PMID- 25935582
OWN - NLM
STAT- MEDLINE
DCOM- 20160204
LR  - 20181113
IS  - 1573-7217 (Electronic)
IS  - 0167-6806 (Print)
IS  - 0167-6806 (Linking)
VI  - 151
IP  - 2
DP  - 2015 Jun
TI  - CYP19A1 polymorphisms and clinical outcomes in postmenopausal women with hormone 
      receptor-positive breast cancer in the BIG 1-98 trial.
PG  - 373-84
LID - 10.1007/s10549-015-3378-3 [doi]
AB  - To determine whether CYP19A1 polymorphisms are associated with abnormal activity 
      of aromatase and with musculoskeletal and bone side effects of aromatase 
      inhibitors. DNA was isolated from tumor specimens of 4861 postmenopausal women 
      with hormone receptor-positive breast cancer enrolled in the BIG 1-98 trial to 
      receive tamoxifen and/or letrozole for 5 years. Tumors were genotyped for six 
      CYP19A1 polymorphisms using PCR-based methods. Associations with breast 
      cancer-free interval (BCFI), distant recurrence-free interval (DRFI), 
      musculoskeletal and bone adverse events (AEs) were assessed using Cox 
      proportional hazards models. All statistical tests were two-sided. No association 
      between the CYP19A1 genotypes and BCFI or DRFI was observed overall. A reduced 
      risk of a breast cancer event for tamoxifen-treated patients with rs700518 
      variants was observed (BCFI CC/TC vs. TT: HR 0.53, 95 % CI 0.34-0.82, interaction 
      P = 0.08), but not observed for letrozole-treated patients. There was an 
      increased risk of musculoskeletal AEs for patients with rs700518 variants CC/TC 
      versus TT (HR 1.22, 95 % CI 1.03-1.45, P = 0.02), regardless of treatment. 
      Tamoxifen-treated patients with rs4646 variants had a reduced risk of bone AEs 
      (AA/CA vs. CC: HR 0.76, 95 % CI 0.59-0.98), whereas an increase of minor allele 
      (C) of rs10046 was associated with an increased risk of bone AEs (HR 1.28, 95 % 
      CI 1.07-1.52). rs936308 variants were associated with a reduced risk of bone AEs 
      in letrozole-treated patients (GG/GC vs. CC: HR 0.73, 95 % CI 0.54-0.99), 
      different from in tamoxifen-treated patients (GG/GC vs. CC: HR 1.32, 95 % CI 
      0.92-1.90, interaction P = 0.01). CYP19A1 rs700518 variants showed associations 
      with BCFI, DRFI, in tamoxifen treated patients and musculoskeletal AEs regardless 
      of treatment. SNPs rs4646, rs10046, and rs936308 were associated with bone AEs.
FAU - Leyland-Jones, Brian
AU  - Leyland-Jones B
AD  - Avera Cancer Institute, 1000 E 23rd Street, Sioux Falls, SD, 57105, USA, 
      bleylandj@aol.com.
FAU - Gray, Kathryn P
AU  - Gray KP
FAU - Abramovitz, Mark
AU  - Abramovitz M
FAU - Bouzyk, Mark
AU  - Bouzyk M
FAU - Young, Brandon
AU  - Young B
FAU - Long, Bradley
AU  - Long B
FAU - Kammler, Roswitha
AU  - Kammler R
FAU - Dell'Orto, Patrizia
AU  - Dell'Orto P
FAU - Biasi, Maria Olivia
AU  - Biasi MO
FAU - Thurlimann, Beat
AU  - Thurlimann B
FAU - Lyng, Maria B
AU  - Lyng MB
FAU - Ditzel, Henrik J
AU  - Ditzel HJ
FAU - Harvey, Vernon J
AU  - Harvey VJ
FAU - Neven, Patrick
AU  - Neven P
FAU - Treilleux, Isabelle
AU  - Treilleux I
FAU - Rasmussen, Birgitte Bruun
AU  - Rasmussen BB
FAU - Maibach, Rudolf
AU  - Maibach R
FAU - Price, Karen N
AU  - Price KN
FAU - Coates, Alan S
AU  - Coates AS
FAU - Goldhirsch, Aron
AU  - Goldhirsch A
FAU - Pagani, Olivia
AU  - Pagani O
FAU - Viale, Giuseppe
AU  - Viale G
FAU - Rae, James M
AU  - Rae JM
FAU - Regan, Meredith M
AU  - Regan MM
LA  - eng
SI  - ClinicalTrials.gov/NCT00004205
GR  - R01 GM099143/GM/NIGMS NIH HHS/United States
GR  - U24 CA075362/CA/NCI NIH HHS/United States
GR  - 1R01GM099143/GM/NIGMS NIH HHS/United States
GR  - CA75362/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20150503
PL  - Netherlands
TA  - Breast Cancer Res Treat
JT  - Breast cancer research and treatment
JID - 8111104
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Receptors, Estrogen)
RN  - 0 (Receptors, Progesterone)
RN  - EC 1.14.14.1 (Aromatase)
RN  - EC 1.14.14.1 (CYP19A1 protein, human)
SB  - IM
MH  - Aged
MH  - Alleles
MH  - Aromatase/*genetics
MH  - Biomarkers, Tumor
MH  - Breast Neoplasms/*genetics/*mortality/pathology/therapy
MH  - Clinical Trials, Phase III as Topic
MH  - Combined Modality Therapy
MH  - Female
MH  - Genotype
MH  - Humans
MH  - Kaplan-Meier Estimate
MH  - Middle Aged
MH  - Neoplasm Grading
MH  - Neoplasm Metastasis
MH  - Neoplasm Staging
MH  - *Polymorphism, Single Nucleotide
MH  - Postmenopause
MH  - Prognosis
MH  - Randomized Controlled Trials as Topic
MH  - Receptors, Estrogen/*genetics
MH  - Receptors, Progesterone/*genetics
MH  - Treatment Outcome
MH  - Tumor Burden
PMC - PMC4763278
MID - NIHMS731990
COIS- Conflict of interest: The remaining authors have no conflicts to declare.
EDAT- 2015/05/04 06:00
MHDA- 2016/02/05 06:00
PMCR- 2016/06/01
CRDT- 2015/05/04 06:00
PHST- 2015/04/07 00:00 [received]
PHST- 2015/04/08 00:00 [accepted]
PHST- 2015/05/04 06:00 [entrez]
PHST- 2015/05/04 06:00 [pubmed]
PHST- 2016/02/05 06:00 [medline]
PHST- 2016/06/01 00:00 [pmc-release]
AID - 10.1007/s10549-015-3378-3 [doi]
PST - ppublish
SO  - Breast Cancer Res Treat. 2015 Jun;151(2):373-84. doi: 10.1007/s10549-015-3378-3. 
      Epub 2015 May 3.