Screening and Preventative Strategies for Patients at High Risk for Breast Cancer.

PURPOSE: Current US guidelines recommend more intensive breast cancer screening and preventive strategies for patients at more than 20% lifetime risk for breast and ovarian cancer (high risk for breast and ovarian cancer [HRBOC]). Guidelines recommend that yearly mammograms alternating with magnetic resonance imaging (MRI) screening should be considered as early as 30 years old. Furthermore, BRCA mutation carriers should consider bilateral mastectomy and bilateral oophorectomy after age 35. It was unclear what the uptake of screening and risk-reducing strategies were for patients who were cancer-free and cancer survivors seen by Kaiser Permanente Mid-Atlantic States (KPMAS) Genetics. METHODS: We retrospectively studied female patients (members of KPMAS between 2005 and 2016) diagnosed as HRBOC and/or tested for breast cancer-related mutations by KPMAS Genetics during 2013-2016. We identified cancer diagnoses, mammogram and breast MRI screening, mastectomies, and oophorectomies that occurred before and after the Genetics visit during the study period. RESULTS: Our cohort included 813 women with a HRBOC diagnosis, with a median 51 years of age at diagnosis, 45% White, 38% Black, and 15% other ethnicity. Most cancers occurred prior to the Genetics visit: 513/527 breast cancer diagnoses and 55/57 ovarian cancer diagnoses. Fewer than five prophylactic mastectomies and 89 prophylactic oophorectomies were identified. Among 228 patients who were 30-75 years old, breast cancer-free at the time of HRBOC diagnosis, and members for over 6 months, 190 (83%) had at least one screening test (mammogram or MRI) after the consultation with Genetic, but 79% never had an MRI before or after the consultation. CONCLUSION: Our findings suggest that earlier detection of patients with HRBOC and closer monitoring is needed.

All-Cause and Cardiovascular Disease Mortality Among Breast Cancer Survivors in CLUE II, a Long-Standing Community-Based Cohort.

BACKGROUND: There is growing evidence that breast cancer survivors have higher cardiovascular disease (CVD) mortality relative to the general population. Information on temporal patterns for all-cause and CVD mortality among breast cancer survivors relative to cancer-free women is limited. METHODS: All-cause and CVD-related mortality were compared in 628 women with breast cancer and 3140 age-matched cancer-free women within CLUE II, a prospective cohort. We calculated adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) using Cox proportional hazards regression for all-cause mortality, and Fine and Gray models for CVD-related mortality to account for competing risks. RESULTS: Over 25 years of follow-up, 916 deaths occurred (249 CVD related). Breast cancer survivors had an overall higher risk of dying compared with cancer-free women (HR = 1.79, 95% CI = 1.53 to 2.09) irrespective of time since diagnosis, tumor stage, estrogen receptor status, and older age at diagnosis (≥70 years). Risk of death was greatest among older survivors at more than 15 years after diagnosis (HR = 2.69, 95% CI = 1.59 to 4.55). CVD (69.1% ischemic heart disease) was the leading cause of death among cancer-free women and the second among survivors. Survivors had an increase in CVD-related deaths compared with cancer-free women beginning at 8 years after diagnosis (HR = 1.65, 95% CI = 1.00 to 2.73), with the highest risk among older survivors (HR = 2.24, 95% CI = 1.29 to 3.88) and after estrogen receptor-positive disease (HR = 1.85, 95% CI = 1.06 to 3.20). CONCLUSIONS: Breast cancer survivors continue to have an elevated mortality compared with the general population for many years after diagnosis. Preventing cardiac deaths, particularly among older breast cancer patients, could lead to reductions in mortality.

Challenges in Studying Modifiable Risk Factors for Birth Defects.

Conducting research to identify modifiable risk factors for birth defects is difficult for a variety of reasons. While some challenges are familiar to researchers across many disciplines, the confluence of issues affecting birth defects research may not be well understood by those outside of the field. This article describes several methodological challenges to the study of birth defects and ways these challenges might be addressed: (1) ascertainment, definition and classification of birth defects; (2) exposure assessment on modifiable risk factors; (3) analytical challenges related to small numbers and multiple statistical tests; (4) the role of genetics, including the collection of specimens and analysis of genetic data; and (5) challenges in translating research and demonstrating public health impact. Understanding these issues is important for researchers planning studies, reviewers evaluating the scientific merit of results from these studies, and consumers of the research, including fellow researchers, policy makers, health care providers, and families.