Impact of Distinct Molecular and Immunological Features of Breast Cancer on the Effectiveness of Therapies in Ghana

Abstract

Breast cancer (BC) is a serious public health concern in sub-Saharan Africa, with Ghana incurring a staggering 5026 cases and 2369 deaths in 2022. The insufficiency of accurate epidemiological information, limited access to health care, late diagnoses, and insufficient screening procedures hinder policy implementation. While numerous treatment methods, such as chemotherapy, radiation, and immunotherapy, exist, patients with BC respond differently. The variation in response can be accounted for by a combination of genetic, environmental, and socioeconomic factors specific to the Ghanaian population. This review examines the unique molecular and immunologic characteristics of BC in Ghana and their implications for therapeutic effectiveness in personalized treatment. Precision medicine is suggested as imperative in the design of biomarker-guided therapies to consider the BC molecular heterogeneity that is prevalent among Ghanaian patients. However, there is still a challenge of late-stage diagnosis due to insufficient diagnostic infrastructure. Early detection efforts through investment in next-generation sequencing and health care training are imperative. Besides, immune checkpoint inhibitors show promising therapeutic utility in triple-negative breast cancer (TNBC), and clinical trials in the Ghanaian population should be considered. This article emphasizes the need for community education to counteract misconceptions and ensure timely health care-seeking behaviours. To minimize mortality rates and improve patient care for BC in Ghana, a concerted approach through research funding, policy reform, and collaborative stakeholder engagement is imperative, in addition to advancements in diagnostics and therapeutics in the local context.

Introduction

The global burden of breast cancer (BC) continues to surge as the years go by, and sub-Saharan Africa (SSA) has not been exempted from its debilitating effects. Breast cancer burden in SSA is highly profound, especially in West Africa, where it is the top cause of female mortality when compared with other cancer types. ¹ According to the Global Cancer Observatory (GLOBOCAN) project, approximately 5026 new cases of BC and 2369 deaths were recorded in Ghana in 2022, making it one of the most prevalent cancers with a high mortality rate in the country. Yet, several studies have reported a paucity of accurate epidemiological data.^{2 -4} Ssentongo et al ⁵ reiterated that low- and middle-income countries (LMICs) have not paid much attention to studying the epidemiology of BC, resulting in data scarcity. This leads to the inability to capture the actual disease burden, ultimately affecting the creation and implementation of comprehensive policies that can aid the effective management of BC. ⁶ Factors such as late clinical presentation, limited access to health care, limited screening uptake, and inadequate pathology services have also hindered the effective management of BC in Ghana.^5,7,8

Ghana has attempted to develop a national cancer registry, but limited resources have impeded the coordination of a fully functioning system. ⁹ Ghana, with a population of about 35 million, has only one regional cancer registry in Kumasi. ¹⁰ The 2012 to 2016 national cancer control strategy recognized 2 hospital-based cancer registries in the country, one at the Korle-Bu Teaching Hospital and the other at Komfo Anokye Teaching Hospital in Kumasi, which served as the foundation for the Kumasi Cancer Registry (KsCR). ¹⁰ Ghana Health Service is expanding health care services, with more district-level health facilities being equipped to provide screening and related services. Also, City Cancer Challenger—a Kumasi registry project—has been phenomenal in digitalizing and streamlining the KsCR at the Komfo Anokye teaching hospital, Kumasi. This aims to improve patient access to care through better referral systems and patient education, and to improve the management of cancer care in Kumasi. ¹¹

Despite all these hurdles, considerable strides have been made towards bringing relief to patients with BC over the years. Chemotherapies, radiotherapies, hormonal therapies, immunotherapies, surgery, and other Indigenous medical practices have been used to treat several histopathological types of BC and other cancers in Ghana. ⁶ For instance, some relapsing and malignant BCs have been treated with chemotherapy, like paclitaxel (Taxol) and doxorubicin. ¹² In addition, the National Centre for Radiotherapy and Nuclear Medicine at Korle Bu Teaching Hospital (KBTH) in Accra has also played a significant role in the use of 3D conformal radiotherapy (3DCRT) for the treatment of BCs annually. ¹³ However, it has been established that the efficacy of BC therapies and their associated treatment outcomes and patient survival rates differ remarkably among different races and ethnic groups.^{14 -16} This disparity in health outcomes results from unique genetic, environmental, and socioeconomic factors existing among different populations.^17,18 A more tailored treatment approach that considers these factors will improve treatment outcomes, survival rates, and reduction in BC mortality in West Africa, especially Ghana.^19,20 This review highlights the unique molecular, biological, and immunological features of BCs in Ghana, discussing their impact on the effectiveness of BC therapies used in the health sector.

