المؤلفون: Lambert, Madeleine, Mendenhall, Emily, Kim, Andrew Wooyoung, Cubasch, Herbert, Joffe, Maureen, Norris, Shane A

مصطلحات موضوعية: Health Services and Systems, Nursing, Health Sciences, Clinical Research, Breast Cancer, Prevention, Cancer, Behavioral and Social Science, Management of diseases and conditions, 7.1 Individual care needs, Adaptation, Psychological, Adult, Aged, Black People, Breast Neoplasms, Cancer Survivors, Comorbidity, Delayed Diagnosis, Female, Health Services Accessibility, Humans, Mastectomy, Middle Aged, Social Support, South Africa, Stress, Psychological, breast cancer, chemotherapy, comorbidity, mastectomy, Paediatrics and Reproductive Medicine, Public Health and Health Services, Obstetrics & Reproductive Medicine, Reproductive medicine, Public health

الوصف: BackgroundBreast cancer is the most common cancer globally and among South African women. Women from socioeconomically disadvantaged South African communities more often present later and receive total mastectomy compared to those from more affluent communities who have more breast conserving surgery (which is less invasive but requires mandatory radiation treatment post-operatively). Standard chemotherapy and total mastectomy treatments are known to cause traumatizing side effects and emotional suffering among South African women; moreover, many women face limited communication with physicians and psychological support.ObjectiveThis article investigates the experiences of women seeking breast cancer treatment at the largest public hospital in South Africa.MethodsWe interviewed 50 Black women enrolled in the South African Breast Cancer Study to learn more about their health system experiences with detection, diagnosis, treatment, and follow-up care for breast cancer. Each interview was between 2-3 hours, addressing perceptions, experiences, and concerns associated with breast cancer and comorbidities such as HIV and hypertension.ResultsWe found most women feared diagnosis, in part, because of the experience of chemotherapy and physical mutilation related to mastectomy. The importance of social support from family, religion, and clinical staff was fundamental for women coping with their condition and adhering to treatment and medication.ConclusionsThese findings exemplify how interventions might promote early detection of breast cancer and better adherence to treatment. Addressing community perceptions of breast cancer, patient needs and desires for treatment, structural barriers to intensive therapies, and the burden of invasive treatments are imperative next steps for delivering better breast cancer care in Soweto and other resource-constrained settings.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/03b4k313Test

المؤلفون: Pumpalova, Yoanna S., Ramakrishnan, Adarsh, May, Michael, Pentz, Audrey, Minkowitz, Shauli, Doherty, Sean, Singh, Elvira, Chen, Wenlong Carl, Rebbeck, Timothy R., Neugut, Alfred I., Joffe, Maureen

المساهمون: Conquer Cancer Foundation, National Institutes of Health

المصدر: Cancer Medicine ; volume 13, issue 1 ; ISSN 2045-7634 2045-7634

الوصف: Background Men of African descent are disproportionately affected by prostate cancer (PCa), and many have metastatic disease at presentation. In South Africa (SA), androgen deprivation therapy (ADT) is the first‐line treatment for stage IV PCa. Objective To identify predictors of overall survival (OS) in Black South African men with stage IV PCa treated with ADT. Design, Setting, and Participants Men diagnosed with prostate cancer (3/22/2016–10/30/2020) at Chris Hani Baragwanath Academic Hospital in Soweto, Johannesburg, were recruited for the Men of African Descent with Cancer of the Prostate study. We included men with newly diagnosed stage IV PCa treated with ADT who had a prostate‐specific antigen (PSA) level drawn prior to initiation of ADT and had ≥1 PSA drawn ≥12 weeks after ADT start. Outcomes Measures and Statistical Analysis We used Kaplan–Meier statistics to estimate OS and Cox regression models to identify predictors of OS. Results and Limitations Of the 1097 men diagnosed with prostate cancer, we included 153 men with stage IV PCa who received ADT and met PSA requirements. The median age was 68.0 years (interquartile range 64–73 years). Median OS from time of ADT initiation was 3.39 years (95% confidence interval (CI): 3.14%–noncalculable), while biochemical progression‐free survival was 2.36 years (95% CI: 2.03%–3.73%). Biochemical progression (HR 3.52, 95% CI: 1.85%–6.70%), PSA nadir level >4 ng/mL (HR 3.77, 95% CI: 1.86%–7.62%), alkaline phosphatase level at diagnosis >150 IU/dL (HR 3.09, 95% CI: 1.64%–5.83%), and hemoglobin at diagnosis <13.5 g/dL (HR 2.90, 95% CI: 1.28%–6.56%) were associated with worse OS. Conclusions In this study, we identified factors associated with poor OS among Black South African men with stage IV PCa treated with ADT. These factors may be useful in identifying patients for upfront treatment escalation, including the use of docetaxel chemotherapy or escalation of therapy at the time of biochemical progression. Patient Summary In this study, we found ...

