Incidence patterns, care continuum and impact of treatment on survival among women with breast cancer in Ghana and the United States

Breast cancer is the most commonly diagnosed cancer among women worldwide. Of the five breast cancer subtypes, triple negative breast cancer (TNBC) is the most aggressive subtype. Black women in the US and Ghana are more likely to be diagnosed with TNBC, at young ages and advanced stages. Combining information from Ghana and the US, this project identified the breast cancer care continuum in Ghana, examined the breast cancer incidence patterns in Ghana and the US and assessed the optimal surgical treatment for TNBC. In the first manuscript, we examined how women in Ghana navigate the healthcare system and factors that influence their decisions and ability to seek and access breast cancer care. We interviewed thirty-one women diagnosed with breast cancer in Kumasi, Ghana. Based on the findings from the interviews, we presented a framework showing specific steps in the pathways and how women transition from one step to another. In the second manuscript, we assessed factors explaining the younger age at breast cancer diagnosis among Ghanaian women compared to women in the US. To achieve these aims we analyzed breast cancer data from the Kumasi Cancer Registry, the only population-based cancer registry in Ghana, and compared it to the US Surveillance, Epidemiology and End Results (SEER) data. Population age structure, screening and cohort effects explain the younger age at breast cancer diagnosis among women in Ghana In the third manuscript, we examined whether the poor prognosis of TNBC warrants a more aggressive surgical approach and whether there is value in expanded use of radiation therapy among women with TNBC who receive mastectomy. We found that breast conserving surgery followed by radiotherapy is an effective treatment for women with early-stage TNBC. Findings from this dissertation are timely due to the rapidly rising burden of breast cancer in sub-Saharan Africa and persistent disparities in the US.

Breast Cancer in the Gaza Strip: The impact of the medical permit regime on public health

For the last 14 years, the Gaza Strip has been subject to an illegal blockade imposed by the Israeli and Egyptian governments. This severe restriction on movement prevents Gazans from accessing critical resources and makes access to health care, even for the most severely ill patients, contingent on a convoluted permit system run by the Israeli military. Consequences of the permit system include major delays in treatment and adverse health outcomes. My thesis explores the impact of the permit system on health outcomes for breast cancer patients in Gaza and offers recommendations for improving public health via community-based and political initiatives

Level of knowledge and practice of female healthcare providers about early detection methods of breast cancer at Debre Tabor Comprehensive Specialised Hospital: a cross-sectional study

Background: Despite the higher mortality rate of breast cancer in low and middle-income countries, the practice of early detection methods is low and the majority of the patients presenting at an advanced stage of the disease need palliative care with low survival rates. Although healthcare providers are the key for practicing early detection methods of breast cancer for themselves and their clients, little is known about their knowledge and practice of early detection methods of breast cancer in Northcentral Ethiopia.

Methods: An institution-based cross-sectional study was conducted among female healthcare providers at Debre Tabor Comprehensive Specialised Hospital. Data were collected using a structured self-administered questionnaire. The data were analysed using SPSS version 23. Descriptive statistics were used to describe the socio-demographic information of participants. Binary and multivariable logistic regression with adjusted odds ratio (AOR) and 95% confidence interval (CI) was used to identify factors associated with the outcome variable. Statistical significance was declared at p 2 years (AOR = 3.2; 95% CI: 1.72, 5.29), history of any breast problem (AOR = 1.4; 95% CI: 1.02, 2.37), family history of breast cancer (AOR = 4.0; 95% CI: 2.58, 15.84), having good knowledge (AOR = 2.9; 95% CI: 1.3, 6.52) and history of comorbidities (AOR = 1.09; 95% CI: 1.09, 3.59) were the factors associated with the practice of breast self-examination.

Conclusion: Our study found that the knowledge and practice of breast cancer early detection methods was low in the study setting. Only less than half of female healthcare providers practiced regular breast self-examination, which suggests the need to provide training for healthcare providers to fill the gap and to promote early detection of breast cancer cases.

