Pharmacogenomic variants influence risk of anthracycline-induced cardiotoxicity in breast cancer patients, with several variants increasing cardiotoxicity risk up to OR 14.1 and others decreasing risk down to OR 0.259.
Systematic Review (n=4,703)
Do specific genetic variants predict the risk of anthracycline-induced cardiotoxicity in breast cancer patients?
Specific genetic variants, such as those in ABCC1 and CBR3, significantly influence the susceptibility to anthracycline-induced cardiotoxicity in breast cancer patients, highlighting the potential for pharmacogenomic-guided precision therapy.
Effect estimate: For 18 genetic variants, ORs indicating increased risk ranged up to 14.1 (ETFB rs79338777, OR 14.1, 95% CI 1.60–124); several variants with ORs > 2.5 (e.g., ABCC1 rs4148350 OR 9.661, NOS3 rs1799983 OR 3.06); 3 variants showing risk reduction (e.g., UGT2B7-161 rs7668258 OR 0.259, 95% CI 0.103–0.651; NCF4 rs1883112 OR 0.49)
Anthracyclines significantly improve overall survival and play a vital role in the treatment of breast cancer. However, they are associated with cardiac dysfunction, which is often irreversible. Although anthracycline-induced cardiotoxicity (AIC) is dose-dependent, the difference in susceptibility patterns suggests the role of pharmacogenomics. Several studies explored the role of genetic variants in AIC. Integrating pharmacogenomic testing with routine anthracycline surveillance will help to predict the individuals who are at risk of developing AIC. Therefore, this current systematic review aims to evaluate and synthesize the evidence on the pharmacogenomics association of cardiotoxicity in individuals receiving anthracyclines for breast cancer treatment. PubMed, Embase, and Scopus databases are systematically searched for the literature. After the initial search, 842 records have been identified. Following screening, 18 studies investigating genetic associations with AIC in breast cancer patients were found to be eligible for inclusion in the study. The quality of studies is assessed with the Q-Genie tool. The data is extracted and summarized with odds ratios and corresponding confidence intervals were reported. A total of 18 candidate gene association studies involving 4,703 breast cancer patients were included in the qualitative synthesis. Out of 57 genetic variants reported, 18 genetic variants (31.5%) are associated with an increased risk, while 3 genetic variants (5.3%) have demonstrated a risk-reducing tendency. Characterizing genetic variants in biological pathways of anthracyclines could inform precision therapy and the development of targeted interventions. The limitations of the synthesized evidence include the inadequate sample size, methodological bias within the included studies, inconsistent findings from different studies, and imprecise effect estimates. The genetic variants influence susceptibility to AIC in breast cancer patients. Further large-scale studies with longer follow-up are warranted to validate these associations and facilitate their translation into clinical practice.
Bulusu et al. (Tue,) conducted a systematic review in Breast cancer patients receiving anthracycline chemotherapy (n=4,703). Anthracycline chemotherapy vs. Patients without specific genetic risk variants or protective variants was evaluated on Anthracycline-induced cardiotoxicity defined by LVEF decline or clinical cardiotoxicity symptoms per various study-specific criteria (For 18 genetic variants, ORs indicating increased risk ranged up to 14.1 (ETFB rs79338777, OR 14.1, 95% CI 1.60–124); several variants with ORs > 2.5 (e.g., ABCC1 rs4148350 OR 9.661, NOS3 rs1799983 OR 3.06); 3 variants showing risk reduction (e.g., UGT2B7-161 rs7668258 OR 0.259, 95% CI 0.103–0.651; NCF4 rs1883112 OR 0.49)). Pharmacogenomic variants influence risk of anthracycline-induced cardiotoxicity in breast cancer patients, with several variants increasing cardiotoxicity risk up to OR 14.1 and others decreasing risk down to OR 0.259.