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.

Do social protection programmes affect the burden of breast and cervical cancer? A systematic review.

Background: Socioeconomic conditions are strongly associated with breast and cervical cancer incidence and mortality patterns; therefore, social protection programmes (SPPs) might impact these cancers. This study aimed to evaluate the effect of SPPs on breast and cervical cancer outcomes and their risk/protective factors. Methods: Five databases were searched for articles that assessed participation in PPS and the incidence, survival, mortality (primary outcomes), screening, staging at diagnosis and risk/protective factors (secondary outcomes) for these cancers. Only peer-reviewed quantitative studies of women receiving SPPs compared to eligible women not receiving benefits were included. Independent reviewers selected articles, assessed eligibility, extracted data, and assessed the risk of bias. A harvest plot represents the included studies and shows the direction of effect, sample size and risk of bias. Findings: Of 17,080 documents retrieved, 43 studies were included in the review. No studies evaluated the primary outcomes. They all examined the relationship between SPPs and screening, as well as risk and protective factors. The harvest plot showed that in lower risk of bias studies, participants of SPPs had lower weight and fertility, were older at sexual debut, and breastfed their infants for longer. Interpretation: No studies have yet assessed the effect of SPPs on breast and cervical cancer incidence, survival, or mortality; nevertheless, the existing evidence suggests positive impacts on risk and protective factors.

Income Segregation, Conditional Cash Transfers, and Breast Cancer Mortality Among Women in Brazil.

Importance: Women living in income-segregated areas are less likely to receive adequate breast cancer care and access community resources, which may heighten breast cancer mortality risk. Objective: To investigate the association between income segregation and breast cancer mortality and whether this association is attenuated by receipt of the Bolsa Família program (BFP), the world's largest conditional cash-transfer program. Design, Setting, and Participants: This cohort study was conducted using data from the 100 Million Brazilian Cohort, which were linked with nationwide mortality registries (2004-2015). Data were analyzed from December 2021 to June 2023. Study participants were women aged 18 to 100 years. Exposure: Women's income segregation (high, medium, or low) at the municipality level was obtained using income data from the 2010 Brazilian census and assessed using dissimilarity index values in tertiles (low [0.01-0.25], medium [0.26-0.32], and high [0.33-0.73]). Main Outcomes and Measures: The main outcome was breast cancer mortality. Mortality rate ratios (MRRs) for the association of segregation with breast cancer deaths were estimated using Poisson regression adjusted for age, race, education, municipality area size, population density, area of residence (rural or urban), and year of enrollment. Multiplicative interactions of segregation and BFP receipt (yes or no) in the association with mortality (2004-2015) were assessed. Results: Data on 21 680 930 women (mean [SD] age, 36.1 [15.3] years) were analyzed. Breast cancer mortality was greater among women living in municipalities with high (adjusted MRR [aMRR], 1.18; 95% CI, 1.13-1.24) and medium (aMRR, 1.08; 95% CI, 1.03-1.12) compared with low segregation. Women who did not receive BFP had higher breast cancer mortality than BFP recipients (aMRR, 1.17; 95% CI, 1.12-1.22). By BFP strata, women who did not receive BFP and lived in municipalities with high income segregation had a 24% greater risk of death from breast cancer compared with those living in municipalities with low income segregation (aMRR, 1.24: 95% CI, 1.14-1.34); women who received BFP and were living in areas with high income segregation had a 13% higher risk of death from breast cancer compared with those living in municipalities with low income segregation (aMRR, 1.13; 95% CI, 1.07-1.19; P for interaction = .008). Stratified by the amount of time receiving the benefit, segregation (high vs low) was associated with an increase in mortality risk for women receiving BFP for less time but not for those receiving it for more time (<4 years: aMRR, 1.16; 95% CI, 1.07-1.27; 4-11 years: aMRR, 1.09; 95% CI, 1.00-1.17; P for interaction <.001). Conclusions and Relevance: These findings suggest that place-based inequities in breast cancer mortality associated with income segregation may be mitigated with BFP receipt, possibly via improved income and access to preventive cancer care services among women, which may be associated with early detection and treatment and ultimately reduced mortality.

