Functional Variant rs4442975 Modulating FOXA1 Binding Affinity Can Influence Bone Marrow Suppression during...

The expression of the transcription factor FOXA1 is associated with the prognosis of estrogen receptor (ER)-positive breast cancer, and the genetic variant rs4442975 can affect FOXA1 function. Therefore, we investigated the association between rs4442975 and the efficacy of neoadjuvant chemotherapy for luminal A type breast cancer and evaluated its toxic side effects in a Chinese population. One hundred seventy-five patients with luminal A type breast cancer receiving neoadjuvant chemotherapy with a combination protocol of epirubicin and docetaxel (ET protocol) were enrolled in the study. Genotyping was performed in a randomized manner to identify candidate genetic variants. Unconditional logistic regression analysis was used to analyze the association of the variant with the efficacy and side effects of neoadjuvant chemotherapy. The results did not reveal any positive association with the efficacy of neoadjuvant chemotherapy, with an odds ratio (OR) of 0.73 (95% confidence interval = 0.27-1.94) in the additive model. However, analysis of the toxic side effects of neoadjuvant chemotherapy showed that rs4442975 was associated with bone marrow suppression, with an OR of 0.38 (95% confidence interval = 0.17-0.73, p = 0.005) in the dominant model. In summary, the functional genetic variant rs4442975 was associated with bone marrow suppression during neoadjuvant chemotherapy for luminal A type breast cancer. These results may help establish reliable molecular markers for predicting the prognosis of personalized treatment for luminal A type breast cancer and thereby contribute to the development of appropriate therapies.