African Breast Cancer-Disparities in Outcomes (ABC-DO): protocol of a multicountry mobile health prospective study of breast cancer survival in sub-Saharan Africa.

INTRODUCTION: Sub-Saharan African (SSA) women with breast cancer (BC) have low survival rates from this potentially treatable disease. An understanding of context-specific societal, health-systems and woman-level barriers to BC early detection, diagnosis and treatment are needed. METHODS: The African Breast Cancer-Disparities in Outcomes (ABC-DO) is a prospective hospital-based study of overall survival, impact on quality of life (QOL) and delays along the journey to diagnosis and treatment of BC in SSA. ABC-DO is currently recruiting in Namibia, Nigeria, South Africa, Uganda and Zambia. Women aged 18 years or older who present at participating secondary and tertiary hospitals with a new clinical or histocytological diagnosis of primary BC are invited to participate. For consented women, tumour characteristics, specimen and treatment data are obtained. Over a 2-year enrolment period, we aim to recruit 2000 women who, in the first instance, will be followed for between 1 and 3 years. A face-to-face baseline interview obtains information on socioeconomic, cultural and demographic factors, QOL, health and BC attitudes/knowledge, and timing of all prediagnostic contacts with caregivers in orthodox health, traditional and spiritual systems. Responses are immediately captured on mobile devices that are fed into a tailored mobile health (mHealth) study management system. This system implements the study protocol, by prompting study researchers to phone women on her mobile phone every 3 months and, failing to reach her, prompts contact with her next-of-kin. At follow-up calls, women provide updated information on QOL, care received and disease impacts on family and working life; date of death is asked of her next-of-kin when relevant. ETHICS AND DISSEMINATION: The study was approved by ethics committees of all involved institutions. All participants provide written informed consent. The findings from the study will be published in peer-reviewed scientific journals, presented to funders and relevant local organisations and at scientific conferences

Inequities in breast cancer treatment in sub-Saharan Africa: findings from a prospective multi-country observational study.

BACKGROUND: Improving breast cancer survival in sub-Saharan Africa (SSA) is urgently needed, requiring early diagnosis and improved access to treatment. However, data on the types of and barriers to receiving breast cancer therapy in this region are limited and have not been compared between different SSA countries and treatment settings. METHODS: In different health care settings across Uganda, Nigeria and Namibian sites of the prospective African Breast Cancer - Disparities in Outcomes cohort study, we assessed the percentage of newly diagnosed breast cancer patients who received treatment (systemic, surgery and/or radiotherapy) for cancer and their socio-demographic and clinical determinants. Treatment data were systematically extracted from medical records, as well as self-reported by women during 6-month follow-up interviews, and were used to generate a binary indicator of treatment received within 12 months of diagnosis (yes/no), which was analysed via logistic regression. RESULTS: Of 1325 women, cancer treatment had not been initiated treatment within 1 year of diagnosis for 227 (17%) women and 185 (14%) of women with stage I-III disease. Untreated percentages were highest in two Nigerian regional hospitals where 38% of 314 women were not treated (32% among stage I-III). At a national referral hospital in Uganda, 18% of 430 women were not treated (15% among stage I-III). In contrast, at a cancer care centre in Windhoek, Namibia, where treatment is provided free to the patient, all non-black (100%) and almost all (98.7%) black women had initiated treatment. Percentages of untreated women were higher in women from lower socio-economic groups, women who believed in traditional medicine and, in Uganda, in HIV+ women. Self-reported treatment barriers confirmed treatment costs and treatment refusal as contributors to not receiving treatment. CONCLUSIONS: Financial support to ensure treatment access and education of treatment benefits are needed to improve treatment access for breast cancer patients across sub-Saharan Africa, especially at regional treatment centres, for lower socio-economic groups, and for the HIV-positive woman with breast cancer

Analysis of the Breast Cancer Journey in Namibia.

