Deep Learning Image Analysis of Benign Breast Disease to Identify Subsequent Risk of Breast Cancer.

Background: New biomarkers of risk may improve breast cancer (BC) risk prediction. We developed a computational pathology method to segment benign breast disease (BBD) whole slide images into epithelium, fibrous stroma, and fat. We applied our method to the BBD BC nested case-control study within the Nurses' Health Studies to assess whether computer-derived tissue composition or a morphometric signature was associated with subsequent risk of BC.

Physician Knowledge of Breast Cancer Recurrence and Contralateral Breast Cancer Risk is Associated with Increased Recommendations for Contralateral Prophylactic Mastectomy: a Survey of Physicians at NAPBC-Accredited Centers.

Background: Physician recommendation for contralateral prophylactic mastectomy (CPM) has been shown to influence whether a patient chooses CPM. Few studies have explored physician knowledge about contralateral breast cancer (CBC) and local recurrence (LR) risk and whether knowledge is associated with recommendation for CPM.

Methods: We conducted a cross-sectional survey of physicians at National Accreditation Program for Breast Centers-accredited breast centers across the USA.

Multiscale nonlinear microscopy and widefield white light imaging enables rapid histological imaging of surgical specimen margins.

The ability to histologically assess surgical specimens in real-time is a long-standing challenge in cancer surgery, including applications such as breast conserving therapy (BCT). Up to 40% of women treated with BCT for breast cancer require a repeat surgery due to postoperative histological findings of close or positive surgical margins using conventional formalin fixed paraffin embedded histology. Imaging technologies such as nonlinear microscopy (NLM), combined with exogenous fluorophores can rapidly provide virtual H&E imaging of surgical specimens without requiring microtome sectioning, facilitating intraoperative assessment of margin status.

Rapid histopathological imaging of skin and breast cancer surgical specimens using immersion microscopy with ultraviolet surface excitation.

Rapid histopathological evaluation of fresh, unfixed human tissue using optical sectioning microscopy would have applications to intraoperative surgical margin assessment. Microscopy with ultraviolet surface excitation (MUSE) is a low-cost optical sectioning technique using ultraviolet illumination which limits fluorescence excitation to the specimen surface. In this paper, we characterize MUSE using high incident angle, water immersion illumination to improve sectioning.

Rapid virtual hematoxylin and eosin histology of breast tissue specimens using a compact fluorescence nonlinear microscope.

Up to 40% of patients undergoing breast conserving surgery for breast cancer require repeat surgeries due to close to or positive margins. The lengthy processing required for evaluating surgical margins by standard paraffin-embedded histology precludes its use during surgery and therefore, technologies for rapid evaluation of surgical pathology could improve the treatment of breast cancer by reducing the number of surgeries required. We demonstrate real-time histological evaluation of breast cancer surgical specimens by staining specimens with acridine orange (AO) and sulforhodamine 101 (SR101) analogously to hematoxylin and eosin (H&E) and then imaging the specimens with fluorescence nonlinear microscopy (NLM) using a compact femtosecond fiber laser.

Breast cancer risk factors in relation to estrogen receptor, progesterone receptor, insulin-like growth factor-1 receptor, and Ki67 expression in normal breast tissue.

Studies have suggested that hormone receptor and Ki67 expression in normal breast tissue are associated with subsequent breast cancer risk. We examined the associations of breast cancer risk factors with estrogen receptor (ER), progesterone receptor (PR), insulin-like growth factor-1 receptor (IGF-1R), and Ki67 expression in normal breast tissue. This analysis included 388 women with benign breast disease (ages 17-67 years) in the Nurses' Health Studies.

Integrated local binary pattern texture features for classification of breast tissue imaged by optical coherence microscopy.

This paper proposes a texture analysis technique that can effectively classify different types of human breast tissue imaged by Optical Coherence Microscopy (OCM). OCM is an emerging imaging modality for rapid tissue screening and has the potential to provide high resolution microscopic images that approach those of histology. OCM images, acquired without tissue staining, however, pose unique challenges to image analysis and pattern classification.

Breast Cancer-Major changes in the American Joint Committee on Cancer eighth edition cancer staging manual.

Answer questions and earn CME/CNE The revision of the eighth edition of the primary tumor, lymph node, and metastasis (TNM) classification of the American Joint Commission of Cancer (AJCC) for breast cancer was determined by a multidisciplinary team of breast cancer experts. The panel recognized the need to incorporate biologic factors, such as tumor grade, proliferation rate, estrogen and progesterone receptor expression, human epidermal growth factor 2 (HER2) expression, and gene expression prognostic panels into the staging system. AJCC levels of evidence and guidelines for all tumor types were followed as much as possible.