Literature Search and Strategy

Important articles were obtained through various databases, including Google Scholar, PubMed, Scopus, and others. Keywords relevant to the review topic, such as tumour microenvironment, breast cancer, molecular alterations, therapies, and triple-negative breast cancer, were used in different combinations to identify relevant studies. A total of 99 sources were scrutinized, with a direct focus on peer-reviewed articles important to Ghana. Other studies were also identified via manual screening of the reference lists of some selected papers. The criteria that were used to include studies were based on their relevance to molecular characteristics, epidemiology, and potential therapeutic targets in breast cancer.

Hereditary Breast Cancer

Breast cancer is sporadic in most cases, but about 5% to 10% of breast cancer cases are hereditary. ²¹ The BRCA genes, BRCA1 and BRCA2, have important cellular functions in embryology, transcriptional regulation, and DNA-damage repair. ²² Germline mutations, promoter methylations, and somatic mutations have been the greater cause of BRCA1 and BRCA2 dysfunction. ²² In a meta-analysis conducted by Wang et al, ²³ notable germline mutations of the BRCA1 are 5382insC, 185delAG, 3819del5, and 4153delA, with frequency 0.09, 0.07, 0.02, and 0.06, respectively. In BRCA2, 4075delGT and 5802del4 with frequencies of 0.02 and 0.07, respectively, have been reported. These mutations can be transferred from one generation to the other. ²⁴

Tissue Subtypes and Their Prevalence

Breast cancer can be widely categorized under 2 main types based on growth patterns and observable characteristics of cancer cells. These are in situ carcinoma and invasive carcinoma. ²⁵ Invasive carcinoma is characterized by the infiltration of malignant cells from the ducts or lobules into adjacent tissues. In situ carcinoma is a non-invasive BC in which cancerous cells within the epithelia of the basement membrane begin to divide and grow excessively.^26,27 The most common histopathological type of BC from a 10-year retrospective study in the Northern region of Ghana was invasive carcinoma. ²⁸ Globally, these 2 manifestations present numerous histopathological subtypes with distinct characteristics. According to World Health Organization’s (WHO) classification of breast tumours, the in situ and invasive carcinomas can further be divided into 19 histological subtypes. ²⁹

Immunohistochemistry has been used to classify BC subtypes based on the presence of hormonal receptors like oestrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). ²⁸ The presence and/or absence and the expression levels of these receptors give 4 main molecular subtypes, namely Luminal A (ER/PR+, HER2−), Luminal B (ER/PR+, HER2+), HER2-enriched (high expression levels of HER2), and the most aggressive form, Triple-negative Breast Cancer (ER−/PR−/HER2−) (TNBC).^30,31 A plethora of studies have elucidated the clinical and pathological characteristics of the molecular subtypes of BC. Clinical and pathological characteristics such as tumour size, tumour grade, histological type, lymph node status, metastatic status, and age at diagnosis have been correlated to the various subtypes to assess which of them has a better or worse prognosis and to suggest appropriate treatment approaches.^32,33

Lumina A tumours present with low tumour grade and less metastasis to the lymph node, while basal-like tumours—a subtype of TNBC—possess high tumour-grade features. ³⁴ Elshamely et al ³⁵ reported luminal A and luminal B HER2-negative as common among patients who had passed the menopause stage and that higher ages heightened the possibility of having these subtypes. This group also had tumours at higher stages. Liu et al ³² analysed 102 breast tumours and found the differences in tumour size, tumour grade, and lymph node metastases among the subtypes to be significant. They observed that HER2-enriched tumours had larger tumour sizes and higher tumour grades, while TNBC frequently metastasized to the lymph nodes (Table 1).

Table 1.

Molecular Subtypes of Breast Cancer Classification in Ghana.

Classification	Subtype	Key characteristics	Distribution
Growth and observable features	In situ carcinoma	Are non-invasive	Less common
	Invasive carcinoma	Infiltrates the surrounding tissue	Most common
Immunohistochemistry	Luminal A	Low grade with ER/PR+ and HER2−	Common in older women
	Luminal B	High grade with ER/PR+ and HER2+	Common in older women
	HER2− enriched	Large size, high grade and aggressive with overexpression of HER2	Less common
	TNBC	Highly aggressive with ER−/PR−/HER2−	Most prevalent

ER, oestrogen receptor; PR, progesterone receptor; HER2, human epidermal growth factor receptor 2; TNBC, triple-negative breast cancer.

