Immune cells are increased in normal breast tissues of BRCA1/2 mutation carriers.

PURPOSE: Breast cancer risk is elevated in pathogenic germline BRCA 1/2 mutation carriers due to compromised DNA quality control. We hypothesized that if immunosurveillance promotes tumor suppression, then normal/benign breast lobules from BRCA carriers may demonstrate higher immune cell densities. METHODS: We assessed immune cell composition in normal/benign breast lobules from age-matched women with progressively increased breast cancer risk, including (1) low risk: 19 women who donated normal breast tissue to the Komen Tissue Bank (KTB) at Indiana University Simon Cancer Center, (2) intermediate risk: 15 women with biopsy-identified benign breast disease (BBD), and (3) high risk: 19 prophylactic mastectomies from women with germline mutations in BRCA1/2 genes. We performed immunohistochemical stains and analysis to quantitate immune cell densities from digital images in up to 10 representative lobules per sample. Median cell counts per mm2 were compared between groups using Wilcoxon rank-sum tests. RESULTS: Normal/benign breast lobules from BRCA carriers had significantly higher densities of immune cells/mm2 compared to KTB normal donors (all p < 0.001): CD8 + 354.4 vs 150.9; CD4 + 116.3 vs 17.7; CD68 + 237.5 vs 57.8; and CD11c + (3.5% vs 0.4% pixels positive). BBD tissues differed from BRCA carriers only in CD8 + cells but had higher densities of CD4 + , CD11c + , and CD68 + immune cells compared to KTB donors. CONCLUSIONS: These preliminary analyses show that normal/benign breast lobules of BRCA mutation carriers contain increased immune cells compared with normal donor breast tissues, and BBD tissues appear overall more similar to BRCA carriers.

Automated quantification of levels of breast terminal duct lobular (TDLU) involution using deep learning.

Convolutional neural networks (CNNs) offer the potential to generate comprehensive quantitative analysis of histologic features. Diagnostic reporting of benign breast disease (BBD) biopsies is usually limited to subjective assessment of the most severe lesion in a sample, while ignoring the vast majority of tissue features, including involution of background terminal duct lobular units (TDLUs), the structures from which breast cancers arise. Studies indicate that increased levels of age-related TDLU involution in BBD biopsies predict lower breast cancer risk, and therefore its assessment may have potential value in risk assessment and management. However, assessment of TDLU involution is time-consuming and difficult to standardize and quantitate. Accordingly, we developed a CNN to enable automated quantitative measurement of TDLU involution and tested its performance in 174 specimens selected from the pathology archives at Mayo Clinic, Rochester, MN. The CNN was trained and tested on a subset of 33 biopsies, delineating important tissue types. Nine quantitative features were extracted from delineated TDLU regions. Our CNN reached an overall dice-score of 0.871 (±0.049) for tissue classes versus reference standard annotation. Consensus of four reviewers scoring 705 images for TDLU involution demonstrated substantial agreement with the CNN method (unweighted κappa = 0.747 ± 0.01). Quantitative involution measures showed anticipated associations with BBD histology, breast cancer risk, breast density, menopausal status, and breast cancer risk prediction scores (p < 0.05). Our work demonstrates the potential to improve risk prediction for women with BBD biopsies by applying CNN approaches to generate automated quantitative evaluation of TDLU involution.

Breast Cancer Risk and Progressive Histology in Serial Benign Biopsies.

Background: More than 1 million women per year in the United States with benign breast biopsies are known to be at elevated risk for breast cancer (BC), with risk stratified on histologic categories of epithelial proliferation. Here we assessed women who had serial benign biopsies over time and how changes in the histologic classification affected BC risk. Methods: In the Mayo Clinic Benign Breast Disease Cohort of 13 466 women, 1414 women had multiple metachronous benign biopsies (10.5%). Both initial and subsequent biopsies were assessed histologically. BC risk for clinical and prognostic factors was assessed using subdistribution models to account for competing risks, and logistic regression/Wilcoxon/chi-square tests to assess covariates. All statistical tests were two-sided. Results: Breast cancer risk for women with serial biopsies, stratified by histologic category in the later biopsies, was similar to women with a single biopsy. We found that changes in histological category between initial and subsequent biopsy statistically significantly impacted BC risk. Women with nonproliferative initial findings and subsequent proliferative findings had an increased risk (hazard ratio [HR] = 1.77, 95% confidence interval [CI] = 1.06 to 2.94, P = .03) compared with no change. Among women with proliferative disease without atypia at initial biopsy, risk decreased if later biopsy regressed to nonproliferative (HR = 0.49, 95% CI = 0.25 to 0.98) and increased if later biopsy showed progression to atypical hyperplasia (HR = 1.49, 95% CI = 0.73 to 3.05) compared with no change ( P = .04). Conclusions: We found that breast cancer risk increases in women with progressive epithelial proliferation over time and decreases in women whose biopsies show less proliferation. This finding has important implications for effective clinical management of the 100 000 women per year who have multiple benign breast biopsies.

Atypical apocrine adenosis of the breast: long-term follow-up in 37 patients.

