Reproductive history and breast cancer survival: Findings from the African breast cancer-Disparities in outcomes cohort and implications of Africa's fertility transition on breast cancer prognosis.

Reproductive characteristics are known risk factors for breast cancer but, other than recent birth, their role as prognostic factors is less clear, and has not been studied in Sub-Saharan Africa (SSA). In this setting, we examined whether reproductive factors independently influence breast cancer survival in a subset of the African Breast Cancer-Disparities in Outcomes cohort study. In 1485 women with incident breast cancer recruited between 2014 and 2017, we examined birth cohort changes in reproductive factors, and used Cox models to examine whether reproductive characteristics were associated with all-cause mortality after adjusting for confounders (age, stage, treatment, HIV, and social factors). Four years after diagnosis, 822 (56%) women had died. Median parity was 4 (IQR = 2, 6) and 209 (28%) of premenopausal women had had a recent birth (<3 years prior to cancer diagnosis). Each pregnancy was associated with a 5% increase (95% CI: 2%, 8%) in mortality rates, which held among postmenopausal women (5%, [1%-9%]). Pre-menopausal women with a recent birth had 52% (20%, 92%) higher mortality rates. Fertility trends by birth cohort showed declining parity, increasing age at first birth and declining age at last birth, however the impact of these population-level changes on future average survival was predicted to be very small (<3% absolute gain).

Treatment guideline concordance, initiation, and abandonment in patients with non-metastatic breast cancer from the African Breast Cancer-Disparities in Outcomes (ABC-DO) cohort in sub-Saharan Africa: a prospective cohort study.

BACKGROUND: Comprehensive breast cancer management is essential to achieve high breast cancer survival; however, detailed reports of the treatment regimens received by patients are scarce in sub-Saharan Africa where survival is low. We aimed to examine treatment initiation, guideline concordance, and abandonment in patients with non-metastatic breast cancer in sub-Saharan Africa from the African Breast Cancer-Disparities in Outcomes (ABC-DO) prospective cohort. METHODS: The ABC-DO prospective cohort study recruited women (aged ≥18 years) with newly diagnosed invasive breast cancer in eight hospitals across five sub-Saharan African countries (Namibia, Nigeria, Uganda, South Africa, and Zambia). We analysed treatments received by women who were classified as non-metastatic (M0) at the initial presentation. Data on surgery, radiotherapy, and systemic therapies were obtained from medical records and a self-reported follow-up questionnaire at 6 months after the diagnosis, follow-up calls every 3 months, and a baseline questionnaire. Initiation, completion, and abandonment of treatment modalities and combined therapy regimens were examined overall, by country-specific groups, and by clinical factors relevant for guideline-based treatment. FINDINGS: Of 2313 women recruited into the ABC-DO study between Sept 10, 2014, and Dec 31, 2017, 2226 had histologically or clinically confirmed breast cancer. Of these 2226 women, 510 were excluded from the present analysis because 378 had metastatic disease, 37 were prevalent cases (defined as those previously diagnosed with breast cancer >2 years before baseline), 82 had unknown TNM stage, and 13 were White or Asian women in South Africa (number was too small for analysis). After a median follow-up of 5·2 years (IQR 4·6-5·9), 1163 (68%) of 1716 women underwent breast cancer surgery. Surgery and systemic therapy (ie, multimodality treatment) with radiotherapy was initiated in 370 (36%) of 1028 women with localised tumours versus 156 (23%) of 688 women with locally advanced tumours, whereas multimodality treatment without radiotherapy was initiated in 386 (38%) versus 167 (24%) women, respectively. Of 1530 patients requiring chemotherapy (which excludes 105 who died within 6 months after baseline), 1013 (66%) initiated treatment of neoadjuvant chemotherapy or surgery within 3 months after baseline, which was adequately completed by 359 (35%) of 1013 women, marginally completed by 284 (28%), abandoned by 200 (20%), and unknown in 151 (15%). 19 (2%) women died within 6 months after chemotherapy initiation. Of 1375 women in whom endocrine therapy was indicated, this treatment was initiated in 920, and lasted at least 3 years in 367 (40%) women. Treatment disparities between country-specific groups were substantial for all therapy regimens. INTERPRETATION: A high proportion of patients with non-metastatic breast cancer did not initiate, did not fully complete, or abandoned treatment with surgery, systemic therapy, radiotherapy, or an appropriate combination of these, highlighting the need for improved treatment access and completion in sub-Saharan Africa to potentially prevent premature breast cancer deaths. FUNDING: National Institutes of Health (National Cancer Institute), Susan G Komen, and the International Agency for Research on Cancer.

