Visual Intratumor Heterogeneity and Breast Tumor Progression.

High intratumoral heterogeneity is thought to be a poor prognostic indicator. However, the source of heterogeneity may also be important, as genomic heterogeneity is not always reflected in histologic or 'visual' heterogeneity. We aimed to develop a predictor of histologic heterogeneity and evaluate its association with outcomes and molecular heterogeneity.

Pure Mucinous Carcinoma of the Breast: Radiologic-Pathologic Correlation.

Mucinous carcinoma (MC) of the breast is a rare, specialized subtype of invasive breast carcinoma (IBC) accounting for approximately 1% to 4% of all primary breast malignancies. Mucinous carcinoma occurs predominantly in patients who are postmenopausal or elderly. It is usually detected on screening mammography, but occasionally the patient may present with a palpable mass.

Predicting early breast cancer recurrence from histopathological images in the Carolina Breast Cancer Study.

Approaches for rapidly identifying patients at high risk of early breast cancer recurrence are needed. Image-based methods for prescreening hematoxylin and eosin (H&E) stained tumor slides could offer temporal and financial efficiency. We evaluated a data set of 704 1-mm tumor core H&E images (2-4 cores per case), corresponding to 202 participants (101 who recurred; 101 non-recurrent matched on age and follow-up time) from breast cancers diagnosed between 2008-2012 in the Carolina Breast Cancer Study.

Tamoxifen Response at Single-Cell Resolution in Estrogen Receptor-Positive Primary Human Breast Tumors.

Purpose: In estrogen receptor-positive (ER+)/HER2- breast cancer, multiple measures of intratumor heterogeneity are associated with a worse response to endocrine therapy. We sought to develop a novel experimental model to measure heterogeneity in response to tamoxifen treatment in primary breast tumors.

Experimental Design: To investigate heterogeneity in response to treatment, we developed an operating room-to-laboratory pipeline for the collection of live normal breast specimens and human tumors immediately after surgical resection for processing into single-cell workflows for experimentation and genomic analyses.

Pathological measurement and staging of residual breast cancer after neoadjuvant chemotherapy.

Aims: The 8th Edition of the American Joint Committee on Cancer Staging System (yAJCC) excludes treatment-related fibrosis from the measurement of residual tumour after neoadjuvant chemotherapy (NAC) for breast cancer. The impact of the 8th Ed. yAJCC on post-NAC pathologic staging was examined in 188 breast cancer specimens from 183 patients with measurable residual tumour.

Tamoxifen Response at Single Cell Resolution in Estrogen Receptor-Positive Primary Human Breast Tumors.

In ER+/HER2- breast cancer, multiple measures of intra-tumor heterogeneity are associated with worse response to endocrine therapy. To investigate heterogeneity in response to treatment, we developed an operating room-to-laboratory pipeline for the collection of live human tumors and normal breast specimens immediately after surgical resection for processing into single-cell workflows for experimentation and genomic analyses. We demonstrate differences in tamoxifen response by cell type and identify distinctly responsive and resistant subpopulations within the malignant cell compartment of human tumors.

Incorporating RNA-based Risk Scores for Genomic Instability to Predict Breast Cancer Recurrence and Immunogenicity in a Diverse Population.

Unlabelled: Markers of genomic instability, including TP53 status and homologous recombination deficiency (HRD), are candidate biomarkers of immunogenicity and immune-mediated survival, but little is known about the distribution of these markers in large, population-based cohorts of racially diverse patients with breast cancer. In prior clinical trials, DNA-based approaches have been emphasized, but recent data suggest that RNA-based assessment can capture pathway differences conveniently and may be streamlined with other RNA-based genomic risk scores. Thus, we used RNA expression to study genomic instability (HRD and TP53 pathways) in context of the breast cancer immune microenvironment in three datasets (total = 4,892), including 1,942 samples from the Carolina Breast Cancer Study, a population-based study that oversampled Black ( = 1,026) and younger women ( = 1,032).

Reproducibility and intratumoral heterogeneity of the PAM50 breast cancer assay.

Background: The PAM50 assay is used routinely in clinical practice to determine breast cancer prognosis and management; however, research assessing how technical variation and intratumoral heterogeneity contribute to misclassification and reproducibility of these tests is limited.

Methods: We evaluated the impact of intratumoral heterogeneity on the reproducibility of results for the PAM50 assay by testing RNA extracted from formalin-fixed paraffin embedded breast cancer blocks sampled at distinct spatial locations. Samples were classified according to intrinsic subtype (Luminal A, Luminal B, HER2-enriched, Basal-like, or Normal-like) and risk of recurrence with proliferation score (ROR-P, high, medium, or low).

