+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Neoadjuvant Metformin Added to Systemic Therapy Decreases the Proliferative Capacity of Residual Breast Cancer

Neoadjuvant Metformin Added to Systemic Therapy Decreases the Proliferative Capacity of Residual Breast Cancer

Journal of Clinical Medicine 8(12)

The proliferative capacity of residual breast cancer (BC) disease indicates the existence of partial treatment resistance and higher probability of tumor recurrence. We explored the therapeutic potential of adding neoadjuvant metformin as an innovative strategy to decrease the proliferative potential of residual BC cells in patients failing to achieve pathological complete response (pCR) after pre-operative therapy. We performed a prospective analysis involving the intention-to-treat population of the (Metformin and Trastuzumab in Neoadjuvancy) METTEN study, a randomized multicenter phase II trial of women with primary, non-metastatic (human epidermal growth factor receptor 2) HER2-positive BC evaluating the efficacy, tolerability, and safety of oral metformin (850 mg twice-daily) for 24 weeks combined with anthracycline/taxane-based chemotherapy and trastuzumab (arm A) or equivalent regimen without metformin (arm B), before surgery. We centrally evaluated the proliferation marker Ki67 on sequential core biopsies using visual assessment (VA) and an (Food and Drug Administration) FDA-cleared automated digital image analysis (ADIA) algorithm. ADIA-based pre-operative values of high Ki67 (≥20%), but not those from VA, significantly predicted the occurrence of pCR in both arms irrespective of the hormone receptor status (p = 0.024 and 0.120, respectively). Changes in Ki67 in residual tumors of non-pCR patients were significantly higher in the metformin-containing arm (p = 0.025), with half of all patients exhibiting high Ki67 at baseline moving into the low-Ki67 (<20%) category after neoadjuvant treatment. By contrast, no statistically significant changes in Ki67 occurred in residual tumors of the control treatment arm (p = 0.293). There is an urgent need for innovative therapeutic strategies aiming to provide the protective effects of decreasing Ki67 after neoadjuvant treatment even if pCR is not achieved. Metformin would be evaluated as a safe candidate to decrease the aggressiveness of residual disease after neoadjuvant (pre-operative) systemic therapy of BC patients.

Please choose payment method:

(PDF emailed within 1 workday: $29.90)

Accession: 069613104

Download citation: RISBibTeXText

PMID: 31835708

Related references

Prognostic Value of Residual Disease after Neoadjuvant Therapy in HER2-Positive Breast Cancer Evaluated by Residual Cancer Burden, Neoadjuvant Response Index, and Neo-Bioscore. Clinical Cancer Research 25(16): 4985-4992, 2019

Residual nodal disease in biopsy proven n1/n2 breast cancer following neoadjuvant systemic therapy. World Journal of Surgery 34(2): 256-260, 2010

The effects of metformin on pathologic complete response (pCR) rates in diabetic breast cancer (BC) patients receiving neoadjuvant systemic therapy (NST). Journal of Clinical Oncology 26(15_Suppl): 528-528, 2016

Contrast-Enhanced Spectral Mammography is Comparable to MRI in the Assessment of Residual Breast Cancer Following Neoadjuvant Systemic Therapy. Annals of Surgical Oncology 25(5): 1350-1356, 2018

Comparing Accuracy of Mammography and Magnetic Resonance Imaging for Residual Calcified Lesions in Breast Cancer Patients Undergoing Neoadjuvant Systemic Therapy. Clinical Breast Cancer 18(5): E1087-E1091, 2018

Phase II Randomized Study of Ixabepilone Versus Observation in Patients With Significant Residual Disease After Neoadjuvant Systemic Therapy for HER2-Negative Breast Cancer. Clinical Breast Cancer 15(5): 325-331, 2015

Residual Mammographic Microcalcifications and Enhancing Lesions on MRI After Neoadjuvant Systemic Chemotherapy for Locally Advanced Breast Cancer: Correlation with Histopathologic Residual Tumor Size. Annals of Surgical Oncology 23(4): 1135-1142, 2016

Functional proteomics characterization of residual breast cancer after neoadjuvant systemic chemotherapy. Annals of Oncology 24(4): 909-916, 2013

Neoadjuvant systemic therapy in patients with operable primary breast cancer: more benefits than breast-conserving therapy. Nederlands Tijdschrift Voor Geneeskunde 152(46): 2519-2525, 2008

Residual Disease after Neoadjuvant Therapy for Breast Cancer: Can MRI Help?. Radiology 289(2): 335-336, 2018

Breast conserving therapy after neoadjuvant systemic therapy in patients with T3 breast cancer is feasible. European Journal of Cancer 92: S82-S83, 2018

The anti-proliferative effect of metformin in triple-negative MDA-MB-231 breast cancer cells is highly dependent on glucose concentration: implications for cancer therapy and prevention. Biochimica et Biophysica Acta 1840(6): 1943-1957, 2014

Procedure for intraoperative material examination in breast cancer after neoadjuvant therapy to estimate residual cancer burden using the RCB system. Arkhiv Patologii 78(2): 41-46, 2016

Neoadjuvant systemic therapy in breast cancer. Orvosi Hetilap 150(2): 65-71, 2009

Neoadjuvant systemic therapy for breast cancer. Voprosy Onkologii 61(2): 162-168, 2015