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We aimed to examine the association between the use of metformin and other anti‐diabetic medications and breast cancer incidence within two large prospective cohort studies. We followed 185,181 women who participated in the Nurses' Health Study (NHS; 1994–2016) and the NHSII (1995–2017), with baseline corresponding to the date metformin was approved for type 2 diabetes (T2D) treatment in the US Information on T2D diagnosis, anti‐diabetes medications, and other covariates was self‐reported at baseline and repeatedly assessed by follow‐up questionnaires every 2 years. Breast cancer cases were self‐reported and confirmed by medical record review. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between medication use and breast cancer were estimated using Cox proportional hazards regression models, adjusting for breast cancer risk factors. During 3,324,881 person‐years of follow‐up, we ascertained 9,192 incident invasive breast cancer cases, of which 451 were among women with T2D. Compared with women without T2D (n = 169,263), neither metformin use (HR = 0.97; 95% CI = 0.81–1.15) nor other anti‐diabetic medications use (HR = 1.11; 95% CI = 0.90–1.36) associated with significantly lower breast cancer incidence. Among women with T2D (n = 15,918), compared with metformin never users, metformin ever use was not significantly inversely associated with breast cancer (HR = 0.92; 95% CI = 0.74–1.15). Although we observed that past use of metformin was inversely associated with breast cancer in the T2D population (HR = 0.67; 95% CI = 0.48–0.94), current use (HR = 1.01; 95% CI = 0.80–1.27) and longer duration of metformin use were not associated with breast cancer (each 2‐year interval: HR = 1.01; 95% CI = 0.95–1.07). Overall, metformin use was not associated with the risk of developing breast cancer among the overall cohort population or among women with T2D. [ABSTRACT FROM AUTHOR]

Background Branched chain amino acids (BCAAs) are essential amino acids common throughout the US diet. Although circulating BCAAs have been implicated in insulin resistance and some obesity-related cancers, the relationship between dietary intake of BCAAs and incident breast cancer is unknown. We sought to evaluate the association between long-term dietary intakes of BCAAs and invasive breast cancer risk. Methods Our analyses included 196 161 women from the Nurses' Health Study and Nurses' Health Study II longitudinal cohorts. Average intakes of total and individual BCAAs (isoleucine, leucine, valine) were estimated from repeated diet questionnaires and incident self-reported breast cancer cases were confirmed via medical record review. Cox proportional hazards models, adjusted for reproductive history, lifestyle, body mass index, and other breast cancer risk factors, were used to estimate hazard ratios and 95% confidence intervals. Results We observed 10 046 incident cases of breast cancer over a median of 20.8 years of follow-up. No associations between dietary intakes of total or individual BCAAs with breast cancer risk were observed. Compared with women in the bottom quintile of BCAA intake, the hazard ratio of breast cancer for those in the top quintile was 1.05 (95% confidence interval = 0.98 to 1.12; 2-sided P trend =.20). Findings were consistent across molecular subtypes and according to type 2 diabetes diagnosis and body mass index categories. Conclusions Dietary intakes of BCAAs are not likely a risk factor for breast cancer. [ABSTRACT FROM AUTHOR]

Introduction: The WHO recommends antiretroviral treatment (ART) for all HIV‐positive patients regardless of CD4 count or disease stage, referred to as "Early Access to ART for All" (EAAA). The health systems effects of EAAA implementation are unknown. This trial was implemented in a government‐managed public health system with the aim to examine the "real world" impact of EAAA on care retention and viral suppression. Methods: In this stepped‐wedge randomized controlled trial, 14 public sector health facilities in Eswatini were paired and randomly assigned to stepwise transition from standard of care (SoC) to EAAA. ART‐naïve participants ≥18 years who were not pregnant or breastfeeding were eligible for enrolment. We used Cox proportional hazard models with censoring at clinic transition to estimate the effects of EAAA on retention in care and retention and viral suppression combined. Results: Between September 2014 and August 2017, 3405 participants were enrolled. In SoC and EAAA respectively, 12‐month HIV care retention rates were 80% (95% CI: 77 to 83) and 86% (95% CI: 83 to 88). The 12‐month combined retention and viral suppression endpoint rates were 44% (95% CI: 40 to 48) under SoC compared to 80% (95% CI: 77 to 83) under EAAA. EAAA increased both retention (HR: 1·60, 95% CI: 1·15 to 2·21, p = 0.005) and retention and viral suppression combined (HR: 4.88, 95% CI: 2.96 to 8.05, p < 0.001). We also identified significant gaps in current health systems ability to provide viral load (VL) monitoring with 80% participants in SoC and 66% in EAAA having a missing VL at last contact. Conclusions: The observed improvement in retention in care and on the combined retention and viral suppression provides an important co‐benefit of EAAA to HIV‐positive adults themselves, at least in the short term. Our results from this "real world" health systems trial strongly support EAAA for Eswatini and countries with similar HIV epidemics and health systems. VL monitoring needs to be scaled up for appropriate care management. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Retention on antiretroviral therapy (ART) is critical for the successful adoption of the test and treat policy by sub‐Saharan African countries, and for realizing the United Nations programme on HIV and AIDS target of 90‐90‐90. This qualitative study explores HIV positive clients’ reasons for discontinuing ART under the MaxART test and treat implementation study in Swaziland. Methods: Clients identified as lost to follow‐up (LTFU) in the programme database, who had initiated ART under the intervention arm of the MaxART study, were purposively selected from two facilities. LTFU was defined as stopping ART refill for three months or longer from the date of last appointment, and not being classified as transferred out or deceased. Semi‐structured face‐to‐face interviews were conducted with nine clients and one treatment supporter between July and August 2017. All interviews were conducted in the local language, audio‐recorded, summarized or transcribed and translated to English for thematic analysis. Results: Respondents described mobility as the first step in a chain of events that affected retention in care. It was entwined with precarious employment, care delivery, interactions with health workers, lack of social support, anticipated stigma and ART‐related side‐effects, including the exacerbation of hunger. The chains of events involved several intersecting reasons that occurred one after the other as a series of contiguous and linked events that led to clients’ eventual discontinuation of ART. The individual accounts of step‐by‐step decision‐making revealed the influence of multi‐layered contexts and the importance of critical life‐events. Conclusions: Clients’ reasons for abandoning ART are a complex, inextricably interwoven chain of events rather than a single occurrence. Mobility is often the first step in the process and commonly results from precarious economic and social circumstances. Currently the health system poorly caters to the reality of people's mobile lives. Interventions should seek to increase healthcare workers’ understanding of the chain of events leading up to discontinuation on ART and the social dilemmas that clients face. [ABSTRACT FROM AUTHOR]