IMPORTANCE: Breast cancer (BC) is the leading cancer among women in Namibia. Examining the BC journey in this multiracial country where inequalities remain large is needed to inform effective interventions to reduce BC mortality. OBJECTIVE: To describe the entire BC journey of Namibian women by race, utilizing the World Health Organization Global Breast Cancer Initiative (GBCI) framework. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used the Namibian subset of the African Breast Cancer-Disparities in Outcomes prospective cohort. Participants were all Namibian residents with confirmed incident BC who presented at the main national public oncology center of the Windhoek Central Hospital (WCH). Follow-up started from recruitment (September 8, 2014, to October 5, 2016) and ended up to 3 years after diagnosis (December 13, 2014, to September 27, 2019). Data analysis was conducted from June 2022 to August 2023. EXPOSURES: Participants' self-reported ethnicities were aggregated into 3 population groups: Black, mixed ancestry, and White. MAIN OUTCOMES AND MEASURES: Three-year overall survival (OS) was examined using Cox models, and summary statistics were used to describe women's BC journey, including GBCI pillar key performance indicators: (1) early stage (TNM I or II) diagnosis (population benchmark ≥60%), (2) prompt diagnosis, ie, 60 days or less to first health care practitioner visit (population benchmark 100%), and (3) completion of recommended multimodal treatment (MT, ie, surgery plus chemotherapy) (population benchmark ≥80%). RESULTS: Of 405 women, there were 300 (74%) Black (mean [SD] age, 53 [15] years), 49 (12%) mixed ancestry (mean [SD] age, 53 [7] years), and 56 (14%) White (mean [SD] age, 59 [12] years) patients. Three-year OS was lowest in Black women (60% [95% CI, 54%-66%]; mixed ancestry: 80% [95% CI, 65%-89%]; White: 89% [95% CI, 77%-95%]), who had lower prevalence of early stage diagnosis (Black: 37% [95% CI, 31%-42%]; mixed ancestry and White: 75% [95% CI, 66%-83%]) and timely diagnosis (Black: 60% [95% CI, 54%-66%]; mixed ancestry and White: 77% [95% CI, 69%-85%]), while MT completion (Black: 53% [95% CI, 46%-59%]; mixed ancestry and White: 63% [95% CI, 50%-73%]) was low in all women. CONCLUSIONS AND RELEVANCE: In this cohort study of 405 Namibian residents with BC, marked racial disparities in survival were paralleled by inequities all along the BC journey. To improve BC survival, interventions are needed to promote earlier diagnosis in Black Namibian women and to increase MT initiation and completion in all women

Drivers of advanced stage at breast cancer diagnosis in the multicountry African breast cancer - disparities in outcomes (ABC-DO) study.

Breast cancer (BC) survival rates in sub-Saharan Africa (SSA) are low in part due to advanced stage at diagnosis. As one component of a study of the entire journey of SSA women with BC, we aimed to identify shared and setting-specific drivers of advanced stage BC. Women newly diagnosed in the multicountry African Breast Cancer-Disparities in Outcomes (ABC-DO) study completed a baseline interview and their stage information was extracted from medical records. Ordinal logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for advanced stage (I, II, III, IV) in relation to individual woman-level, referral and biological factors. A total of 1795 women were included from Nigeria, Uganda, Zambia, and the multiracial populations of Namibia and South Africa, 1091 of whom (61%) were stage III/IV. Stage was lower in women with greater BC knowledge (OR 0.77 (95% CI: 0.70, 0.85) per point on a 6 point scale). More advanced stage was associated with being black (4.00 (2.79, 5.74)), having attended <secondary education (1.75 (1.42, 2.16)), having never heard of BC (1.64 (1.31, 2.06)), an unskilled job (1.77 (1.43, 2.20)) and pregnancy in the past 3 years (30% of ≤45 year olds) (1.63 (1.15, 2.31)), and were mediated through delays to diagnosis: symptom duration of ≥ 1 year (OR 2.47 (1.93, 3.15)). These findings provide further evidence that late-stage BC in SSA is largely attributed to modifiable factors and strategies to improve BC education and awareness in women and the health system should be intensified

