Faculty Bibliography

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.

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.

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.

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

BACKGROUND:Mammographic density is one of the strongest risk factors for breast cancer. In the general population, mammographic density can be modified by various exposures; whether this is true for women a strong family history is not known. Thus, we evaluated the association between reproductive, hormonal, and lifestyle risk factors and mammographic density among women with a strong family history of breast cancer but no BRCA1 or BRCA2 mutation. METHODS:We included 97 premenopausal and 59 postmenopausal women (age range: 27-68 years). Risk factor data was extracted from the research questionnaire closest in time to the mammogram performed nearest to enrollment. The Cumulus software was used to measure percent density, dense area, and non-dense area for each mammogram. Multivariate generalized linear models were used to evaluate the relationships between breast cancer risk factors and measures of mammographic density, adjusting for relevant covariates. RESULTS:; P=0.002). Among postmenopausal women, former smokers had a higher mean percent density (19.5% vs. 10.8%; P=0.003) and dense area (26.9% vs. 16.4%; P=0.01) compared to never smokers. After applying the Bonferroni correction, the association between body weight and percent density among premenopausal women remained statistically significant. CONCLUSIONS:In this cohort of women with a strong family history of breast cancer, body weight was associated with mammographic density. These findings suggest that mammographic density may explain the underlying relationship between some of these risk factors and breast cancer risk, and lend support for the inclusion of mammographic density into risk prediction models.

BACKGROUND:Large-scale population studies demonstrate an association between mothers' deaths and child mortality in both lower and higher income countries. The authors estimated children's deaths in association with mothers' deaths from breast or cervical cancer, 2 common cancers in low-income and middle-income countries affecting women of reproductive age, to develop a comprehensive assessment of the death burden of these cancers. METHODS:A Monte Carlo simulation model was devised whereby women were at risk of dying from breast cancer, cervical cancer, or another cause. Compared with children who have living mothers, children of women who die before they reached age 10 years have an elevated risk of death from all causes. Therefore, simulations were conducted, and the impact of mothers' deaths from cervical and breast cancer on associated child mortality was quantified for Bangladesh, Burkina Faso, and Denmark (benchmark analysis), then the analyses were extended to all African countries. RESULTS:Benchmark estimates of child deaths associated with mothers' deaths from breast and cervical cancer resulted in an increment in cancer-related mortality of approximately 2% in Bangladesh, 14% in Burkina Faso, and less than 1% in Denmark. The model predicted an increment in comprehensive cancer deaths when including child death estimates by as high as 30% in certain African countries. CONCLUSIONS:To the authors' knowledge, this is the first study to estimate the impact of a mother's death from cancer on child mortality. The model's estimates call for further investigation into this correlation and underscore the relevance of adequate access to prevention and treatment among women of childbearing age.