Polygenic risk score for the prediction of breast cancer is related to lesser terminal duct lobular unit involution of the breast.

Terminal duct lobular units (TDLUs) are the predominant anatomical structures where breast cancers originate. Having lesser degrees of age-related TDLU involution, measured as higher TDLUs counts or more epithelial TDLU substructures (acini), is related to increased breast cancer risk among women with benign breast disease (BBD). We evaluated whether a recently developed polygenic risk score (PRS) based on 313-common variants for breast cancer prediction is related to TDLU involution in the background, normal breast tissue, as this could provide mechanistic clues on the genetic predisposition to breast cancer.

Molecular characterization of breast cancer needle core biopsy specimens by the 21-gene Breast Recurrence Score test.

Background And Objective: Recent COVID-19 pandemic guidelines recommend genomic assessment of core biopsies to help guide treatment decisions in estrogen receptor (ER)-positive early-stage breast cancer. Herein we characterize biopsy and excisional breast cancer specimens submitted for 21-gene testing.

Methods: US samples submitted to Genomic Health for 21-gene testing (01/2004-04/2020) were assessed by pathologists and analyzed by a standardized quantitative reverse transcription-polymerase chain reaction.

Comparison of residual cancer burden, American Joint Committee on Cancer staging and pathologic complete response in breast cancer after neoadjuvant chemotherapy: results from the I-SPY 1 TRIAL (CALGB 150007/150012; ACRIN 6657).

Purpose: Several pathologic staging systems characterize residual tumor in patients undergoing neoadjuvant chemotherapy for breast cancer. Pathologic complete response (pCR) is now accepted by the Food and Drug Administration as an endpoint for granting accelerated drug approval. Two other systems of post-neoadjuvant pathologic tumor staging-residual cancer burden (RCB) and the American Joint Committee on Cancer post-neoadjuvant therapy staging system (yAJCC)-have been developed to characterize residual tumors when patients do not achieve pCR.

Mesothelial Inclusions in Pelvic Lymph Nodes Initially Diagnosed as Metastatic Prostate Cancer; the Utility of Second Opinions and Genomic Testing in the Setting of Unexpected Results.

Benign mesothelial inclusions in pelvic lymph nodes may be mistaken for metastatic disease in the setting of pelvic malignancy. In this case-report a patient with Low-Risk prostate cancer (confirmed by biopsy and genomic testing) underwent radical prostatectomy with pelvic lymph node dissection. The initial pathological diagnosis was organ-confined Gleason 3 + 3 = 6 cancer with metastasis to a pelvic lymph node.

Association between breast cancer genetic susceptibility variants and terminal duct lobular unit involution of the breast.

Terminal duct lobular units (TDLUs) are the predominant source of future breast cancers, and lack of TDLU involution (higher TDLU counts, higher acini count per TDLU and the product of the two) is a breast cancer risk factor. Numerous breast cancer susceptibility single nucleotide polymorphisms (SNPs) have been identified, but whether they are associated with TDLU involution is unknown. In a pooled analysis of 872 women from two studies, we investigated 62 established breast cancer SNPs and relationships with TDLU involution.

Ages at menarche- and menopause-related genetic variants in relation to terminal duct lobular unit involution in normal breast tissue.

Reduced levels of terminal duct lobular unit (TDLU) involution, as reflected by higher numbers of TDLUs and acini per TDLU, have been associated with higher breast cancer risk. Younger age at menarche and older age at menopause have been previously related to lower levels of TDLU involution. To determine a possible genetic link, we examined whether single-nucleotide polymorphisms (SNPs) previously established in genome-wide association studies (GWAS) for ages at menarche and menopause are associated with TDLU involution.

Lymph node content of supraclavicular and thoracodorsal-based axillary flaps for vascularized lymph node transfer.

Objective: Microvascular transfer of lymph node flaps has recently gained popularity as a treatment for secondary lymphedema often occurring after axillary, groin, or pelvic lymph node dissections. This study aimed to delineate the lymph node contents and pedicle characteristics of the supraclavicular (SC) and thoracodorsal (TD)-based axillary flaps as well as to compare lymph node quantification of surgeon vs pathologist.

Methods: SC and TD flaps were dissected from fresh female cadavers.

Breast DCE-MRI Kinetic Heterogeneity Tumor Markers: Preliminary Associations With Neoadjuvant Chemotherapy Response.

