46P - Predicting toxicity following cancer chemotherapy by detecting transporter gene ABCB1 (C1236T, G2677T/A, C3435CT) polymorphism in breast cancer patients receiving chemotherapy with anthracycline and taxane either sequentially or concomitantly

Background

ABCB1 gene reported to affect chemo-induced toxicity through drug disposition and efflux mechanisms. This study aims to evaluate the influence of ABCB1 (C1236T, G2677T/A, C3435T) polymorphisms on, chemotoxicity, and survival outcomes in BC patients treated with anthracycline and taxane either sequentially or concomitantly.

Methods

100 patients were included who received sequential or concomitant anthracycline and taxane as per clinician discretion and underwent modified radical mastectomy. Chemotoxicity grade was analyzed by CTCAE v.4. All patients received standard premedication with 5HT₃, NK1 receptor antagonist, dexamethasone, H2 blocker/ PPI. SNP of ABCB1 (C1236T, G2677T/A, C3435T) gene was detected by PCR-RFLP and sequencing.

Results

Patients mostly reported at Stage III (52.89%) with infiltrating ductal carcinoma subtype (90.9%) who received sequential (50%) & concomitant (50%) chemotherapy. Grade ≥2 chemo toxicity like neutropenic fever, significantly associated with C1236T SNP with odd ratio (OR) for TT genotypes was 2.00 (95% CI: 0.125-31.975, p=0.000), while in CT genotypes, it stood at 1.100 (95% CI: 0.063-15.988; p = 0.035). Meanwhile, vomiting was significantly associated with C3435T for TT genotypes, with an OR of 3.031 (95% CI: 0.031-7.994, p=0.05). TT genotypes (C1236T) were significantly associated with nausea (OR: 2.667; 95% CI: 1.043-6.815; p = 0.04). Alopecia was observed 88% patients. However, ABCB1 showed no significant (p = 0.416, Log-rank) correlation for overall survival. Although, no significant associations were found for G2677T/A in terms of toxicity and survival.

Conclusions

The homozygous mutant TT genotypes (C1236T and C3435T) and heterozygous CT genotypes (C1236T) showed significant association to chemo-induced toxicity (hematological toxicity, nausea, vomiting, alopecia) in patients underwent anthracycline and taxane. Hence, these SNPs could serve as predictive markers to mitigate chemotherapy's adverse effects and optimize treatment to reduce the grade of toxicity and improves patients quality of life.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

V. D. Nasare.

Funding

This work is funded by Council of Scientific and Industrial Research, Government of India, File No. 09/030(0085)/2019-EMR-I awarded to Tanuma Mistry.

Disclosure

The author has declared no conflicts of interest.