Meeting
2014 ASCO Annual Meeting
Vitamin B12 (Vit B12) biochemical (BCH) deficiency (DEF) in non-diabetic breast cancer (BC) patients on NCIC CTG MA.32: A phase III randomized adjuvant BC trial comparing metformin (Met) to placebo (Pl).
Authors
Mira F. Liebman
University Health Network, University of Toronto, Toronto, ON, Canada
Mira F. Liebman , William Brien , Wendy R. Parulekar , Karen A. Gelmon , Lois E. Shepherd , Jennifer A. Ligibel , Dawn L. Hershman , Priya Rastogi , Ingrid A. Mayer , Timothy J. Hobday , Julie Lemieux , Alastair Mark Thompson , Kathleen I. Pritchard , Timothy Joseph Whelan , Som Mukherjee , Haji I. Chalchal , Vanessa Bernstein , Vuk Stambolic , Bingshu E. Chen , Pamela Jean Goodwin
Organizations
University Health Network, University of Toronto, Toronto, ON, Canada, NCIC Clinical Trials Group, Cancer Research Institute, Queen's University, Kingston, ON, Canada, NCIC Clinical Trials Group, British Columbia Cancer Agency, University of British Columbia, Vancouver, BC, Canada, Dana-Farber Cancer Institute/Harvard Medical School, Boston, MA, Columbia University Medical Center, New York, NY, National Surgical Adjuvant Breast and Bowel Project and University of Pittsburgh Cancer Institute, Pittsburgh, PA, Vanderbilt-Ingram Cancer Center, Vanderbilt University, School of Medicine, Nashville, TN, Mayo Clinic College of Medicine, Rochester, MN, Centre de Recherche du CHU de Québec, Unité de Recherche en santé des Populations Hôpital du Saint-Sacrement, Quebec, QC, Canada, Dundee Cancer Centre, Dundee, United Kingdom, Sunnybrook Odette Cancer Centre and the University of Toronto, Toronto, ON, Canada, Juravinski Cancer Centre, Hamilton, ON, Canada, Allan Blair Cancer Center, Regina, SK, Canada, British Columbia Cancer Agency, Vancouver Island Center, University of British Columbia, Vancouver, BC, Canada, Ontario Cancer Institute, University Health Network, Princess Margaret Hospital, University of Toronto, Toronto, ON, Canada, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada
Research Funding
Other
Background: Met, a drug used to treat type 2 diabetes, is being evaluated as an anti-cancer agent. Long-term use is associated with BCH Vit B12 DEF in up to 30%; a subset may develop symptomatic DEF. It is unknown if Vit B12 DEF is due to diabetes or Met use. We examined Vit B12 DEF in NCIC CTG MA.32, an RCT of adjuvant Met vs Pl in non-diabetic BC patients (pts). Methods: This was a DSMC approved central lab analysis in the first 492 (of 3649) high risk N0/N1-3 BC pts receiving standard therapy randomized onto MA.32 (Met 850 mg bid vs Pl bid for 5 years). VitB12 was analysed in baseline and 6 month (mo) fasting plasma; levels <181 pmol/L were DEF, 181 to 221 pmol/L borderline. Methylmalonic acid (MMA) and homocysteine (HC) (elevated in clinical Vit B12 DEF) were assayed in those with Vit B12 levels <222 pmol/L at either time. Hgb was measured locally. Analysis used Spearman’s rank correlation coefficients and Wilcoxon signed rank test for continuous variables and Chi-square test for 2 by 2 tables. Results: Mean age was 52.4±9.7 yrs. 237 received Met and 255 Pl; arms were balanced for hormone receptors (73% +ve), BMI (mean 28.3 kg/m2), adjuvant chemo (88%), stage, type of surgery/radiation. Median (Inter Quartile Range) baseline Vit B12 was 390 (281 to 556) and 370 (290 to 552) pmol/L in the Met and Pl arms respectively (p=0.97). 6 mo median levels were MET 320 (244 to 419) and Pl 380 (286 to 546) pmol/L (p=0.0001). 15 pts (11 Met and 4 Pl) had BCH Vit B12 DEF (<181 pmol/L) at diagnosis; 15 Met and 3 Pl at 6 mo (p=0.004). Mean Hgb was similar at baseline 130.1±9.1 (MET) and 131.0±9.9 g/L (Pl), p=0.38 and 6 mo 131.3±9.5 (MET) and 132.7±9.6 g/L (Pl), p=0.11); and in those +/- BCH Vit B12 DEF. Of the 74 with Vit B12 <222 pmol/L (45 Met, 29 Pl), MMA was normal in all pts at baseline; 2 had elevated HC (>15 umol/L). At 6 mo 1 Met pt had MMA >0.4 umol/L and 3 (2 Met, 1 Pl) had HC >15 umol/L. Conclusions: There was an increased rate of BCH, but not clinical, Vit B12 DEF after 6 mo of Met. This suggests that Met (not diabetes) lowers VitB12 and supports recommendations to monitor Vit B12 with Met use. Longer follow-up will evaluate clinical VitB12 DEF. Clinical trial information: NCT01101438.
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Abstract Details
Session Type
Poster Session
Session Title
Breast Cancer - HER2/ER
Track
Breast Cancer
Sub Track
ER+
Clinical Trial Registration Number
NCT01101438
Citation
J Clin Oncol 32:5s, 2014 (suppl; abstr 542)
DOI
10.1200/jco.2014.32.15_suppl.542
Abstract #
542
Poster Bd #
6
Abstract Disclosures
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