الإتاحة: https://doi.org/10.1002/cam4.6739Test

المؤلفون: Chiwambutsa, Shingirai M., Ayeni, Oluwatosin, Kapungu, Nyasha, Kanji, Comfort, Thelingwani, Roslyn, Chen, Wenlong Carl, Mokone, Dikeledi H., O'Neil, Daniel S., Neugut, Alfred I., Jacobson, Judith S., Ruff, Paul, Cubasch, Herbert, Joffe, Maureen, Masimirembwa, Collen

المصدر: Clinical Pharmacology & Therapeutics ; volume 114, issue 1, page 127-136 ; ISSN 0009-9236 1532-6535

الوصف: Clinical outcomes of tamoxifen (TAM) treatment show wide interindividual variability. Comedications and genetic polymorphisms of enzymes involved in TAM metabolism contributes to this variability. Drug–drug and drug–gene interactions have seldom been studied in African Black populations. We evaluated the effects of commonly co‐administered medicines on TAM pharmacokinetics in a cohort of 229 South African Black female patients with hormone‐receptor positive breast cancer. We also investigated the pharmacokinetic effects of genetic polymorphism in enzymes involved in TAM metabolism, including the variants CYP2D6*17 and *29 , which have been mainly reported in people of African descent. TAM and its major metabolites, N‐desmethyltamoxifen (NDM), 4‐OH‐tamoxifen, and endoxifen (ENDO), were quantified in plasma using the liquid chromatography‐mass spectrometry. The GenoPharm open array was used to genotype CYP2D6 , CYP3A5 , CYP3A4 , CYP2B6 , CYP2C9 , and CYP2C19 . Results showed that CYP2D6 diplotype and CYP2D6 phenotype significantly affected endoxifen concentration ( P < 0.001 and P < 0.001). CYP2D6*17 and CYP2D6*29 significantly reduced the metabolism of NDM to ENDO. Antiretroviral therapy had a significant effect on NDM levels and the TAM/NDM and NDM/ENDO metabolic ratios but did not result in significant effects on ENDO levels. In conclusion, CYP2D6 polymorphisms affected endoxifen concentration and the variants CYP2D6*17 and CYP2D6*29 significantly contributed to low exposure levels of ENDO. This study also suggests a low risk of drug–drug interaction in patients with breast cancer on TAM.

الإتاحة: https://doi.org/10.1002/cpt.2904Test

المؤلفون: Montaño, Michalina A., Mtisi, Takudzwa, Ndlovu, Ntokozo, Borok, Margaret, Bula, Agatha, Joffe, Maureen, Bender Ignacio, Rachel, Chagomerana, Maganizo B.

المساهمون: National Institute of Allergy and Infectious Diseases, National Cancer Institute