CONTEXT: Atypical apocrine adenosis is a rare breast lesion in which the cellular population demonstrates cytologic alterations that may be confused with malignancy. The clinical significance and management of atypical apocrine adenosis are unclear because of the lack of long-term follow-up studies. OBJECTIVE: To determine the breast cancer risk in a retrospective series of patients with atypical apocrine adenosis diagnosed in otherwise benign, breast excisional biopsies. DESIGN: We identified 37 atypical apocrine adenosis cases in the Mayo Benign Breast Disease Cohort (9340 women) between 1967 and 1991 with a blinded pathology rereview. Breast cancer diagnoses subsequent to initial atypical apocrine adenosis biopsy were identified (average follow-up, 14 years). RESULTS: The mean age at diagnosis of atypical apocrine adenosis in the group was 59 years. Breast carcinoma subsequently developed in 3 women (8%) with atypical apocrine adenosis, diagnosed after follow-up intervals of 4, 12, and 18 years. The tumor from 1 of the 3 cases (33%) was ductal carcinoma in situ, contralateral to the original biopsy, and the other 2 cases (66%) were invasive carcinoma. Ages at the time of diagnosis of atypical apocrine adenosis were 55, 47, and 63 years for those that developed in situ or invasive carcinoma. CONCLUSIONS: (1) Atypical apocrine adenosis was a rare lesion during the accrual era of our cohort (<1% of cases); (2) women found to have atypical apocrine adenosis were, on average, older than were other patients with benign breast disease, however, there does not seem to be an association with age and risk for developing carcinoma in patients diagnosed with atypical apocrine adenosis, as previously suggested; and (3) atypical apocrine adenosis does not appear to be an aggressive lesion and should not be regarded as a direct histologic precursor to breast carcinoma.

An analysis of breast cancer risk in women with single, multiple, and atypical papilloma.

Breast papillomas may be single or multiple and associated with atypical ductal or lobular hyperplasias (ADH/ALH). The risk of breast carcinoma development in patients with papillomas, particularly those with multiple or atypical lesions, is incompletely defined. Fibrocystic lesions were histopathologically classified in a benign breast disease cohort of 9155 who underwent biopsy from 1967 to 1991, with papilloma assessment in 9108. Individuals with papillomas (N=480) were classified into 4 groups: single papilloma (SP, N=372), single papilloma with ADH or ALH (SP+A, N=54), multiple (>5) papillomas (MP, N=41), and multiple papillomas with ADH or ALH (MP+A, N=13). Those without papillomas were classified as nonproliferative (NP, N=6053), proliferative without atypia (PDWA, N=2308), and ADH/ALH [atypical hyperplasia (AH), N=267]. The relative risk of cancer development within our cohort was compared to that expected in the general population using standardized incidence ratios. The relative risk of breast cancer development associated with SP [2.04, 95% confidence interval (CI) 1.43-2.81] was greater than NP (1.28, 95% CI 1.16-1.42) but similar to PDWA (1.90, 95% CI 1.66-2.16). The risk associated with SP+A (5.11, 95% CI 2.64-8.92) was highly elevated but not substantively different than atypical hyperplasia (4.17, 95% CI 3.10-5.50). Patients with MP are at increased risk compared with PDWA or SP (3.01, 95% CI 1.10-6.55), particularly those with MP+A (7.01, 95% CI 1.91-17.97). There was a marginal increase in breast cancer risk (16%) among patients with proliferative disease if a papilloma was present, but this did not reach statistical significance (P=0.29). The observed frequency of ipsilateral (vs. contralateral) breast cancer development in papilloma subsets was not significantly different than other patient groups. We conclude that SP imparts a cancer risk similar to conventional proliferative fibrocystic change. The presence of papilloma in, or associated with, atypia does not modify the risk connotation of ADH/ALH overall. MP constitutes a proliferative breast disease subset having unique clinical and biologic behavior.

Stories of breast cancer through art.

PURPOSE/OBJECTIVES: To describe the use of an art exhibit, created in response to breast cancer survivor stories, and additional supplementary activities to increase cancer awareness and provide support to those with cancer. DATA SOURCES: Published articles and books, personal experiences. DATA SYNTHESIS: Art has been used to educate and promote the expression of emotions. Using an art exhibit as the central feature, a planning committee composed of staff members and volunteers developed a repertoire of activities to improve cancer awareness and provide support to cancer survivors. Visitor and staff reactions to the event were profound. CONCLUSIONS: Art can capture the most intimate and personal aspects of the cancer experience. This event was a novel and effective way to increase awareness about the cancer experience. The event brought together patients, family members, friends, staff members, and the community and facilitated new partnerships to help people with cancer. IMPLICATIONS FOR NURSING: Nurses are well equipped to direct the therapeutic use of art and support the potential reactions of viewers. Nurses can promote the benefit of art exhibits for cancer education, support, and awareness and use their knowledge and skills in planning and implementing supplementary activities.

Twin quilts--stories to be told.

A perusal of the literature reveals the many ways quilt design and personal communication is interwoven. We selected quilt making to provide those affected by breast cancer-as a patient, friend or relative-the opportunity to communicate their experience through quilt making. With the participation of community quilters, a concept and quilt design was developed to incorporate the work of patients and others in making a quilt. The project pattern and materials were presented. Contributors were invited to write about what inspired them to participate. For the 80 blocks that were constructed as twin quilts, 36 individuals wrote something about their block. Analysis of the vignettes identified major categories. The most common theme was honoring a specific person's life and their breast cancer journey. Displayed together with their accompanying vignettes, the quilts have become a focal point for interaction among patients and their families.