Patterns of care of breast cancer patients in Morocco – A study of variations in patient profile, tumour characteristics and standard of care over a decade

Guided by a national cancer plan (2010–19), Morocco made significant investments in improving breast cancer detection and treatment. A breast cancer pattern-of-care study was conducted to document the socio-demographic profiles of patients and tumour characteristics, measure delays in care, and assess the status of dissemination and impact of state-of-the-art management. The retrospective study conducted among 2120 breast cancer patients registered during 2008–17 at the two premier-most oncology centres (Centre Mohammed VI or CM-VI and Institut National d’Oncologie or INO) also measured temporal trends of the different variables.

Median age (49 years) and other socio-demographic characteristics of the patients remained constant over time. A significant improvement in coverage of the state-financed health insurance scheme for indigent populations was observed over time. Median interval between onset of symptoms and first medical consultation was 6 months with a significant reduction over time. Information on staging and molecular profile were available for more than 90% and 80% of the patients respectively. Approximately 55% of the patients presented at stage I/II and proportion of triple-negative cancers was 16%; neither showing any appreciable temporal variation. Treatment information was available for more than 90% of the patients; 69% received surgery with chemotherapy and/or radiation. Treatment was tailored to stage and molecular profiles, though breast conservation therapy was offered to less than one-fifth. When compared using the EUSOMA quality indicators for breast cancer management, INO performed better than CM-VI. This was reflected in nearly 25% difference in 5-year disease-free survival for early-stage cancers between the centres.

Health system factors that influence diagnostic and treatment intervals in women with breast cancer in sub-Saharan Africa: a systematic review

Background
Breast cancer patients in sub-Saharan Africa experience long time intervals between their first presentation to a health care facility and the start of cancer treatment. The role of the health system in the increasing treatment time intervals has not been widely investigated. This review aimed to identify existing information on health system factors that influence diagnostic and treatment intervals in women with breast cancer in sub-Saharan Africa to contribute to the reorientation of health policies in the region.

Methods
PubMed, ScienceDirect, African Journals Online, Mendeley, ResearchGate and Google Scholar were searched to identify relevant studies published between 2010 and July 2020. We performed a qualitative synthesis in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Related health system factors were extracted and classified according to the World Health Organization’s six health system building blocks. The quality of qualitative and quantitative studies was assessed by using the Critical Appraisal Skills Program Quality-Assessment Tool and the National Institute of Health Quality Assessment Tool, respectively. In addition, we used the Confidence in the Evidence from Reviews of Qualitative Research tool to assess the evidence for each qualitative finding.

Results
From 14,184 identified studies, this systematic review included 28 articles. We identified a total of 36 barriers and 8 facilitators that may influence diagnostic and treatment intervals in women with breast cancer. The principal health system factors identified were mainly related to human resources and service delivery, particularly difficulty accessing health care, diagnostic errors, poor management, and treatment cost.

Conclusion
The present review shows that diagnostic and treatment intervals among women with breast cancer in sub-Saharan Africa are influenced by many related health system factors. Policy makers in sub-Saharan Africa need to tackle the financial accessibility to breast cancer treatment by adequate universal health coverage policies and reinforce the clinical competencies for health workers to ensure timely diagnosis and appropriate care for women with breast cancer in this region.

Survival of south african women with breast cancer receiving anti-retroviral therapy for HIV

Purpose
Breast cancer outcomes in sub-Saharan Africa is reported to be poor, with an estimated five-year survival of 50% when compared to almost 90% in high-income countries. Although several studies have looked at the effect of HIV in breast cancer survival, the effect of ARTs has not been well elucidated.