Expression of estrogen receptor, progesterone receptor, and Ki67 in normal breast tissue in relation to subsequent risk of breast cancer.

Although expression of estrogen receptor (ER), progesterone receptor (PR), and cell proliferation marker Ki67 serve as predictive and prognostic factors in breast cancers, little is known about their roles in normal breast tissue. Here in a nested case-control study within the Nurses' Health Studies (90 cases, 297 controls), we evaluated their expression levels in normal breast epithelium in relation to subsequent breast cancer risk among women with benign breast disease. Tissue microarrays were constructed using cores obtained from benign biopsies containing normal terminal duct lobular units and immunohistochemical stained for these markers.

Direct comparison between confocal and multiphoton microscopy for rapid histopathological evaluation of unfixed human breast tissue.

Rapid histopathological examination of surgical specimen margins using fluorescence microscopy during breast conservation therapy has the potential to reduce the rate of positive margins on postoperative histopathology and the need for repeat surgeries. To assess the suitability of imaging modalities, we perform a direct comparison between confocal fluorescence microscopy and multiphoton microscopy for imaging unfixed tissue and compare to paraffin-embedded histology. An imaging protocol including dual channel detection of two contrast agents to implement virtual hematoxylin and eosin images is introduced that provides high quality imaging under both one and two photon excitation.

National Accreditation Program for Breast Centers Demonstrates Improved Compliance with Post-Mastectomy Radiation Therapy Quality Measure.

Background: The National Accreditation Program for Breast Centers (NAPBC) was established in 2008 by the American College of Surgeons as a quality-improvement program for patients with breast disease. An NAPBC quality measure states post-mastectomy patients with ≥4 positive lymph nodes should receive lymph node radiation therapy (PMRT). Our objective was to examine how NAPBC accreditation has affected compliance with this quality measure.

Virtual Hematoxylin and Eosin Transillumination Microscopy Using Epi-Fluorescence Imaging.

We derive a physically realistic model for the generation of virtual transillumination, white light microscopy images using epi-fluorescence measurements from thick, unsectioned tissue. We demonstrate this technique by generating virtual transillumination H&E images of unsectioned human breast tissue from epi-fluorescence multiphoton microscopy data. The virtual transillumination algorithm is shown to enable improved contrast and color accuracy compared with previous color mapping methods.

Rapid imaging of surgical breast excisions using direct temporal sampling two photon fluorescent lifetime imaging.

Two photon fluorescent lifetime imaging is a modality that enables depth-sectioned, molecularly-specific imaging of cells and tissue using intrinsic contrast. However, clinical applications have not been well explored due to low imaging speed and limited field of view, which make evaluating large pathology samples extremely challenging. To address these limitations, we have developed direct temporal sampling two photon fluorescent lifetime imaging (DTS-FLIM), a method which enables a several order of magnitude increase in imaging speed by capturing an entire lifetime decay in a single fluorescent excitation.

Breast cancer risk by extent and type of atypical hyperplasia: An update from the Nurses' Health Studies.

Background: Women with atypical hyperplasia (AH) on a benign breast biopsy specimen are at increased risk for the development of breast cancer. However, the relation between the type and extent of AH (atypical ductal hyperplasia [ADH] vs atypical lobular hyperplasia [ALH]) and the magnitude of the breast cancer risk is not well defined.

Methods: A nested case-control study of benign breast disease and breast cancer risk was conducted.

Intakes of fat and micronutrients between ages 13 and 18 years and the incidence of proliferative benign breast disease.

Purpose: Dietary exposures during adolescence may exert important effects on breast development and future breast cancer risk. This study evaluated the associations between high school intakes of fat and micronutrients and the incidence of proliferative benign breast disease (BBD), a marker of increased breast cancer risk.

Methods: 29,480 women (mean age 43.

Assessment of breast pathologies using nonlinear microscopy.

Rapid intraoperative assessment of breast excision specimens is clinically important because up to 40% of patients undergoing breast-conserving cancer surgery require reexcision for positive or close margins. We demonstrate nonlinear microscopy (NLM) for the assessment of benign and malignant breast pathologies in fresh surgical specimens. A total of 179 specimens from 50 patients was imaged with NLM using rapid extrinsic nuclear staining with acridine orange and intrinsic second harmonic contrast generation from collagen.

