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PurposeBreast cancer is the most frequently diagnosed cancer and leading cause of cancer death among women, representing a considerable public health burden in South Africa and other low-middle income countries. Short- and long-term complications of these treatments include shoulder morbidities such as pain, decreased range of motion, tightness, weakness, pain, numbness and lymphoedema and may be present for up to 6 years post-treatment. An understanding of baseline demographic and clinical risk factors can guide rehabilitation and management strategies for high-risk patients. The aims of this study were to quantify the burden of shoulder pain and disability in a tertiary academic hospital in Cape Town, South Africa, and identify potential risk factors for the development of shoulder morbidity.MethodsThis study was a cross-sectional analysis of the prevalence of shoulder pain and dysfunction in women attending their post-treatment annual follow-up visit for unilateral breast carcinoma.ResultsThree in four patients reported a presence of any pain or disability while only 9% experienced severe pain and disability. Multivariable ordinal logistic regression analysis identified race, side, axillary surgery, chemotherapy and age as significant predictors of pain and chemotherapy a significant predictor of disability.ConclusionThe substantial burden of shoulder morbidity in this population represents a significant public health burden. The use of identified clinical and demographic characteristics may guide in the development of survivorship programmes incorporating surveillance and management of these high-risk patients.

Tamoxifen, a selective estrogen receptor modulator, is used to treat hormone receptor‐positive breast cancer. Tamoxifen acts as a prodrug, with its primary therapeutic effect mediated by its principal metabolite, endoxifen. However, tamoxifen has complex pharmacokinetics involving several drug‐metabolizing enzymes and transporters influencing its disposition. Genes encoding enzymes involved in tamoxifen disposition exhibit genetic polymorphisms which vary widely across world populations. This review highlights the lack of data on tamoxifen pharmacogenetics among African populations. Gaps in data are described in this study with the purpose that future research can address this dearth of research on the pharmacogenetics of tamoxifen among African breast cancer patients. Initiatives such as the African Pharmacogenomics Network (APN) are crucial in promoting comprehensive pharmacogenetics studies to pinpoint important variants in pharmacogenes that could be used to reduce toxicity and improve efficacy.

Upper limb morbidity is a well-recognised consequence of treatment for breast cancer that can develop for up to 6 years after treatment. However, the capacity to fully integrate evidence-based rehabilitation pathways into routine care for all patients is questionable due to limited resources. A long term surveillance programme must therefore be accessible to all patients, should identify those at risk of developing morbidity and target the interventions at the high risk population of patients. The proposed model uses a surrogate marker for assessing risk of morbidity, incorporated into an Early Warning System (EWS), to produce a technology-lead, prospective surveillance programme.

Chronic shoulder pain and disability is a common adverse effect experienced by >40% of breast cancer survivors (BCS). Pain management protocols for acute and chronic pain include the use of opioids and opioid derivatives. Furthermore, pain-modulating genes, such as COMT and OPRM1, have been linked to the aetiology of chronic pain. This study aimed to investigate the association between genetic variants of major pain modulator genes and chronic pain/disability in BCS. Assessment of pain, disability and combined (pain and disability) symptoms were determined using the Shoulder Pain and Disability Index (SPADI). Participants were grouped according to their scores such as no-low (<30%) and moderate-high (≥30%) groups of pain, disability and combined (pain and disability). Genotyping of the COMT rs6269 (A > G), rs4633 (C > T), rs4818 (C > G) and the functional rs4680(G > A) SNPs within the BCS (N = 252) cohort were conducted using TaqMan® SNP assays. Genotype, allele, haplotype, and allele–allele combination frequencies were evaluated. Statistical analysis was applied, with significance accepted at p < 0.05. The COMT rs4680:A/A genotype was significantly associated with moderate-high pain (p = 0.024, OR: 3.23, 95% CI: 1.33–7.81) and combined (pain and disability) (p = 0.015, OR: 3.81, 95% CI: 1.47–9.85). The rs4680:A allele was also significantly associated with moderate-high pain (p = 0.035, OR: 1.58, 95% CI: 1.03–2.43) and combined (pain and disability) (p = 0.017, OR: 1.71, 95% CI: 1.07–2.71). For the inferred COMT (rs6269 A > G-rs4680 G > A) haplotype analyses, the G-G (p = 0.026, OR: 0.67, 95% CI: 0.38–1.18) and A-A (p = 0.007, OR: 2.09, 95% CI: 0.89–4.88) haplotypes were significantly associated with reduced and increased likelihoods of reporting moderate-high pain, respectively. The inferred A-A (p = 0.003, OR: 2.18, 95% CI: 0.92–5.17) haplotype was also significantly associated with combined (pain and disability). Gene–gene interaction analyses further showed allele–allele combinations for COMT (rs4680 G > A)-OPRM1 (rs1799971 A > G) and COMT (rs4680 G > A)-OPRM1(rs540825 T > A) were associated with reporting pain and combined (pain and disability) symptoms, p < 0.05. The findings of this study suggest that COMT and OPRM1 SNPs play a role in the development of chronic shoulder pain/disability in BCS in a unique South African cohort from the Western Cape.

