Tumor microenvironmental determinants of high-risk DCIS progression.

Ductal carcinoma in situ (DCIS) constitutes an array of morphologically recognized intraductal neoplasms in the mammary ductal tree defined by an increased risk for subsequent invasive carcinomas at or near the site of biopsy detection. However, only 15-45% of untreated DCIS cases progress to invasive cancer, so understanding mechanisms that prevent progression is key to avoid overtreatment and provides a basis for alternative therapies and prevention. This study was designed to characterize the tumor microenvironment and molecular profile of high-risk DCIS that grew to a large size but remained as DCIS. All patients had DCIS lesions >5cm in size with at least one additional high-risk feature: young age (<45 years), high nuclear grade, hormone receptor negativity, HER2 positivity, the presence of comedonecrosis, or a palpable mass. The tumor immune microenvironment was characterized using multiplex immunofluorescence to identify immune cells and their spatial relationships within the ducts and stroma. Gene copy number analysis and whole exome DNA sequencing identified the mutational burden and driver mutations, and quantitative whole-transcriptome/gene expression analyses were performed. There was no association between the percent of the DCIS genome characterized by copy number variants (CNAs) and recurrence events (DCIS or invasive). Mutations, especially missense mutations, in the breast cancer driver genes PIK3CA and TP53 were common in this high-risk DCIS cohort (47% of evaluated lesions). Tumor infiltrating lymphocyte (TIL) density was higher in DCIS lesions with TP53 mutations (p=0.0079) compared to wildtype lesions, but not in lesions with PIK3CA mutations (p=0.44). Immune infiltrates were negatively associated with hormone receptor status and positively associated with HER2 expression. High levels of CD3+CD8- T cells were associated with good outcomes with respect to any subsequent recurrence (DCIS or invasive cancer), whereas high levels of CD3+Foxp3+ Treg cells were associated with poor outcomes. Spatial proximity analyses of immune cells and tumor cells demonstrated that close proximity of T cells with tumor cells was associated with good outcomes with respect to any recurrence as well as invasive recurrences. Interestingly, we found that myoepithelial continuity (distance between myoepithelial cells surrounding the involved ducts) was significantly lower in DCIS lesions compared to normal tissue (p=0.0002) or to atypical ductal hyperplasia (p=0.011). Gene set enrichment analysis identified several immune pathways associated with low myoepithelial continuity and a low myoepithelial continuity score was associated with better outcomes, suggesting that gaps in the myoepithelial layer may allow access/interactions between immune infiltrates and tumor cells. Our study demonstrates the immune microenvironment of DCIS, in particular the spatial proximity of tumor cells and T cells, and myoepithelial continuity are important determinants for progression of disease.

Successful Breast Conservation After Neoadjuvant Chemotherapy in Lobular Breast Cancer: The Role of Menopausal Status in Response to Treatment.

BACKGROUND: While neoadjuvant chemotherapy (NAC) has been shown to increase rates of breast conservation surgery (BCS) for breast cancer, response rates in invasive lobular carcinoma (ILC) appear lower than other histologic subtypes. Some data suggest higher response rates to NAC in premenopausal versus postmenopausal patients, but this has not been studied in ILC. We evaluated the rates of successful BCS after NAC in patients with ILC stratified by menopausal status. PATIENTS AND METHODS: We analyzed data from a single-institution cohort of 666 patients with stage I-III hormone receptor positive HER-2 negative ILC. We used t-tests, chi-squared tests, and multivariable logistic regression to investigate rates of NAC use, attempted BCS, and associations between NAC and successful BCS by menopausal status. RESULTS: In 217 premenopausal and 449 postmenopausal patients, NAC was used more often in the premenopausal group (15.2% vs. 9.8%, respectively, p = 0.041). Among those who attempted breast conservation (51.3% of pre- and 64.8% of postmenopausal cohorts), NAC was not associated with successful BCS in either group. Interestingly, for postmenopausal patients, receipt of NAC was significantly associated with increased rates of completion mastectomy in those who had positive margins at the first attempt at BCS. CONCLUSION: NAC was not associated with successful BCS in either premenopausal or postmenopausal patients with ILC. Although premenopausal patients were more likely to receive NAC, these data suggest that menopausal status may not be a good predictor of response to chemotherapy. Better predictors of response and more efficacious treatment for patients with ILC are needed.

Recovery of Screening Mammogram Cancellations During COVID-19.

BACKGROUND: In response to the COVID-19 pandemic, the American Society of Breast Surgeons and American College of Radiology released a joint statement recommending that all breast screening studies be postponed effective March 26, 2020. STUDY DESIGN: A retrospective review of all canceled mammograms at a single tertiary care institution from January 1-August 31, 2020 was performed to evaluate the effect of this recommendation by quantifying both the number and reason for mammogram cancellations before and after March 26, 2020. Utilization of the electronic patient portal for appointment cancellation as a surrogate for telehealth uptake was noted. RESULTS: During the study period, 5340 mammogram appointments were kept and 2784 mammogram appointments were canceled. From a baseline of 30 (10.8%) canceled mammograms in January, cancellations peaked in March (576, 20.6%) and gradually decreased to a low in August (197, 7%). Reasons for cancellations varied significantly by month (P < .0001) and included COVID-19 related (236, 8.5%), unspecified patient reasons (1,210, 43.5%), administrative issues (147, 5.3%), provider requests (46, 1.7%), sooner appointments available (31, 1.1%), and reasons not given (486, 17.5%). In addition, compared to a baseline in January (51, 16.5%), electronic patient portal access peaked in August (67, 34.0%). CONCLUSION: Screening mammogram cancellations have gradually recovered after early COVID-19 restrictions were lifted and increasing use of electronic patient access appears to be sustained. Consequences for future staging at the time of diagnosis remain unknown. Understanding to what extent the pandemic affected screening may help surgeons plan for post-pandemic breast cancer care.

