Estrogen-receptor positivity in tumour, often requiring long-term tamoxifen therapy, is thought to characterise between 43% and 65% of breast cancer cases in Nigeria. The patient population is further marked by late-stage diagnosis which significantly heightens the tendency for tumour relapse in the course of tamoxifen therapy. Despite tamoxifen being considered a reliable chemopreventive in high-risk individuals and an effective adjuvant therapy for hormone-sensitive tumours, mortality has remained high among breast cancer patients in the West African region where Nigeria belongs. The Nigerian breast cancer population, like other similar patient-populations in the West African region, provides a mix of intrinsic genome-diversity and perhaps unique tumour biology and evolution. These peculiarities suggest the need for a rational approach to tumour management and a personalised delivery of therapy in Nigeria's dominant estrogen-receptor-positive patient population. Herein, critical indices of tamoxifen-therapy success are discussed in the context of the Nigerian breast cancer population with emphasis on salient aspects of tamoxifen-biotransformation, host- and tumour-genomics, and epigenetics.