A study performed in Ghana by Seshie et al ³³ found no significant associations between molecular subtypes and certain clinical and pathological characteristics due to the small sample size. It has been shown that certain features are associated with the subtypes in other regions and may be crucial factors for predicting their prognoses. ³² Consistent with results from studies in African countries like Rwanda and Uganda, TNBC has the highest prevalence compared with other BC subtypes in Ghana. ¹² ,^{36 -38} TNBC subtype usually begins at an early age and tends to progress towards advanced stages faster. ³⁹ The surge in advanced-stage BC in Ghana may partly be due to late screening and diagnoses ³⁸ (Figure 1).

Figure 1.

TNBC prevalence across African countries. ³⁹

Oncogenic Signatures and Genetic Mutations

The role of genetic mutations in the progression, prognosis, and resistance of BC in Ghana cannot be overemphasized. In Ghana, BC exhibits unique genetic characteristics that influence its response to treatment regimens and exacerbate its aggressiveness. ⁴⁰ Recent studies revealed the high prevalence of multidrug-resistant (MDR) genes that code for ATP-binding cassette (ABC) transporter proteins—a class of proteins that are involved in drug efflux. ¹² Single-nucleotide polymorphisms (SNPs) in ABC transporters may alter their function, decreasing proper treatment outcomes and overall survival rates among BC patients in Ghana. ⁴¹ Particularly, the homozygous wild-type genotypes and alleles for ABC subfamily B1 (ABCB1), ABC subfamily C1, and ABC subfamily G2 were highly expressed in BC tissues that were analysed, suggesting a strong genetic predisposition to multidrug resistance. ¹²

Inactivation or mutation of the tumour suppressor gene p53 (TP53) is a widespread occurrence leading to several types of BC. In the 2022 Ghana Breast Health Study (GBHS) performed by Ahearn et al, ⁴² pathogenic variants of TP53 were identified in 5 BC cases. TP53 mutations are usually found in TNBC, which is the most prevalent subtype among Ghanaians, suggesting that they may contribute to the aggressiveness of TNBC.^43,44 Boaitey et al ⁴¹ reported the high expression of TP53 mutations in 83% of TNBC cases in Ghanaian and African American women as compared with 35% in hormonal receptor-positive (HR+; ER+/PR+) cases. To buttress this, a cohort study by Opoku et al found high levels of TP53, leading to their conclusion that TP53 elevation may be a suitable marker for the poor prognosis of TNBC in Ghana. Furthermore, GATA-binding protein 3 (GATA3) and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutations were found to be more frequently expressed in HR+ BC than in TNBC. ⁴¹ Breast cancer 1/2 (BRCA1/2) and Partner and Localiser of BRCA2 (PALB2) mutations have also been linked to an increased risk of BC development in Ghanaians. ⁴²

Specific processes generate unique patterns of mutations in cancer genomes known as mutational signatures. ⁴⁵ One unique mutational signature observed in Ghanaian patients with BC is a higher frequency of Signature 3. This mutational signature is associated with germline BRCA1/2 mutations and failure of DNA double-strand break-repair due to homologous recombination deficiency (HRD). This signature is also more common in TNBC cases. ⁴¹ Research has also shown that early-onset breast cancer (EOBC) cases associated with more aggressive histopathological and molecular features are common in Ghana. ⁴⁶

Early-onset breast cancer encompasses BC diagnosed before age 40 and is usually TNBC, suggesting the possibility of a genetic predisposition to this aggressive subtype. ⁴⁶ Although data on the genetic drivers of EOBC in Ghana are scarce, studies in other parts of Africa have demonstrated that the poorer pathological features of EOBCs are driven by a combination of genetic mutations, including germline and somatic mutations in genes such as BRCA1/2, TP53, F-box and WD repeat domain containing 7 (FBXW7), and WW and C2 domain containing 1 (WWC1). These mutations contribute to aggressive tumour characteristics, such as high histological grade, hormone receptor negativity, and increased metastatic potential.^{47 -49}

Immunological Profiles and Tumour Microenvironment

Immunological profiles and the tumour microenvironment (TME) of BC are essential for BC risk and progression and therefore call for population-based studies of the TME among Ghanaian patients. Stromal microenvironment (SME) factors, including the tumour-stroma ratio (TSR) and tumour-associated stromal cellular density (Ta-SCD), have also been linked with tumour aggressiveness and responsiveness to treatment. High Ta-SCD is associated with aggressive and high-grade tumours and with enhanced tumour aggressiveness when TSR is low. The number of births and body size also significantly influence Ta-SCD, but not TSR. ⁵⁰