Background: Tamoxifen remains the cornerstone of endocrine therapy for hormone receptor-positive breast cancer across Africa. Understanding the factors that influence tamoxifen tolerability is critical, as treatment-related side effects can reduce adherence and compromise therapeutic outcomes. Yet, the contribution of pharmacogenetic variation to tamoxifen-related toxicity remains poorly characterized in African populations. This study, therefore, investigated whether genetic variation in key pharmacogenes influences the risk of treatment-related side effects in a South African breast cancer cohort. Methods: A total of 166 women of Mixed and African Ancestry treated with 20 mg/day tamoxifen at Groote Schuur Hospital, South Africa, were included in the study. Genetic variation across 28 variants in nine pharmacogenes, including CYP2D6, CYP3A4/5, UGT1A4, UGT2B7/15, SULT1A1/2, and SULT1E1, was assessed using various genotyping methods. Associations between genetic and non-genetic factors and tamoxifen side effects were evaluated with logistic regression. Results: Over 70% of participants reported at least one treatment-related side effect. Overall side-effect burden was associated with SULT1A1 copy number variation (p = 0.030) and SULT1E1 rs3736599 (p = 0.042). Musculoskeletal complaints were the most common (40%) and were associated with UGT2B7 rs7439366 (p = 0.040) and CYP3A4 rs2242480 (p = 0.051). Gynecological symptoms affected more than 20% of participants and were linked to SULT1A2*2 (p = 0.050), SULT1E1 rs3736599 (p = 0.016), and UGT2B15 rs4148269 (p = 0.039). Hot flashes were frequent, affecting 33% of patients, but showed no clear pharmacogenetic associations. Conclusions: This study demonstrates that pharmacogenetic variation is associated with interindividual differences in treatment-related side effects, underscoring the need to expand research in African populations to better inform precision endocrine therapy.

This study aimed to explore the contextual and multilevel challenges to promoting exercise engagement among prostate cancer survivors in a low-resource setting, with a focus on integrating exercise-based rehabilitation into routine care and survivorship care planning, using a qualitative approach grounded in interpretative description. Sixteen prostate cancer survivors (aged 53-77 years) were purposively sampled from public and private healthcare facilities in Cape Town, South Africa. Semi-structured telephonic interviews were conducted using a topic guide informed by prior research. Interviews were audio-recorded, transcribed verbatim, and analysed thematically. Four major themes were identified. Findings highlighted stark contrasts in exercise engagement between men treated in private versus public healthcare settings. Exercise was essential to private patients, whereas most public patients showed limited interest. Factors influencing engagement included knowledge gaps, treatment complications, fear of worsening symptoms, and age-related comorbidities. Socio-environmental barriers-such as neighbourhood safety and poor work-life balance-reduced exercise opportunities. Facility-level issues included inconsistent messaging from providers, lack of exercise oncology pathways, and absent referral systems. Our study identified key multilevel influences surrounding exercise promotion and integration in routine care for prostate cancer survivors receiving treatment in private and public healthcare settings. While highlighting the opportunities/challenges surrounding integrating exercise programs in routine management, our findings offer program planners valuable insights for planning and developing interventions in resource-constrained settings.