High-risk and selected benign breast lesions diagnosed on core needle biopsy: Evidence for and against immediate surgical excision.

The vast majority of image-detected breast abnormalities are diagnosed by percutaneous core needle biopsy (CNB) in contemporary practice. For frankly malignant lesions diagnosed by CNB, the standard practice of excision and multimodality therapy have been well-defined. However, for high-risk and selected benign lesions diagnosed by CNB, there is less consensus on optimal patient management and the need for immediate surgical excision.

The Landscape of Immune Microenvironments in Racially Diverse Breast Cancer Patients.

Background: Immunotherapy is a rapidly evolving treatment option in breast cancer; However, the breast cancer immune microenvironment is understudied in Black and younger (<50 years) patients.

Methods: We used histologic and RNA-based immunoprofiling methods to characterize the breast cancer immune landscape in 1,952 tumors from the Carolina Breast Cancer Study (CBCS), a population-based study that oversampled Black (n = 1,030) and young women (n = 1,039). We evaluated immune response leveraging markers for 10 immune cell populations, compared profiles to those in The Cancer Genome Atlas (TCGA) Project [n = 1,095 tumors, Black (n = 183), and young women (n = 295)], and evaluated in association with clinical and demographic variables, including recurrence.

JOINT AND INDIVIDUAL ANALYSIS OF BREAST CANCER HISTOLOGIC IMAGES AND GENOMIC COVARIATES.

The two main approaches in the study of breast cancer are histopathology (analyzing visual characteristics of tumors) and genomics. While both histopathology and genomics are fundamental to cancer research, the connections between these fields have been relatively superficial. We bridge this gap by investigating the Carolina Breast Cancer Study through the development of an integrative, exploratory analysis framework.

Risk-Associated Lesions of the Breast in Core Needle Biopsies: Current Approaches to Radiological-Pathological Correlation.

Image-guided core needle biopsies (CNBs) of the breast frequently result in a diagnosis of a benign or atypical lesion associated with breast cancer risk. The subsequent clinical management of these patients is variable, reflecting a lack of consensus on criteria for selecting patients for clinical and radiological follow-up versus immediate surgical excision. In this review, the evidence from prospective studies of breast CNB with radiological-pathological correlation is evaluated and summarized.

Quantitative analysis of breast cancer tissue composition and associations with tumor subtype.

The tumor microenvironment is an important determinant of breast cancer progression, but standard methods for describing the tumor microenvironment are lacking. Measures of microenvironment composition such as stromal area and immune infiltrate are labor-intensive and few large studies have systematically collected this data. However, digital histologic approaches are becoming more widely available, allowing high-throughput, quantitative estimation.

Evaluating the efficacy of a priming dose of cyclophosphamide prior to pembrolizumab to treat metastatic triple negative breast cancer.

Purpose: Triple negative breast cancer (TNBC) is characterized by the presence of immune cells in the tumor microenvironment, however, the response to single-agent immune checkpoint inhibitor (ICI) therapy is modest. Preclinical models have demonstrated that intratumoral regulatory T cells (T) dampen the antitumor response to ICI. We performed a single-arm phase II trial to evaluate the efficacy of a single low dose of cyclophosphamide (Cy) to deplete T administered before initiating pembrolizumab.

Clinical and Financial Implications of Second-Opinion Surgical Pathology Review.

Objectives: Second-opinion pathology review identifies clinically significant diagnostic discrepancies for some patients. Discrepancy rates and laboratory-specific costs in a single health care system for patients referred from regional affiliates to a comprehensive cancer center ("main campus") have not been reported.

Methods: Main campus second-opinion pathology cases for 740 patients from eight affiliated hospitals during 2016 to 2018 were reviewed.

Protein-based immune profiles of basal-like vs. luminal breast cancers.

Tumor-infiltrating lymphocytes play an important, but incompletely understood role in chemotherapy response and prognosis. In breast cancer, there appear to be distinct immune responses by subtype, but most studies have used limited numbers of protein markers or bulk sequencing of RNA to characterize immune response, in which spatial organization cannot be assessed. To identify immune phenotypes of Basal-like vs.

Outcomes of Hormone-Receptor Positive, HER2-Negative Breast Cancers by Race and Tumor Biological Features.

Background: Black women have higher hormone receptor positive (HR+) breast cancer mortality than White women. Early recurrence rates differ by race, but little is known about genomic predictors of early recurrence among HR+ women.

Methods: Using data from the Carolina Breast Cancer Study (phase III, 2008-2013), we estimated associations between race and recurrence among nonmetastatic HR+/HER2-negative tumors, overall and by PAM50 Risk of Recurrence score, PAM50 intrinsic subtype, and tumor grade using survival curves and Cox models standardized for age and stage.