A higher density stroma which contains tumour-infiltrating lymphocytes (TILs) is associated with more aggressive tumour phenotypes such as TNBC. ⁵¹ Tumour-infiltrating lymphocytes are made up of T cells, macrophages, B cells, NK cells, and other immune cells. Approximately 11.3% of cases in West Africa showed high TILs levels, with significant variations across different molecular subtypes. ⁵² In HER2-positive breast cancer, it has been reported that high levels of TILs are related to a better response to neoadjuvant chemotherapy combined with trastuzumab. The predictive role of TIL in HR+ and HER2− negative breast cancer subtypes (luminal A and luminal B) is not well established. ⁵³ Inside this group, TILs are rapidly detected in the more aggressive Luminal B subtype than in the Luminal A subtype.^54,55 Routine analysis of TILs in HR-positive/HER2-negative breast cancer is not currently recommended for use as a predictive biomarker. ⁵³

Nuclear factor kappa B (NF-kB) (p65) is highly expressed in BC tissues and significantly correlates with tumour grade, Ki67 proliferation index, and molecular subtype. ⁵⁶ Triple-negative breast cancer demonstrates the most NF-kB overexpression among BC subtypes compared with the Luminal A and Luminal B subtypes, and not with HER2-enriched cases. ⁵⁶ This suggests a positive correlation between NF-kB activation and aggressive tumour proliferation. Nuclear factor kappa B expression is not significantly associated with age, hormonal receptors, lymphovascular invasion, tumour stage, or HER2 status. With its prevalence in aggressive subtypes like TNBC, NF-kB may be used as a BC prognostic biomarker for patients from Ghana and could be further investigated as a therapeutic target. ⁵⁶

Triple-negative breast cancer occurs with a frequency of approximately 10% of BC cases in the United States and occurs with increased frequency within the African American and Ghanaian populations and results in poorer prognoses than within European ancestry populations. ⁵⁷ ALDH (Aldehyde dehydrogenase) + breast cancer stem cells (BCSCs) gene expression patterns within TNBC reveal appreciable ethnic differences between the Ghanaian, African American, and White populations. Ghanaian patients’ tumour samples are enriched with immune-related genes, including CD274 (PD-L1), CXCR9, CXCR10, and IFI27, compared with the samples from the African American and White patients. This reflects the increased inflammatory and immune signature for TNBC within the population with African ancestry, with PD-L1 expression found significantly within PDXs from the patients. ⁵⁸

Histological concordance and marker expression between PDXs and primary tumours also validate the potential for immune-related pathways—particularly PD-L1 and IFI27—to be employed as therapeutic targets for the aggressive biology of TNBC within populations with African ancestry. ⁵⁸ Transcriptomic profiling within TNBC also detects a 613-gene signature enriched with immune cell-trafficking pathways, with increased tumour-associated leukocyte infiltration, notably TILs (B- and T-cells). ⁵⁷

Presentation of Breast Cancer in Young and Older Patients

Generally, BC is more predominant and of a higher grade in Africans.^6,59 Triple-negative breast cancer was seen across both young and older women. However, it was more prevalent in early-onset status than in late-onset status, with percentages of 26.4% and 24.30%, respectively. In the same study, early-onset breast cancer patients exhibited a slightly higher proportion of Luminal A subtype than late-onset breast cancer patients, that is, 11.30% vs 10.80%, respectively. This was not the same for Luminal B patients with HER2-negative tumours, as their proportion was 22.10% vs 19.10%, which was commonly presented in older patients. ⁴⁶ The tumours in younger Ghanaian patients were not only fast-growing, as Ki-67 surpassed the 20% threshold in 82.4% of cases, but were also more frequently associated with lymph node involvement already established at diagnosis. It is important to note that TNBC in the Ghanaian population remains significantly higher than in global populations. ⁴⁶

Effectiveness of Current Therapies in Ghana

The effectiveness of currently available therapies for BC treatment in Ghana—surgery, radiotherapy, chemotherapy, hormonal therapy, and targeted therapies—depends on several factors, such as the stage of diagnosis, tumour biology, and patient access to care, influenced by access to resources and the availability of some of these advanced treatments.^7,60,61 In addition, a lack of knowledge about BC is a major hindrance in patients seeking health care. ⁶² Studies have shown that a comprehensive and often multidisciplinary approach to care, tied to precision medicine, is essential for treating BC and improving the life expectancy of patients significantly.^63,64 However, due to a lack of/or access to such resources in Ghana, this is hardly achieved, reducing the success rate of available treatment options. Beyond this, early detection and willingness to seek treatment will decrease the need for more advanced treatment options because they are relatively difficult to achieve. ⁶²

