SCHOOL OF POSTGRADUATE STUDIES
COMPREHENSIVE INVESTIGATION INTO CLINICAL OUTCOMES AND
RECURRENCE PATTERNS AMONG PATIENTS WITH TRIPLE NEGATIVE BREAST
CANCER VERSUS NON-TRIPLE NEGATIVE BREAST CANCER: A COMPARATIVE
STUDY AT CANCER DISEASES HOSPITAL, LUSAKA, ZAMBIA
BY
FIRST NAME MIDDLE NAME LAST NAME
STUDENT NUMBER
MASTER OF PUBLIC HEALTH
SUPERVISOR
SUPERVISOR NAME
A research proposal submitted to the University of Lusaka in partial fulfilment of the
requirements of a Master’s Degree in Public Health
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CHAPTER 1
INTRODUCTION
Globally, breast cancer is one of the primary public health issues as an estimated millions
get affected this condition annually. Like many other developing countries, breast cancer is
among the leading cancers in Zambia; with significant impact on morbidity and mortality.
Published data from Zambia showed a prevalence of breast cancer 8.6% which is the third after
two cancers cervix and conjunctiva for females, 41.5% and 9% respectively. These statistics then
also emphasize the vast weight of breast cancer carried by Zambian health care system and call
to action targeted prevention, early detection approaches that would reduce impact on healthcare
resources.
Understanding the molecular basis of both clinical behavior and response, breast cancer
is a group of diseases with dramatic heterogeneity which are characterized by different biological
subtypes. Triple-negative breast cancer (TNBC) is an example of such subtype characterized by
the lack of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth
factor receptor 2 (HER2) expression. TNBC represent about 15-20% of the breast cancers in
general population, and this tumor category is highly characterized by an aggressive nature
which presents challenges management wise as well as prognostically.
The comparison between TNBC and other subtypes of breast cancer demonstrates that
TNBC is related to increased risk for early recurrence, distant metastasis, and poorer overall
survival compared to other breast cancer subtypes. In addition, TNBC mainly occurs in younger
women and those of the African race at a comparatively higher rate. These disparities, however,
point to the fact that more research and interventions are required so as TNBC can be addressed
differently from other diseases since it affects some populations in particular ways.
Though TNBC has lately been recognized as a specific clinical entity, however
significant studies have not yet been conducted on data from the prevalence rates of TNBC
compared to non-triple negative breast cancer (non –TBNC) in Zambian breast cancer patients.
This lack of data prevents achieving the improvement interventions allocation resources and
targeted strategies for managing TNBC.
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There is need to comprehend the incidence, demographic attributes of susceptible
population and use pattern treatment options that TNBC in Zambian environment since creating
knowledge informs on relation based intervention methods which ensure improved health
outcomes limiting burden presented by breast cancer management. This study aims to identify
this important gap TNBC cases versus non-TNBC patients matched for receipt of usual care
Cancer Diseases Hospital, Lusaka Zambia. This study therefore seeks to analyze patient records
and demographic data from the perspective of elaborately determining an exceptional
epidemiological profile for TNBC in Zambia, with a view as informing context-appropriate
programs on breast cancer treatment.
Statement of the Problem:
Despite advances in breast cancer research and treatment, there is a notable gap in the
understanding of how clinical outcomes and recurrence patterns vary between TNBC and
non-TNBC patients in the specific setting of Cancer Diseases Hospital, Lusaka, Zambia.
Addressing this gap is essential for tailoring effective interventions and improving the overall
management of breast cancer in this region.
Justification of the Study:
This research is critical for several reasons. Firstly, it fills a significant gap in the current
literature by providing localized insights into the clinical outcomes and recurrence patterns of
TNBC in Zambia. Secondly, the findings can inform healthcare professionals in tailoring
treatment strategies based on the unique characteristics of TNBC in this population. Lastly, the
study contributes to the broader goal of improving breast cancer care and outcomes in resource-
constrained settings.
Objectives:
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The primary objective of this research is to evaluate and compare the clinical outcomes
and patterns of recurrence in patients with TNBC and non-TNBC at Cancer Diseases Hospital,
Lusaka, Zambia.
Specific objectives include:
1. Assess the demographic characteristics of breast cancer patients at Cancer Diseases
Hospital.
2. Evaluate the treatment modalities administered to TNBC and non-TNBC patients.
3. Compare overall survival rates and disease-free survival rates between TNBC and
non-TNBC cohorts.
4. Investigate patterns of recurrence, including locoregional and distant recurrences, in
TNBC and non-TNBC patients.
5. Explore potential influencing factors on clinical outcomes, such as genetic markers,
socioeconomic factors, and access to healthcare.