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.

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.

Few Losses to Follow-up in a Sub-Saharan African Cancer Cohort via Active Mobile Health Follow-up.

Accurate survival estimates are needed for guiding cancer control efforts in sub-Saharan Africa, but previous studies have been hampered by unknown biases due to excessive loss to follow-up (LTFU). In the African Breast Cancer-Disparities in Outcomes Study, a prospective breast cancer cohort study, we implemented active mobile health follow-up, telephoning each woman or her next-of-kin (NOK) trimonthly on her mobile phone to update information on her vital status. Dates of every contact with women/NOK were analyzed from diagnosis in 2014-2017 to the earliest of September 1, 2018, death, or 3 years postdiagnosis. The cumulative incidence of being LTFU was calculated considering deaths as competing events. In all, 1,490 women were followed for a median of 24.2 (interquartile range (IQR), 14.2-34.5) months, corresponding to 8,529 successful contacts (77% of total contacts) with the women/NOK. Median time between successful contacts was 3.0 (IQR, 3.0-3.7) months. In all, 71 women (5.3%) were LTFU at 3 years: 0.8% in Nigeria, 2.2% in Namibia, and 5.6% in Uganda. Because of temporary discontinuity of active follow-up, 20.3% of women were LTFU after 2 years in Zambia. The median time to study notification of a death was 9.1 (IQR, 3.9-14.0) weeks. Although the present study was not a randomized controlled trial, in this cancer cohort with active mobile health follow-up, LTFU was much lower than in previous studies and enabled estimation of up-to-date and reliable cancer survival.

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.

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

Breast cancer awareness in the sub-Saharan African ABC-DO cohort: African Breast Cancer-Disparities in Outcomes study.

A greater understanding of the nature and drivers of poor breast cancer (BC) awareness in sub-Saharan Africa (SSA) will inform much needed awareness programmes. We aimed to assess the level and nature of BC awareness in the multi-country African Breast Cancer-Disparities in Outcome (ABC-DO) cohort of women newly diagnosed with BC during 2014-2017. Awareness indicators were assessed during a baseline interview at/near diagnosis. Logistic/ordinal regression was used to estimate odds ratios (OR) for indicators of BC awareness in relation to woman-level characteristics for individual settings and then meta-analyzed. In the 1,451 women included, almost all Namibian non-black women (n = 104) knew of BC and its curability, while in Namibian black and Zambian women, one in 7 (~ 15%) had not previously heard of BC and 25-40% did not know it was curable. In Uganda and Nigeria awareness was lowest: one in four women had no BC awareness, and 2 in 3 had no knowledge of its cure potential. Low educational level, unskilled employment, low socioeconomic position, rural residence, older age, being unmarried, and in some settings HIV-positivity, were associated with lower BC awareness-e.g., having unskilled employment was associated with not having heard of BC (summary OR 3.37; 95% confidence interval (CI) 2.17-5.23), believing that it is incurable (2.43; 1.81-3.26), and not recognizing a breast lump symptom (1.85; 1.41-2.43) but with between-setting variation (I2 > 68% for all). The findings provide evidence of the level and difference in BC awareness and beliefs across different settings, highlighting the urgent need for context-specific education programmes in the SSA region.