Abstract STUDY QUESTION What is the evidence pertaining to availability, effectiveness and safety of ART in sub-Saharan Africa? SUMMARY ANSWER According to overall limited and heterogeneous evidence, availability and utilization of ART are very low, clinical pregnancy rates largely compare to other regions but are accompanied by high multiple pregnancy rates, and in the near absence of data on deliveries and live births the true degree of effectiveness and safety remains to be established. WHAT IS KNOWN ALREADY In most world regions, availability, utilization and outcomes of ART are monitored and reported by national and regional ART registries. In sub-Saharan Africa there is only one national and no regional registry to date, raising the question what other evidence exists documenting the status of ART in this region. STUDY DESIGN, SIZE, DURATION A systematic review was conducted searching Pubmed, Scopus, Africawide, Web Of Science and CINAHL databases from January 2000 to June 2017. A total of 29 studies were included in the review. The extracted data were not suitable for meta-analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS The review was conducted according to Preferred Reporting Items for Systematic Reviews (PRISMA) guidelines. All peer-reviewed manuscripts irrespective of language or study design that presented original data pertaining to availability, effectiveness and safety of ART in sub-Saharan Africa were eligible for inclusion. Selection criteria were specified prior to the search. Two authors independently reviewed studies for possible inclusion and critically appraised selected manuscripts. Data were analysed descriptively, being unsuitable for statistical analysis. MAIN RESULTS AND THE ROLE OF CHANCE The search yielded 810 references of which 29 were included based on the predefined selection and eligibility criteria. Extracted data came from 23 single centre observational studies, two global ART reports, two reviews, one national data registry and one community-based study. ART services were available in 10 countries and delivered by 80 centres in six of these. Data pertaining to number of procedures existed from three countries totalling 4619 fresh non-donor aspirations in 2010. The most prominent barrier to access was cost. Clinical pregnancy rates ranged between 21.2% and 43.9% per embryo transfer but information on deliveries and live births were lacking, seriously limiting evaluation of ART effectiveness. When documented, the rate of multiple pregnancy was high with information on outcomes similarly lacking. LIMITATIONS, REASONS FOR CAUTION The findings in this review are based on limited data from a limited number of countries, and are derived from heterogeneous studies, both in terms of study design and quality, many of which include small sample sizes. Although representing best available evidence, this requires careful interpretation regarding the degree of representativeness of the current status of ART in sub-Saharan Africa. WIDER IMPLICATIONS OF THE FINDINGS The true extent and outcome of ART in sub-Saharan Africa could not be reliably documented as the relevant information was not available. Current efforts are underway to establish a regional ART data registry in order to report and monitor availability, effectiveness and safety of ART thus contributing to evidence-based practice and possible development strategies. STUDY FUNDING/COMPETING INTERESTS No funding was received for this study. The authors had no competing interests. TRIAL REGISTRATION NUMBER PROSPERO CRD42016032336

Shoulder morbidity is a well-documented sequela of breast cancer treatment, which includes various manifestations such as pain, reduced range of motion, and lymphedema, among others. The multifactorial nature of such morbidities has long been appreciated, and research on reliable risk predictors of development thereof still continues. Previous studies have demonstrated the potential of different types of physical therapy to treat such shoulder problems, and the integration of such interventions into routine care for breast cancer survivors is a requirement in most high-income countries. Although patients at risk for developing shoulder problems would most likely benefit from posttreatment physical therapy, currently, there is no gold standard for identifying this patient group. This is particularly important in low- and middle-income countries where scarce monetary resources need to be directed specifically to those most in need. Modulators of the angiogenesis pathway have been implicated in noncancer shoulder conditions such as rotator cuff disease, adhesive capsulitis, and tendon injuries. The present review summarizes the role of angiogenesis in the development of shoulder morbidity among breast cancer survivors and sets forth the rationale for our belief that angiogenesis signaling may help explain a proportion of the reported clinical variability noted in the development of shoulder pain and dysfunction and upper-limb lymphedema after breast cancer treatment.

