Neighborhood social and built environments have been recognized as important contexts in which health is shaped. The authors reviewed the extent to which these neighborhood factors have been addressed in population‐level cancer research by scanning the literature for research focused on specific social and/or built environment characteristics and their association with outcomes across the cancer continuum, including incidence, diagnosis, treatment, survivorship, and survival. The commonalities and differences in methodologies across studies, the current challenges in research methodology, and future directions in this research also were addressed. The assessment of social and built environment factors in relation to cancer is a relatively new field, with 82% of the 34 reviewed articles published since 2010. Across the wide range of social and built environment exposures and cancer outcomes considered by the studies, numerous associations were reported. However, the directions and magnitudes of associations varied, in large part because of the variation in cancer sites and outcomes studied, but also likely because of differences in study populations, geographic regions, and, importantly, choice of neighborhood measures and geographic scales. The authors recommend that future studies consider the life‐course implications of cancer incidence and survival, integrate secondary and self‐report data, consider work neighborhood environments, and further develop analytical and statistical approaches appropriate to the geospatial and multilevel nature of the data. Incorporating social and built environment factors into research on cancer etiology and outcomes can provide insights into disease processes, identify vulnerable populations, and generate results with translational impact of relevance for interventionists and policy makers. Cancer 2015;121:2314–2330. © 2015 American Cancer Society.

Introduction: Breast cancers are increasingly recognized as heterogeneous based on expression of receptors for estrogen (ER), progesterone (PR), and human epidermal growth factor receptor 2 (HER2). Triple-negative tumors (ER^-/PR^-/HER2^-) have been reported to be more common among younger women, but occurrence of the spectrum of breast cancer subtypes in adolescent and young adult (AYA) women aged between 15 and 39 years is otherwise poorly understood. Methods: Data regarding all 5,605 AYA breast cancers diagnosed in California during the period 2005 to 2009, including ER and PR status (referred to jointly as hormone receptor (HR) status) and HER2 status, was obtained from the population-based California Cancer Registry. Incidence rates were calculated by subtype (triple-negative; HR⁺/HER2^-; HR⁺/HER2⁺; HR^-/HER2⁺), and logistic regression was used to evaluate differences in subtype characteristics by age group. Results: AYAs had higher proportions of HR⁺/HER2⁺, triple-negative and HR^-/HER2⁺ breast cancer subtypes and higher proportions of patients of non-White race/ethnicity than did older women. AYAs also were more likely to be diagnosed with stage III/IV disease and high-grade tumors than were older women. Rates of HR⁺/HER2^- and triple-negative subtypes in AYAs varied substantially by race/ethnicity. Conclusions: The distribution of breast cancer subtypes among AYAs varies from that observed in older women, and varies further by race/ethnicity. Observed subtype distributions may explain the poorer breast cancer survival previously observed among AYAs.

Hair morphogenesis takes place through reciprocal epithelial and mesenchymal signaling; however, the mechanisms controlling signal exchange are poorly understood. Laminins are extracellular proteins that play critical roles in adhesion and signaling. Here we demonstrate the mechanism of how laminin-511 controls hair morphogenesis. Dermal papilla (DP) from laminin-511 mutants showed developmental defects by E16.5, including a failure to maintain expression of the key morphogen noggin. This maintenance was critical as exogenous introduction of noggin or sonic hedgehog (Shh) produced downstream from noggin was sufficient to restore hair follicle development in lama5^−/− (laminin-511-null) skin. Hair development required the β1 integrin binding but not the heparin binding domain of laminin-511. Previous studies demonstrated that Shh signaling requires primary cilia, microtubule-based signaling organelles. Laminin-511 mutant DP showed decreased length and structure of primary cilia in vitro and in vivo. Laminin-511, but not laminin-111, restored primary cilia formation in lama5^−/− mesenchyme and triggered noggin expression in an Shh- and PDGF-dependent manner. Inhibition of laminin-511 receptor β1 integrin disrupted DP primary cilia formation as well as hair development. These studies show that epithelial-derived laminin-511 is a critical early signal that directs ciliary function and DP maintenance as a requirement for hair follicle downgrowth.

Introduction: Young women have poorer survival after breast cancer than do older women. It is unclear whether this survival difference relates to the unique distribution of hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2)-defined molecular breast cancer subtypes among adolescent and young adult (AYA) women aged 15 to 39 years. The purpose of our study was to examine associations between breast cancer subtypes and short-term survival in AYA women, as well as to determine whether the distinct molecular subtype distribution among AYA women explains the unfavorable overall breast cancer survival statistics reported for AYA women compared with older women. Methods: Data for 5,331 AYA breast cancers diagnosed between 2005 and 2009 were obtained from the California Cancer Registry. Survival by subtype (triple-negative; HR+/HER2-; HR+/HER2+; HR-/HER2+) and age-group (AYA versus 40- to 64-year-olds) was analyzed with Cox proportional hazards regression with follow-up through 2010. Results: With up to 6 years of follow-up and a mean survival time of 3.1 years (SD = 1.5 years), AYA women diagnosed with HR-/HER + and triple-negative breast cancer experienced a 1.6-fold and 2.7-fold increased risk of death, respectively, from all causes (HR-/HER + hazard ratio: 1.55; 95% confidence interval (CI): 1.10 to 2.18; triple-negative HR: 2.75; 95% CI, 2.06 to 3.66) and breast cancer (HR-/HER + hazard ratio: 1.63; 95% CI, 1.12 to 2.36; triple-negative hazard ratio: 2.71; 95% CI, 1.98 to 3.71) than AYA women with HR+/HER2- breast cancer. AYA women who resided in lower socioeconomic status neighborhoods, had public health insurance, and were of Black, compared with White, race/ethnicity experienced worse survival. This race/ethnicity association was attenuated somewhat after adjusting for breast cancer subtypes (hazard ratio, 1.33; 95% CI, 0.98 to 1.82). AYA women had similar all-cause and breast cancer-specific short-term survival as older women for all breast cancer subtypes and across all stages of disease. Conclusions: Among AYA women with breast cancer, short-term survival varied by breast cancer subtypes, with the distribution of breast cancer subtypes explaining some of the poorer survival observed among Black, compared with White, AYA women. Future studies should consider whether distribution of breast cancer subtypes and other factors, including differential receipt of treatment regimens, influences long-term survival in young compared with older women.