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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 (less than three 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 (

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.

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., What's new? In sub‐Saharan Africa, most women with breast cancer are diagnosed long after symptoms first arise. Here, the authors studied the diagnostic journey for breast cancer among the African Breast Cancer‐Disparities in Outcome cohort. This is the largest study to quantify the length of the diagnostic journey across various settings in sub‐Saharan Africa. Time to final diagnosis decreased substantially when a woman recognized her symptoms as cancer. Most delays, they found, were due to extended time between first examination and final diagnosis. Promotion of breast cancer awareness among both women and healthcare providers could help reduce these delays.

Esophageal sponge cytology is an endoscopy alternative well accepted by patients with extensive data for accuracy in the context of adenocarcinoma. Few studies have assessed its feasibility in asymptomatic community members, and fewer still in East Africa, where esophageal squamous cell carcinoma (ESCC) rates are high. We aimed to assess the feasibility of a capsule-based diagnosis of esophageal squamous dysplasia (ESD), an ESCC precursor, which may benefit epidemiological and early detection research. We collected Cytosponge collections in 102 asymptomatic adults from Kilimanjaro, Tanzania. Uptake, acceptability and safety were assessed. Participants scored acceptability immediately following the procedure and 7 days later on a scale of 0 (least) to 10 (most acceptable). Slides from paraffin-embedded cell clots were read by two pathologists for ESD and other pathologies. All participants (52 men, 50 women, aged 30-77) swallowed the device at first attempt, 100 (98%) of which gave slides of adequate cellularity. Acceptability scores were 10 (53%), 9 (24%), 8 (21%), 7 (2%) and 6 (1%), with no differences by age, sex or time of asking. Cytological findings were esophageal inflammation (4%), atypical squamous cells of uncertain significance (1%), low-grade dysplasia (1%), gastritis (22%) and suspected intestinal metaplasia (6%). Setting-specific logistical and ethical considerations of study implementation are discussed. We demonstrate the safety, acceptability and feasibility of Cytosponge sampling in this setting, paving the way for innovative etiology and early-detection research. Targeted sampling strategies and biomarker development will underpin the success of such initiatives. The study protocol is registered on ClinicalTrials.gov (NCT04090554).

There is a growing population of older women living with HIV/AIDS (WLWHA). Breast cancer is a common cancer in women worldwide, but the global number of breast cancers in WLWHA is not known. We estimated, for each UN sub-region, the number and age distribution of WLWHA who were diagnosed with breast cancer in 2012, by combining IARC-GLOBOCAN estimates of age-country specific breast cancer incidence with corresponding UNAIDS HIV prevalence. Primary analyses assumed no HIV-breast cancer association, and a breast cancer risk reduction scenario was also considered. Among 16.0 million WLWHA aged 15+ years, an estimated 6,325 WLWHA were diagnosed with breast cancer in 2012, 74% of whom were in sub-Saharan Africa, equally distributed between Eastern, Southern and Western Africa. In most areas, 70% of HIV-positive breast cancers were diagnosed under age 50. Among all breast cancers (regardless of HIV status), HIV-positive women constituted less than 1% of the clinical burden, except in Eastern, Western and Middle Africa where they comprised 4-6% of under age 50 year old breast cancer patients, and in Southern Africa where this patient subgroup constituted 26 and 8% of breast cancers diagnosed under and over age 50 respectively. If a deficit of breast cancer occurs in WLWHA, the global estimate would reduce to 3,600. In conclusion, worldwide, the number of HIV-positive women diagnosed with breast cancer was already substantial in 2012 and with an expected increase within the next decade, early detection and treatment research targeted to this population are needed.

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 multi-country 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 multi-racial 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

Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers in most Eastern and Southern African countries, but its etiology has been understudied to date. To inform its research agenda, we undertook a review to identify, of the ESCC risk factors which have been established or strongly suggested worldwide, those with a high prevalence or high exposure levels in any ESCC-affected African setting and the sources thereof. We found that for almost all ESCC risk factors known to date, including tobacco, alcohol, hot beverage consumption, nitrosamines and both inhaled and ingested PAHs, there is evidence of population groups with raised exposures, the sources of which vary greatly between cultures across the ESCC corridor. Research encompassing these risk factors is warranted and is likely to identify primary prevention strategies.

