Bridging the Gap in Breast Cancer Care for LMICs: Cost-effective PCR-based testing as an alternative to the ctDNA sequencing method to detect ESR1 mutation

Abstract

Breast cancer is the most common cancer among women worldwide, with disproportionately high mortality in low- and middle-income countries (LMICs) due to delays in diagnosis and limited access to treatment. In countries such as Pakistan, breast cancer tends to present at a younger age and is associated with poorer survival outcomes. Precision oncology approaches are needed to guide treatment, particularly for hormone receptor (HR)-positive, HER2-negative advanced breast cancer, where estrogen receptor 1 (ESR1) mutations drive endocrine resistance. Selective estrogen receptor degraders (SERDs) improve outcomes when ESR1 mutations are detected early, yet circulating tumor DNA (ctDNA) sequencing, the standard testing method, is costly and infrastructure-dependent. Polymerase chain reaction (PCR)-based methods, especially droplet digital PCR (ddPCR), offer a sensitive, affordable, and scalable alternative. Adopting PCR-based ESR1 testing in LMICs can enable timely therapeutic switching, reduce ineffective treatment, and improve survival outcomes. This approach represents a practical pathway to precision oncology in resource-limited healthcare systems.