Faculty Bibliography

Inequitable access to high-quality cancer control and care remains one of the greatest public health challenges in countries at all resource levels. Core issues include the limited oncology health care workforce and equitable access to affordable (essential) cancer diagnostics, medicines, surgery, systemic therapies, and radiotherapy, compounded by existing social inequalities. To reduce cancer health disparities globally and subnationally, countries can enhance their capabilities to deliver high-quality, affordable care closer to where most people live. Decentralization and integration of health services can be part of the solution, offloading the strained capacity of tertiary facilities where possible and expanding cadres of trained providers to support some aspects of cancer prevention and control that require a lesser degree of specialization. The strategy to eliminate cervical cancer provides a salient example of a data-driven effort that optimizes resources to dramatically reduce one of the greatest cancer health disparities globally. Here, we highlight two responses to meet the challenge through greater engagement of the primary care workforce and by adoption of universal health care coverage to ensure access to cancer prevention.

BACKGROUND:The Breast Health Global Initiative (BHGI) established a series of resource-stratified, evidence-based guidelines to address breast cancer control in the context of available resources. Here, the authors describe methodologies and health system prerequisites to support the translation and implementation of these guidelines into practice. METHODS:In October 2018, the BHGI convened the Sixth Global Summit on Improving Breast Healthcare Through Resource-Stratified Phased Implementation. The purpose of the summit was to define a stepwise methodology (phased implementation) for guiding the translation of resource-appropriate breast cancer control guidelines into real-world practice. Three expert consensus panels developed stepwise, resource-appropriate recommendations for implementing these guidelines in low-income and middle-income countries as well as underserved communities in high-income countries. Each panel focused on 1 of 3 specific aspects of breast cancer care: 1) early detection, 2) treatment, and 3) health system strengthening. RESULTS:Key findings from the summit and subsequent article preparation included the identification of phased-implementation prerequisites that were explored during consensus debates. These core issues and concepts are key components for implementing breast health care that consider real-world resource constraints. Communication and engagement across all levels of care is vital to any effectively operating health care system, including effective communication with ministries of health and of finance, to demonstrate needs, outcomes, and cost benefits. CONCLUSIONS:Underserved communities at all economic levels require effective strategies to deploy scarce resources to ensure access to timely, effective, and affordable health care. Systematically strategic approaches translating guidelines into practice are needed to build health system capacity to meet the current and anticipated global breast cancer burden.

BACKGROUND:Breast cancer is the leading cause of female mortality in low-income and middle-income countries (LMICs). Early detection of breast cancer, either through screening or early diagnosis initiatives, led by community health workers (CHWs) has been proposed as a potential way to address the unjustly high mortality rates. We therefore document: (1) where and how CHWs are currently deployed in this role; (2) how CHWs are trained, including the content, duration and outcomes of training; and (3) the evidence on costs associated with deploying CHWs in breast cancer early detection. METHODS:We conducted a systematic scoping review and searched eight major databases, as well as the grey literature. We included original studies focusing on the role of CHWs to assist in breast cancer early detection in a country defined as a LMIC according to the World Bank. FINDINGS/RESULTS:16 eligible studies were identified. Several roles were identified for CHWs including awareness raising and community education (n=13); history taking (n=7); performing clinical breast examination (n=9); making onward referrals (n=7); and assisting in patient navigation and follow-up (n=4). Details surrounding training programmes were poorly reported and no studies provided a formal cost analysis. CONCLUSIONS:Despite the relative paucity of studies addressing the role of CHWs in breast cancer early detection, as well as the heterogeneity of existing studies, evidence suggests that CHWs can play a number of important roles in breast cancer early detection initiatives in LMICs. However, if they are to realise their full potential, they must be appropriately supported within the wider health system.

When breast cancer is detected and treated early, the chances of survival are very high. However, women in many settings face complex barriers to early detection, including social, economic, geographic, and other interrelated factors, which can limit their access to timely, affordable, and effective breast health care services. Previously, the Breast Health Global Initiative (BHGI) developed resource-stratified guidelines for the early detection and diagnosis of breast cancer. In this consensus article from the sixth BHGI Global Summit held in October 2018, the authors describe phases of early detection program development, beginning with management strategies required for the diagnosis of clinically detectable disease based on awareness education and technical training, history and physical examination, and accurate tissue diagnosis. The core issues address include finance and governance, which pertain to successful planning, implementation, and the iterative process of program improvement and are needed for a breast cancer early detection program to succeed in any resource setting. Examples are presented of implementation, process, and clinical outcome metrics that assist in program implementation monitoring. Country case examples are presented to highlight the challenges and opportunities of implementing successful breast cancer early detection programs, and the complex interplay of barriers and facilitators to achieving early detection for breast cancer in real-world settings are considered.

BACKGROUND:Breast cancer is the most common cancer among women in India. Jhpiego, a not-for-profit health organization, is providing technical assistance for developing an evidence-based model of breast health care in the states of Uttar Pradesh and Jharkhand in India. METHODS:A situational assessment of breast health care services using validated tools was conducted in the 2 states. RESULTS:Findings of the assessment were presented to the Breast Health Technical Advisory Committee comprised of subject experts and government functionaries. The committee, guided by Breast Health Global Initiative resource-stratified guidelines, developed a conceptual framework for integration of breast health services into the existing health system. This conceptual framework was presented to the Technical Advisory Groups (TAGs) of the respective state governments. Each TAG then developed an operationally feasible, contextually appropriate implementation plan in alignment with the national guidelines for noncommunicable diseases. This implementation plan guided the rollout of the breast health care program in the Lucknow (Uttar Pradesh) and Ranchi (Jharkhand) districts. CONCLUSIONS:Early results from the implementation suggest that it is feasible to integrate the breast health care pathway with the ongoing National Cancer Control Program of India.

Introduction: Differences in the expression of estrogen-regulated genes (ERG), and proliferation-associated genes (PAG) have been shown in ER+ tumours as a result of the major changes in hormone levels during the menstrual cycle. Here, we extend that observation in a prospective study.
Aim(s): To determine if there are changes in the expression of ERGs, PAGs and progesterone-regulated genes (PRG) in ER+ breast cancer during the menstrual cycle.
Method(s): Paired tumour samples from 96 patients in two independent prospective studies were used. Tumours were assigned to one of three pre-defined menstrual cycle windows: W1 (days 27-35 and 1-6; low E2 and low progesterone), W2 (days 7-16; high E2 and low progesterone) and W3 (days 17-26; intermediate E2 and high progesterone) based on plasma hormone measurements. RNA expression of 50 genes, including 27 ERGs, 11 PRGs and seven PAGs was measured.
Result(s): The AvERG, a composite measure of ERG expression, showed significant changes between the individual windows (Kruskal- Wallis (KW) P = 0.0002), increasing between W1 and W2 (fold change (FC) 2.2) and decreasing between W2 and W3 (FC 0.62) and between W3 and W1 (FC 0.58). PAG expression also changed significantly (KW P = 0.012), but to a lesser extent. 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 (FC 1.3-2.4; FDR 0.016-0.05). Mean protein levels of PgR increased between W1 and W2 or W3 (+18.3%; FDR 0.024). The AvProg, a composite measure of PRG expression, increased significantly (FC 1.5, Spearman P = 0.026) in W3 compared to W1 or W2.
Conclusion(s): Significant changes in ERG, PRG and PAG expression in ER+ breast tumours occur during the menstrual cycle that may affect the assessment and interpretation of prominent biomarkers

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/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.