المصدر: Infectious Agents and Cancer ; volume 18, issue 1 ; ISSN 1750-9378

مصطلحات موضوعية: Cancer Research, Infectious Diseases, Oncology, Epidemiology

الوصف: Introduction In East and Southern Africa, people with HIV (PWH) experience worse cancer-related outcomes and are at higher risk of developing certain cancers. Siloed care delivery pathways pose a substantial barrier to co-management of HIV and cancer care delivery. Methods We conducted cross-sectional studies of adult cancer patients at public radiotherapy and oncology units in Malawi (Kamuzu Central Hospital), Zimbabwe (Parirenyatwa Group of Hospitals), and South Africa (Charlotte Maxeke Hospital) between 2018 and 2019. We abstracted cancer- and HIV-related data from new cancer patient records and used Poisson regression with robust variance to identify patient characteristics associated with HIV documentation. Results We included 1,648 records from Malawi (median age 46 years), 1,044 records from South Africa (median age 55 years), and 1,135 records from Zimbabwe (median age 52 years). Records from all three sites were predominately from female patients; the most common cancers were cervical (Malawi [29%] and Zimbabwe [43%]) and breast (South Africa [87%]). HIV status was documented in 22% of cancer records from Malawi, 92% from South Africa, and 86% from Zimbabwe. Patients with infection-related cancers were more likely to have HIV status documented in Malawi (adjusted prevalence ratio [aPR]: 1.92, 95% confidence interval [CI]: 1.56–2.38) and Zimbabwe (aPR: 1.16, 95%CI: 1.10–1.22). Patients aged ≥ 60 years were less likely to have HIV status documented (Malawi: aPR: 0.66, 95% CI: 0.50–0.87; Zimbabwe: aPR: 0.76, 95%CI: 0.72–0.81) than patients under age 40 years. Patient age and cancer type were not associated with HIV status documentation in South Africa. Conclusion Different cancer centers have different gaps in HIV status documentation and will require tailored strategies to improve processes for ascertaining and recording HIV-related information in cancer records. Further research by our consortium to identify opportunities for integrating HIV and cancer care delivery is underway.

الإتاحة: https://doi.org/10.1186/s13027-023-00548-1Test

المؤلفون: Phakathi, Boitumelo, Dix-Peek, Therese, Van Den Berg, Eunice, Dickens, Caroline, Nietz, Sarah, Cubasch, Herbert, Joffe, Maureen, Neugut, Alfred I., Jacobson, Judith S., Ruff, Paul, Duarte, Raquel

المساهمون: NIH/NCI grant, R01 Grant, The South African Medical Research Council/University of the Witwatersrand Common Epithelial Cancer Research Center, The South African National Research Foundation major equipment grant, Prof Bongani Mayosi Clinical scholarship, University of KwaZulu-Natal

المصدر: Breast Cancer Research and Treatment ; volume 200, issue 3, page 337-346 ; ISSN 0167-6806 1573-7217

مصطلحات موضوعية: Cancer Research, Oncology

الوصف: Purpose Treatment decision making for patients with breast cancer increasingly depends on analysis of markers or systems for estimating risk of breast cancer recurrence. Breast cancer intrinsic subtypes and risk of recurrence (ROR) scores have been found to be valuable in predicting survival and determining optimal treatment for individual patients. We studied the association of breast cancer survival with the PAM50 gene expression assay in HIV-positive and HIV-negative patients. Method RNA was extracted from formalin-fixed paraffin-embedded specimens of histologically confirmed invasive carcinoma and was purified using the AllPrep® DNA/RNA FFPE kit, Qiagen (Hilden, Germany). The NanoString RUO PAM50 algorithm was used to determine the molecular subtype and the risk of recurrence score of each sample. The overall and disease-free survival were determined with comparison made among HIV-positive and -negative patients. We then generated Kaplan–Meier survival curves, calculated p-values and estimated hazard ratios and their 95% confidence intervals using Cox regression models. Results Of the 384 RNA samples analysed, 98.4% met the required RNA quality standard and the specified QC threshold for the test. Luminal B was the most common PAM50 intrinsic subtype and 82.1% of patients were at high risk for disease recurrence based on ROR score. HIV infection, PAM50-based HER2-enriched and basal-like intrinsic subtypes, and high ROR were associated with poor overall and disease-free survival. HIV-positive patients with luminal A & B subtypes had significantly worse survival outcomes than HIV-negative luminal patents. Conclusion Aggressive tumour biology was common in our cohort. HIV infection, PAM50 HER2-enriched,basal-like intrinsic subtypes and high ROR score were associated with poor overall and disease-free survival. HIV infection impacted survival in patients with luminal subtypes only.

الإتاحة: https://doi.org/10.1007/s10549-023-06969-1Test

المؤلفون: Dix-Peek, Thérèse, Phakathi, Boitumelo P., van den Berg, Eunice J., Dickens, Caroline, Augustine, Tanya N., Cubasch, Herbert, Neugut, Alfred I., Jacobson, Judith S., Joffe, Maureen, Ruff, Paul, Duarte, Raquel A. B.

