Prevalence of Preferences for End-of-Life Place of Care and Death Among Patients With Cancer in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis.

PURPOSE: There is limited information on preferences for place of care and death among patients with cancer in low- and middle-income countries (LMICs). The aim was to report the prevalence and determinants of preferences for end-of-life place of care and death among patients with cancer in LMICs and identify concordance between the preferred and actual place of death. METHODS: Systematic review and meta-analysis guided by Preferred Reporting Items for Systematic Reviews and Meta-Analyses was conducted. Four electronic databases were searched to identify studies of any design that reported on the preferred and actual place of care and death of patients with cancer in LMICs. A random-effects meta-analysis estimated pooled prevalences, with 95% CI, with subgroup analyses for region and risk of bias. RESULTS: Thirteen studies were included. Of 3,837 patients with cancer, 62% (95% CI, 49 to 75) preferred to die at home; however, the prevalence of actual home death was 37% (95% CI, 13 to 60). Subgroup analyses found that preferences for home as place of death varied from 55% (95% CI, 41 to 69) for Asia to 64% (95% CI, 57 to 71) for South America and 72% (95% CI, 48 to 97) for Africa. The concordance between the preferred and actual place of death was 48% (95% CI, 41 to 55) for South Africa and 92% (95% CI, 88 to 95) for Malaysia. Factors associated with an increased likelihood of preferred home death included performance status and patients with breast cancer. CONCLUSION: There is very little literature from LMICs on the preferences for end-of-life place of care and death among patients with cancer. Rigorous research is needed to help understand how preferences of patients with cancer change during their journey through cancer.

African Ancestry-Associated Gene Expression Profiles in Triple-Negative Breast Cancer Underlie Altered Tumor Biology and Clinical Outcome in Women of African Descent.

Women of sub-Saharan African descent have disproportionately higher incidence of triple-negative breast cancer (TNBC) and TNBC-specific mortality across all populations. Population studies show racial differences in TNBC biology, including higher prevalence of basal-like and quadruple-negative subtypes in African Americans (AA). However, previous investigations relied on self-reported race (SRR) of primarily U.S. populations. Due to heterogeneous genetic admixture and biological consequences of social determinants, the true association of African ancestry with TNBC biology is unclear. To address this, we conducted RNA sequencing on an international cohort of AAs, as well as West and East Africans with TNBC. Using comprehensive genetic ancestry estimation in this African-enriched cohort, we found expression of 613 genes associated with African ancestry and 2,000+ associated with regional African ancestry. A subset of African-associated genes also showed differences in normal breast tissue. Pathway enrichment and deconvolution of tumor cellular composition revealed that tumor-associated immunologic profiles are distinct in patients of African descent. SIGNIFICANCE: Our comprehensive ancestry quantification process revealed that ancestry-associated gene expression profiles in TNBC include population-level distinctions in immunologic landscapes. These differences may explain some differences in race-group clinical outcomes. This study shows the first definitive link between African ancestry and the TNBC immunologic landscape, from an African-enriched international multiethnic cohort. See related commentary by Hamilton et al., p. 2496. This article is highlighted in the In This Issue feature, p. 2483.

Breast Cancer Risk in Women from Ghana Carrying Rare Germline Pathogenic Mutations.

BACKGROUND: Risk estimates for women carrying germline mutations in breast cancer susceptibility genes are mainly based on studies of European ancestry women. METHODS: We investigated associations between pathogenic variants (PV) in 34 genes with breast cancer risk in 871 cases [307 estrogen receptor (ER)-positive, 321 ER-negative, and 243 ER-unknown] and 1,563 controls in the Ghana Breast Health Study (GBHS), and estimated lifetime risk for carriers. We compared results with those for European, Asian, and African American ancestry women. RESULTS: The frequency of PV in GBHS for nine breast cancer genes was 8.38% in cases and 1.22% in controls. Relative risk estimates for overall breast cancer were: (OR, 13.70; 95% confidence interval (CI), 4.03-46.51) for BRCA1, (OR, 7.02; 95% CI, 3.17-15.54) for BRCA2, (OR, 17.25; 95% CI, 2.15-138.13) for PALB2, 5 cases and no controls carried TP53 PVs, and 2.10, (0.72-6.14) for moderate-risk genes combined (ATM, BARD1, CHEK2, RAD51C, RAD52D). These estimates were similar to those previously reported in other populations and were modified by ER status. No other genes evaluated had mutations associated at P < 0.05 with overall risk. The estimated lifetime risks for mutation carriers in BRCA1, BRCA2, and PALB2 and moderate-risk genes were 18.4%, 9.8%, 22.4%, and 3.1%, respectively, markedly lower than in Western populations with higher baseline risks. CONCLUSIONS: We confirmed associations between PV and breast cancer risk in Ghanaian women and provide absolute risk estimates that could inform counseling in Ghana and other West African countries. IMPACT: These findings have direct relevance for breast cancer genetic counseling for women in West Africa.

C/Can City Engagement Process: An Implementation Framework for Strengthening Cancer Care in Cities in Low- and Middle-Income Countries.

The effective implementation of locally adapted cancer care solutions in low- and middle-income countries continues to be a challenge in the face of fragmented and inadequately resourced health systems. Consequently, the translation of global cancer care targets to local action for patients has been severely constrained. City Cancer Challenge (C/Can) is leveraging the unique value of cities as enablers in a health systems response to cancer that prioritizes the needs of end users (patients, their caregivers and families, and health care providers). C/Can's City Engagement Process is an implementation framework whereby local stakeholders lead a staged city-wide process over a 2- to 3-year period to assess, plan, and execute locally adapted cancer care solutions. Herein, the development and implementation of the City Engagement Process Framework (CEPF) is presented, specifying the activities, outputs, processes, and indicators across the process life cycle. Lessons learned on the application of the framework in the first so-called Key Learning cities are shared, focusing on the early outputs from Cali, Colombia, the first city to join C/Can in 2017. Creating lasting change requires the creation of a high-trust environment to engage the right stakeholders as well as adapting to local context, leveraging local expertise, and fostering a sustainability mindset from the outset. In the short term, these early learnings inform the refinement of the approach in new cities. Over time, the implementation of this framework is expected to validate the proof-of-concept and contribute to a global evidence base for effective complex interventions to improve cancer care in low- and middle-income countries.