The roles of specific fatty acids in breast cancer etiology are unclear, particularly among premenopausal women. We examined 34 individual fatty acids, measured in blood erythrocytes collected between 1996 and 1999, and breast cancer risk in a nested case‐control study of primarily premenopausal women in the Nurses' Health Study II. Breast cancer cases diagnosed after blood collection and before June 2010 (n = 794) were matched to controls and conditional logistic regression was used to estimate OR's (95% CI's) for associations of fatty acids with breast cancer; unconditional logistic regression was used for stratified analyses. Fatty acids were not significantly associated with breast cancer risk overall; however, heterogeneity by body mass index (BMI) was observed. Among overweight/obese women (BMI ≥ 25), several odd‐chain saturated (SFA, e.g. 17:0, ORQ4vsQ1(95% CI) =1.85 (1.18–2.88), ptrend=0.006 pint<0.001), trans (TFA, e.g. 18:1, ORQ4vsQ1(95% CI) =2.33 (1.45–3.77), ptrend<0.001, pint=0.007) and dairy‐derived fatty acids (SFA 15:0 + 17:0 + TFA 16:1n‐7t; ORQ4vsQ1(95% CI) =1.83(1.16–2.89), ptrend=0.005, pint<0.001) were positively associated, and n‐3 polyunsaturated fatty acids (n‐3 PUFA, e.g. alpha‐linolenic acid; ORQ4vsQ1(95% CI) =0.57 (0.36–0.89), ptrend=0.017, pint=0.03) were inversely associated with breast cancer. Total SFA were inversely associated with breast cancer among women with BMI < 25 (ORQ4vsQ1(95% CI) =0.68 (0.46–0.98), ptrend=0.05, pint=0.01). Thus, while specific fatty acids were not associated with breast cancer overall, our findings suggest positive associations of several SFA, TFA and dairy‐derived fatty acids and inverse associations of n‐3 PUFA with breast cancer among overweight/obese women. Given these fatty acids are influenced by diet, and therefore are potentially modifiable, further investigation of these associations among overweight/obese women is warranted. [ABSTRACT FROM AUTHOR]

Background: Epidemiologic data suggest that parity increases risk of hormone receptor-negative breast cancer and that breastfeeding attenuates this association. Prospective data, particularly on the joint effects of higher parity and breastfeeding, are limited.Methods: We investigated parity, breastfeeding, and breast cancer risk by hormone-receptor (estrogen (ER) and progesterone receptor (PR)) and molecular subtypes (luminal A, luminal B, HER2-enriched, and basal-like) in the Nurses' Health Study (NHS; 1976-2012) and NHSII (1989-2013). A total of 12,452 (ER+ n = 8235; ER- n = 1978) breast cancers were diagnosed among 199,514 women. We used Cox proportional hazards models, adjusted for breast cancer risk factors, to calculate hazard ratios (HR) and 95% confidence intervals (CI).Results: Parous women had lower risk of ER+ breast cancer (vs. nulliparous, HR = 0.82 [0.77-0.88]); no association was observed for ER- disease (0.98 [0.84-1.13]; Phet = 0.03). Among parous women, breastfeeding was associated with lower risk of ER- (vs. never 0.82 [0.74-0.91]), but not ER+, disease (0.99 [0.94-1.05]; Phet < 0.001). Compared to nulliparous women, higher parity was inversely associated with luminal B breast cancer regardless of breastfeeding (≥ 3 children: ever breastfed, 0.78 [0.62-0.98]; never breastfed, 0.76 [0.58-1.00]) and luminal A disease only among women who had breastfed (≥ 3 children, 0.84 [0.71-0.99]). Basal-like breast cancer risk was suggestively higher among women with higher parity who never breastfed; associations were null among those who ever breastfed.Conclusions: This study provides evidence that breastfeeding is inversely associated with hormone receptor-negative breast cancers, representing an accessible and cost-effective risk-reduction strategy for aggressive disease subtypes. [ABSTRACT FROM AUTHOR]