Geospatial disparities in survival of patients with breast cancer in sub-Saharan Africa from the African Breast Cancer-Disparities in Outcomes cohort (ABC-DO): a prospective cohort study.

BACKGROUND: There is an urgent need to improve breast cancer survival in sub-Saharan Africa. Geospatial barriers delay diagnosis and treatment, but their effect on survival in these settings is not well understood. We examined geospatial disparities in 4-year survival in the African Breast Cancer-Disparities in Outcomes cohort. METHODS: In this prospective cohort study, women (aged ≥18 years) newly diagnosed with breast cancer were recruited from eight hospitals in Namibia, Nigeria, South Africa, Uganda, and Zambia. They reported sociodemographic information in interviewer-administered questionnaires, and their clinical and treatment data were collected from medical records. Vital status was ascertained by contacting participants or their next of kin every 3 months. The primary outcome was all-cause mortality in relation to rural versus urban residence, straight-line distance, and modelled travel time to hospital, analysed using restricted mean survival time, Cox proportional hazards, and flexible parametric survival models. FINDINGS: 2228 women with breast cancer were recruited between Sept 8, 2014, and Dec 31, 2017. 127 were excluded from analysis (58 had potentially recurrent cancer, had previously received treatment, or had no follow-up; 14 from minority ethnic groups with small sample sizes; and 55 with missing geocoded home addresses). Among the 2101 women included in analysis, 928 (44%) lived in a rural area. 1042 patients had died within 4 years of diagnosis; 4-year survival was 39% (95% CI 36-42) in women in rural areas versus 49% (46-52) in urban areas (unadjusted hazard ratio [HR] 1·24 [95% CI 1·09-1·40]). Among the 734 women living more than 1 h from the hospital, the crude 4-year survival was 37% (95% CI 32-42) in women in rural areas versus 54% (46-62) in women in urban areas (HR 1·35 [95% CI 1·07-1·71] after adjustment for age, stage, and treatment status). Among women in rural areas, mortality rates increased with distance (adjusted HR per 50 km 1·04, 1·01-1·07) and travel time (adjusted HR per h 1·06, 1·02-1·10). Among women with early-stage breast cancer receiving treatment, women in rural areas had a strong survival disadvantage (overall HR 1·54, 1·14-2·07 adjusted for age and stage; >1 h distance adjusted HR 2·14, 1·21-3·78). INTERPRETATION: Geospatial barriers reduce survival of patients with breast cancer in sub-Saharan Africa. Specific attention is needed to support patients with early-stage breast cancer living in rural areas far from cancer treatment facilities. FUNDING: US National Institutes of Health (National Cancer Institute), Susan G Komen for the Cure, and the International Agency for Research on Cancer.

Regional Variation in the Tumor Microenvironment, Immune Escape and Prognostic Factors in Breast Cancer in Sub-Saharan Africa.

The low overall survival rates of patients with breast cancer in sub-Saharan Africa (SSA) are driven by regionally differing tumor biology, advanced tumor stages at diagnosis, and limited access to therapy. However, it is not known whether regional differences in the composition of the tumor microenvironment (TME) exist and affect patients' prognosis. In this international, multicentre cohort study, 1,237 formalin-fixed, paraffin-embedded breast cancer samples, including samples of the "African Breast Cancer-Disparities in Outcomes (ABC-DO) Study," were analyzed. The immune cell phenotypes, their spatial distribution in the TME, and immune escape mechanisms of breast cancer samples from SSA and Germany (n = 117) were investigated using histomorphology, conventional and multiplex IHC, and RNA expression analysis. The data revealed no regional differences in the number of tumor-infiltrating lymphocytes (TIL) in the 1,237 SSA breast cancer samples, while the distribution of TILs in different breast cancer IHC subtypes showed regional diversity, particularly when compared with German samples. Higher TIL densities were associated with better survival in the SSA cohort (n = 400), but regional differences concerning the predictive value of TILs existed. High numbers of CD163+ macrophages and CD3+CD8+ T cells accompanied by reduced cytotoxicity, altered IL10 and IFNγ levels and downregulation of MHC class I components were predominantly detected in breast cancer samples from Western SSA. Features of nonimmunogenic breast cancer phenotypes were associated with reduced patient survival (n = 131). We therefore conclude that regional diversity in the distribution of breast cancer subtypes, TME composition, and immune escape mechanisms should be considered for therapy decisions in SSA and the design of personalized therapies. See related Spotlight by Bergin et al., p. 705.