The intersection of race/ethnicity and socioeconomic status: inequalities in breast and cervical cancer mortality in 20,665,005 adult women from the 100 Million Brazilian Cohort.

OBJECTIVES: There is limited evidence regarding the impact of race/racism and its intersection with socioeconomic status (SES) on breast and cervical cancer, the two most common female cancers globally. We investigated racial inequalities in breast and cervical cancer mortality and whether SES (education and household conditions) interacted with race/ethnicity. DESIGN: The 100 Million Brazilian Cohort data were linked to the Brazilian Mortality Database, 2004-2015 (n = 20,665,005 adult women). We analysed the association between self-reported race/ethnicity (White/'Parda'(Brown)/Black/Asian/Indigenous) and cancer mortality using Poisson regression, adjusting for age, calendar year, education, household conditions and area of residence. Additive and multiplicative interactions were assessed. RESULTS: Cervical cancer mortality rates were higher among Indigenous (adjusted Mortality rate ratio = 1.80, 95%CI 1.39-2.33), Asian (1.63, 1.20-2.22), 'Parda'(Brown) (1.27, 1.21-1.33) and Black (1.18, 1.09-1.28) women vs White women. Breast cancer mortality rates were higher among Black (1.10, 1.04-1.17) vs White women. Racial inequalities in cervical cancer mortality were larger among women of poor household conditions, and low education (P for multiplicative interaction <0.001, and 0.02, respectively). Compared to White women living in completely adequate (3-4) household conditions, the risk of cervical cancer mortality in Black women with 3-4, 1-2, and none adequate conditions was 1.10 (1.01-1.21), 1.48 (1.28-1.71), and 2.03 (1.56-2.63), respectively (Relative excess risk due to interaction-RERI = 0.78, 0.18-1.38). Among 'Parda'(Brown) women the risk was 1.18 (1.11-1.25), 1.68 (1.56-1.81), and 1.84 (1.63-2.08), respectively (RERI = 0.52, 0.16-0.87). Compared to high-educated White women, the risk in high-, middle- and low-educated Black women was 1.14 (0.83-1.55), 1.93 (1.57-2.38) and 2.75 (2.33-3.25), respectively (RERI = 0.36, -0.05-0.77). Among 'Parda'(Brown) women the risk was 1.09 (0.91-1.31), 1.99 (1.70-2.33) and 3.03 (2.61-3.52), respectively (RERI = 0.68, 0.48-0.88). No interactions were found for breast cancer. CONCLUSION: Low SES magnified racial inequalities in cervical cancer mortality. The intersection between race/ethnicity, SES and gender needs to be addressed to reduce racial health inequalities.

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.

Are mammography image acquisition factors, compression pressure and paddle tilt, associated with breast cancer detection in screening?

OBJECTIVES: To assess the associations between objectively measured mammographic compression pressure and paddle tilt and breast cancer (BC) detected at the same ("contemporaneous") screen, subsequent screens, or in-between screens (interval cancers). METHODS: Automated pressure and paddle tilt estimates were derived for 80,495 mammographic examinations in a UK population-based screening programme. Adjusted logistic regression models were fitted to estimate the associations of compression parameters with BC detected at contemporaneous screen (777 cases).Nested case-control designs were used to estimate associations of pressure and tilt with: (a) interval cancer (148 cases/625 age-matched controls) and (b) subsequent screen-detected cancer (344/1436), via conditional logistic regression. RESULTS: Compression pressure was negatively associated with odds of BC at contemporaneous screen (odds ratio (OR) for top versus bottom third of the pressure distribution: 0.74; 95% CI 0.60, 0.92; P-for-linear-trend (Pt) = 0.007). There was weak evidence that moderate pressure at screening was associated with lower odds of interval cancer (OR for middle versus bottom third: 0.63; 95% CI 0.38, 1.05; p = 0.079), but no association was found between pressure and the odds of BC at subsequent screen. There was no evidence that paddle tilt was associated with the odds of contemporaneous, subsequent screen or interval cancer detection. CONCLUSIONS: Findings are consistent with compression pressure, but not paddle tilt, affecting the performance of mammographic screening by interfering with its ability to detect cancers. ADVANCES IN KNOWLEDGE: Inadequate or excessive compression pressure at screening may contribute to a reduced ability to detect cancers, resulting in a greater number of interval cancer cases.

