Adjuvant Effect of Molecular Iodine in Conventional Chemotherapy for Breast Cancer. Randomized Pilot Study

Abstract

This study analyzes oral supplement of molecular iodine (I2) alone and in combination with the neoadjuvant therapy 5-fluorouracil/epirubicin/cyclophosphamide or taxotere/epirubicin (FEC/TE) in women with Early (stage II) and Advanced (stage III) breast cancer. In the Early group, 30 women were treated with I2 (5 mg/day) or placebo (colored water) for 7–35 days before surgery. For the Advanced group, 30 patients received I2 or placebo along with FEC/TE treatment. After surgery, all patients received FEC/TE + I2 for 170 days. I2 supplementation showed a significant attenuation of the side effects and absence of tumor chemoresistance. Control, I2, FEC/TE, and FEC/TE+I2 groups exhibit response rate of 0, 33%, 73%, and 100%, respectively, and a pathologic complete response of 18%, and 36% in the last two groups. Five-year disease-free survival rate was significantly higher in patients with I2 supplement before and after surgery compared to those receiving the supplement only after surgery (82% vs. 46%). I2-treated tumors exhibit less invasive potential, and significant increases in apoptosis, estrogen receptor expression, and immune cell infiltration. Transcriptomic analysis indicated activation of the antitumoral immune response. The results led us to register a phase III clinical trial analyzing chemotherapy + I2 treatment for advanced breast cancer.

Effects of Molecular Iodine/Chemotherapy in the Immune Component of Breast Cancer Tumoral Microenvironment

“…We previously demonstrated in a breast cancer pilot study that I 2 supplementation exerted adjuvant effects when combined with conventional chemotherapy, reducing the residual tumor size, and increasing disease-free survival [17]. The RNA-seq analysis showed that I 2 -treated tumors exhibited significant activation of Th1, NK, and CD8 cytotoxicity pathways [17]. In the present study and using the same transcriptomic bank, we analyzed I 2 and the chemotherapy treatment (Cht) in the immune scenario.…”

“…Molecular iodine is a micronutrient that shows antineoplastic properties in preclinical and clinical studies of breast cancer [10,24,25]. The mechanisms of action include direct antioxidant actions such as scavenging ROS and modulating mitochondrial functionality, as well as indirect actions activating PPARγ receptors, triggering apoptosis, and cell redifferentiation [13,17,[26][27][28]. In a previous analysis of this protocol, it was demonstrated that the I 2 supplement plus chemotherapy generated the best antitumor response (smaller tumor size and cancellation of chemoresistance) and increased the disease-free survival from 63 to 92% in five years in patients who received the I 2 supplement before and after surgery [17].…”

“…This iodolipid is an active ligand of peroxisomal-activated receptor type gamma (PPARγ), inducing re-differentiation by inhibiting stem signaling and triggering apoptosis [15]. In addition, I 2 supplementation exerts effects on the immune system, acting as a direct genetic modifier [16] or as an attractor, increasing the amount of CD8+ lymphocytes within the tumor [17]. We previously demonstrated in a breast cancer pilot study that I 2 supplementation exerted adjuvant effects when combined with conventional chemotherapy, reducing the residual tumor size, and increasing disease-free survival [17].…”

“…In addition, I 2 supplementation exerts effects on the immune system, acting as a direct genetic modifier [16] or as an attractor, increasing the amount of CD8+ lymphocytes within the tumor [17]. We previously demonstrated in a breast cancer pilot study that I 2 supplementation exerted adjuvant effects when combined with conventional chemotherapy, reducing the residual tumor size, and increasing disease-free survival [17]. The RNA-seq analysis showed that I 2 -treated tumors exhibited significant activation of Th1, NK, and CD8 cytotoxicity pathways [17].…”

Jod – unverzichtbar für die Gesundheit der Brust: Ein neuer Ansatz zur Prävention und Therapie vom Mammakarzinom

“…I 2 -treated tumors exhibit less invasive potential, and significant increases in apoptosis, estrogen receptor expression, and immune cell infiltration." [21][22][23][24] Um unsere Brüste prophylaktisch ausreichend mit Jod zu versorgen, müssen wir also unsere Jodzufuhr -am besten über eine entsprechende jodreiche Kost -deutlich erhöhen. Hier ist ein grundsätzliches Umdenken unserer Ernährungsgewohnheiten erforderlich.…”