Despite the benefit of adjuvant hormonal therapy (HT) on mortality among women with breast cancer (BC), many women are non-adherent with its use. We investigated the effects of early discontinuation and non-adherence to HT on mortality in women enrolled in Kaiser Permanente of Northern California (KPNC). We identified women diagnosed with hormone-sensitive stage I–III BC, 1996–2007, and used automated pharmacy records to identify prescriptions and dates of refill. We categorized patients as having discontinued HT early if 180 days elapsed from the prior prescription. For those who continued, we categorized patients as adherent if the medication possession ratio was ≥80%. We used Cox proportional hazards models to estimate the association between discontinuation and non-adherence with all-cause mortality. Among 8,769 women who filled at least one prescription for HT, 2,761 (31%) discontinued therapy. Of those who continued HT, 1,684 (28%) were non-adherent. During a median follow-up of 4.4 years, 813 women died. Estimated survival at 10 years was 80.7% for women who continued HT versus 73.6% for those who discontinued (P < 0.001). Of those who continued, survival at 10 years was 81.7 and 77.8% in women who adhered and non-adhered, respectively (P < 0.001). Adjusting for clinical and demographic variables, both early discontinuation (HR 1.26, 95% CI 1.09–1.46) and non-adherence (HR 1.49, 95% CI 1.23–1.81), among those who continued, were independent predictors of mortality. Both early discontinuation and non-adherence to HT were common and associated with increased mortality. Interventions to improve continuation of and adherence to HT may be critical to improve BC survival.

The Eph receptor tyrosine kinases and their membrane-tethered ephrin ligands provide critical guidance cues at points of cell-to-cell contact. It has recently been reported that the ephrin-B2 ligand is a molecular marker for the arterial endothelium at the earliest stages of embryonic angiogenesis, while its receptor EphB4 reciprocally marks the venous endothelium. These findings suggested that ephrin-B2 and EphB4 are involved in establishing arterial versus venous identity and perhaps in anastamosing arterial and venous vessels at their junctions. By using a genetically engineered mouse in which the lacZ coding region substitutes and reports for the ephrin-B2 coding region, we demonstrate that ephrin-B2 expression continues to selectively mark arteries during later embryonic development as well as in the adult. However, as development proceeds, we find that ephrin-B2 expression progressively extends from the arterial endothelium to surrounding smooth muscle cells and to pericytes, suggesting that ephrin-B2 may play an important role during formation of the arterial muscle wall. Furthermore, although ephrin-B2 expression patterns vary in different vascular beds, it can extend into capillaries about midway between terminal arterioles and postcapillary venules, challenging the classical conception that capillaries have neither arterial nor venous identity. In adult settings of angiogenesis, as in tumors or in the female reproductive system, the endothelium of a subset of new vessels strongly expresses ephrin-B2, once again contrary to earlier views that such new vessels lack arterial/venous characteristics and derive from postcapillary venules. While earlier studies had focused on a role for ephrin-B2 during the earliest embryonic stages of arterial/venous determination, our current findings using ephrin-B2 as an arterial marker in the adult challenge prevailing views of the arterial/venous identity of quiescent as well as remodeling adult microvessels and also highlight a possible role for ephrin-B2 in the formation of the arterial muscle wall.

Introduction The aim of this study was to describe breast tumor subtypes by common breast cancer risk factors and to determine correlates of subtypes using baseline data from two pooled prospective breast cancer studies within a large health maintenance organization.

Background Body composition may partially explain the U-shaped association between BMI and colorectal cancer (CRC) survival. Methods Muscle and adiposity at CRC diagnosis and survival were examined in a retrospective cohort using Kaplan Meier curves, multivariable Cox regression, and restricted cubic splines in 3,262 early stage (I-III) male (50%) and female (50%) patients. Sarcopenia was defined using optimal stratification and sex- and BMI-specific cut points. High adiposity was defined as the highest tertile of sex-specific total adipose tissue (TAT). Primary outcomes were overall mortality (OM) and CRC specific mortality (CRCsM). Results Forty-two percent of patients were sarcopenic. During 6.0 years of follow-up, 788 deaths occurred, including 433 from CRC. Sarcopenic patients had a 27% (HR 1.27; 95% CI 1.09, 1.48) higher risk of OM, than those who were not sarcopenic. Females with both low muscle and high adiposity had a 64% higher risk of OM (HR 1.64; 95% CI 1.05, 2.57) when compared to females with adequate muscle and lower adiposity. The lowest risk of OM was seen in patients with a BMI between 25-<30-kg/m2, a range associated with the greatest number of patients (58.6%) who were not at increased risk of OM due to either low muscle or high adiposity. Conclusions Sarcopenia is prevalent among non-metastatic CRC patients, and should, along with adiposity be a standard oncological marker. Impact Our findings suggest a biological explanation for the obesity paradox in CRC and refute the notion that the association between overweight and lower mortality is due solely to methodological biases.