Surgical Therapies

Surgical options for BC treatment are tailored to the individual patient’s needs and the stage of the disease. Lumpectomy, a breast-conserving surgery that removes the tumour along with a margin of healthy tissue, is an option for early-stage cancers and is often followed by radiation therapy to reduce recurrence risks. For more advanced cases, mastectomy may be performed, involving the removal of one or both breasts. Axillary dissection and sentinel lymph node biopsy are also surgical procedures used to evaluate and address the potential lymphatic spread of cancer, with the latter being less invasive and aimed at preserving more healthy tissue. In addition, for women undergoing mastectomy, breast reconstruction offers a way to restore breast shape and can be done using implants or the patient’s tissue. ⁶¹ While these surgical options are available, access to timely and comprehensive BC care in Ghana can be influenced by factors such as health care resource availability and public awareness of the disease.

A recent study by Schoenhals et al ⁶⁵ found that BC surgical treatment in Ghana is severely limited, with only 9 out of 328 surveyed hospitals offering level 3 care, which includes essential procedures like mastectomy and axillary lymph node sampling. Mastectomy is the predominant surgical option, yet it often lacks appropriate complementary treatments, leading to incomplete care, especially in patients presenting with late-stage disease. There is an urgent need for enhanced surgical training and resources to improve the quality of surgical care, particularly in techniques such as axillary lymph node dissection. In addition, the research identified opportunities for hospitals to expand their services, which could significantly increase the population’s accessibility to comprehensive BC treatment within reasonable travel distances. ⁶⁵

Another study in the Eastern region of Ghana observed significant limitations in surgical treatment options for BC. Only 13 hospitals (approximately 39.4%) provided surgical interventions, with 6 offering both mastectomy and wide local excision, while the rest performed only wide local excisions. Importantly, no facilities were equipped to conduct sentinel lymph node biopsies, a critical procedure for accurate staging and treatment planning. ⁶⁶ Despite these limitations, Okifo et al ⁶⁷ reported a postoperative complication rate of less than 10% among patients with BC in Cape Coast, suggesting relatively favourable surgical outcomes in that region.

Hormone Therapy and Targeted Treatments

Breast cancer management in Ghana is significantly challenged by limited access to and variable efficacy of systemic therapies. While tamoxifen is the most widely available endocrine treatment, its utility is constrained by the high prevalence of TNBC, a subtype unresponsive to hormonal interventions.^65,68 Aromatase inhibitors and HER2-targeted therapies, such as trastuzumab and lapatinib, are critically underutilized due to resource limitations and infrastructural deficits, severely impacting outcomes for HR+ and HER2-positive patients, respectively. This disparity is compounded by inconsistent receptor status testing, hindering personalized treatment strategies and the elucidation of resistance mechanisms. ⁶⁹ The observed scarcity of comprehensive chemotherapy regimens, with limited availability of essential agents like doxorubicin and fluorouracil, further underscores the urgent need for improved cancer care infrastructure and accessible multidisciplinary treatment protocols. ⁶⁵

Emerging resistance mechanisms further complicate the effectiveness of systemic therapies in Ghanaian BC patients. Genetic heterogeneity, tumour microenvironmental factors, and potential pharmacogenomic variations within the Ghanaian population likely contribute to treatment resistance. Notably, the high incidence of aggressive TNBC, known for its intrinsic resistance to targeted therapies, necessitates innovative treatment approaches. Furthermore, the lack of robust molecular profiling and biomarker assessment limits our understanding of the specific resistance pathways operative in this population. ⁷⁰ Addressing these challenges requires a concerted effort to enhance diagnostic capabilities, expand access to advanced therapies, and conduct comprehensive genomic and transcriptomic studies to identify actionable targets and develop personalized treatment strategies tailored to the unique biological characteristics of Ghanaian BC patients. This approach is crucial for improving patient survival and reducing the significant morbidity associated with this disease in the region. ⁶⁵