XPERT® breast cancer STRAT4 as an alternative method of identifying breast cancer phenotype in Cape Verde (preliminary results).

Introduction: Breast cancer (BC) is a public health problem in developing countries, including Cape Verde. Immunohistochemistry (IHC) is the gold standard technique used for BC phenotypic characterisation to support efficient therapeutic decisions. However, IHC is a demanding technique that requires knowledge, trained technicians, expensive antibodies and reagents, controls, and results validation. The low number of cases in Cape Verde increases the risk of expiring the validity of the antibodies, and manual procedures often jeopardise the quality of the results. Thus, IHC is limited in Cape Verde, and an alternative technically easy solution is needed. A point-of-care messenger RNA (mRNA) STRAT4 BC assay to assess estrogen (ER), progesterone (PR), hormone growth factor 2 receptor (HER2), and Ki67, using the GeneXpert platform, has been recently validated on tissues from internationally accredited laboratories, showing excellent concordance with IHC results.To assess whether this technology can be implemented in Cape Verde to guide BC treatment we decided to study the level of agreement between the findings yielded by BC STRAT4 and the results are the same cases obtained by IHC. Methods: Formalin-fixed and paraffin-embedded (FFPE) tissue samples from 29 Cabo Verdean BC patients diagnosed in Agostinho Neto University Hospital were analysed by applying IHC and BC STRAT4 assay. The time between sample collection and pre-analytic procedures is unknown. All the samples were pre-processed in Cabo Verde (fixed in formalin and embedded in paraffin). IHC studies were performed in referenced laboratories in Portugal. STRAT4 and IHC result concordance was assessed by calculating the percentage of results agreement and Cohen's Kappa (K) statistics. Results: STRAT4 assay failed in 2 out of the 29 analysed samples. Of the 27 successfully analysed samples, STRAT4/IHC results for ER, PR, HER2, and Ki67 were concordant in 25, 24, 25, and 18 cases, respectively. Ki67 was indeterminate in three cases, and PR was indeterminate once.The percentage of agreement between STRAT4 and IHC results for ER, PR, HER2, and Ki67 was 92.59%, 92.31%, 92.59% and 81.82%, respectively. The Cohen's K statistic coefficients for each biomarker were 0.809, 0.845, 0.757 and 0.506, respectively. Conclusions: According to our preliminary results, a point-of-care mRNA STRAT4 BC assay may be an alternative in laboratories unable to provide quality and/or cost-efficient IHC services. However, more data and improvement on sample pre-analytic processes are required to implement this BC STRAT4 Assay in Cape Verde.

To what extent are objectively measured mammographic imaging techniques associated with compression outcomes.

OBJECTIVE: To describe the association between objectively measurable imaging techniques and the resulting compression thickness and dose. METHODS: The study included 80,495 routine screens from the South-West London Breast Screening Service between March 2013 and July 2017. Average compression force, paddle tilt and dose were calculated. The Volpara® DensityTM algorithm was used to estimate pressure, breast volume and density.Linear regression models, using generalized estimating equations (GEEs) to account for clustering by practitioner, assessed the strength of the associations between the imaging compression outcomes, (thickness, dose) and imaging techniques (force, pressure and paddle tilt), adjusting for the subject's characteristics (age, ethnicity, breast volume and percent mammographic density). RESULTS: Fully adjusted linear regression models showed that compression thickness decreased by ~1 mm (~2% of mean thickness) for every 1daN increase in force and decreased by ~0.8 mm with an increase of 1 kPa of pressure (at median pressure). Increasing pressure above 15 kPa resulted in minimal reduction in thickness. Dose increased with increased force but decreased by ~1% of mean dose with every increase in 1 kPa of pressure. For 1o increase in paddle tilt, the compression thickness increased by ~1.5 mm (~2.5%) and dose increased by ~2.5%, (Pt <0.001 in all cases). CONCLUSION: Differences in imaging technique are associated with imaging outcome measures (thickness and dose). A better understanding of the association between objective image acquisition parameters and tumour conspicuity could lead to clearer guidelines for practitioners. ADVANCES IN KNOWLEDGE: Increased paddle tilt is associated with increased compression thickness and increased dose after adjustment for breast volume and force applied.