Methods
All females newly diagnosed with invasive breast cancer from May 2015–September 2017 at Charlotte Maxeke Johannesburg Academic and Chris Hani Baragwanath Academic Hospital were enrolled. We analysed overall survival and disease-free survival, comparing HIV positive and negative patients. Kaplan-Meier survival curves were generated with p-values calculated using a log-rank test of equality while hazard ratios and their 95% confidence intervals (CIs) were estimated using Cox regression models.

Results
Of 1019 patients enrolled, 22% were HIV positive. The overall survival (95% CI) was 53.5% (50.1–56.7%) with a disease-free survival of 55.8% (52.1–59.3) after 4 years of follow up. HIV infection was associated with worse overall survival (HR (95% CI): 1.50 (1.22–1.85), p < 0.001) and disease-free survival (OR (95% CI):2.63 (1.71–4.03), p < 0.001), especially among those not on ART at the time of breast cancer diagnosis. Advanced stage of the disease and hormone-receptor negative breast cancer subtypes were also associated with poor survival. Conclusion HIV infection was associated with worse overall and disease-free survival. HIV patients on ARTs had favourable overall and disease-free survival and with ARTs now being made accessible to all the outcome of women with HIV and breast cancer is expected to improve.

Economic Evaluations of Breast Cancer Care in Low- and Middle-Income Countries: A Scoping Review

Background
Understanding the cost of delivering breast cancer (BC) care in low- and middle-income countries (LMICs) is critical to guide effective care delivery strategies. This scoping review summarizes the scope of literature on the costs of BC care in LMICs and characterizes the methodological approaches of these economic evaluations.

Materials and Methods
A systematic literature search was performed in five databases and gray literature up to March 2020. Studies were screened to identify original articles that included a cost outcome for BC diagnosis or treatment in an LMIC. Two independent reviewers assessed articles for eligibility. Data related to study characteristics and methodology were extracted. Study quality was assessed using the Drummond et al. checklist.

Results
Ninety-one articles across 38 countries were included. The majority (73%) of studies were published between 2013 and 2020. Low-income countries (2%) and countries in Sub-Saharan Africa (9%) were grossly underrepresented. The majority of studies (60%) used a health care system perspective. Time horizon was not reported in 30 studies (33%). Of the 33 studies that estimated the cost of multiple steps in the BC care pathway, the majority (73%) were of high quality, but studies varied in their inclusion of nonmedical direct and indirect costs.

Conclusion
There has been substantial growth in the number of BC economic evaluations in LMICs in the past decade, but there remain limited data from low-income countries, especially those in Sub-Saharan Africa. BC economic evaluations should be prioritized in these countries. Use of existing frameworks for economic evaluations may help achieve comparable, transparent costing analyses.

Invasive breast Cancer treatment in Tanzania: landscape assessment to prepare for implementation of standardized treatment guidelines

Background
Incidence of breast cancer continues to rise in low- and middle-income countries, with data from the East African country of Tanzania predicting an 82% increase in breast cancer from 2017 to 2030. We aimed to characterize treatment pathways, receipt of therapies, and identify high-value interventions to increase concordance with international guidelines and avert unnecessary breast cancer deaths.

Methods
Primary data were extracted from medical charts of patients presenting to Bugando Medical Center, Tanzania, with breast concerns and suspected to have breast cancer. Clinicopathologic features were summarized with descriptive statistics. A Poisson model was utilized to estimate prevalence ratios for variables predicted to affect receipt of life-saving adjuvant therapies and completion of therapies. International and Tanzanian guidelines were compared to current care patterns in the domains of lymph node evaluation, metastases evaluation, histopathological diagnosis, and receptor testing to yield concordance scores and suggest future areas of focus.

