What are the benefits of Motsc (Motofen) in breast cancer treatment?

MOTS-c and Breast Cancer: No Established Clinical Role

There is currently no evidence supporting the use of MOTS-c (mitochondrial-derived peptide) in breast cancer treatment, and it should not be considered as a therapeutic option. The available evidence is limited to a single observational study measuring circulating MOTS-c levels in breast cancer patients, which found no clinically meaningful changes.

Current Evidence on MOTS-c in Breast Cancer

Single Observational Study

• A study measuring circulating MOTS-c levels in HER2-positive breast cancer patients receiving neoadjuvant chemotherapy with trastuzumab (with or without metformin) found no significant alterations in MOTS-c levels after 24 weeks of treatment 1
• Changes in circulating MOTS-c levels did not correlate with pathological complete response (pCR), regardless of metformin treatment 1
• The study used a competitive ELISA assay (CEX132Hu) to measure MOTS-c and found no regulatory effects of metformin on circulating MOTS-c levels 1

Mechanistic Understanding

• MOTS-c is described as a mitochondrially-encoded "exercise-mimetic peptide" primarily expressed in skeletal muscle and detectable as a circulating hormone 1
• Its mechanisms involve insulin sensitization, enhanced glucose utilization, and suppression of mitochondrial respiration, which theoretically overlap with metformin's actions 1
• However, metformin's inability to effectively target skeletal muscle (the major tissue for MOTS-c production) may limit any potential regulatory effects 1

Established Breast Cancer Treatment Standards

For Hormone Receptor-Positive Disease

• Tamoxifen remains the gold standard endocrine therapy for both premenopausal and postmenopausal women with hormone receptor-positive breast cancer, with 5 years of treatment at 20 mg daily being the established standard 2
• Extended tamoxifen therapy for 10 years (versus 5 years) reduces recurrence risk and breast cancer mortality 2, 3
• For postmenopausal women, aromatase inhibitors (anastrozole, letrozole, exemestane) either as initial therapy or sequential therapy after tamoxifen provide superior disease-free survival compared to tamoxifen alone 2, 3

For Advanced/Metastatic Disease

• Endocrine therapy should be offered as first-line treatment for hormone receptor-positive, HER2-negative metastatic breast cancer except in cases of visceral crisis 2
• Options include tamoxifen, aromatase inhibitors with GnRH agents (in premenopausal women), fulvestrant, and CDK4/6 inhibitors combined with endocrine therapy 2, 3, 4
• CDK4/6 inhibitors (such as ribociclib) combined with aromatase inhibitors have significantly improved survival outcomes in metastatic HR+/HER2- breast cancer 4

For Male Breast Cancer

• Men with early-stage, hormone receptor-positive breast cancer should receive at least 5 years of tamoxifen therapy 2
• For advanced disease in men, treatment options mirror those used in women, including tamoxifen, aromatase inhibitors with GnRH agents, and fulvestrant 2

Critical Gaps in MOTS-c Research

Absence of Clinical Trial Data

• No randomized controlled trials have evaluated MOTS-c as a therapeutic intervention in breast cancer 1
• No studies have examined MOTS-c effects on breast cancer outcomes including survival, recurrence, or quality of life 1
• The single available study was purely observational and measured circulating levels rather than therapeutic administration 1

Lack of Mechanistic Evidence in Cancer

• While MOTS-c has metabolic effects in preclinical models, there is no evidence demonstrating anti-tumor activity specifically in breast cancer 1
• The relationship between circulating MOTS-c levels and breast cancer prognosis or treatment response remains undefined 1

Clinical Recommendation

Patients with breast cancer should receive evidence-based treatments according to established guidelines 2, 3. These include:

• Hormone receptor-positive disease: Tamoxifen (premenopausal and postmenopausal) or aromatase inhibitors (postmenopausal only) 2, 3
• HER2-positive disease: Trastuzumab-based regimens combined with chemotherapy 1
• Metastatic disease: Sequential endocrine therapies, CDK4/6 inhibitors, or chemotherapy depending on disease characteristics 2, 3, 4

MOTS-c has no established role in breast cancer management and should not be pursued outside of properly designed clinical trials with appropriate regulatory oversight 1.