Self-reported arm and shoulder problems in breast cancer survivors in Sub-Saharan Africa: the African Breast Cancer-Disparities in Outcomes cohort study

BACKGROUND: Arm and shoulder problems (ASP), including lymphedema, were common among women with breast cancer in high-income countries before sentinel lymph node biopsy became the standard of care. Although ASP impair quality of life, as they affect daily life activities, their frequency and determinants in Sub-Saharan Africa remain unclear. METHODS: All women newly diagnosed with breast cancer at the Namibian, Ugandan, Nigerian, and Zambian sites of the African Breast Cancer-Disparities in Outcomes (ABC-DO) cohort study were included. At each 3-month follow-up interview, women answered the EORTC-QLQ-Br23 questionnaire, including three ASP items: shoulder/arm pain, arm stiffness, and arm/hand swelling. We estimated the cumulative incidence of first self-reported ASP, overall and stratified by study and treatment status, with deaths treated as competing events. To identify determinants of ASP, we estimated cause-specific hazard ratios using Cox models stratified by study site. RESULTS: Among 1476 women, up to 4 years after diagnosis, 43% (95% CI 40-46), 36% (33-38) and 23% (20-25), respectively, self-reported having experienced arm/shoulder pain, stiffness and arm/hand swelling at least once. Although risks of self-reported ASP differed between sites, a more advanced breast cancer stage at diagnosis, having a lower socioeconomic position and receiving treatment increased the risk of reporting an ASP. CONCLUSION: ASP are very common in breast cancer survivors in Sub-Saharan Africa. They are influenced by different factors than those observed in high-income countries. There is a need to raise awareness and improve management of ASP within the African setting

Maternally Orphaned Children and Intergenerational Concerns Associated With Breast Cancer Deaths Among Women in Sub-Saharan Africa.

IMPORTANCE: Low breast cancer survival in sub-Saharan Africa's young population increases the likelihood that breast cancer deaths result in maternal orphans, ie, children (<18 years) losing their mother. OBJECTIVE: To estimate the number of maternal orphans and their ages for every 100 breast cancer deaths in sub-Saharan African settings during 2014-2019 and to describe family concerns about the orphaned children. DESIGN, SETTING, AND PARTICIPANTS: Deaths occurring between September 1, 2014, and July 1, 2019, in the African Breast Cancer-Disparities in Outcomes (ABC-DO) were examined in a cohort of women diagnosed with breast cancer during 2014-2017 at major cancer treatment hospitals in Namibia, Nigeria, Uganda, and Zambia. The cohort was actively followed up for vital status via a trimonthly mobile phone call to each woman or her next of kin (typically a partner, husband, or child). MAIN OUTCOMES AND MEASURES: The number (Poisson counts) and ages of new orphans at the time of maternal death. RESULTS: This cohort study found that a total of 795 deaths resulted in 964 new maternal orphans, with deaths occurring in women younger than 50 years accounting for 85% of the orphans. For every 100 deaths in women younger than 50 years, there were 210 new orphans (95% CI, 196-225) overall, with country-specific estimates of 189 in Nigerian, 180 in Namibian, 222 in Ugandan, and 247 in Zambian Black women. For every 100 deaths of the women at any age, there were 121 maternal orphans, 17% of whom were younger than 5 years, 32% aged 5 to 9 years, and 51% aged 10 to 17 years at the time of maternal death. In follow-up interviews, families' concerns for children's education and childcare were reported to be exacerbated by the financial expenses associated with cancer treatment. CONCLUSIONS AND RELEVANCE: This study provides evidence that the number of maternal orphans due to breast cancer exceeds the number of breast cancer deaths among women in sub-Saharan Africa. The intergenerational consequences associated with cancer deaths in sub-Saharan Africa appear to be large and support the need for continued action to improve survival

Dissecting the journey to breast cancer diagnosis in sub-Saharan Africa: Findings from the multicountry ABC-DO cohort study.

