TY - JOUR
T1 - Effects of metformin versus placebo on vitamin B12 metabolism in non-diabetic breast cancer patients in CCTG MA.32
AU - From the CCTG, Alliance, SWOG, ECOG, NSABP Cooperative Groups
AU - Lohmann, Ana Elisa
AU - Liebman, Mira F.
AU - Brien, William
AU - Parulekar, Wendy R.
AU - Gelmon, Karen A.
AU - Shepherd, Lois E.
AU - Ligibel, Jennifer A.
AU - Hershman, Dawn L.
AU - Rastogi, Priya
AU - Mayer, Ingrid A.
AU - Hobday, Timothy J.
AU - Lemieux, Julie
AU - Thompson, Alastair Mark
AU - Pritchard, Kathleen I.
AU - Whelan, Timothy Joseph
AU - Mukherjee, Som D.
AU - Chalchal, Haji I.
AU - Bernstein, Vanessa
AU - Stambolic, Vuk
AU - Chen, Bingshu E.
AU - Goodwin, Pamela Jean
N1 - Publisher Copyright:
© 2017, Springer Science+Business Media New York.
PY - 2017/7/1
Y1 - 2017/7/1
N2 - Background: Metformin is associated with low levels of vitamin B12 (VitB12) in patients with diabetes. The CCTG/MA.32 trial investigates the effects of metformin vs placebo on breast cancer (BC) outcomes in non-diabetic high-risk BC patients. We analyzed VitB12 at baseline and after 6 months of metformin (versus placebo) in the first 492 patients with paired blood samples. Methods: VitB12 was analyzed centrally in baseline and 6-month fasting plasma. Levels <181 pmol/L were considered deficient, 181–221 pmol/L borderline, and ≥222 pmol/L sufficient. Methylmalonic acid (MMA) and homocysteine (HC) were assayed in those with VitB12 levels <222 pmol/L. Statistical analyses used Spearman’s rank correlation coefficients and Wilcoxon signed-rank test for continuous variables and Chi-square test for categorical variables. Results: 237 patients received metformin and 255 received placebo; median (inter quartile range) baseline VitB12 levels were 390 (290, 552) and 370 (290, 552) pmol/L in the metformin and placebo arms, respectively (p = 0.97). At 6 months, the median levels were 320 (244, 419) in the metformin versus 380 (286, 546) pmol/L in the placebo arm (p = 0.0001). At baseline, 15 patients (11 metformin and 4 placebo) had VitB12 <181 pmol/L, and at 6 months, 18 patients (15 metformin and 3 placebo) (p = 0.004). Median hemoglobin was similar at baseline, metformin, 130 g/L (124–137), and placebo arms, 131 g/L (124–137) (p = 0.38), and at 6 months, metformin, 131 g/L (91–162), and 131 g/L (106–169) in placebo group (p = 0.11). Of the 74 subjects with vitamin B12 <222 pmol/L at either time point (45 metformin, 29 placebo), at baseline MMA was normal in all patients and two had elevated HC (>15μmol/L). At 6 months, one patient (metformin) had MMA >0.4μmol/L and 3 (2 metformin, 1 placebo) had HC > 15μmol/L. Conclusions: There was an increased rate of biochemical VitB12 deficiency after 6 months of metformin; this was not associated with anemia. Further research will investigate VitB12 levels in all subjects at baseline and at 6 and 60 months.
AB - Background: Metformin is associated with low levels of vitamin B12 (VitB12) in patients with diabetes. The CCTG/MA.32 trial investigates the effects of metformin vs placebo on breast cancer (BC) outcomes in non-diabetic high-risk BC patients. We analyzed VitB12 at baseline and after 6 months of metformin (versus placebo) in the first 492 patients with paired blood samples. Methods: VitB12 was analyzed centrally in baseline and 6-month fasting plasma. Levels <181 pmol/L were considered deficient, 181–221 pmol/L borderline, and ≥222 pmol/L sufficient. Methylmalonic acid (MMA) and homocysteine (HC) were assayed in those with VitB12 levels <222 pmol/L. Statistical analyses used Spearman’s rank correlation coefficients and Wilcoxon signed-rank test for continuous variables and Chi-square test for categorical variables. Results: 237 patients received metformin and 255 received placebo; median (inter quartile range) baseline VitB12 levels were 390 (290, 552) and 370 (290, 552) pmol/L in the metformin and placebo arms, respectively (p = 0.97). At 6 months, the median levels were 320 (244, 419) in the metformin versus 380 (286, 546) pmol/L in the placebo arm (p = 0.0001). At baseline, 15 patients (11 metformin and 4 placebo) had VitB12 <181 pmol/L, and at 6 months, 18 patients (15 metformin and 3 placebo) (p = 0.004). Median hemoglobin was similar at baseline, metformin, 130 g/L (124–137), and placebo arms, 131 g/L (124–137) (p = 0.38), and at 6 months, metformin, 131 g/L (91–162), and 131 g/L (106–169) in placebo group (p = 0.11). Of the 74 subjects with vitamin B12 <222 pmol/L at either time point (45 metformin, 29 placebo), at baseline MMA was normal in all patients and two had elevated HC (>15μmol/L). At 6 months, one patient (metformin) had MMA >0.4μmol/L and 3 (2 metformin, 1 placebo) had HC > 15μmol/L. Conclusions: There was an increased rate of biochemical VitB12 deficiency after 6 months of metformin; this was not associated with anemia. Further research will investigate VitB12 levels in all subjects at baseline and at 6 and 60 months.
KW - Anemia
KW - Breast cancer
KW - Homocysteine
KW - Megaloblastic anemia
KW - Metformin
KW - Methylmalonic acid
KW - Vitamin B12
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UR - http://www.scopus.com/inward/citedby.url?scp=85018320413&partnerID=8YFLogxK
U2 - 10.1007/s10549-017-4265-x
DO - 10.1007/s10549-017-4265-x
M3 - Article
C2 - 28447237
AN - SCOPUS:85018320413
SN - 0167-6806
VL - 164
SP - 371
EP - 378
JO - Breast Cancer Research and Treatment
JF - Breast Cancer Research and Treatment
IS - 2
ER -