المساهمون: Division of Cancer Epidemiology and Genetics, National Cancer Institute, South African Medical Research Council, South African National Research Foundation, University of the Witwatersrand

المصدر: Breast Cancer Research and Treatment ; volume 199, issue 1, page 1-12 ; ISSN 0167-6806 1573-7217

مصطلحات موضوعية: Cancer Research, Oncology

الوصف: Purpose Breast cancer is a heterogeneous disease with different gene expression profiles, treatment options and outcomes. In South Africa, tumors are classified using immunohistochemistry. In high-income countries multiparameter genomic assays are being utilized with implications for tumor classification and treatment. Methods In a cohort of 378 breast cancer patients from the SABCHO study, we investigated the concordance between tumor samples classified by IHC and the PAM50 gene assay. Results IHC classified patients as ER-positive (77.5%), PR-positive (70.6%), and HER2-positive (32.3%). These results, together with Ki67, were used as surrogates for intrinsic subtyping, and showed 6.9% IHC-A-clinical, 72.7% IHC-B-clinical, 5.3% IHC-HER2-clinical and 15.1% triple negative cancer (TNC). Typing using the PAM50 gave 19.3% luminal-A, 32.5% luminal-B, 23.5% HER2-enriched and 24.6% basal-like. The basal-like and TNC had the highest concordance, while the luminal-A and IHC-A group had the lowest concordance. By altering the cutoff for Ki67, and realigning the HER2/ER/PR-positive patients to IHC-HER2, we improved concordance with the intrinsic subtypes. Conclusion We suggest that the Ki67 be changed to a cutoff of 20–25% in our population to better reflect the luminal subtype classifications. This change would inform treatment options for breast cancer patients in settings where genomic assays are unaffordable.

الإتاحة: https://doi.org/10.1007/s10549-023-06886-3Test

المؤلفون: Ayeni, Oluwatosin A., Joffe, Maureen, Mapanga, Witness, Chen, Wenlong Carl, O’Neil, Daniel S., Phakathi, Boitumelo, Nietz, Sarah, Buccimazza, Ines, Čačala, Sharon, Stopforth, Laura W., Jacobson, Judith S., Crew, Katherine D., Neugut, Alfred I., Ramiah, Duvern, Ruff, Paul, Cubasch, Herbert, Chirwa, Tobias, McCormack, Valerie, Micklesfield, Lisa K., Norris, Shane A.

المساهمون: NIH/NCI, The South African Medical Research Council/University of the Witwatersrand Common Epithelial Cancer Research Center, Cancer Association of South Africa

المصدر: Breast Cancer Research ; volume 25, issue 1 ; ISSN 1465-542X

الوصف: Background Breast cancer survival in South Africa is low, but when diagnosed with breast cancer, many women in South Africa also have other chronic conditions. We investigated the impact of multimorbidity (≥ 2 other chronic conditions) on overall survival among women with breast cancer in South Africa. Methods Between 1 July 2015 and 31 December 2019, we enrolled women newly diagnosed with breast cancer at six public hospitals participating in the South African Breast Cancer and HIV Outcomes (SABCHO) Study. We examined seven chronic conditions (obesity, hypertension, diabetes, HIV, cerebrovascular diseases (CVD), asthma/chronic obstructive pulmonary disease, and tuberculosis), and we compared socio-demographic, clinical, and treatment factors between patients with and without each condition, and with and without multimorbidity. We investigated the association of multimorbidity with overall survival using multivariable Cox proportional hazard models. Results Of 3,261 women included in the analysis, 45% had multimorbidity; obesity (53%), hypertension (41%), HIV (22%), and diabetes (13%) were the most common individual conditions. Women with multimorbidity had poorer overall survival at 3 years than women without multimorbidity in both the full cohort (60.8% vs. 64.3%, p = 0.036) and stage groups: stages I–II, 80.7% vs. 86.3% ( p = 0.005), and stage III, 53.0% vs. 59.4% ( p = 0.024). In an adjusted model, women with diabetes (hazard ratio (HR) = 1.20, 95% confidence interval (CI) = 1.03–1.41), CVD (HR = 1.43, 95% CI = 1.17–1.76), HIV (HR = 1.21, 95% CI = 1.06–1.38), obesity + HIV (HR = 1.24 95% CI = 1.04–1.48), and multimorbidity (HR = 1.26, 95% CI = 1.13–1.40) had poorer overall survival than women without these conditions. Conclusions Irrespective of the stage, multimorbidity at breast cancer diagnosis was an important prognostic factor for survival in our SABCHO cohort. The high prevalence of multimorbidity in our cohort calls for more comprehensive care to improve outcomes for South African women with ...