Most breast cancer patients in sub-Saharan Africa are diagnosed at advanced stages after prolonged symptomatic periods. In the multicountry African Breast Cancer-Disparities in Outcomes cohort, we dissected the diagnostic journey to inform downstaging interventions. At hospital presentation for breast cancer, women recalled their diagnostic journey, including dates of first noticing symptoms and health-care provider (HCP) visits. Negative binomial regression models were used to identify correlates of the length of the diagnostic journey. Among 1429 women, the median (inter-quartile range) length (months) of the diagnostic journey ranged from 11.3 (5.7-21.2) in Ugandan, 8.2 (3.4-16.4) in Zambian, 6.5 (2.4-15.7) in Namibian-black to 5.6 (2.3-13.1) in Nigerian and 2.4 (0.6-5.5) in Namibian-non-black women. Time from first HCP contact to diagnosis represented, on average, 58% to 79% of the diagnostic journey in each setting except Nigeria where most women presented directly to the diagnostic hospital with advanced disease. The median number of HCPs visited was 1 to 4 per woman, but time intervals between visits were long. Women who attributed their initial symptoms to cancer had a 4.1 months (absolute) reduced diagnostic journey than those who did not, while less-educated (none/primary) women had a 3.6 months longer journey than more educated women. In most settings the long journey to breast cancer diagnosis was not primarily due to late first presentation but to prolonged delays after first presentation to diagnosis. Promotion of breast cancer awareness and implementation of accelerated referral pathways for women with suspicious symptoms are vital to downstaging the disease in the region

Geospatial barriers to healthcare access for breast cancer diagnosis in sub-Saharan African settings: The African Breast Cancer-Disparities in Outcomes Cohort Study.

We examined the geospatial dimension of delays to diagnosis of breast cancer in a prospective study of 1541 women newly diagnosed in the African Breast Cancer-Disparities in Outcomes (ABC-DO) Study. Women were recruited at cancer treatment facilities in Namibia, Nigeria, Uganda and Zambia. The baseline interview included information used to generate the geospatial features: urban/rural residence, travel mode to treatment facility and straight-line distances from home to first-care provider and to diagnostic/treatment facility, categorized into country/ethnicity (population)-specific quartiles. These factors were investigated in relation to delay in diagnosis (≥3 months since first symptom) and late stage at diagnosis (TNM: III, IV) using logistic regression, adjusted for population group and sociodemographic characteristics. The median (interquartile range) distances to first provider and diagnostic and treatment facilities were 5 (1-37), 17 (3-105) and 62 (5-289) km, respectively. The majority had a delay in diagnosis (74%) and diagnosis at late stage (64%). Distance to first provider was not associated with delay in diagnosis or late stage at diagnosis. Rural residence was associated with delay, but the association did not persist after adjustment for sociodemographic characteristics. Distance to the diagnostic/treatment facility was associated with delay (highest vs lowest quartile: odds ratio (OR) = 1.56, 95% confidence interval (CI) = 1.08-2.27) and late stage (overall: OR = 1.47, CI = 1.05-2.06; without Nigerian hospitals where mostly local residents were treated: OR = 1.73, CI = 1.18-2.54). These findings underscore the need for measures addressing the geospatial barriers to early diagnosis in sub-Saharan African settings, including providing transport or travel allowance and decentralizing diagnostic services

Preexisting morbidity profile of women newly diagnosed with breast cancer in sub-Saharan Africa: African Breast Cancer-Disparities in Outcomes study.