Results
We identified 164 patients treated for suspected breast cancer from April 2015–January 2019. Women were predominantly post-menopausal (43%) and without documented insurance (70%). Those with a confirmed histopathology diagnosis (69%) were 3 times more likely to receive adjuvant therapy (PrR [95% CI]: 3.0 [1.7–5.4]) and those documented to have insurance were 1.8 times more likely to complete adjuvant therapy (1.8 [1.0–3.2]). Out of 164 patients, 4% (n = 7) received concordant care based on the four evaluated management domains. The first most common reason for non-concordance was lack of hormone receptor testing as 91% (n = 144) of cases did not undergo this testing. The next reason was lack of lymph node evaluation (44% without axillary staging) followed by absence of abdominopelvic imaging in those with symptoms (35%) and lack of histopathological confirmation (31%).

Conclusions
Patient-specific clinical data from Tanzania show limitations of current breast cancer management including axillary staging, receipt of formal diagnosis, lack of predictive biomarker testing, and low rates of adjuvant therapy completion. These findings highlight the need to adapt and adopt interventions to increase concordance with guidelines including improving capacity for pathology, developing complete staging pathways, and ensuring completion of prescribed adjuvant therapies.

Opportunities For Improvement in The Administration of Neoadjuvant Chemotherapy For T4 Breast Cancer: A Comparison of The United States and Nigeria

BACKGROUND
Neoadjuvant chemotherapy (NAC) is an integral component of T4 breast cancer (BCa) treatment. We compared response to NAC for T4 BCa in the U.S. and Nigeria to direct future interventions.

MATERIALS AND METHODS
Cross‐sectional retrospective analysis included all non‐metastatic T4 BCa patients treated from 2010‐2016 at Memorial Sloan Kettering Cancer Center (New York, U.S.) and Obafemi Awolowo University Teaching Hospitals Complex (Ile Ife, Nigeria). Pathologic complete response (pCR) and survival were compared and factors contributing to disparities evaluated.

RESULTS
308 patients met inclusion criteria: 157 (51%) in the U.S. and 151 (49%) in Nigeria. All U.S. patients received NAC and surgery compared with 93 (62%) Nigerian patients. 56/93 (60%) Nigerian patients completed their prescribed course of NAC. In Nigeria, older age and higher socioeconomic status were associated with treatment receipt.

Fewer patients in Nigeria had immunohistochemistry performed (100% U.S. vs. 18% Nigeria). Of those with available receptor subtype, 18% (28/157) of U.S. patients were triple negative vs. 39% (9/23) of Nigerian patients. Overall pCR was seen in 27% (42/155) of U.S. patients and 5% (4/76) of Nigerian patients. Five‐year survival was significantly shorter in Nigeria vs. the U.S. (61% vs. 72%). However, among the subset of patients who received multimodality therapy, including NAC and surgery with curative intent, 5‐year survival (67% vs. 72%) and 5‐year recurrence‐free survival (48% vs. 61%) did not significantly differ between countries.

CONCLUSION
Addressing health system, socioeconomic, and psychosocial barriers is necessary for administration of complete NAC to improve BCa outcomes in Nigeria.

Recommendations for streamlining precision medicine in breast cancer care in Latin America.

Background
The incidence of breast cancer (BC) in LMICs has increased by more than 20% within the last decade. In areas such as Latin America (LA), addressing BC at national levels evoke discussions surrounding fragmented care, limited resources, and regulatory barriers. Precision Medicine (PM), specifically companion diagnostics (CDx), links disease diagnosis and treatment for better patient outcomes. Thus, its application may aid in overcoming these barriers.
Recent findings
A panel of LA experts in fields related to BC and PM were provided with a series of relevant questions to address prior to a multi-day conference. Within this conference, each narrative was edited by the entire group, through numerous rounds of discussion until a consensus was achieved. The panel proposes specific, realistic recommendations for implementing CDx in BC in LA and other LMIC regions. In these recommendations, the authors strived to address all barriers to the widespread use and access mentioned previously within this manuscript.
Conclusion
This manuscript provides a review of the current state of CDx for BC in LA. Of most importance, the panel proposes practical and actionable recommendations for the implementation of CDx throughout the Region in order to identify the right patient at the right time for the right treatment.