When breast cancer is detected and treated early, the chances of survival are very high. However, women in many settings face complex barriers to early detection, including social, economic, geographic, and other interrelated factors, which can limit their access to timely, affordable, and effective breast health care services. Previously, the Breast Health Global Initiative (BHGI) developed resource-stratified guidelines for the early detection and diagnosis of breast cancer. In this consensus article from the sixth BHGI Global Summit held in October 2018, the authors describe phases of early detection program development, beginning with management strategies required for the diagnosis of clinically detectable disease based on awareness education and technical training, history and physical examination, and accurate tissue diagnosis. The core issues address include finance and governance, which pertain to successful planning, implementation, and the iterative process of program improvement and are needed for a breast cancer early detection program to succeed in any resource setting. Examples are presented of implementation, process, and clinical outcome metrics that assist in program implementation monitoring. Country case examples are presented to highlight the challenges and opportunities of implementing successful breast cancer early detection programs, and the complex interplay of barriers and facilitators to achieving early detection for breast cancer in real-world settings are considered. Cancer 2020;126:2379-2393.

Purpose:To investigate whether qualitative magnetic resonance (MR) imaging assessments of background parenchymal enhancement (BPE), amount of fibroglandular tissue (FGT), and mammographic density are associated with risk of developing breast cancer in women who are at high risk. Materials and Methods:In this institutional review board-approved HIPAA-compliant retrospective study, all screening breast MR images obtained from January 2006 to December 2011 in women aged 18 years or older and at high risk for but without a history of breast cancer were identified. Women in whom breast cancer was diagnosed after index MR imaging comprised the cancer cohort, and one-to-one matching (age and BRCA status) of each woman with breast cancer to a control subject was performed by using MR images obtained in women who did not develop breast cancer with follow-up time maximized. Amount of BPE, BPE pattern (peripheral vs central), amount of FGT at MR imaging, and mammographic density were assessed on index images. Imaging features were compared between cancer and control cohorts by using conditional logistic regression. Results:Twenty-three women at high risk (mean age, 47 years 6 10 [standard deviation]; six women had BRCA mutations) with no history of breast cancer underwent screening breast MR imaging; in these women, a diagnosis of breast cancer (invasive, n = 12; in situ, n = 11) was made during the follow-up interval. Women with mild, moderate, or marked BPE were nine times more likely to receive a diagnosis of breast cancer during the follow-up interval than were those with minimal BPE (P = .007; odds ratio = 9.0; 95% confidence interval: 1.1, 71.0). BPE pattern, MR imaging amount of FGT, and mammographic density were not significantly different between the cohorts (P = .5, P = .5, and P = .4, respectively). Conclusion:Greater BPE was associated with a higher probability of developing breast cancer in women at high risk for cancer and warrants further study.q RSNA, 2015

Platforms that allow parallel, quantitative analysis of single cells will be integral to realizing the potential of postgenomic biology. In stem cell biology, the study of clonal stem cells in multiwell formats is currently both inefficient and time-consuming. Thus, to investigate low-frequency events of interest, large sample sizes must be interrogated. We report a simple, versatile, and efficient micropatterned arraying system conducive to the culture and dynamic monitoring of stem cell proliferation. This platform enables: 1) parallel, automated, long-term ( approximately days to weeks), live-cell microscopy of single cells in culture; 2) tracking of individual cell fates over time (proliferation, apoptosis); and 3) correlation of differentiated progeny with founder clones. To achieve these goals, we used microfabrication techniques to create an array of approximately 10,000 microwells on a glass coverslip. The dimensions of the wells are tunable, ranging from 20 to >500 microm in diameter and 10-500 microm in height. The microarray can be coated with adhesive proteins and is integrated into a culture chamber that permits rapid (approximately min), addressable monitoring of each well using a standard programmable microscope stage. All cells share the same media (including paracrine survival signals), as opposed to cells in multiwell formats. The incorporation of a coverslip as a substrate also renders the platform compatible with conventional, high-magnification light and fluorescent microscopy. We validated this approach by analyzing the proliferation dynamics of a heterogeneous adult rat neural stem cell population. Using this platform, one can further interrogate the response of distinct stem cell subpopulations to microenvironmental cues (mitogens, cell-cell interactions, and cell-extracellular matrix interactions) that govern their behavior. In the future, the platform may also be adapted for the study of other cell types by tailoring the surface coatings, microwell dimensions, and culture environment, thereby enabling parallel investigation of many distinct cellular responses.

There is increasing interest in the potential benefits and harms of screening ultrasound to supplement mammographic screening of women with dense breast tissue. We review the current evidence regarding adjunctive screening breast ultrasound (US) and provide a summary for clinicians who counsel patients with dense breasts. We conducted a comprehensive literature review of published clinical trials and observational cohort studies assessing the efficacy of screening handheld US (HHUS) and automated breast US (ABUS) to supplement mammography among women with dense breasts. From a total of 189 peer-reviewed publications on the performance of screening US, 12 studies were relevant to our analysis. The reporting of breast cancer risk factors varied across studies; however, the study populations tended to be at greater than average risk for developing breast cancer. There is consistent evidence that adjunctive screening US detects more invasive cancers compared to mammography alone, but there is currently no evidence of associated long-term breast cancer mortality reduction. The studies also collectively found that US was associated with an additional 11.7–106.6 biopsies/1,000 examinations (Median 52.2), and detected an additional 0.3–7.7 cancers/1,000 examinations (Median 4.2). The associated number of unnecessary breast biopsies resulting from adjunct US screening exceeds that observed with screening mammography alone by approximately 5-fold. Adjunctive screening with ultrasound should also be considered in the context of screening mammography. It is important for clinicians to be aware that improvements in cancer detection in mammographically dense breasts have been achieved with the transition from film to digital mammography, reducing a limitation of film mammography. Clinicians should discuss breast density as one of several important breast cancer risk factors, consider the potential harms of adjunctive screening, and arrive at a shared decision consistent with each woman’s preferences and values.