The presence of preexisting morbidities poses a challenge to cancer patient care. There is little information on the profile and prevalence of multi-morbidities in breast cancer patients across middle income countries (MIC) to lower income countries (LIC) in sub-Saharan Africa (SSA). The African Breast Cancer-Disparities in Outcomes (ABC-DO) breast cancer cohort spans upper MICs South Africa and Namibia, lower MICs Zambia and Nigeria and LIC Uganda. At cancer diagnosis, seven morbidities were assessed: obesity, hypertension, diabetes, asthma/chronic obstructive pulmonary disease, heart disease, tuberculosis and HIV. Logistic regression models were used to assess determinants of morbidities and the influence of morbidities on advanced stage (stage III/IV) breast cancer diagnosis. Among 2189 women, morbidity prevalence was the highest for obesity (35%, country-specific range 15-57%), hypertension (32%, 15-51%) and HIV (16%, 2-26%) then for diabetes (7%, 4%-10%), asthma (4%, 2%-10%), tuberculosis (4%, 0%-8%) and heart disease (3%, 1%-7%). Obesity and hypertension were more common in upper MICs and in higher socioeconomic groups. Overall, 27% of women had at least two preexisting morbidities. Older women were more likely to have obesity (odds ratio: 1.09 per 10 years, 95% CI 1.01-1.18), hypertension (1.98, 1.81-2.17), diabetes (1.51, 1.32-1.74) and heart disease (1.69, 1.37-2.09) and were less likely to be HIV positive (0.64, 0.58-0.71). Multi-morbidity was not associated with stage at diagnosis, with the exception of earlier stage in obese and hypertensive women. Breast cancer patients in higher income countries and higher social groups in SSA face the additional burden of preexisting non-communicable diseases, particularly obesity and hypertension, exacerbated by HIV in Southern/Eastern Africa

Disparities in breast cancer survival between women with and without HIV across sub-Saharan Africa (ABC-DO): a prospective, cohort study.

BACKGROUND: Studies have shown increased mortality among women living with HIV diagnosed with breast cancer compared with HIV-negative women with breast cancer. We aimed to examine how this HIV differential varies by patient or breast tumour characteristics. METHODS: The African Breast Cancer-Disparities in Outcomes (ABC-DO) study is a prospective cohort of women (aged ≥18 years) with incident breast cancer recruited consecutively at diagnosis (2014-17) from hospitals in Namibia, Nigeria, South Africa, Uganda, and Zambia. Detailed clinical and epidemiological data, including self-reported or tested HIV status, were collected at baseline. Participants were actively followed up via telephone calls every 3 months. The primary outcome was all-cause mortality, assessed in all women who had at least one updated vital status after baseline interview. Using Cox regression, we examined differences in overall survival by HIV status in the cohort, and across country and patient subgroups, adjusted for age, tumour grade, and tumour stage at cancer diagnosis. FINDINGS: Between Sept 8, 2014, and Dec 31, 2017, we recruited 2154 women with primary breast cancer, 519 of whom were excluded due to their countries having small numbers of women with HIV for comparison. Among the remaining 1635 women, 313 (19%) were living with HIV, 1184 (72%) were HIV negative, and 138 (9%) had unknown HIV status. At breast cancer diagnosis, women with HIV were younger and had lower body-mass index (BMI) than their HIV-negative counterparts, but had similar tumour stage, grade, and receptor subtypes. At the end of the follow-up (Jan 1, 2019), a higher proportion of women with HIV (137 [44%] of 313) had died than had HIV-negative women (432 [37%] of 1184). Crude 3-year survival was 9% lower for women with HIV (46% [95% CI 40-53]) than for HIV-negative women (55% [52-59]; hazard ratio (HR) 1·41 [1·15-1·74]). The HIV survival differential did not differ by age, BMI, tumour subtype, or tumour grade, but was stronger in women with non-metastatic disease (3-year survival 52% HIV-positive vs 63% HIV-negative women, adjusted HR 1·65 [1·30-2·10]), whereas women with metastatic cancer had low survival, regardless of HIV status. INTERPRETATION: The larger survival deficit among women with HIV with non-metastatic breast cancer calls for a better understanding of the reasons underlying this differential (eg, biological mechanisms, health behaviours, detrimental HIV-breast cancer treatment interactions, or higher HIV background mortality) to inform strategies for reducing mortality among this patient group. FUNDING: Susan G Komen, International Agency for Research on Cancer, National Cancer Institute, and UK-Commonwealth Scholarships