Doxorubicin, although commonly used in chemotherapeutic regimens, has significant dose-dependent cardiotoxicity, reportedly due to the production of reaction oxygen species (ROS). In conjunction with the rapid development of tumour resistance, these are clinical issues that need to be addressed. In breast cancers, several studies have combined BH3-mimetics (e.g. ABT-737) with doxorubicin in an attempt to enhance apoptosis, though few have explored the associated time-dependent molecular changes. In this study, the underlying mechanisms of doxorubicin and ABT-737 were investigated in T47D breast cancer cell lines (oestrogen-positive; ER+). Using various cell culture analyses of viability, ROS levels, membrane potential changes and caspase activity, the specific molecular changes were examined following 4 hours treatment (with doxorubicin, ABT-737 and doxorubicin/ABT-737 respectively) and recovery periods (2, 4, 24 and 48 hours). Results indicate that combination treatment showed a progressive decline in necrosis with a steady increase in apoptosis, accompanied by an overall diminished ROS production. Moreover, the efficacy of combination treatment as compared to doxorubicin-treated cells was markedly enhanced. The findings also revealed a more constant activity of caspase, despite changes in mitochondrial membrane potential after 24 hours. This suggests that alternative pathways such as autophagy could have contributed to doxorubicin cytotoxicity initially. Overall, these findings provide evidence for the combined use of doxorubicin and ABT-737 in ER+ breast cancers, to mitigate the considerable cardiotoxicities associated with doxorubicin. They also suggest alternative pathways for therapeutic interventions in combination with doxorubicin.