Improvement in Breast Reconstruction Disparities following Medicaid Expansion under the Affordable Care Act.

BACKGROUND:  Under the Affordable Care Act, Medicaid expansion effective 1 January 2014 aimed to increase access to health care. We sought to determine the association of Medicaid expansion with disparities in utilization of breast reconstruction. METHODS: Non-Hispanic Black (NHB) and White (NHW) breast cancer patients undergoing mastectomy +/- reconstruction between 2010 and 2017 were selected from the National Cancer Database. Annual trends for utilization of breast reconstruction by race, income, and education were evaluated by Medicaid expansion status using difference-in-differences regression analyses. Medicaid expansion was categorized by expansion date as early (2010-2013), 2014 (1/2014), late (after 1/2014), or no expansion. RESULTS: Of 443,607 patients, 36.3% (n = 161,128) underwent reconstruction, 13.1% (n = 58,249) were NHB, 16.8% (n = 74,430) had median income < $40,227, and 17.1% (n = 75,718) were in the lowest education quartile. In non-expansion states, lower proportions of NHB patients underwent reconstruction than NHW patients in all years, with the smallest disparity (NHB% - NHW%) (- 6.4%) in 2017. Decreases in disparities between NHB and NHW patients were seen with the smallest difference observed in 2014 (- 2.5%) in early-expansion states, in 2017 (- 0.7%) in 1/2014 expansion states, and in 2017 (- 4.5%) in late-expansion states. Similar findings for convergence of reconstruction utilization rates for the lowest two education levels and lowest two income quartiles were found with Medicaid expansion, with no convergence seen in non-expansion states over the study period. CONCLUSIONS: Some improvement in breast reconstruction disparities followed Medicaid expansion. Failure to improve parity without Medicaid expansion should be a consideration with any modifications to Medicaid access.

Retrorectal cyst: proteus in the backyard-case series and literature review.

Retrorectal cysts are cystic lesions located in the retrorectal space and are a distinct subset of retrorectal tumours, which are often misdiagnosed due to their rarity and mimicry of symptoms caused by common diseases. We have described the presentation and management of four patients who were diagnosed with retrorectal cysts from a 10-year retrospective chart review at our institute, a tertiary care centre. In middle-aged women, the following should raise suspicion of retrorectal cyst: gastrointestinal or urinary obstructive features, mass or fullness palpable on the posterior wall on digital rectal examination, presacral dimple, perianal fistula and/or recurrent disease. Such features should prompt an MRI evaluation of the pelvis for definitive diagnosis.

Staging Melanoma: What's Old and New.

The melanoma expert panel devised the evidence-based eighth edition American Joint Committee on Cancer staging system by conducting vigorous analyses of stage I, II, and III patients from the International Melanoma Database and Discovery Platform. Key changes in the eighth edition are regarding subcategorization of T1, M1, pathologic stage grouping of stage I and III, and refining the definitions and terminologies used in the staging system. As the knowledge of tumor biology improves, the staging of melanoma will continue to evolve to enable betterment of care.

Ultra structural changes occurring in duct ectasia and periductal mastitis and their significance in etiopathogenesis.

INTRODUCTION: Duct ectasia (DE) and periductal mastitis (PDM) are the most common benign breast conditions seen in women. The etiopathogenesis of these entities is still not clear and most of the theories regarding the causation are based on the histological features as seen on light microscopy. The ultramicroscopic features associated with these conditions that may give more insight to the etiopathogenesis are unknown. AIM: To study the ultrastructural changes occurring in mammary duct cones in patients with DE and PDM using Transmission Electron Microscopic (TEM). METHOD: Major ducts removed by radical duct excision from 21 patients with final histopathological diagnosis of DE and PDM were subjected to TEM study with 2 normal duct samples as controls. RESULTS: The TEM features of DE were denudation of the epithelial cells with focal loss of microvilli, widening of the inter-epithelial junctions with focal disruption of the T bars, periductal collagenisation without inflammation, and features suggestive of Epithelial Mesenchymal Transition (EMT). PDM features are intact epithelial lining with proliferative epithelium and periductal collagenisation with inflammation. CONCLUSIONS: Based on the TEM findings, we suggest that DE and PDM are two different entities. EMT a novel finding observed in DE in this study.

Duct Ectasia and Periductal Mastitis in Indian Women.

There is very little awareness of the general physicians and surgeons about the benign breast conditions such as duct ectasia (DE) and periductal mastitis (PDM) causing nipple discharge. Not only that these benign breast diseases ring a false alarm of cancer, they are also the second most common cause of benign breast diseases. The objective was to study the clinical and microbiological profiles of duct ectasia and periductal mastitis in Indian women for better understanding of the disease process, in order to be able to treat them well. Forty-one consecutive patients presenting to the Surgical Out-Patient Department with non-bloody nipple discharge with clinical and radiological features suggestive of DE or PDM were included. Microbial culture and cytopathological study of the nipple discharge were done. Histopathological studies and culture of the ductal tissue taken intraoperatively were carried out. There is no significant difference in the age distribution among women with DE and PDM. Smoking is not associated with DE and PDM of Indian patients in contrast to the Western literature evidence. Infective etiology was present in nearly 46 % of the patients in the study population more so in the periductal mastitis cases. The most common isolated pathogens were Staphylococcus aureus and Staphylococcus epidermidis, unlike in Western population where nearly 50 % were anaerobes. Since the isolated organisms were resistant to the routinely used antibiotics in high proportion of cases, culture and sensitivity should be done in all possible cases for appropriately treating the subareolar sepsis before proceeding with the definitive treatment in the form of duct excision.