Molecular iodine impairs chemotherapy resistance and adverse effects in breast cancer treatments

Breast cancer takes the first place in incidence and mortality among female cancer patients. Despite efforts being made in prevention and early detection, metastasis and resistance to chemotherapy are still important factors in treatment failure. Our group has demonstrated that molecular iodine (I 2 ) supplementation with conventional chemotherapy inhibited chemoresistance, reduced the severity of side effects, and increased life expectancy. This study is a double-blinded clinical trial (NIH NCT03688958) that analyzes the oral I 2 supplement, alone and in combination with different neoadjuvant therapies (alkylating agents, anthracycline, and hormonotherapy; Neo), in women with early (stage II) and advanced (stage III) breast cancer. In the Early group, 22 women were treated with I 2 (3 mg/day) or placebo (colored water) for 15-30 days before surgery (12 luminal A; 9 luminal B; 2 triple negative). For the advanced group, 16 patients received I 2 or placebo, along with Neo treatment (30-90 days) (3 luminal A; 6 luminal B; 7 triple negative). After surgery, all patients received I 2 (3 mg/day) for 3 years. At the time of surgery, I 2 supplementation impaired the chemoresistance (70%). Neo and Neo+I 2 groups exhibited pathological complete response of 10% and 40%, respectively. After 3 years, three placebo patients (1 luminal B; 2 triple negative) presented recurrence, and one died (triple negative). In contrast, only one patient in the I 2 treatment group presented with recurrence (luminal B), yet no patients died. Iodine treatments attenuated adverse effects without compromising thyroid function. Transcriptomic analysis (DESeq2) showed that I 2 supplementation activated genes involved in differentiation and cellular adhesion, while diminishing those involved in invasion and survival. In conclusion, I 2 supplementation enhances the antineoplastic response of Neo, independent of the pharmacological treatments used or the molecular cancer type, supporting the notion that I 2 is an effective adjuvant in the treatment of chemoresistant breast cancer. Acknowledgments: The authors are grateful for the technical support of Ana Cecilia Santiago and Laura García. PAPIIT-UNAM IN203425 and 217223 supported this work.