Ultrahigh speed spectral-domain optical coherence microscopy.

We demonstrate a compact, ultrahigh speed spectral-domain optical coherence microscopy (SD-OCM) system for multiscale imaging of specimens at 840 nm. Using a high speed 512-pixel line scan camera, an imaging speed of 210,000 A-scans per second was demonstrated. Interchangeable water immersion objectives with magnifications of 10×, 20×, and 40× provided co-registered en face cellular-resolution imaging over several size scales.

Alcohol intake between menarche and first pregnancy: a prospective study of breast cancer risk.

Background: Adult alcohol consumption during the previous year is related to breast cancer risk. Breast tissue is particularly susceptible to carcinogens between menarche and first full-term pregnancy. No study has characterized the contribution of alcohol consumption during this interval to risks of proliferative benign breast disease (BBD) and breast cancer.

Swept source optical coherence microscopy using a 1310 nm VCSEL light source.

We demonstrate high speed, swept source optical coherence microscopy (OCM) using a MEMS tunable vertical cavity surface-emitting laser (VCSEL) light source. The light source had a sweep rate of 280 kHz, providing a bidirectional axial scan rate of 560 kHz. The sweep bandwidth was 117 nm centered at 1310 nm, corresponding to an axial resolution of 13.

Radial scars and subsequent breast cancer risk: results from the Nurses' Health Studies.

Radial scars (RS) are benign proliferative lesions associated with an increased risk of subsequent breast cancer. However, it remains unclear whether RS are an independent risk factor for breast cancer or whether their association with breast cancer is due to their common occurrence with other proliferative lesions known to increase breast cancer risk. We performed an updated analysis of the association between RS and subsequent breast cancer risk in a nested case-control study among 460 cases and 1,792 controls with benign breast disease (BBD) in the Nurses' Health Studies.

Adolescent intakes of vitamin D and calcium and incidence of proliferative benign breast disease.

Vitamin D and calcium have been shown to have protective effects against breast cancer development in animal studies. Vitamin D and calcium play important anticarcinogenic roles in animal studies. Exposures between menarche and first birth may be important in breast development and future breast cancer risk.

Intakes of alcohol and folate during adolescence and risk of proliferative benign breast disease.

Objectives: To examine the combined effect of alcohol and folate intake during adolescence on the risk of proliferative benign breast disease (BBD).

Methods: We used data from 29 117 women in the Nurses' Health Study II who completed both adolescent alcohol consumption questions in 1989 and an adolescent diet questionnaire in 1998. A total of 659 women with proliferative BBD diagnosed between 1991 and 2001 were confirmed by central pathology review.

Insulin-like growth factor-1, insulin-like growth factor binding protein-3 and lobule type in the Nurses' Health Study II.

Introduction: Previous research in the Nurses' Health Study (NHS) and the NHSII observed that, among women diagnosed with benign breast disease (BBD), those with predominant type 1/no type 3 lobules (a marker of complete involution) versus other lobule types were at lower risk of subsequent breast cancer. Studies in animal models suggest that insulin-like growth factor-1 (IGF-1) may inhibit involution of lobules in the breast; however, this has not been studied in humans.

Methods: We conducted a cross-sectional study among 472 women in the NHSII who were diagnosed with biopsy-confirmed proliferative BBD between 1991 and 2002 and provided blood samples between 1996 and 1999.

Integrated optical coherence tomography and optical coherence microscopy imaging of ex vivo human renal tissues.

Purpose: We evaluated the feasibility of using optical coherence tomography and optical coherence microscopy technology to assess human kidney morphology.

Materials And Methods: A total of 35 renal specimens from 19 patients, consisting of 12 normal tissues and 23 tumors (16 clear cell renal cell carcinomas, 5 papillary renal cell carcinomas and 2 oncocytomas) were imaged ex vivo after surgical resection. Optical coherence tomography and optical coherence microscopy images were compared to corresponding hematoxylin and eosin histology to identify characteristic features of normal and pathological renal tissues.

Traditional breast cancer risk factors in relation to molecular subtypes of breast cancer.

At least four major categories of invasive breast cancer have been reproducibly identified by gene expression profiling: luminal A, luminal B, HER2-type, and basal-like. These subtypes have been shown to differ in their outcome and response to treatment. Whether this heterogeneity reflects the evolution of these subtypes through distinct etiologic pathways has not been clearly defined.