Falls are frequent and life-changing events for older adults worldwide. The ageing phenomenon has arrived in developing countries, which experience tensions between curative and rehabilitative services, combined with an increase in non-communicable diseases. Policies addressing issues of ageing have been poorly implemented, and there are few fall prevention initiatives. Compelling evidence from the Global North supports exercise-based interventions to improve balance and reduce fall risk in older adults. More recently, attention has focused on interactive videogaming, known as exergames, as a novel way to manage fall risk with exercise. Commercially available exergames have inherent appeal for low- and middle-income country contexts, where rehabilitation professionals and resources are scanty. The aim of this study was to explore the feasibility of a large-scale randomized control trial comparing an exergaming intervention with the gold-standard Otago Exercise Programme and a no-intervention arm. Exercise adherence was poor in both intervention arms, and this prompted a shift to mixed methodology to explore the construct of falls and participants’ experience of the exergaming intervention. Focus groups were conducted, and the results were analysed using content analysis. Whereas the results demonstrated improvements in physical outcome measures (e.g., Timed-Up-and-Go, MiniBESTest) related to balance and falls that were encouraging in both the gold-standard and exergaming intervention groups, few participants achieved optimal adherence. Attitudes toward falls and fall prevention were explored, as well as participants’ experiences of the exergaming programme. Consistent with a developing country context, participants acknowledged both intrinsic and extrinsic fall risk factors. Exergaming participants enjoyed the fun and playful aspects of the exercise programme, yet these were not sufficient to maximize adherence. The focus groups described the barriers and facilitators to participation, which included motivation. The focus groups discussed strategies to enhance participation, and these are discussed in the context of exergaming.

Background: Tamoxifen is widely used in the treatment of hormone receptor-positive breast cancer and has been shown to successfully reduce recurrence and mortality rates. Nonetheless, variability in patient response to tamoxifen treatment is observed with up to 40% of patients experiencing recurrence. Genetic polymorphisms in pharmacogenes encoding enzymes involved in tamoxifen metabolism have been linked to some of this observed interindividual variability. The pharmacogenetics of tamoxifen in populations of African descent remain understudied, creating difficulties in pinpointing the primary factors behind the observed variable response. To address this gap, this study aimed to investigate the role of genetic variation in tamoxifen treatment outcomes in a South African cohort. Methods: Participants included 166 Mixed and African Ancestry breast cancer patients who had received tamoxifen treatment. Genetic characterization was performed for 53 single nucleotide polymorphisms (SNPs) and two copy number variations across eight drug-metabolizing enzymes, including cytochrome P450s (CYP2D6, CYP3A4, CYP3A5, CYP2B6), UDP-glucuronosyltransferases (UGT1A4), and sulfotransferases (SULT1A1, SULT1E1, SULT2A1). The association between genotypes and disease-free survival (DFS) was evaluated using Cox proportional hazards regression models. Results: The CYP2B6*1/*6 or *4/*9 genotype showed a nominal association with improved DFS (p = 0.049), with a similar trend observed for UGT1A4 rs11888492. In contrast, SULT1E1 rs3775779 heterozygosity showed a nominal association with reduced DFS (p = 0.044). SULT1A1 SNPs (rs4149393, rs4149394, rs1042157) demonstrated trends toward reduced DFS. Conclusions: These exploratory findings highlight the need for more inclusive pharmacogenomic research and point to potential biomarkers for optimizing tamoxifen therapy in African populations.