الإتاحة: https://doi.org/10.1186/s13058-023-01603-wTest

المؤلفون: Mapanga, Witness, Norris, Shane A., Craig, Ashleigh, Ayeni, Oluwatosin A., Chen, Wenlong C., Jacobson, Judith S., Neugut, Alfred I., Ruff, Paul, Cubasch, Herbert, O’Neil, Daniel S., Buccimazza, Ines, Čačala, Sharon, Stopforth, Laura W., Farrow, Hayley A., Nietz, Sarah, Phakathi, Boitumelo, Chirwa, Tobias, McCormack, Valerie A., Joffe, Maureen

المساهمون: Dookeran, Keith Anthony, Foundation for the National Institutes of Health, National Cancer Institute of the National Institutes of Health, University of Witwatersrand/South African Medical Research Council, University of the Witwatersrand

المصدر: PLOS ONE ; volume 18, issue 2, page e0281916 ; ISSN 1932-6203

الوصف: Objective In low- and middle-income countries (LMICs), advanced-stage diagnosis of breast cancer (BC) is common, and this contributes to poor survival. Understanding the determinants of the stage at diagnosis will aid in designing interventions to downstage disease and improve survival from BC in LMICs. Methods Within the South African Breast Cancers and HIV Outcomes (SABCHO) cohort, we examined factors affecting the stage at diagnosis of histologically confirmed invasive breast cancer at five tertiary hospitals in South Africa (SA). The stage was assessed clinically. To examine the associations of the modifiable health system, socio-economic/household and non-modifiable individual factors, hierarchical multivariable logistic regression with odds of late-stage at diagnosis (stage III-IV), was used. Results The majority (59%) of the included 3497 women were diagnosed with late-stage BC disease. The effect of health system-level factors on late-stage BC diagnosis was consistent and significant even when adjusted for both socio-economic- and individual-level factors. Women diagnosed in a tertiary hospital that predominantly serves a rural population were 3 times (OR = 2.89 (95% CI: 1.40–5.97) as likely to be associated with late-stage BC diagnosis when compared to those diagnosed at a hospital that predominantly serves an urban population. Taking more than 3 months from identifying the BC problem to the first health system entry (OR = 1.66 (95% CI: 1.38–2.00)), and having luminal B (OR = 1.49 (95% CI: 1.19–1.87)) or HER2-enriched (OR = 1.64 (95% CI: 1.16–2.32)) molecular subtype as compared to luminal A, were associated with a late-stage diagnosis. Whilst having a higher socio-economic level (a wealth index of 5) reduced the probability of late-stage BC at diagnosis, (OR = 0.64 (95% CI: 0.47–0.85)). Conclusion Advanced-stage diagnosis of BC among women in SA who access health services through the public health system was associated with both modifiable health system-level factors and non-modifiable individual-level ...

الإتاحة: https://doi.org/10.1371/journal.pone.0281916Test

المؤلفون: Tshabalala, Gugulethu, Blanchard, Charmaine, Mmoledi, Keletso, Malope, Desiree, O’Neil, Daniel S., Norris, Shane A., Joffe, Maureen, Dietrich, Janan Janine

المساهمون: Moodley, Jennifer, South African Medical Research Council, Bristol-Myers Squibb Foundation

المصدر: PLOS Global Public Health ; volume 3, issue 5, page e0001826 ; ISSN 2767-3375