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.

Incidence and prevalence of drugs used for chronic diseases in survivors of adult-onset gynaecological cancer - A nationwide cohort study.

OBJECTIVES: To evaluate both incidence and prevalence of drugs used for chronic diseases in survivors of adult-onset gynaecological cancer. DESIGN: A prospective study. SETTING: Population-based registries. POPULATION: 1.76 million women, including 17 500 women with gynaecological cancers. METHODS: Data from the Cancer Registry of Norway was linked to the Norwegian Prescription Database and other national databases. MAIN OUTCOME MEASURES: Prevalence ratios (PRs) and hazard ratios (HRs), with 95% confidence intervals (CIs), of dispensed drugs in gynaecological cancer patients (up to 15 years after diagnosis) were estimated by log-binomial and Cox regression, respectively, with cancer-free women as reference. RESULTS: For gynaecological cancer patients, the incidence of drugs used for pain control was higher than in cancer-free women, especially the first 5 years after diagnosis, and the prevalence was high at least 10 years after. The prevalence of sex hormones was high in women with gynaecological cancer at least 10 years after diagnosis (cervical and ovarian cancer PR = 23, 95% CI 18-30 and PR = 29, 95% CI 15-38, respectively), but low in cancer-free women (0.3%). Patients with uterine corpus cancer had a higher prevalence of antidiabetics before and at least 10 years after diagnosis, most pronounced in women diagnosed before age 50 (PR = 10, 95% CI 5.0-21). The prevalence of antidepressants was moderately elevated in women with gynaecological cancers. CONCLUSIONS: Gynaecological cancer survivors, particularly cervical and ovarian cancer survivors, had an increased long-term use of drugs for pain control and sex hormones. Survivors of uterine corpus cancer used antidiabetics more often, both before and after diagnosis.

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).

Global and regional estimates of orphans attributed to maternal cancer mortality in 2020.

Despite women being disproportionally affected by cancer deaths at young ages, there are no global estimates of the resulting maternal orphans, who experience health and education disadvantages throughout their lives. We estimated the number of children who became maternal orphans in 2020 due to their mother dying from cancer in that year, for 185 countries worldwide and by cause of cancer-related death. Female cancer deaths-by country, cancer type and age (derived from GLOBOCAN estimates)-were multiplied by each woman's estimated number of children under the age of 18 years at the time of her death (fertility data were derived from United Nations World Population Prospects for birth cohort), accounting for child mortality and parity-cancer risk associations. Globally, there were 1,047,000 such orphans. Over half of these were orphans due to maternal deaths from breast (258,000, 25%), cervix (210,000, 20%) and upper-gastrointestinal cancers (136,000, 13%), and most occurred in Asia (48%: India 15%, China 10%, rest of Asia 23%) and Africa (35%). Globally, there were 40 new maternal orphans due to cancer per 100,000 children, with a declining trend with a higher Human Development Index (range: 121 in Malawi to 15 in Malta). An estimated 7 million children were prevalent maternal orphans due to cancer in mid-2020. Accelerating the implementation of the World Health Organization's cervical and breast cancer initiatives has the potential to avert not only millions of preventable female cancer deaths but also the associated, often-overlooked, intergenerational consequences of these deaths.

The association of age at menarche and adult height with mammographic density in the International Consortium of Mammographic Density.