Chemotherapy and Radiotherapy Responses

Chemotherapy remains a cornerstone of BC treatment in Ghana, yet resource constraints and molecular heterogeneity significantly influence its accessibility and efficacy.^65,70 While standard regimens, including anthracycline- and taxane-based combinations, are employed, their consistent delivery is hampered by logistical challenges, including drug availability and infrastructure limitations. The variable response to these regimens is further compounded by the high prevalence of TNBC, which often exhibits intrinsic resistance to conventional chemotherapy. Moreover, the absence of routine molecular profiling and receptor status testing impedes the ability to tailor treatment strategies, leading to suboptimal outcomes. ⁶ This lack of personalized approaches and late-stage diagnoses exacerbates the challenges in achieving effective therapeutic responses. ⁷¹

The heterogeneity of BC at the molecular level significantly affects chemotherapy responses in Ghanaian patients. Variations in hormone receptor and HER2 status necessitate individualized treatment plans, yet the lack of widespread access to advanced diagnostic tools limits the implementation of such strategies. Genetic polymorphisms affecting drug metabolism and tumour-specific molecular profiles further contribute to the variability in treatment outcomes and toxicity. The high incidence of TNBC, a subtype known for its aggressive behaviour and limited therapeutic options, ⁷² underscores the urgent need for innovative approaches. Integrating molecular profiling into routine clinical practice, enhancing access to targeted therapies, and conducting pharmacogenomic studies to identify predictive biomarkers are crucial steps towards optimizing chemotherapy efficacy and improving patient survival. ⁷³ Furthermore, addressing the logistical barriers to consistent drug delivery and strengthening health care infrastructure is essential to ensuring equitable access to effective cancer care.

Immunotherapy and Emerging Treatments

Immunotherapy, particularly immune checkpoint inhibitors (ICIs), represents a promising frontier in BC treatment, yet its integration into standard care in Ghana remains in its infancy.^74,75 While ICIs such as pembrolizumab and atezolizumab have demonstrated efficacy in advanced TNBC and select HER2-positive cases in Western clinical trials, their application in Ghana is severely constrained. The nation’s health care infrastructure, primarily focused on established modalities like surgery, chemotherapy, and endocrine therapy, lacks the capacity for widespread ICI administration. ⁷⁴ Resource limitations, including the high cost of ICIs and the absence of robust insurance coverage, pose significant barriers to access. ⁷⁶ Moreover, the necessity for specialized diagnostic capabilities, such as PD-L1 testing, and expertise in managing immune-related adverse events further impedes the feasibility of implementing immunotherapy on a large scale. Consequently, while the potential of ICIs is recognized, their current role in Ghanaian BC management is minimal, highlighting a critical gap in advanced treatment options.

Overcoming the challenges to immunotherapy implementation in Ghana requires a multifaceted approach. First, strategic investment in health care infrastructure is essential to establish specialized oncology centres equipped for ICI administration and monitoring. Second, targeted research initiatives are needed to evaluate the efficacy and safety of ICIs within the Ghanaian population, considering potential genetic and environmental factors that may influence treatment response. Studies focusing on the prevalence of PD-L1 expression and other predictive biomarkers in local BC subtypes are crucial for patient selection. Furthermore, collaborations with international research institutions and pharmaceutical companies can facilitate technology transfer and provide access to affordable ICI therapies. Finally, the development of national guidelines and training programmes for health care professionals is imperative to ensure the safe and effective integration of immunotherapy into standard practice. As the global landscape of BC treatment evolves, addressing these challenges will be vital to ensure Ghanaian patients benefit from the advances in immunotherapy, thereby improving survival rates and quality of life.

Barriers to Effective BC Treatment in Ghana

Despite the known benefits of early detection and treatment, most patients with BC in Ghana are diagnosed late, leading to low survival rates. ⁷⁷ Several factors contribute to these delays, including barriers at the patient, provider, and system levels.

One of the major patient-related barriers is the prevalence of misconceptions about BC. Many believe the disease is caused by supernatural forces, such as witchcraft or sin, leading them to seek alternative treatments like herbal medicine and faith healing. Fear of mastectomy, chemotherapy side effects, and concerns about hospital reputations also discourage early medical intervention. In addition, financial constraints make chemotherapy and other medications unaffordable due to their high costs.

Health care provider–related barriers include negative attitudes from some medical staff, corruption that results in preferential treatment for well-connected individuals, and instances of bribery. Reports also indicate that some nurses mislead patients by advising them to pursue alternative treatments instead of biomedical care.