Research Questions:
1. What is the prevalence of triple-negative breast cancer compared to non-triple-
negative breast cancer at Cancer Diseases Hospital?
2. How do demographic characteristics differ between patients with TNBC and
non-TNBC?
3. What are the distribution patterns of treatment modalities for TNBC and non-TNBC
cases?
4. Are there significant differences in survival rates between TNBC and non-TNBC
cohorts?
5. What factors may contribute to the prevalence of TNBC in this population?
Hypothesis:
The prevalence of TNBC differs significantly from non-TNBC among breast cancer
patients at Cancer Diseases Hospital, Lusaka, Zambia.
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Scope of the Study:
This research will focus on establishing the prevalence of TNBC compared to non-TNBC
among breast cancer patients at Cancer Diseases Hospital, Lusaka, Zambia. The scope extends to
analyzing patient records within a specified timeframe to determine the prevalence rates and
demographic characteristics of TNBC and non-TNBC cases. Additionally, the study will explore
the distribution of treatment modalities administered to these patients and assess any variations
in survival rates between the two cohorts. While the primary focus is on prevalence and
demographic characteristics, the research will also delve into potential factors influencing the
prevalence of TNBC within this specific population. The study will encompass both newly
diagnosed and recurrent cases within the designated timeframe, providing a comprehensive
overview of the prevalence landscape at Cancer Diseases Hospital.
METHODOLOGY
1. Study Design: Undertake a rigorous retrospective cohort study utilizing meticulously curated
medical records of breast cancer patients treated at Cancer Diseases Hospital during a
specified temporal framework.
2. Implement a comprehensive data collection strategy, systematically reviewing patient records
to extract essential details such as demographics, tumor characteristics, treatment specifics,
outcomes, and pertinent follow-up information.
3. Statistical Analysis: Descriptive statistics will be used to compare outcomes between the two
groups, as well as to discern variations in survival rates, recurrence patterns, and the impact
of potential influencing factors on the observed outcomes.
EXPECTED RESULTS
1. TNBC patients may exhibit shorter overall survival and disease-free survival compared to
non-TNBC patients.
2. TNBC patients may experience more aggressive recurrences, such as distant metastases.
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3. Treatment responses may differ significantly between the two groups.
SIGNIFICANCE
This research aspires to contribute significantly to the current body of knowledge
surrounding breast cancer by offering nuanced insights into the clinical profile of TNBC patients
in the unique setting of Zambia. The anticipated findings hold promise for informing tailored
treatment strategies, thereby enhancing the overall management and prognosis of breast cancer
patients in the region.
ETHICAL CONSIDERATIONS
Commitment to ensuring the utmost confidentiality of patient information, obtaining
requisite ethical approvals, and adhering rigorously to established guidelines for handling
sensitive medical data will be paramount throughout the research process. The ethical framework
will be a guiding principle, ensuring the respect and protection of the rights and privacy of all
participants involved.
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CHAPTER 2
LITERATURE REVIEW
Breast cancer remains a serious global health challenge, and its impact is pronounced in
diverse populations, including those in Lusaka, Zambia. It is with different subtypes
necessitating nuanced approaches to diagnosis, treatment, and prognosis. Among these subtypes,
triple-negative breast cancer (TNBC) is highlighted for its distinctive biological characteristics
and clinical behavior, presenting unique challenges in its management. The term
“triple-negative” refers to the fact that the cancer cells lack estrogen receptors (ER), progesterone
receptors (PR), and also do not produce significant amounts of the protein called human
epidermal growth factor receptor 2 (HER2); essentially, these cancer cells test “negative” for all
three of these marker (Dass et al., 2021).
TNBC accounts for approximately 15-20% of all breast cancers in the world
(Mani, Hande and Boichuk, 2022). Compared to the other subtypes, TNBC is more aggressive,
recurs, and metastasizes more frequently (Dent et al., 2008), and women of African origin are
disproportionately affected (Lukong, Ogunbolude, and Kamdem, 2017). In fact, TNBC is most
commonly reported in women of African heritage three times more frequently (Boyle, 2012).
According to Anyigba, Awandare, and Paemka (2021), approximately 18,383,955 breast cancer
cases were recorded in Zambia in 2020. However, no details regarding the type of breast cancer
—whether TNBC or non-TNBC—were reported.
Zambia faces high mortality rates due to the fact that over two-thirds of female breast
cancer patients present with advanced illness. Delays in symptom recognition and diagnosis
contribute significantly to the underlying causes of this issue (Songiso et al., 2020). One of the
possible reasons for these delays is the lack of cancer research in the region. Kayamba et al.
