Faculty Bibliography

Background/UNASSIGNED:Cervical cancer, although almost entirely preventable through cervical cancer screening (CCS) and human papillomavirus vaccination, is the leading cause of cancer deaths among women in Tanzania. Barriers to attending CCS include lack of awareness of CCS, affordability concerns regarding screening and travel cost. We aimed to compare the effectiveness of SMS (short message service) behaviour change communication (BCC) messages and of SMS BCC messages delivered with a transportation electronic voucher (eVoucher) on increasing uptake of CCS versus the control group. Methods/UNASSIGNED:Door-to-door recruitment was conducted between 1 February and 13 March 2016 in randomly selected enumeration areas in the catchment areas of two hospitals, one urban and one rural, in Northern Tanzania. Women aged 25-49 able to access a mobile phone were randomised using a computer-generated 1:1:1 sequence stratified by urban/rural to receive either (1) 15 SMS, (2) an eVoucher for return transportation to CCS plus the same SMS, or (3) one SMS informing about the nearest CCS clinic. Fieldworkers and participants were masked to allocation. All areas received standard sensitisation including posters, community announcements and sensitisation similar to community health worker (CHW) sensitisation. The primary outcome was attendance at CCS within 60 days of randomisation. Findings/UNASSIGNED:281). By day 60 of follow-up, 101 women (11.9%) attended CCS. Intervention group participants were more likely to attend than control group participants (SMS + eVoucher OR: 4.7, 95% CI 2.9 to 7.4; SMS OR: 3.0, 95% CI 1.5 to 6.2). Trial registration number/UNASSIGNED:NCT02680613.

The major changes in hormone levels that occur through the menstrual cycle have been postulated to affect the expression of hormone-regulated and proliferation-associated genes (PAGs) in premenopausal ER+ breast cancer. Whilst previous studies have demonstrated differences in gene expression, here, we investigated if there are within patient changes in the expression of oestrogen- and progesterone-regulated genes (ERGs and PRGs) and PAGs in ER+ breast cancer during the menstrual cycle. Samples from 96 patients in two independent prospective studies of the effect of menstrual cycle on ER+ breast cancer were used. Plasma hormone measurements were used to assign tumours to one of three pre-defined menstrual cycle windows: W1 (days 27-35 and 1-6; low oestradiol and low progesterone), W2 (days 7-16; high oestradiol and low progesterone) and W3 (days 17-26; intermediate oestradiol and high progesterone). RNA expression of 50 genes, including 27 ERGs, 11 putative PRGs and seven PAGs was measured. The AvERG (geomean of PGR, GREB1, TFF1 and PDZK1) was used as a composite measure of ERG expression and showed significant changes between the three windows of the menstrual cycle increasing over 2.2-fold between W1 and W2 and decreasing between W2 and W3 and between W3 and W1. Proliferation gene expression also varied significantly, following the same pattern of changes as ERG expression, but the changes were of lower magnitude (1.4-fold increase between W1 and W2). Significant changes in the expression of eight individual ERGs, including GREB1, PGR and TFF1, and two PAGs were observed between W1 and either W2 or W3 with all genes showing higher levels in W2 or W3 (1.3-2.4-fold; FDR 0.016-0.05). The AvProg, a composite measure of PRG expression, increased significantly (1.5-fold) in W3 compared to W1 or W2 but no significant changes were observed for individual PRGs. In conclusion, we observed significant changes in ERG, PRG and PAG expression in ER+ breast tumours during the menstrual cycle that may affect the assessment and interpretation of prominent biomarkers (e.g. PgR) and commonly used multigene prognostic signatures in premenopausal ER+ breast cancer.

BACKGROUND:Nearly 70% of all cancer deaths occur in low- and middle-income countries (LMICs) and many of these cancer deaths are preventable. In high-income countries (HICs), patient navigation strategies have been successfully implemented to facilitate the patient's journey at multiple points along the cancer care continuum. The purpose of this scoping review is to understand and describe the scope of patient navigation interventions and services employed in LMICs. METHODS:A systematic search of published articles was conducted including Medline, Biosis, Embase, Global Health, and Web of Science. Articles were examined for evidence of patient navigation interventions used in cancer care in LMICs. Evidence was synthesized by navigation service provided and by type of outcome. RESULTS:Fourteen studies reported on patient navigation interventions in cancer care in low-income and middle-income countries in Asia, South America, and Africa. Most studies reported on women's cancers and included navigation interventions at most points along the cancer care continuum i.e. awareness, education, screening participation, adherence to treatment and surveillance protocols. CONCLUSION/CONCLUSIONS:Few studies report on cancer patient navigation in LMICs. With the use of an implementation science framework, patient navigation research can explore a broader range of outcomes to better evaluate its potential role in improving cancer control in LMICs.

