-rank tests. Results: Median age of patients was 53 years (range 37-77 years) at initial benign biopsy and developed breast cancer at median of 5.6 years (range: 2.3-12.8 years) later. The initial benign biopsies were for proliferative disease without atypia in the majority (59%), while 23% had non-proliferative lesions and 18% atypical hyperplasia. The average structural model index was consistent with a near rod-like shape (median 2.99, range: 2.71-3.29). Paired comparisons between benign and cancer blocks showed that the average surface area of MCs was significantly higher in the cancer samples (p=0.0467), as was the average volume of MCs (p=0.0298) (Table 1). Conclusions: Preliminarily, we demonstrate that microCT of routinely prepared pathology blocks of breast tissues may be useful in characterizing the 3-D morphometry of MCs with suggestive differences in benign and cancer tissues. Given that MCs are a sentinel radiologic marker of DCIS but are common in benign breast disease, developing improved approaches for classifying MCs may have value in breast cancer screening and management. Table 1. Comparison of MC parameters in biopsy tissues (IQR = Interquartile Range). Benign sample from women who later developed breast cancer Breast cancer after prior benign sample Paired Differences (Cancer - Benign) Wilcoxon signed-rank p value (N=22) (N=22) (N=22) Number of Objects (Median (IQR)) 43.5 (14, 789) 69.5 (33, 289) -6 (-139, 67) 0.6830 Average Surface Area (mm2)(Median (IQR)) 0.0225 (0.0134, 0.0393) 0.0342 (0.0185, 0.0656) 0.0113 (-0.0027, 0.0322) 0.0467 Average Volume (mm3) (Median (IQR)) 0.0003 (0.0001, 0.0007) 0.0007 (0.0003, 0.0022) 0.0003 (0.000002, 0.0020) 0.0298 Average Surface Area/Volume (mm−1)(Median (IQR)) 214.92 (162.25, 328.39) 199.55 (151.89, 230.52) -20.85 (-86.05, 27.04) 0.1433 Average Structural Thickness (mm)(Median (IQR)) 0.0341(0.0196, 0.0446) 0.0395 (0.0336, 0.0505) 0.0074 (-0.0062, 0.0153) 0.1173 Average Structural Model Index (Median (IQR)) 2.9758 (2.8465, 3.1175) 3.0026 (2.9281, 3.0927) 0.0075 (-0.1073, 0.1381) 0.7656 Citation Format: Sarah E. Schrup, Thomas de Bel, Tanya Hoskin, Teresa Allers, Stacey Winham, Derek Radisky, Laura Pacheco-Spann, Lisa Seymour, Amy Degnim, Mark Sherman. High resolution microCT to analyze the 3D morphology of microcalcifications in benign breast disease and breast cancer biopsy tissues. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3587.

Abstract Purpose: To evaluate the impact of trimodality treatment versus monotherapy or dual therapy for radiation-associated angiosarcoma of the breast (RAASB) after prior breast cancer treatment. Experimental Design: With Institutional Review Board approval, we identified patients diagnosed with RAASB and abstracted data on disease presentation, treatment, and oncologic outcomes. Trimodality therapy included (i) taxane induction, (ii) concurrent taxane/radiation, and then (iii) surgical resection with wide margins. Results: A total of 38 patients (median age 69 years) met inclusion criteria. Sixteen received trimodality therapy and 22 monotherapy/dual therapy. Skin involvement and disease extent were similar in both groups. All trimodality patients required reconstructive procedures for wound closure/coverage, compared with 48% of monotherapy/dual therapy patients (P < 0.001). Twelve of 16 (75%) patients receiving trimodality therapy had a pathologic complete response (pCR). With median follow-up of 5.6 years, none had local recurrence, 1 patient (6%) had distant recurrence, and no patients died. Among 22 patients in the monotherapy/dual therapy group, 10 (45%) had local recurrence, 8 (36%) had distant recurrence, and 7 (32%) died of disease. Trimodality therapy demonstrated significantly better 5-year recurrence-free survival [RFS; 93.8% vs. 42.9%; P = 0.004; HR, 7.6 (95% confidence interval, CI: 1.3–44.2)]. Combining all patients with RAASB regardless of treatment, local recurrence was associated with subsequent distant recurrence (HR, 9.0; P = 0.002); distant recurrence developed in 3 of 28 (11%) patients without local recurrence compared with 6 of 10 (60%) with local recurrence. The trimodality group had more surgical complications that required reoperation or prolonged healing. Conclusions: Trimodality therapy for RAASB was more toxic but is promising, with a high rate of pCR, durable local control, and improved RFS.