(2021) highlight that the production of cancer research from Africa remains extremely low, with
the majority of publications concentrated in a few nations. Understanding the complex landscape
of TNBC, particularly in the context of specific populations, is imperative for tailoring effective
interventions and improving patient outcomes. TNBC presents distinctive challenges, yet in the
context of Lusaka, Zambia, there remains a critical knowledge gap. Currently, no research has
been conducted to establish comprehensive data on the prevalence of TNBC compared to
non-TNBC. This absence of data hinders the optimization of interventions, highlighting the
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pressing need for focused research. This study aims to address this gap and contribute to our
understanding of breast cancer in the region.
This study embarks on a comprehensive exploration of clinical outcomes and recurrence
patterns, delving into the comparative analysis of patients with TNBC and non-TNBC at the
Cancer Diseases Hospital in Lusaka, Zambia. As breast cancer remains a leading cause of
morbidity and mortality worldwide, the need for localized insights, especially in resource-
constrained settings like Zambia, becomes paramount.
The demographic composition of breast cancer patients often varies across populations,
influencing disease presentation, treatment choices, and overall outcomes. Consequently, an
examination of these demographics is a crucial starting point. Furthermore, the treatment
landscape for breast cancer, encompassing surgical, chemotherapy, and radiotherapy
interventions, is evolving rapidly, necessitating an in-depth analysis of the specific regimens
employed in the Zambian context. Survival rates, both overall and disease-free, serve as
fundamental benchmarks for evaluating treatment efficacy and shaping future therapeutic
strategies.
Recurrence patterns, a critical aspect of cancer management, warrant meticulous scrutiny
to identify potential trends and risk factors. This study aims to unravel the intricate tapestry of
recurrence, distinguishing between locoregional and distant recurrences in TNBC and
non-TNBC patients. By shedding light on these patterns, the research seeks to contribute
valuable insights into the long-term trajectories of breast cancer survivors.
Moreover, the study acknowledges the multifaceted nature of factors influencing clinical
outcomes. From genetic markers to socioeconomic determinants and access to healthcare, a
holistic exploration of these variables is essential for formulating targeted interventions. This
research aligns with the global endeavor to bridge the gap in breast cancer research, addressing
the specific needs of the Zambian breast cancer patient population.
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Conceptual Framework:
The conceptual framework for this study is based on the premise that the prevalence of
TNBC among breast cancer patients at Cancer Diseases Hospital, Lusaka, Zambia, is influenced
by a multitude of factors operating at individual, healthcare system, and societal levels. The
framework draws upon the socio-ecological model, which posits that health outcomes are shaped
by the interplay of factors at multiple levels, including intrapersonal, interpersonal, institutional,
community, and policy levels.
Intrapersonal Level: At the intrapersonal level, individual factors such as age, genetic
predisposition, reproductive history, and lifestyle behaviors may influence the likelihood of
developing TNBC. For example, younger age at diagnosis has been associated with a higher
prevalence of TNBC, while certain genetic mutations, such as BRCA1, are more commonly
found in TNBC patients.
Interpersonal Level: Interpersonal factors, including social support networks, cultural
beliefs, and access to healthcare information, can impact an individual’s awareness of breast
cancer risks, timely detection, and engagement in healthcare-seeking behaviors. Disparities in
access to healthcare services and information may disproportionately affect certain demographic
groups, potentially contributing to differential prevalence rates of TNBC.
Institutional Level: The healthcare system’s capacity and resources, including availability
of screening programs, diagnostic facilities, and treatment modalities, play a critical role in
detecting and managing TNBC. Limited resources and infrastructure constraints may hinder
early detection and optimal treatment, thereby influencing the prevalence of TNBC compared to
non-TNBC.
Community Level: Community-level factors, such as socio-economic status, cultural
norms, and healthcare utilization patterns, can shape individuals’ access to preventive services
and adherence to treatment regimens. Socio-economic disparities may contribute to differential
prevalence rates of TNBC, with marginalized populations facing greater barriers to care.
Policy Level: Policy interventions, including healthcare financing mechanisms, cancer
control strategies, and regulatory frameworks, can impact the availability, accessibility, and
quality of breast cancer services. Policies aimed at promoting early detection, improving
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treatment access, and addressing social determinants of health may contribute to reducing
disparities in TNBC prevalence.
By adopting a socio-ecological framework, this study aims to elucidate the complex
interplay of factors influencing the prevalence of TNBC among breast cancer patients at Cancer
Diseases Hospital, Lusaka, Zambia. This holistic approach acknowledges the multifaceted nature
of health outcomes and underscores the importance of addressing factors at multiple levels to
effectively mitigate disparities in TNBC prevalence and improve overall breast cancer care.
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