The ability to predict response to neoadjuvant chemotherapy for women diagnosed with breast cancer, either before or early on in treatment, is critical to judicious patient selection and tailoring the treatment regimen. In this paper, we investigate the role of contrast agent kinetic heterogeneity features derived from breast dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for predicting treatment response. We propose a set of kinetic statistic descriptors and present preliminary results showing the discriminatory capacity of the proposed descriptors for predicting complete and non-complete responders as assessed from pre-treatment imaging exams.

Feasibility of the internal mammary lymph node flap as a vascularized lymph node transfer: A cadaveric dissection study.

Background: We performed cadaveric dissections to examine the feasibility of an internal mammary-based lymph node flap as a donor site for vascularized lymph node transfer.

Methods: Internal mammary vessels and adjacent nodes were dissected in ten fresh cadaver specimens. Surgeon inspection and palpation identified the number of nodes in the specimen.

Pharmacokinetic Tumor Heterogeneity as a Prognostic Biomarker for Classifying Breast Cancer Recurrence Risk.

Goal: Heterogeneity in cancer can affect response to therapy and patient prognosis. Histologic measures have classically been used to measure heterogeneity, although a reliable noninvasive measurement is needed both to establish baseline risk of recurrence and monitor response to treatment. Here, we propose using spatiotemporal wavelet kinetic features from dynamic contrast-enhanced magnetic resonance imaging to quantify intratumor heterogeneity in breast cancer.

Circulating sex hormones and terminal duct lobular unit involution of the normal breast.

Background: Terminal duct lobular units (TDLU) are the predominant source of breast cancers. Lesser degrees of age-related TDLU involution have been associated with increased breast cancer risk, but factors that influence involution are largely unknown. We assessed whether circulating hormones, implicated in breast cancer risk, are associated with levels of TDLU involution using data from the Susan G.

Terminal duct lobular unit involution of the normal breast: implications for breast cancer etiology.

Background: Greater degrees of terminal duct lobular unit (TDLU) involution have been linked to lower breast cancer risk; however, factors that influence this process are poorly characterized.

Methods: To study this question, we developed three reproducible measures that are inversely associated with TDLU involution: TDLU counts, median TDLU span, and median acini counts/TDLU. We determined factors associated with TDLU involution using normal breast tissues from 1938 participants (1369 premenopausal and 569 postmenopausal) ages 18 to 75 years in the Susan G.

Optically measured microvascular blood flow contrast of malignant breast tumors.

Microvascular blood flow contrast is an important hemodynamic and metabolic parameter with potential to enhance in vivo breast cancer detection and therapy monitoring. Here we report on non-invasive line-scan measurements of malignant breast tumors with a hand-held optical probe in the remission geometry. The probe employs diffuse correlation spectroscopy (DCS), a near-infrared optical method that quantifies deep tissue microvascular blood flow.

Pretreatment vitamin D level and response to neoadjuvant chemotherapy in women with breast cancer on the I-SPY trial (CALGB 150007/150015/ACRIN6657).

Laboratory studies suggest that vitamin D (vitD) enhances chemotherapy-induced cell death. The objective of this study was to determine whether pretreatment vitD levels were associated with response to neoadjuvant chemotherapy (NACT) in women with breast cancer. Study patients (n = 82) were enrolled on the I-SPY TRIAL, had HER2-negative tumors, and available pretreatment serum.

Identification of intrinsic imaging phenotypes for breast cancer tumors: preliminary associations with gene expression profiles.

Purpose: To present a method for identifying intrinsic imaging phenotypes in breast cancer tumors and to investigate their association with prognostic gene expression profiles.

Materials And Methods: The authors retrospectively analyzed dynamic contrast material-enhanced (DCE) magnetic resonance (MR) images of the breast in 56 women (mean age, 55.6 years; age range, 37-74 years) diagnosed with estrogen receptor-positive breast cancer between 2005 and 2010.

Computerized image analysis for identifying triple-negative breast cancers and differentiating them from other molecular subtypes of breast cancer on dynamic contrast-enhanced MR images: a feasibility study.

Purpose: To determine the feasibility of using a computer-aided diagnosis (CAD) system to differentiate among triple-negative breast cancer, estrogen receptor (ER)-positive cancer, human epidermal growth factor receptor type 2 (HER2)-positive cancer, and benign fibroadenoma lesions on dynamic contrast material-enhanced (DCE) magnetic resonance (MR) images.

Materials And Methods: This is a retrospective study of prospectively acquired breast MR imaging data collected from an institutional review board-approved, HIPAA-compliant study between 2002 and 2007. Written informed consent was obtained from all patients.

