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Impact of low BMI and ABCC2 genotype on the clinical response of sequential anthracycline-taxane chemotherapy receiving breast cancer patients: a hospital-based study

The Pharmacogenomics Journal volume 25, Article number: 22 (2025) Cite this article

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Abstract

This study investigates combine effect of low BMI and possible pharmacogenetic influence of ABC gene polymorphisms in treatment responses of BC patients. BMI was analysed prior to commencement of chemotherapy. Clinical response was evaluated by radiological imaging and categorised as per RECISTv.1 criteria. SNPs (C1236T, C3435T, C58626A) in ABCB1 and ABCC2 gene were selected. 148 patients were analysed using PCR-RFLP. ABCC2 (58626AA) was significantly associated with treatment non-responsiveness in all genetic models namely dominant (OR 2.954; [1.442–6.051]; p = 0.003), recessive (OR 5.723; [2.48–13.20]; p < 0.0001), codominant (χ2 21.219; p < 0.0001). The proportion of ORR and NRs were significantly different between low (<18.5) and high (≥18.5) BMI classes (OR 16.097; [7.12–36.35]; p < 0.0001). Furthermore, when treatment response was combined with BMI groups, significant associations were observed for C58626A SNP across all genetic models among low BMI group: dominant (OR 3.324; [1.012–10.406]; p = 0.041), recessive (OR 7.250; [1.533–34.278]; p = 0.012) and codominant (χ2 8.657; p = 0.013). Both PFS (35.31 months; p = 0.005) and OS (39.75 months; p = 0.032) were lowered among AA genotype (ABCC2) while the hazard risk of this genotype was further increased in low BMI patients (HR 1.963). 3435CT genotypes in ABCB1 gene showed 87% reduction in risk of death (HR 0.13; p = 0.025). Low BMI independently and jointly with 58626AA genotype of ABCC2 gene was responsible for poor chemotherapy response and survival outcome among AC-T regimen receiving BC patients. Together, this study underscores the importance of genetic counselling and nutritional assessment for favourable treatment outcomes.

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Fig. 1: A brief overview of study design.
Fig. 2: Kaplan–Meier curves of progression-free and overall survivals of BC patients receiving anthracycline-taxane sequential chemotherapy with respect to different genotype classes.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

The authors would like to acknowledge the study participants and their respective guardians for their invaluable participation in this study. We also extend our gratitude to the Director of CNCI for providing the necessary infrastructure to facilitate this study and the funding agency (CSIR-HRDG, GOI; Grant no. 09/030(0085)/2019-EMR-I).

Funding

This study was funded by Council of Scientific and Industrial Research (CSIR)- Human Resource Development Group (HRDG), Government of India; Grant no. 09/030(0085)/2019-EMR-I awarded to Tanuma Mistry.

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Authors and Affiliations

  1. Department of Pathology & Cancer Screening, Chittaranjan National Cancer Institute, Kolkata, West Bengal, India

    Tanuma Mistry & Vilas D. Nasare

  2. Department of Life Science & Biotechnology, Jadavpur University, Kolkata, West Bengal, India

    Tanuma Mistry

  3. Department of Biochemistry, University of Calcutta, Kolkata, West Bengal, India

    Sanghamitra Sengupta

  4. Molecular Biology Division, ICMR-National Institute of Cancer Prevention and Research, I-7, Sector 39, Noida, Uttar Pradesh, India

    R. Suresh Kumar

  5. Department of Health Research (DHR), Ministry of Health & Welfare, IRCS Building 1, New Delhi, India

    Nisha Thakur

  6. Department of Medical Oncology, Chittaranjan National Cancer Institute, Kolkata, West Bengal, India

    Partha Nath

  7. Department of Surgical Oncology, Chittaranjan National Cancer Institute, Kolkata, West Bengal, India

    Neyaz Alam

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  1. Tanuma Mistry
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Contributions

Study concepts by TM, VDN; Study Design by TM, SSG, VDN; Data acquisition by TM, PN, NA; Quality control of data and algorithms by TM, PN, NA, VDN; Data analysis and interpretation by TM, SSG, RSK, NT, VDN; Statistical analysis TM, SSG, VDN, Manuscript preparation TM, SSG, VDN; Manuscript editing TM, SSG, RSK, NT, VDN; Manuscript reviewed by All authors.

Corresponding author

Correspondence to Vilas D. Nasare.

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The authors declare no competing interests.

Ethics approval

The study protocol was reviewed and approved by Institutional Ethical Committee and was conducted according to Good Clinical Practice under the Declaration of Helsinki [Reference id: CNCI-IEC-DL-2020-6].

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All patients have provided written informed consent in their preferred language (Bengali/Hindi/English) before taking part in this study.

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Mistry, T., Sengupta, S., Kumar, R.S. et al. Impact of low BMI and ABCC2 genotype on the clinical response of sequential anthracycline-taxane chemotherapy receiving breast cancer patients: a hospital-based study. Pharmacogenomics J 25, 22 (2025). https://doi.org/10.1038/s41397-025-00380-3

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