BACKGROUND: Early age at menarche and tall stature are associated with increased breast cancer risk. We examined whether these associations were also positively associated with mammographic density, a strong marker of breast cancer risk. METHODS: Participants were 10,681 breast-cancer-free women from 22 countries in the International Consortium of Mammographic Density, each with centrally assessed mammographic density and a common set of epidemiologic data. Study periods for the 27 studies ranged from 1987 to 2014. Multi-level linear regression models estimated changes in square-root per cent density (√PD) and dense area (√DA) associated with age at menarche and adult height in pooled analyses and population-specific meta-analyses. Models were adjusted for age at mammogram, body mass index, menopausal status, hormone therapy use, mammography view and type, mammographic density assessor, parity and height/age at menarche. RESULTS: In pooled analyses, later age at menarche was associated with higher per cent density (ß√PD = 0.023 SE = 0.008, P = 0.003) and larger dense area (ß√DA = 0.032 SE = 0.010, P = 0.002). Taller women had larger dense area (ß√DA = 0.069 SE = 0.028, P = 0.012) and higher per cent density (ß√PD = 0.044, SE = 0.023, P = 0.054), although the observed effect on per cent density depended upon the adjustment used for body size. Similar overall effect estimates were observed in meta-analyses across population groups. CONCLUSIONS: In one of the largest international studies to date, later age at menarche was positively associated with mammographic density. This is in contrast to its association with breast cancer risk, providing little evidence of mediation. Increased height was also positively associated with mammographic density, particularly dense area. These results suggest a complex relationship between growth and development, mammographic density and breast cancer risk. Future studies should evaluate the potential mediation of the breast cancer effects of taller stature through absolute breast density.

Global disparities in access to cancer care.

Despite the significant advances made in our understanding of cancer and how to treat it over the last hundred years, there are wide global disparities in access to cancer care and in who gets to benefit from cutting-edge cancer research.

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.

Does Cardiovascular Mortality Overtake Cancer Mortality During Cancer Survivorship?: An English Retrospective Cohort Study.

Background: Cancer survivors have a higher risk for developing cardiovascular diseases than the general population. Objectives: The aim of this study was to investigate whether cardiovascular mortality overtakes cancer-specific mortality during cancer survivorship and, if so, at what point cardiovascular disease becomes the dominant cause of death. Methods: This cohort study used linked English electronic health records, including death registration data. The study population included 104,028 adults ≥40 years of age whose first cancer diagnosis was for 1 of 9 common cancers and who were alive and followed up at least 1 year after diagnosis. Age-stratified mortality rates were estimated from cardiovascular disease or cancer by predicting from Poisson models incorporating categorical age at diagnosis and time since diagnosis. Where cardiovascular disease mortality overtook cancer mortality, the crossover point was estimated using interpolation. Results: Mortality from cardiovascular causes overtook mortality due to the primary cancer at 2 to 11 years after cancer diagnosis in survivors of all 9 cancer types ≥80 years of age at diagnosis and after 5 to 17 years in survivors of 7 cancer types 60 to 79 years of age at diagnosis. Cardiovascular mortality overtook all cancer mortality for 6 and 2 cancer sites in the ≥80-year and 60- to 79-year age groups, respectively, over a longer time period. Cardiovascular mortality did not overtake cancer mortality during the observation period in patients aged 40 to 59 years, except among survivors of uterine cancer. Conclusions: In older survivors of 9 common cancers, cardiovascular mortality becomes dominant over mortality from the primary cancer, though not always over total cancer mortality, as time passes since cancer diagnosis.

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.

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.

Mendelian randomisation study of smoking exposure in relation to breast cancer risk.

BACKGROUND: Despite a modest association between tobacco smoking and breast cancer risk reported by recent epidemiological studies, it is still equivocal whether smoking is causally related to breast cancer risk. METHODS: We applied Mendelian randomisation (MR) to evaluate a potential causal effect of cigarette smoking on breast cancer risk. Both individual-level data as well as summary statistics for 164 single-nucleotide polymorphisms (SNPs) reported in genome-wide association studies of lifetime smoking index (LSI) or cigarette per day (CPD) were used to obtain MR effect estimates. Data from 108,420 invasive breast cancer cases and 87,681 controls were used for the LSI analysis and for the CPD analysis conducted among ever-smokers from 26,147 cancer cases and 26,072 controls. Sensitivity analyses were conducted to address pleiotropy. RESULTS: Genetically predicted LSI was associated with increased breast cancer risk (OR 1.18 per SD, 95% CI: 1.07-1.30, P = 0.11 × 10-2), but there was no evidence of association for genetically predicted CPD (OR 1.02, 95% CI: 0.78-1.19, P = 0.85). The sensitivity analyses yielded similar results and showed no strong evidence of pleiotropic effect. CONCLUSION: Our MR study provides supportive evidence for a potential causal association with breast cancer risk for lifetime smoking exposure but not cigarettes per day among smokers.