Metformin improves responses to chemotherapy in nondiabetic breast cancer

Use of metformin in nondiabetic breast cancer patients improves their clinical and pathological response to neoadjuvant AC-T chemotherapy, reveals a recent study.

This beneficial effect of metformin is driven by stimulating directionally opposite changes in the expressions of death receptors (DRs) and CD133, a glycoprotein biomarker of breast cancer stem cells.

Seventy nondiabetic breast cancer patients were randomized 1:1 to receive either neoadjuvant AC-T chemotherapy (four cycles of Adriamycin 60 mg/m² and cyclophosphamide 600 mg/m², followed by 12 cycles of weekly paclitaxel 80 mg/m²) or AC-T with adjunct metformin (850 mg twice/day).

The investigators quantified the expressions of DR4, DR5, and CD133 in excised tissue samples with residual tumour cells.

Patients in the metformin arm showed significant improvements in the overall clinical response (odds ratio [OR], 22.67, 95 percent confidence interval [CI], 2.77‒185.18; p=0.004), breast-conserving surgery (OR, 3.67, 95 percent CI, 1.303‒10.321; p=0.014), and pathological complete response rates (β, 2.49, 95 percent CI, 0.274‒4.721; p=0.028).

Tissues obtained from patients in the metformin arm, compared with those in the control arm, exhibited upregulated mRNA expression of DR4 (mean delta cycle thresholds: 2.68 vs 4.87; p=0.0003) and DR5 (0.21 vs 4.29; p=0.0004).

A negative correlation was observed between the enhanced expression of DR and that of CD133 + breast cancer stem cells, which was significantly reduced by metformin at both cytoplasmic/membranous (43.48 percent vs 100.00 percent; p<0.0001) and nuclear sites (4.35 percent vs 95.00 percent; p<0.0001).

“Clinical data demonstrate that metformin exhibits antiproliferative, proapoptotic, and antimetastatic actions,” the investigators said.