Prognostic associations of 25 hydroxy vitamin D in NCIC CTG MA.21, a phase III adjuvant randomized clinical trial of three chemotherapy regimens in high-risk breast cancer

Ana Elisa Lohmann, Judy Anne W Chapman, Margot J. Burnell, Mark Norman Levine, Elena Tsvetkova, Kathleen I. Pritchard, Karen A. Gelmon, Patti O’Brien, Lei Han, Hope S. Rugo, Kathy S. Albain, Edith A. Perez, Theodore A. Vandenberg, Haji I. Chalchal, Ravinder Pal Singh Sawhney, Lois E. Shepherd, Pamela Jean Goodwin

Research output: Contribution to journalArticle

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Abstract

Low vitamin D levels have been associated with poor breast cancer outcomes in observational studies. We examined the association of vitamin D blood levels with relapse-free survival (RFS), breast cancer-specific survival (BCSS), and overall survival (OS) in the MA.21 randomized clinical trial. Fasting blood was collected pre-chemotherapy in 934/2104 (44.4 %) of subjects; 25 hydroxy vitamin D was measured (radioimmunoassay, Diasorin) in one batch. Vitamin D was assessed as a transformed continuous factor, and categorically (quartiles and clinical classifications). Univariate and multivariate prognostic analyses (adjusted for treatment, stratification factors, and baseline imbalances) were performed using Cox models. Most patients were young (median 47.8 years), white (91.6 %) and premenopausal (69.4 %) with grade III (52 %), HER2 negative or missing (89.5 %), ER positive (61.9 %), T1-2 (89.4 %), N + (72.7 %) breast cancer. Compared to the full population, those with vitamin D levels were more likely to be white, PS 1 or 2, to have undergone mastectomy, and to have an ER + tumor. Mean vitamin D was 69.7 nmol/L (27.9 ng/ml) and did not vary by tumor subtype. The majority (80.5 %) had levels >50 nmol/L (20 ng/ml), considered adequate by Institute of Medicine. Continuous vitamin D was not multivariately associated with RFS, BCSS, or OS (p = 0.36, 0.26, 0.33, respectively); categorical vitamin D was also not associated with outcome. Vitamin D associations with RFS did not differ within ER/HER2 subgroups. There was no evidence that vitamin D blood level was associated with RFS, BCSS, and OS in MA.21; the majority of subjects had adequate vitamin D levels at study entry.

Original languageEnglish (US)
Pages (from-to)605-611
Number of pages7
JournalBreast Cancer Research and Treatment
Volume150
Issue number3
DOIs
StatePublished - Apr 1 2015

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Vitamin D
Randomized Controlled Trials
Breast Neoplasms
Drug Therapy
Survival
Recurrence
National Academies of Science, Engineering, and Medicine (U.S.) Health and Medicine Division
Mastectomy
Proportional Hazards Models
Radioimmunoassay
Observational Studies
Fasting
Neoplasms
Multivariate Analysis

Keywords

  • Breast cancer
  • Breast cancer specific survival
  • Chemotherapy
  • MA.21 trial
  • Overall survival
  • Randomized clinical trial
  • Relapse-freesurvival
  • Vitamin D
  • Vitamin D blood level

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Prognostic associations of 25 hydroxy vitamin D in NCIC CTG MA.21, a phase III adjuvant randomized clinical trial of three chemotherapy regimens in high-risk breast cancer. / Lohmann, Ana Elisa; Chapman, Judy Anne W; Burnell, Margot J.; Levine, Mark Norman; Tsvetkova, Elena; Pritchard, Kathleen I.; Gelmon, Karen A.; O’Brien, Patti; Han, Lei; Rugo, Hope S.; Albain, Kathy S.; Perez, Edith A.; Vandenberg, Theodore A.; Chalchal, Haji I.; Sawhney, Ravinder Pal Singh; Shepherd, Lois E.; Goodwin, Pamela Jean.