Systemic issues within the health care sector further exacerbate treatment delays. Long wait times, delayed biopsy results, a shortage of cancer specialists, and limited access to essential medications create significant bottlenecks in patient care. Addressing these issues requires a multifaceted approach, including public education to dispel myths and reduce fear, providing psychosocial support for patients, and improving health care infrastructure and workforce capacity. Expanding Ghana’s National Health Insurance Scheme (NHIS) to cover a broader range of cancer treatments is crucial for ensuring timely and effective care. ⁷⁷

Religious and cultural beliefs also significantly impact treatment adherence among patients with BC in Ghana. Studies show that women practicing Islam are more likely to discontinue treatment, often prioritizing faith-based healing over biomedical care. ⁷⁸ Many patients also turn to traditional healers after diagnosis, leading to delays or abandonment of conventional treatment. Fear and misinformation further contribute to the non-completion of treatment, with concerns about social stigma, severe side effects, and fatalistic beliefs that BC is incurable, discouraging many from pursuing or continuing therapy.

Beyond psychological and cultural barriers, systemic challenges also drive treatment discontinuation. Frequent shortages of chemotherapy drugs force patients to either delay or stop treatment altogether. In addition, inadequate BC education leaves many unaware of their condition and the available treatment options. Financial constraints remain a major obstacle, as the high out-of-pocket costs for chemotherapy and related treatments make access difficult, even under Ghana’s NHIS.^12,70,78

Challenges in Molecular Diagnostics and Treatment

Limitations in molecular diagnostics continue to hinder effective BC treatment in Ghana. Advanced techniques such as immunohistochemistry (IHC) and next-generation sequencing (NGS) remain uncommon in major hospitals, with only 200 out of 1057 patients receiving IHC testing. ¹² The lack of genomic profiling prevents the identification of key biomarkers, leading to delays and reliance on empirical treatments. This limitation restricts precise BC subtyping and ultimately prevents personalized therapy.

Cost remains a significant barrier, limiting access to essential diagnostic tests. In addition, the reliance on open surgical biopsies contributes to delays and increases the risk of patient loss to follow-up. The absence of BRCA mutation testing further hampers the identification of high-risk individuals who could benefit from targeted interventions. As a result, many patients miss out on therapies such as tamoxifen for hormone receptor-positive BC and trastuzumab (Herceptin) for HER2-positive BC due to diagnostic gaps.

Despite initiatives like the Ghana-Michigan partnership, which has enhanced immunohistochemistry training, the widespread adoption of molecular diagnostics remains limited. Addressing these challenges requires significant investment in infrastructure, funding, and research collaborations to integrate molecular profiling into routine BC care, ultimately improving treatment precision and patient outcomes. ⁷⁹

Ghana also lacks a national BC screening protocol, leading to late-stage diagnoses. Mammography machines are scarce and concentrated in urban centres, making early detection inaccessible for many women. The absence of a population-based cancer registry further complicates the ability to track incidence, mortality, and treatment outcomes. Delays in histopathology reports, missing biopsy results, and the high cost of imaging technologies contribute to inefficiencies in treatment. As a result, nearly half (47.6%) of BC cases in Ghana present with metastatic disease. ¹²

Logistical barriers, misinformation, and the absence of structured follow-up mechanisms cause many patients to abandon treatment. Poor coordination among health care departments exacerbates delays, increasing the risk of disease progression. In addition, navigating the health care system is challenging, as patients often receive inadequate guidance on treatment pathways, leading to confusion and non-compliance.^12,70

Limitations in Pharmacogenetics and Targeted Therapies

Breast cancer treatment in Ghana is hindered by the limited availability of pharmacogenetic testing, which is crucial for predicting individual responses to therapy. Genetic diversity among African populations leads to variations in drug metabolism, yet most treatment guidelines are based on studies from European and Asian populations, which may not be directly applicable to Ghanaian patients. ⁸⁰ Differences in key enzymes like CYP2D6, CYP2C9, and CYP3A4/5 significantly affect the effectiveness and toxicity of essential drugs such as tamoxifen.

Access to targeted therapies remains a major challenge. The high cost and limited availability of treatments like aromatase inhibitors and HER2-targeted therapies, such as trastuzumab, further widen disparities in care. Currently, only 21% to 29% of eligible BC patients in Ghana, Nigeria, and Kenya receive aromatase inhibitors.^58,80 In addition, genetic variations influence drug metabolism, making pharmacogenetic testing critical for optimizing treatment outcomes. ⁸¹

Expanding pharmacogenetic testing in Ghana could improve drug efficacy, reduce adverse effects, and enable more personalized treatment approaches. Greater access to molecular diagnostics and targeted therapies would significantly enhance BC care, ensuring that patients receive treatments best suited to their genetic profiles.