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.

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.

Breast cancer survival and survival gap apportionment in sub-Saharan Africa (ABC-DO): a prospective cohort study.

BACKGROUND: Breast cancer is the second leading cause of death from cancer in women in sub-Saharan Africa, yet there are few well characterised large-scale survival studies with complete follow-up data. We aimed to provide robust survival estimates in women in this setting and apportion the survival gaps. METHODS: The African Breast Cancer-Disparities in Outcomes (ABC-DO) prospective cohort study was done at eight hospitals across five sub-Saharan African countries (Namibia, Nigeria, South Africa, Uganda, and Zambia). We prospectively recruited women (aged ≥18 years) who attended these hospitals with suspected breast cancer. Women were actively followed up by use of a telephone call once every 3 months, and a mobile health application was used to keep a dynamic record of follow-up calls due. We collected detailed sociodemographic, clinical, and treatment data. The primary outcome was 3-year overall survival, analysed by use of flexible proportional mortality models, and we predicted survival under scenarios of modified distributions of risk factors. FINDINGS: Between Sept 8, 2014, and Dec 31, 2017, 2313 women were recruited from these eight hospitals, of whom 85 did not have breast cancer. Of the remaining 2228 women with breast cancer, 58 women with previous treatment or recurrence, and 14 women from small racial groups (white and Asian women in South Africa), were excluded. Of the 2156 women analysed, 1840 (85%) were histologically confirmed, 129 (6%) were cytologically confirmed, and 187 (9%) were clinically confirmed to have breast cancer. 2156 (97%) women were followed up for up to 3 years or up to Jan 1, 2019, whichever was earlier. Up to this date, 879 (41%) of these women had died, 1118 (52%) were alive, and 159 (7%) were censored early. 3-year overall survival was 50% (95% CI 48-53), but we observed variations in 3-year survival between different races in Namibia (from 90% in white women to 56% in Black women) and in South Africa (from 76% in mixed-race women to 59% in Black women), and between different countries (44-47% in Uganda and Zambia vs 36% in Nigeria). 215 (10%) of all women had died within 6 months of diagnosis, but 3-year overall survival remained low in women who survived to this timepoint (58%). Among survival determinants, improvements in early diagnosis and treatment were predicted to contribute to the largest increases in survival, with a combined absolute increase in survival of up to 22% in Nigeria, Zambia, and Uganda, when compared with the contributions of other factors (such as HIV or aggressive subtypes). INTERPRETATION: Large variations in breast cancer survival in sub-Saharan African countries indicate that improvements are possible. At least a third of the projected 416 000 breast cancer deaths that will occur in this region in the next decade could be prevented through achievable downstaging and improvements in treatment. Improving survival in socially disadvantaged women warrants special attention. FUNDING: Susan G Komen and the International Agency for Research on Cancer.

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.

Scrotal cystocele in a 2-year-old Nigerian child.

Total herniation of the urinary bladder into the scrotum, also known as scrotal cystocele, is a rare condition. It has mostly been described in elderly patients, who often have obstructive symptoms. We report a case of scrotal cystocele in a 2-year-old Nigerian child with no evidence of obstructive uropathy. The diagnosis was made at operation. The bladder was reduced into the abdominal cavity followed by a herniorrhaphy. The child has remained symptom-free 8 months after the procedure.