IMPORTANCE Medical imaging increased rapidly from 2000 to 2006, but trends in recent years have not been analyzed. OBJECTIVE To evaluate recent trends in medical imaging. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study of patterns of medical imaging between 2000 and 2016 among 16 million to 21 million patients enrolled annually in 7 US integrated and mixed-model insurance health care systems and for individuals receiving care in Ontario, Canada. EXPOSURES Calendar year and country (United States vs Canada). MAIN OUTCOMES AND MEASURES Use of computed tomography (CT), magnetic resonance imaging (MRI), ultrasound, and nuclear medicine imaging. Annual and relative imaging rates by imaging modality, country, and age (children [<18 years], adults [18-64 years], and older adults [Ն65 years]). RESULTS Overall, 135 774 532 imaging examinations were included; 5 439 874 (4%) in children, 89 635 312 (66%) in adults, and 40 699 346 (30%) in older adults. Among adults and older adults, imaging rates were significantly higher in 2016 vs 2000 for all imaging modalities other than nuclear medicine. For example, among older adults, CT imaging rates

Objective-We examined the association between body mass index (BMI) around the time of diagnosis, weight change post-diagnosis, and breast cancer prognosis in a prospective cohort study of 1,692 breast cancer survivors.Methods-Pre-diagnosis weight, weight at study entry, and height was obtained from mailed questionnaires and then weight change and BMI were calculated. After approximately seven years of follow-up, 207 recurrences, 99 deaths due to breast cancer, and 162 deaths due to any cause were reported. Delayed entry Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI), controlling for treatment and known prognostic factors.Results-Being obese one year before diagnosis was associated with an increased risk of death from any cause (HR = 1.6; 95% CI: 1.1-2.3) and a suggestion of increased risk of death from breast cancer (HR = 1.6; 95% CI: 0.9-2.7). However, weight gain up to four years after a breast cancer diagnosis was not associated with an increased risk of recurrence or death from any cause nor did moderate weight loss (5-10%) decrease risk of these outcomes. There was some evidence Correspondence to: Bette J. Caan, bette.caan@kp.org. that women who had larger weight losses (≥10%) between pre-diagnosis and study entry had an increased risk of recurrence (HR = 1.7; 95% CI 1.0-2.6) and death due to any cause (HR = 2.1; 95% CI 1.3-3.4) compared to being weight stable. This elevated risk was more pronounced among women who were obese before diagnosis (BMI ≥ 30 kg/m 2 ) or who had ER− or PR− tumors. NIH Public AccessConclusion-We found that being obese before breast cancer diagnosis was associated with increased risk of recurrence and poorer survival, corroborating results from previous studies. However, weight gain after diagnosis did not confer additional risk. Body weight pre-diagnosis appears to be the strongest predictor of an adverse breast cancer prognosis.

Prediagnosis inflammation was associated with at-diagnosis sarcopenia. Sarcopenia combined with inflammation nearly doubled risk of death, suggesting that these commonly collected biomarkers could enhance prognostication. A better understanding of how the host inflammatory/immune response influences changes in skeletal muscle may open new therapeutic avenues to improve cancer outcomes.

Background Weight change after a breast cancer diagnosis has been linked to lower survival. To further understand effects of post-diagnostic weight variation on survival, we examined the relationship by comorbid status and initial BMI. Methods The current analysis included 12,915 breast cancer patients diagnosed between 1990 and 2006 with Stage I–III tumors from four prospective cohorts in the US and China Hazard ratios (HR) and 95% confidence intervals (CI) representing the associations of five weight change categories (within <5% [reference]; 5–<10% and ≥10% loss and gain) with mortality were estimated using Cox proportional hazards models. Results Mean weight change was 1.6 kg. 14.7% of women lost and 34.7% gained weight. Weight stability in the early years post-diagnosis was associated with the lowest overall mortality risk. Weight loss ≥10% was related to a 40% increased risk of death (HR=1.41; 95% CI: 1.14, 1.75) in the US and over three times the risk of death (HR=3.25; 95% CI: 2.24, 4.73) in Shanghai. This association varied by pre-diagnosis BMI, and in the US lower survival were seen for women who lost weight and had comorbid conditions. Weight gain ≥10% was associated with a non-significant increased risk of death. Conclusions Prevention of excessive weight gain is a valid public health goal for breast cancer survivors. Although intentionality of weight loss could not be determined, women with comorbid conditions may be particularly at risk of weight loss and mortality. Impact Weight control strategies for breast cancer survivors should be personalized to the individual’s medical history.