In an era where breast cancer remains the most commonly diagnosed cancer among women worldwide, new research from Botswana is shedding light on the molecular underpinnings unique to African populations. Breast cancer’s global toll continues to rise, with over two million new cases reported in 2018 alone, marking a significant increase from 1.4 million cases in 2011. This disturbing trend is accompanied by an alarming rise in mortality, with deaths rising from approximately 458,000 in 2011 to over 626,000 in 2018. Amidst this global crisis, low- and middle-income countries, including Botswana, bear a disproportionate burden of both incidence and mortality rates, highlighting the urgent need to delve deeper into tumor biology particular to these populations.
Researchers from Botswana have conducted a pivotal retrospective study analyzing 125 archived mastectomy specimens collected between 2006 and 2009. Their efforts focus on classifying breast tumors by leveraging immunohistochemistry (IHC) biomarkers, a technique pivotal in tumor profiling that involves staining tissue with antibodies targeting specific cancer markers. This study goes beyond classic assessments by investigating the expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), as well as proliferative marker Ki-67, cytokeratin 5/6 (CK5/6), and epidermal growth factor receptor 1 (EGFR1). Each of these markers serves to unravel the complex molecular landscape defining breast cancer subtypes.
Molecular classification is crucial because it guides therapeutic decisions and prognostic expectations. The Botswana study’s findings reveal a heterogeneous distribution of tumor subtypes distinct in their biology and potential treatment response. Luminal A tumors, generally characterized by positive hormone receptors and low proliferation, constituted the largest group at 35.2%. This subtype often correlates with better prognosis and response to hormone-based therapies. However, almost equally significant were Luminal B and triple-negative breast cancers (TNBC), each accounting for 18.4% of cases. TNBC, defined by the lack of ER, PR, and HER2 expression, is notorious for aggressive behavior and limited targeted treatment options, underscoring a pressing clinical challenge.
HER2 enriched tumors, which overexpress the HER2 receptor, made up 13.6% of the tumors studied. This subtype is known for its aggressive clinical course but also for its responsiveness to HER2-targeted treatments like trastuzumab. Interestingly, a subset of tumors in this population—7.2%—were classified as Luminal B HER2 enriched, presenting a hybrid molecular profile that could influence clinical outcomes and necessitate nuanced therapeutic approaches. Another 7.2% were basal-like tumors, frequently associated with TNBC and characterized by expression of basal markers such as CK5/6 and EGFR. Notably, 12.8% of tumors expressed CK5/6, a finding that underscores the presence of a biologically distinct basal compartment within the breast tumors from Botswana.
A particularly intriguing discovery in this study was the identification of basal positive luminal tumors—tumors expressing both basal markers and luminal hormone receptors. These hybrids challenge the conventional four-subtype molecular classification currently used worldwide and suggest the need to extend biomarker panels beyond the usual quartet. The presence of such dual-expressing tumors may have profound implications for prognosis and treatment planning, particularly for African women who may harbor unique tumor biology not adequately captured by current classification systems.
Histologically, 76% of the tumors were classified as invasive ductal carcinoma not otherwise specified (IDC-NOS), which aligns with global breast cancer trends. The rest, categorized as special types, included mucinous carcinoma comprising 6.4% of cases. Grading of tumors further revealed that the majority were grade 2 (40%), followed by grade 1 (30.4%) and grade 3 (23.2%). Tumor grade directly correlates with aggressiveness and likelihood of metastasis, reinforcing the need for detailed histopathological assessment alongside molecular profiling.
Despite these valuable insights, clinical staging and tumor involvement data were incomplete in the analyzed specimens. This limitation highlights an ongoing challenge in resource-limited settings, where comprehensive clinical information may not always accompany archived tissue samples. However, the robust molecular characterization provided by the study compensates by emphasizing tumor biology over clinical presentation alone.
The implications of this research extend far beyond Botswana, offering a roadmap for how integrating extended immunohistochemical panels can redefine cancer subtyping for populations of African descent. The current standard of classifying breast tumors into four main molecular subtypes may overlook clinically significant groups, particularly those expressing both basal and luminal markers. Expanding the IHC panel to six or more antibodies promises more precise risk stratification, essential for tailoring effective therapeutic regimens in diverse patient populations.
This study’s approach of coupling traditional histology with expanded molecular markers aligns with cutting-edge cancer research trends emphasizing personalized medicine. By identifying tumor subtypes with unique marker profiles, oncologists could improve patient outcomes through targeted therapies and avoid one-size-fits-all treatments that may underperform in underrepresented populations. Moreover, this research could serve as a template for similar investigations in other low- and middle-income countries facing comparable breast cancer burdens.
With breast cancer mortality rates disproportionately high in Botswana and many African countries, studies like this bring hope for improved prognostic evaluations and more effective, individualized treatment compared to the often generic protocols currently employed. Characterizing the molecular heterogeneity of tumors at a population level represents a crucial step in confronting global health disparities in cancer care.
The identification of basal positive luminal tumors also opens the door for further research into the biological mechanisms driving this unique co-expression. Whether this hybrid phenotype portends a distinct clinical trajectory or treatment resistance remains to be explored, but its presence challenges established paradigms and underscores the necessity for ongoing molecular research inclusive of diverse genetic backgrounds.
Furthermore, the reliance on archived tissue specimens spanning several years demonstrates the value of biobanking in enabling retrospective studies that can unearth critical findings long after clinical treatment. This resource maximizes research opportunities in contexts where prospective cohort studies may be difficult due to financial and infrastructural limitations.
Advancing breast cancer classification in African populations will rely not only on molecular diagnostics but also on improving healthcare infrastructure to enable coherent clinical staging and follow-up. Together, these efforts can lead to comprehensive care pathways integrating diagnosis, risk stratification, and treatment tailored to molecular tumor characteristics.
Ultimately, the Botswana study invites the global cancer research community to rethink and recalibrate molecular classification frameworks to better represent diverse populations. This mindfulness will promote equity in cancer treatment and ensure that therapeutic advances are universally applicable across ethnicities and geographies, potentially transforming breast cancer outcomes worldwide.
Subject of Research: Female breast cancer molecular classification using immunohistochemistry biomarkers in Botswana
Article Title: Female breast cancer classification using immunohistochemistry biomarkers staining in Botswana
Article References:
Ndlovu, A.K., Kasvosve, I., Rantshabeng, P.S. et al. Female breast cancer classification using immunohistochemistry biomarkers staining in Botswana. BMC Cancer 25, 893 (2025). https://doi.org/10.1186/s12885-025-14251-4
Image Credits: Scienmag.com
DOI: https://doi.org/10.1186/s12885-025-14251-4