In: Breast Cancer Research and Treatment, Vol. 150, No. 3, 01.04.2015, p. 605-611.

Research output: Contribution to journalArticle

Lohmann, AE, Chapman, JAW, Burnell, MJ, Levine, MN, Tsvetkova, E, Pritchard, KI, Gelmon, KA, O’Brien, P, Han, L, Rugo, HS, Albain, KS, Perez, EA, Vandenberg, TA, Chalchal, HI, Sawhney, RPS, Shepherd, LE & Goodwin, PJ 2015, 'Prognostic associations of 25 hydroxy vitamin D in NCIC CTG MA.21, a phase III adjuvant randomized clinical trial of three chemotherapy regimens in high-risk breast cancer', Breast Cancer Research and Treatment, vol. 150, no. 3, pp. 605-611. https://doi.org/10.1007/s10549-015-3355-x
Lohmann, Ana Elisa ; Chapman, Judy Anne W ; Burnell, Margot J. ; Levine, Mark Norman ; Tsvetkova, Elena ; Pritchard, Kathleen I. ; Gelmon, Karen A. ; O’Brien, Patti ; Han, Lei ; Rugo, Hope S. ; Albain, Kathy S. ; Perez, Edith A. ; Vandenberg, Theodore A. ; Chalchal, Haji I. ; Sawhney, Ravinder Pal Singh ; Shepherd, Lois E. ; Goodwin, Pamela Jean. / Prognostic associations of 25 hydroxy vitamin D in NCIC CTG MA.21, a phase III adjuvant randomized clinical trial of three chemotherapy regimens in high-risk breast cancer. In: Breast Cancer Research and Treatment. 2015 ; Vol. 150, No. 3. pp. 605-611.
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AU - Chapman, Judy Anne W

AU - Burnell, Margot J.

AU - Levine, Mark Norman

AU - Tsvetkova, Elena

AU - Pritchard, Kathleen I.

AU - Gelmon, Karen A.

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AU - Albain, Kathy S.

AU - Perez, Edith A.

AU - Vandenberg, Theodore A.

AU - Chalchal, Haji I.

AU - Sawhney, Ravinder Pal Singh

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N2 - Low vitamin D levels have been associated with poor breast cancer outcomes in observational studies. We examined the association of vitamin D blood levels with relapse-free survival (RFS), breast cancer-specific survival (BCSS), and overall survival (OS) in the MA.21 randomized clinical trial. Fasting blood was collected pre-chemotherapy in 934/2104 (44.4 %) of subjects; 25 hydroxy vitamin D was measured (radioimmunoassay, Diasorin) in one batch. Vitamin D was assessed as a transformed continuous factor, and categorically (quartiles and clinical classifications). Univariate and multivariate prognostic analyses (adjusted for treatment, stratification factors, and baseline imbalances) were performed using Cox models. Most patients were young (median 47.8 years), white (91.6 %) and premenopausal (69.4 %) with grade III (52 %), HER2 negative or missing (89.5 %), ER positive (61.9 %), T1-2 (89.4 %), N + (72.7 %) breast cancer. Compared to the full population, those with vitamin D levels were more likely to be white, PS 1 or 2, to have undergone mastectomy, and to have an ER + tumor. Mean vitamin D was 69.7 nmol/L (27.9 ng/ml) and did not vary by tumor subtype. The majority (80.5 %) had levels >50 nmol/L (20 ng/ml), considered adequate by Institute of Medicine. Continuous vitamin D was not multivariately associated with RFS, BCSS, or OS (p = 0.36, 0.26, 0.33, respectively); categorical vitamin D was also not associated with outcome. Vitamin D associations with RFS did not differ within ER/HER2 subgroups. There was no evidence that vitamin D blood level was associated with RFS, BCSS, and OS in MA.21; the majority of subjects had adequate vitamin D levels at study entry.

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