Faculty Bibliography

BACKGROUND:Physical activity is inversely associated with the risk of breast cancer among women in the general population. It is not clear whether or not physical activity is associated with the risk of BRCA-associated breast cancer. METHODS:We conducted a case-control study of 443 matched pairs of BRCA mutation carriers to evaluate the association between physical activity and breast cancer risk. Moderate and vigorous physical activities at ages 12-13, ages 14-17, ages 18-22, ages 23-29 and ages 30-34 were determined using the Nurses' Health Study II Physical Activity Questionnaire. We estimated mean metabolic equivalent task hours/week for moderate, vigorous and total physical activities overall (ages 12-34), during adolescence (ages 12-17) and during early adulthood (ages 18-34). Logistic regression analysis was used to estimate the odds ratios (OR) and 95% confidence intervals (CI) for total, moderate and strenuous recreational physical activities and breast cancer risk, by menopausal status. RESULTS:Overall, there was no significant association between total physical activity and subsequent breast cancer risk (ORQ4 vs. Q1 = 1.01, 95% CI 0.69-1.47; P-trend = 0.72). Moderate physical activity between ages 12-17 was associated with a 38% decreased risk of premenopausal breast cancer (ORQ4 vs. Q1 = 0.62; 95% CI 0.40-0.96; P-trend = 0.01). We found no association between exercise and breast cancer diagnosed after menopause. CONCLUSIONS:These findings suggest that early-life physical activity is associated with a reduced risk of premenopausal breast cancer among BRCA mutation carriers. IMPACT/CONCLUSIONS:Future prospective analyses, complemented by mechanistic evidence, are warranted in this high-risk population.

PURPOSE/OBJECTIVE:Mammographic density is a risk factor for breast cancer but the mechanism behind this association is unclear. The receptor activator of nuclear factor κB (RANK)/RANK ligand (RANKL) pathway has been implicated in the development of breast cancer. Given the role of RANK signaling in mammary epithelial cell proliferation, we hypothesized this pathway may also be associated with mammographic density. Osteoprotegerin (OPG), a decoy receptor for RANKL, is known to inhibit RANK signaling. Thus, it is of interest to evaluate whether OPG levels modify breast cancer risk through mammographic density. METHODS:We quantified serum OPG levels in 57 premenopausal and 43 postmenopausal women using an enzyme-linked immunosorbent assay (ELISA). Cumulus was used to measure percent density, dense area, and non-dense area for each mammographic image. Subjects were classified into high versus low OPG levels based on the median serum OPG level in the entire cohort (115.1 pg/mL). Multivariate models were used to assess the relationship between serum OPG levels and the measures of mammographic density. RESULTS:; P = 0.02) compared to those with high serum OPG levels after covariate adjustment. CONCLUSIONS:These findings suggest that low OPG levels may be associated with high mammographic density, particularly in postmenopausal women. Targeting RANK signaling may represent a plausible, non-surgical prevention option for high-risk women with high mammographic density, especially those with low circulating OPG levels.

Breast cancer survival rates in lower-income countries like Bangladesh are approximately 50%, versus over 80% in high income countries. Anecdotal reports suggest that, beyond economic and health system barriers, sociocultural factors may influence a woman's care-seeking behavior and resultant early stage diagnoses. To understand these barriers, we conducted 63 interviews (43 women with breast cancer symptoms and 20 men) in Khulna, Bangladesh. We identified socio-cultural barriers like neglect and indifference toward women, women's lack of power to use resources, and reduced support from family due to stigma. Interventions must address these barriers and improve the status of women in Bangladesh.

BACKGROUND:About half of births in rural Tanzania are assisted by skilled providers. Point-of-care mobile phone applications hold promise in boosting job support for community health workers aiming to ensure safe motherhood through increased facility delivery awareness, access and uptake. We conducted a controlled comparison to evaluate a smartphone-based application designed to assist community health workers with data collection, education delivery, gestational danger sign identification, and referrals. METHODS:Community health workers in 32 randomly selected villages were cluster-randomized to training on either smartphone (intervention) or paper-based (control) protocols for use during household visits with pregnant women. The primary outcome measure was postnatal report of delivery location by 572 women randomly selected to participate in a survey conducted by home visit. A mixed-effects model was used to account for clustering of subjects and other measured factors influencing facility delivery. FINDINGS/RESULTS:The smartphone intervention was associated with significantly higher facility delivery: 74% of mothers in intervention areas delivered at or in transit to a health facility, versus 63% in control areas. The odds of facility delivery among women counseled by smartphone-assisted health workers were double the odds among women living in control villages (OR, 1.96; CI, 1.21-3.19; adjusted analyses). Women in intervention areas were more likely to receive two or more visits from a community health worker during pregnancy than women in the control group (72% vs. 60%; chi-square = 6.9; p < 0.01). Previous facility delivery, uptake of antenatal care, and distance to the nearest facility were also strong independent predictors of facility delivery. INTERPRETATION/CONCLUSIONS:Community health worker use of smartphones increased facility delivery, likely through increased frequency of prenatal home visits. Smartphone-based job aids may enhance community health worker support and effectiveness as one component of intervention packages targeting safe motherhood. TRIAL REGISTRATION/BACKGROUND:NCT03161184.

