Liquid Biopsy – The necessary first step towards democratising precision oncology?African biotech holds the key to transforming not just the health of African people, but our economies as well

In April 2022 Ama (not her real name), a middle-aged mother of three who lives in a small farming village in the Central Region of Ghana presented at the Cape Coast Teaching Hospital with a large mass in her right breast. A week later, she was diagnosed with advanced right breast cancer with metastases to the lungs. Unfortunately, Ama’s story is not uncommon as a growing number of women in Ghana (and many African countries) suffer and die from breast cancer every year. Breast cancer is the leading cause of cancer-related deaths in women across the globe, and sub-Saharan African countries bear a disproportionate burden of this mortality. The 5-year survival rate for breast cancer is 40% in sub-Saharan Africa, compared to 90% in high income countries. What makes Ama’s story different, is the speed and manner in which Ama received a diagnosis.

Ama is one of thirty-seven women who consented to participate in the AMBER study. AMBER – Liquid biopsy for detection of Actionable genomic Mutations in women of African descent with advanced Breast CancER, is a unique collaboration between Yemaachi Biotech (a cancer research company headquartered in Accra, Ghana) and Lucence (a next generation cancer diagnostics maker, based in Palo Alto, US). Working in partnership with doctors at the Cape Coast Teaching Hospital, the AMBER study was conducted to evaluate the utility of using liquid biopsy (a blood-based test) for the detection of mutations of clinical significance in women of African descent with advanced breast cancer. As a study participant Ama underwent immunohistochemical, radiological and molecular analysis prior to diagnosis.

Immunohistochemistry (IHC) revealed she had Triple negative breast cancer (TNBC) based on a lack of expression of oestrogen receptors (ER), progesterone receptors (PR), and undetectable amplification of human epidermal growth factor receptor-2 (HER2)/neu. TNBCs are very aggressive and are not amenable to targeted endocrine agents or the relatively affordable anti-HER2/neu agents, often resulting in poorer prognoses. TNBC is relatively common among women of Black African descent, whether they reside on the African continent or not. This characteristic epidemiology seems to suggest that TNBC has a hereditary basis and may partially explain the high breast cancer-related mortality reported in sub-Saharan Africa.

While IHC and imaging are useful for diagnosing and staging cancers, they are limited in their ability to inform clinical decision-making regarding the use of increasingly available targeted therapies that are revolutionising cancer care in developed countries.  For this, more advanced molecular tests are required, and next generation sequencing-based liquid biopsy tests are at the cutting edge. These minimally invasive tests enable clinicians to screen for the presence of any of a large number of actionable genetic variants, allowing them to identify which targeted therapy is best-suited for a particular patient.

As a participant of AMBER, Ama is one of very few Ghanaian women to have received a liquid biopsy and her results were particularly interesting. Her test detected a particular mutation implicated in some breast cancers. This BRCA2 T630Qfs*12 mutation has been classified as a pathogenic variant and was first identified in an African American woman. Discovery of this mutation meant her cancer was amenable to targeted treatment. Unfortunately however, this treatment is not currently available in Ghana.

Treatment of breast cancer has traditionally involved surgery, radiotherapy, and chemotherapy. Over the last two decades, additional targeted approaches have been developed to more specifically treat cancer with reduced toxicity. The genetic, hormonal and immunological characteristics of breast cancer inform the choice of targeted and personalised treatment making access to adequate diagnostics a prerequisite for targeted therapy. The results of the AMBER study clearly demonstrate the potential utility of deploying advanced molecular diagnostics in an African setting. Liquid biopsy in particular, appears to have certain advantages over tissue-based molecular analysis and may present a “leap-frog” opportunity for the continent.

In order to fully take advantage of this opportunity, more work will be needed to better characterise the genetic landscape of cancers in African populations and identify which pathogenic variants (both novel and existing) are most druggable (currently only 2% of globally available genomic information is derived from people of African ancestry). Ultimately, the actionability of a pathogenic variant depends on the accessibility of the drug. While this undoubtedly will involve multiple stakeholders, ensuring that the companion diagnostic tests are accessible is clearly the necessary first step.