Heterogeneity wavelet kinetics from DCE-MRI for classifying gene expression based breast cancer recurrence risk.

Breast tumors are heterogeneous lesions. Intra-tumor heterogeneity presents a major challenge for cancer diagnosis and treatment. Few studies have worked on capturing tumor heterogeneity from imaging.

Opportunities for molecular epidemiological research on ductal carcinoma in-situ and breast carcinogenesis: interdisciplinary approaches.

Most invasive breast cancers arise from ductal carcinoma in-situ (DCIS), a non-obligate precursor of invasive breast cancer. Given that the natural history of individual DCIS lesions is unpredictable, many women with DCIS receive extensive treatments, which may include surgery, radiation and endocrine therapy, even though many of these lesions may have limited potential to progress to invasion and metastasize. In contrast to valid concerns about overtreatment, the fact that invasive breast cancers outnumber DCIS lesions by more than three-to-one, suggests that many cancer precursors (particularly DCIS, but LCIS also) progress to invasion prior to detection.

Fibroblast activation protein expression by stromal cells and tumor-associated macrophages in human breast cancer.

Fibroblast activation protein (FAP) has long been known to be expressed in the stroma of breast cancer. However, very little is known if the magnitude of FAP expression within the stroma may have a prognostic value and reflect the heterogeneous biology of the tumor cell. An earlier study had suggested that stromal FAP expression in breast cancer was inversely proportional to prognosis.

Cutaneous metastatic breast carcinoma with clear cell features.

Breast carcinoma remains one of the most common sources of skin metastases in women. Cutaneous breast carcinoma metastases have variable clinical and histopathologic presentations that can make diagnosis challenging. We report a unique case of metastatic breast carcinoma with prominent clear cell features, thus mimicking a xanthomatous process.

Multi-field-of-view framework for distinguishing tumor grade in ER+ breast cancer from entire histopathology slides.

Modified Bloom-Richardson (mBR) grading is known to have prognostic value in breast cancer (BCa), yet its use in clinical practice has been limited by intra- and interobserver variability. The development of a computerized system to distinguish mBR grade from entire estrogen receptor-positive (ER+) BCa histopathology slides will help clinicians identify grading discrepancies and improve overall confidence in the diagnostic result. In this paper, we isolate salient image features characterizing tumor morphology and texture to differentiate entire hematoxylin and eosin (H and E) stained histopathology slides based on mBR grade.

Optical malignancy parameters for monitoring progression of breast cancer neoadjuvant chemotherapy.

We introduce and demonstrate use of a novel, diffuse optical tomography (DOT) based breast cancer signature for monitoring progression of neoadjuvant chemotherapy. This signature, called probability of malignancy, is obtained by statistical image analysis of total hemoglobin concentration, blood oxygen saturation, and scattering coefficient distributions in the breast tomograms of a training-set population with biopsy-confirmed breast cancers. A pilot clinical investigation adapts this statistical image analysis approach for chemotherapy monitoring of three patients.

A multichannel Markov random field framework for tumor segmentation with an application to classification of gene expression-based breast cancer recurrence risk.

We present a methodological framework for multichannel Markov random fields (MRFs). We show that conditional independence allows loopy belief propagation to solve a multichannel MRF as a single channel MRF. We use conditional mutual information to search for features that satisfy conditional independence assumptions.

Intraosseous hibernoma: a potential mimic of metastatic carcinoma.

Intraosseous hibernoma is a rare benign bone tumor, with only 3 cases reported in English literature. In this report, we describe a 50-year-old woman with a history of stage IIB breast cancer and posterolateral right hip pain. Imaging studies showed a sclerotic lesion in the right ilium, which was biopsied and showed mildly thickened bone trabeculae and multivacuolated brown fat cells replacing the normal white fat and hematopoietic elements, diagnostic of intraosseous hibernoma.

Pathologic complete response predicts recurrence-free survival more effectively by cancer subset: results from the I-SPY 1 TRIAL--CALGB 150007/150012, ACRIN 6657.

Purpose: Neoadjuvant chemotherapy for breast cancer provides critical information about tumor response; how best to leverage this for predicting recurrence-free survival (RFS) is not established. The I-SPY 1 TRIAL (Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging and Molecular Analysis) was a multicenter breast cancer study integrating clinical, imaging, and genomic data to evaluate pathologic response, RFS, and their relationship and predictability based on tumor biomarkers.

Patients And Methods: Eligible patients had tumors ≥ 3 cm and received neoadjuvant chemotherapy.