There is limited information on stage at breast cancer diagnosis in Canadian immigrant women. We compared stage at diagnosis between immigrant women and Canadian-born women, and determined whether ethnicity was an independent factor associated with stage. 41,213 women with invasive breast cancer from 2007 to 2012 were identified from the Ontario Cancer Registry. Women were classified as either immigrants or Canadian-born by linkage with the Immigration, Refugees, and Citizenship Canada's Permanent Resident database. Women's ethnicity was classified as Chinese, South Asian, or remaining women in Ontario. Logistic regression was performed to calculate the odds ratio (OR) of being diagnosed at stage I breast cancer (versus stage II-IV). 4,353 (10.6%) women were immigrants and 36,860 (89.4%) were Canadian-born women. The mean age at breast cancer diagnosis was 53.5 years for immigrants versus 62.3 years for Canadian-born women (p < 0.0001). Immigrant women were less likely than Canadian-born women to be diagnosed with stage I breast cancers (adjusted OR = 0.85; 95% CI: 0.79-0.91; p < 0.0001). The adjusted OR of being stage I was 1.28 (95% CI: 1.14-1.43; p < 0.0001) for women of Chinese ethnicity and was 0.82 (95% CI: 0.70-0.96; p = 0.01) for women of South Asian ethnicity, compared to the remaining women in Ontario. Canadian immigrant women were less likely than Canadian-born women to be diagnosed with early-stage breast cancers. Ethnicity was a greater contributor to the stage disparity than was immigrant status. South Asian women, regardless of immigration status, might benefit from increased breast cancer awareness programs.

We already know what causes cervical cancer, how to prevent it, and how to treat it, even in resource-constrained settings. Inequitable access to human papillomavirus vaccine for girls and screening and precancer treatment for women in low- and middle-income countries is unacceptable on ethical, social, and financial grounds. The burden of cervical cancer falls on the poor and extends beyond the narrow bounds of the family, affecting national economic development and community life, as family resources are drained and poverty tightens its grip. Proven solutions are available and the priorities for the next few years are clear, as shown by the papers in this Supplement. Sustained political commitment and strategic investments in cervical cancer prevention can not only save millions of lives over the next 10 years, but can also pave the way for the broader fight against all cancers.

Objective To quantify the impact of cancer (all cancers combined and major sites) compared with cardiovascular disease (CVD) on longevity worldwide during 1981-2010.Design Retrospective demographic analysis using aggregated data.Setting National civil registration systems in member states of the World Health Organization.Participants 52 populations with moderate to high quality data on cause specific mortality.Main outcome measures Disease specific contributions to changes in life expectancy in ages 40-84 (LE40-84) over time in populations grouped by two levels of Human Development Index (HDI) values.Results Declining CVD mortality rates during 1981-2010 contributed to, on average, over half of the gains in LE40-84; the corresponding gains were 2.3 (men) and 1.7 (women) years, and 0.5 (men) and 0.8 (women) years in very high and medium and high HDI populations, respectively. Declines in cancer mortality rates contributed to, on average, 20% of the gains in LE40-84, or 0.8 (men) and 0.5 (women) years in very high HDI populations, and to over 10% or 0.2 years (both sexes) in medium and high HDI populations. Declining lung cancer mortality rates brought about the largest LE40-84 gain in men in very high HDI populations (up to 0.7 years in the Netherlands), whereas in medium and high HDI populations its contribution was smaller yet still positive. Among women, declines in breast cancer mortality rates were largely responsible for the improvement in longevity, particularly among very high HDI populations (up to 0.3 years in the United Kingdom). In contrast, losses in LE40-84 were observed in many medium and high HDI populations as a result of increasing breast cancer mortality rates.Conclusions The control of CVD has led to substantial gains in LE40-84 worldwide. The inequality in improvement in longevity attributed to declining cancer mortality rates reflects inequities in implementation of cancer control, particularly in less resourced populations and in women. Global actions are needed to revitalize efforts for cancer control, with a specific focus on less resourced countries.