There is a growing population of older women living with HIV/AIDS (WLWHA). Breast cancer is a common cancer in women worldwide, but the global number of breast cancers in WLWHA is not known. We estimated, for each UN sub-region, the number and age distribution of WLWHA who were diagnosed with breast cancer in 2012, by combining IARC-GLOBOCAN estimates of age-country specific breast cancer incidence with corresponding UNAIDS HIV prevalence. Primary analyses assumed no HIV-breast cancer association, and a breast cancer risk reduction scenario was also considered. Amongst 16.0 million WLWHA aged 15+ years, an estimated 6325 WLWHA were diagnosed with breast cancer in 2012, 74% of whom were in sub-Saharan Africa, equally distributed between Eastern, Southern and Western Africa. In most areas, 70% of HIV-positive breast cancers were diagnosed under age 50. Among all breast cancers (regardless of HIV status), HIV-positive women constituted <1% of the clinical burden, except in Eastern, Western and Middle Africa where they comprised 4 to 6% of under age 50 year old breast cancer patients, and in Southern Africa where this patient subgroup constituted 26% and 8% of breast cancers diagnosed under and over age 50 respectively. If a deficit of breast cancer occurs in WLWHA, the global estimate would reduce to 3600. In conclusion, worldwide, the number of HIV-positive women diagnosed with breast cancer was already substantial in 2012 and with an expected increase within the next decade, early detection and treatment research targeted to this population are needed.

Purpose/UNASSIGNED:While Ir-192 remains the mainstay isotope for gynecologic high-dose-rate (HDR) brachytherapy in the U.S., Co-60 is used abroad. Co-60 has a longer half-life than Ir-192, which may lead to long-term cost savings; however, its higher energy requires greater shielding. This study analyzes Co-60 acceptability based on a one-time expense of additional shielding and reports the financial experience of Co-60 in Peru's National Cancer Institute, which uses both isotopes. Material and methods/UNASSIGNED:A nationwide survey was undertaken assessing physician knowledge of Co-60 and willingness-to-pay (WTP) for additional shielding, assuming a source more cost-effective than Ir-192 was available. With 440 respondents, 280 clinicians were decision-makers and provided WTPs, with results previously reported. After completing a shielding report, we estimated costs for shielding expansion, noting acceptability to decision makers' WTP. Using activity-based costing, we note the Peruvian fiscal experience. Results/UNASSIGNED:Shielding estimates ranged from $173,000 to $418,000. The percentage of respondents accepting high-density modular or lead shielding (for union and non-union settings) were 17.5%, 11.4%, 3.9%, and 3.2%, respectively. Shielding acceptance was associated with greater number of radiation oncologists in a respondent's department but not time in practice or the American Brachytherapy Society membership. Peru's experience noted cost savings with Co-60 of $52,400 annually. Conclusions/UNASSIGNED:By comparing the cost of additional shielding for a sample institution's HDR suite with radiation oncologists' WTP, this multi-institutional collaboration noted < 20% of clinicians would accept additional shielding. Despite low acceptability in the US, Co-60 demonstrates cost-favorability in Peru and may similarly in other locations.

OBJECTIVES/OBJECTIVE:Lynch syndrome (LS) accounts for the majority of inherited endometrial cancers (EC), and the identification of probands presents a unique opportunity to treat and prevent multiple cancers. The diagnosis of EC can provide the indication for women with specific risk factors to undergo genetic testing (GT). We sought to evaluate genetic counseling referrals (GCR) and subsequent GT rates in an ethnically diverse group of high-risk women. METHODS:All women diagnosed with EC between 2011 and 2016 were identified. Risk factors for LS including age, family and personal histories of Lynch-related cancers and loss of tumor mismatch repair (MMR) protein expression were identified from laboratory and medical records. Standard two-sided statistical tests were used. RESULTS:Of 583 women diagnosed with EC, 184 (31.6%) were found to have at least one high-risk characteristic for LS. Among these high-risk women, 58% were given GCR and resulting in only 35% undergoing GT. Ten of the 65 high-risk women who had GT (15.4%) were diagnosed with Lynch syndrome, and all ten met high-risk criteria. Two women of Asian race had tumors exhibiting retained MMR protein expression despite germline testing demonstrating Lynch syndrome. CONCLUSIONS:Many high-risk women do not receive GCR despite a high rate of germline mutations among these women. Improving GCR among high-risk women will lead to more subsequent GT to identify more Lynch syndrome families and prevent additional cancers. Among our ethnically diverse cohort, two women diagnosed with LS had retained MMR protein expression. GCR should be offered to women who possess high-risk characteristics despite normal MMR protein expression.

Purpose of Review: The burden of breast cancer in low-income and middle-income countries transitioning to higher levels of human development is a public health crisis, set to increase dramatically in the coming decades. This paper provides an overview of the burden in human and economic terms, a summary of the costs, and cost-effective analyses for breast cancer interventions and suggests a way forward through research to better inform national, regional, and global policies for breast cancer control. Recent Findings: Inequitable access to effective health services for breast cancer is striking between and within countries, where much of the costs are shouldered through out-of-pocket expenditures. A variety of factors can influence opportunities for women with breast symptoms to seek care and to access effective and affordable early detection and treatment services. Summary: Research into disparities and solutions to overcome these, including an evidence-informed investment case for breast cancer control, can help to garner the necessary political will and sustained commitments to ensure adequate and sustainable resources are available to reduce disparities in breast cancer survival.