Health Care System Fragmentation and Specialist Shortages

Ghana’s fragmented referral system significantly delays BC diagnosis and treatment. Many patients initially seek care at lower-tier facilities that lack the necessary expertise and resources for proper management. Inefficient referral processes to tertiary institutions, such as Korle Bu and Komfo Anokye Teaching Hospitals, often result in patients reaching specialist care at advanced stages. ⁷⁰

A shortage of trained oncology specialists and pathologists further prolongs waiting times for consultations, treatment initiation, and follow-up care. Limited access to radiation therapy also remains a major obstacle, with only a few centres available, primarily in Accra and Kumasi. The high cost of radiation treatment further restricts access for patients outside these regions, worsening disparities in cancer care. ⁷⁰

Addressing these challenges requires systemic reforms, including improving referral efficiency, increasing specialist training, and expanding radiation facilities to ensure timely and equitable cancer care.

Future Directions and Recommendations

The evolving landscape of BC treatment calls for precision medicine, particularly in Ghana, where the molecular and immunological diversity of tumours plays a crucial role in determining therapeutic outcomes. Moving forward, comprehensive molecular and genomic profiling of local populations should be a priority to better understand the genetic factors influencing BC pathology. These studies can aid in developing biomarker-based treatment protocols tailored to the specific genetic profiles of Ghanaian patients. ⁸² Implementing targeted molecular therapies can enhance treatment efficacy, ensuring that patients receive interventions best suited to their cancer subtype.

However, Ghana’s current health care infrastructure presents major challenges to early diagnosis and effective treatment, often resulting in late-stage presentations.^83,84 Addressing these issues requires policy-driven improvements in diagnostic facilities and broader health care accessibility. Investments in advanced diagnostic technologies, such as next-generation sequencing and digital pathology, alongside specialized training for health care professionals, are essential. Strengthening health care infrastructure will not only facilitate early detection but also ensure that patients receive timely and appropriate treatments, ultimately improving survival rates.

Integrating immunotherapy into BC treatment in Ghana represents a promising avenue for enhancing patient outcomes. Emerging research highlights the role of exosomes in optimizing therapeutic delivery mechanisms and supporting immunotherapies.^49,85 Given Ghana’s unique TME, exploring immunotherapy options tailored to local needs is important. For instance, TNBC, known for its immunogenicity, could be effectively treated with immune checkpoint inhibitors, which have demonstrated efficacy across various populations.^86,87 Expanding research on immunotherapeutic interventions for Ghanaian patients will provide valuable insights into their applicability and effectiveness.

In addition, vaccine development targeting breast neoplasms presents an exciting new frontier in cancer treatment. With growing evidence supporting the efficacy of cancer vaccines in high-risk populations,^88,89 exploring their potential within the Ghanaian context could be transformative. Conducting clinical trials focused on immunotherapy and vaccine effectiveness among Ghanaian patient cohorts will generate critical data to refine treatment protocols and broaden therapeutic options for diverse populations.

Beyond clinical advancements, community-based educational initiatives are essential in addressing socio-cultural beliefs contributing to delayed diagnosis and treatment. Misconceptions about BC, including spiritual and traditional attributions, hinder early medical intervention.^90,91 Targeted educational campaigns should focus on dispelling misinformation and raising awareness of the benefits of early detection, routine screenings, lifestyle changes, and modern treatment options.

Moreover, enhancing education and training for health care providers is equally vital. Ensuring clinicians are well-informed about the importance of early diagnosis and available treatment options can foster trust between health care providers and patients, encouraging proactive health-seeking behaviours^92,93 and investing in local research and development in Ghana is key. ⁹⁴ A health care system that prioritizes patient education and engagement will cultivate a culture of early intervention, ultimately reducing the high mortality rates associated with late-stage BC presentations.

Conclusions

Addressing the challenges of BC treatment in Ghana requires a comprehensive approach that includes precision medicine, improvements in health care infrastructure, and the integration of innovative treatments like immunotherapy to complement existing strategies. Current research highlights significant gaps in molecular and genomic data specific to Ghanaian populations, underscoring the need for increased investment in local research and development by prioritizing these areas and fostering collaborations among stakeholders. Ghana can strengthen its capacity to deliver high-quality care and contribute to the global fight against BC. Future research should not only investigate the unique molecular and immunological characteristics of BC in Ghana but also assess how these insights can improve treatment outcomes.