الوصف: Low-and-middle income countries (LMICs) contribute approximately 70% of global cancer deaths, and the cancer incidence in these countries is rapidly increasing. Sub-Saharan African (SSA) countries, including South Africa (SA), bear some of the world’s highest cancer case fatality rates, largely attributed to late diagnosis. We explored contextual enablers and barriers for early detection of breast and cervical cancers according to facility managers and clinical staff at primary healthcare clinics in the Soweto neighbourhood of Johannesburg, South Africa. We conducted qualitative in-depth interviews (IDIs) between August and November 2021 amongst 13 healthcare provider nurses and doctors as well as 9 facility managers at eight public healthcare clinics in Johannesburg. IDIs were audio-recorded, transcribed verbatim, and entered into NVIVO for framework data analysis. Analysis was stratified by healthcare provider role and identified apriori around the themes of barriers and facilitators for early detection and management of breast and cervical cancers. Findings were conceptualised within the socioecological model and then explored within the capability, opportunity and motivation model of behaviour (COM-B) for pathways that potentially influence the low screening provision and uptake. The findings revealed provider perceptions of insufficient South African Department of Health (SA DOH) training support and staff rotations resulting in providers lacking knowledge and skills on cancer, screening policies and techniques. This coupled with provider perceptions of poor patient cancer and screening knowledge revealed low capacity for cancer screening. Providers also perceived opportunity for cancer screening to be undermined by the limited screening services mandated by the SA DOH, insufficient providers, inadequate facilities, supplies and barriers to accessing laboratory results. Providers perceived women to prefer to self-medicate and consult with traditional healers and access primary care for curative services ...

الإتاحة: https://doi.org/10.1371/journal.pgph.0001826Test

المؤلفون: Mapanga, Witness, Ayeni, Oluwatosin A., Chen, Wenlong Carl, Jacobson, Judith S., Neugut, Alfred I., Ruff, Paul, Cubasch, Herbert, O’Neil, Daniel S., Buccimazza, Ines, Čačala, Sharon, Stopforth, Laura W., Farrow, Hayley A., Nietz, Sarah, Phakathi, Boitumelo, Chirwa, Tobias, McCormack, Valerie A., Joffe, Maureen

المساهمون: Shafique, Kashif, National Cancer Institute of the National Institutes of Health, University of Witwatersrand/South African Medical Research Council

المصدر: PLOS Global Public Health ; volume 3, issue 10, page e0002432 ; ISSN 2767-3375

الوصف: The South African Breast Cancer and HIV Outcomes prospective cohort (SABCHO) study was established to investigate survival determinants among HIV-positive and HIV-negative SA women with breast cancer. This paper describes common and unique characteristics of the cancer centres and their participants, examining disparities in pathways to diagnosis, treatment resources and approaches adopted to mitigate resource constraints. The Johannesburg (Jhb), Soweto (Sow), and Durban (Dbn) sites treat mainly urban, relatively better educated and more socioeconomically advantaged patients whereas the Pietermaritzburg (Pmb) and Empangeni (Emp) sites treat predominantly rural, less educated and more impoverished communities The Sow, Jhb, and Emp sites had relatively younger patients (mean ages 54 ±14.5, 55±13.7 and 54±14.3 respectively), whereas patients at the Dbn and Pmb sites, with greater representation of Asian Indian women, were relatively older (mean age 57 ±13.9 and 58 ±14.6 respectively). HIV prevalence among the cohort was high, ranging from 15%-42%, (Cohort obesity (BMI ≥ 30 kg/m 2 ) at 60%, self-reported hypertension (41%) and diabetes (13%). Direct referral of patients from primary care clinics to cancer centre occurred only at the Sow site which uniquely ran an open clinic and where early stage (I and II) proportions were highest at 48.5%. The other sites relied on indirect patient referral from regional hospitals where significant delays in diagnostics occurred and early-stage proportions were a low (15%- 37.3%). The Emp site referred patients for all treatments to the Dbn site located 200km away; the Sow site provided surgery and endocrine treatment services but referred patients to the Jhb site 30 Km away for chemo- and radiation therapy. The Jhb, Dbn and Pmb sites all provided complete oncology treatment services. All treatment centres followed international guidelines for their treatment approaches. Findings may inform policy interventions to address national and regional disparities in breast cancer care.

الإتاحة: https://doi.org/10.1371/journal.pgph.0002432Test