Advanced stage at diagnosis contributes to low breast cancer survival rates in sub-Saharan Africa. Living far from health services is known to delay presentation, but the effect of distance, the radius at which the effect sets in and the women most affected has not been quantified. In a peri-urban South African setting, we examined the effect of a GIS-measured straight-line distance, from a patient’s residence to diagnostic hospital, on stage at diagnosis in 1071 public-sector breast cancer patients diagnosed during 2006–12. Generalized linear models were used to estimate risk ratios for late stage (stage III/IV vs stage I/II) associated with distance, adjusting for year of diagnosis, age, race and socioeconomic indicators. Mean age of patients was 55 years, 90% were Black African, and diagnoses were at stages I (5%), II (41%), III (46%) and IV (8%). 62% of patients with distances >20 km (n=347) had a late stage at diagnosis compared to 50% with distances

Recent cohort studies suggest that increased breast cancer risks were associated with longer smoking duration, higher pack-years and a dose-response relationship with increasing pack-years of smoking between menarche and first full-term pregnancy (FFTP). Studies with comprehensive quantitative life-time measures of passive smoking suggest an association between passive smoking dose and breast cancer risk. We conducted a study within the European Prospective Investigation into Cancer and Nutrition to examine the association between passive and active smoking and risk of invasive breast cancer and possible effect modification by known breast cancer risk factors. Among the 322,988 women eligible for the study, 9,822 developed breast cancer (183,608 women with passive smoking information including 6,264 cases). When compared to women who never smoked and were not being exposed to passive smoking at home or work at the time of study registration, current, former and currently exposed passive smokers were at increased risk of breast cancer (hazard ratios (HR) [95% confidence interval (CI)] 1.16 [1.05–1.28], 1.14 [1.04–1.25] and 1.10 [1.01–1.20], respectively). Analyses exploring associations in different periods of life showed the most important increase in risk with pack-years from menarche to FFTP (1.73 [1.29–2.32] for every increase of 20 pack-years) while pack-years smoked after menopause were associated with a significant decrease in breast cancer risk (HR = 0.53, 95% CI: 0.34–0.82 for every increase of 20 pack-years). Our results provide an important replication, in the largest cohort to date, that smoking (passively or actively) increases breast cancer risk and that smoking between menarche and FFTP is particularly deleterious.

Purpose: To compare and evaluate intensity-based registration methods for computation of serial x-ray mammogram correspondence. Methods: X-ray mammograms were simulated from MRIs of 20 women using finite element methods for modeling breast compressions and employing a MRI/x-ray appearance change model. The parameter configurations of three registration methods, affine, fluid, and free-form deformation (FFD), were optimized for registering x-ray mammograms on these simulated images. Five mammography film readers independently identified landmarks (tumor, nipple, and usually two other normal features) on pairs of diagnostic and corresponding prediagnostic digitized images from 52 breast cancer cases. Landmarks were independently reidentified by each reader. Target registration errors were calculated to compare the three registration methods using the reader landmarks as a gold standard. Data were analyzed using multilevel methods. Results: Between-reader variability varied with landmark (p = 40%), the affine and fluid methods outperformed FFD. For breasts with lower density, the affine registration surpassed both fluid and FFD. Mean accuracy (mm) of the affine registration varied between 3.16 (95% CI 2.56, 3.90) for nipple points in breasts with density 20%-39% and 5.73 (4.80, 6.84) for tumor points in breasts with density

Associations between larger size at birth and increased rates of adult cancer have been proposed but few empirical studies have examined this hypothesis. We investigated overall and site-specific cancer incidence in relation to birth characteristics in a Swedish population-based cohort of 11,166 singletons born in 1915-1929 for whom we have detailed obstetric data and who were alive in 1960. A total of 2,685 first primary cancers were registered during follow-up from 1960 to 2001. A standard deviation (SD) increase in birth weight for gestational age (GA) was associated with (sex-adjusted) increases of 13% (95% CI = 0.03-0.23) in the rates of digestive cancers and of 17% (95% CI = 0.01-0.35) in the rates of lymphatic cancers. Women who had higher birth weights also had increased rates of breast cancer under age 50 years (by 39% per SD increase; 95% CI = 0.09-0.79), but reduced rates (by 24%; 95% CI = 0.07-0.38) of endometrial (corpus uteri) cancer at all ages. There was no evidence of associations with other cancer sites. For overall cancer incidence, men had an 8% increased risk at all ages per SD increase in birth weight for GA while women only had an increased risk under age 50 years (mainly driven by the association with breast cancer). These findings provide evidence of a modest association of birth size and adult cancer risk, resulting from positive associations with a few cancer sites and a possible inverse association with endometrial cancer.