Lack of association between oestrogen receptor polymorphisms and change in bone mineral density with tamoxifen therapy.
BACKGROUND
Tamoxifen, a selective oestrogen receptor (ER) modulator, increases bone mineral density (BMD) in postmenopausal women and decreases BMD in premenopausal women. We hypothesised that inherited variants in candidate genes involved in oestrogen signalling and tamoxifen metabolism might be associated with tamoxifen effects in bone.


METHODS
A total of 297 women who were initiating tamoxifen therapy were enrolled in a prospective multicentre clinical trial. Lumbar spine and total hip BMD values were measured using dual-energy X-ray absorptiometry (DXA) at baseline and after 12 months of tamoxifen therapy. Single-nucleotide polymorphisms (SNPs) in ESR1, ESR2, and CYP2D6 were tested for associations in the context of menopausal status and previous chemotherapy, with a mean percentage change in BMD over 12 months.


RESULTS
The percentage increase in BMD was greater in postmenopausal women and in those patients who had been treated with chemotherapy. No significant associations between tested SNPs and either baseline BMD or change in BMD with 1 year of tamoxifen therapy were detected.


CONCLUSIONS
The evaluated SNPs in ESR and CYP2D6 do not seem to influence BMD in tamoxifen-treated subjects.
Henry
N L
NL
Breast Oncology Program, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI 48109, USA. norahh@med.umich.edu
Nguyen
A
A
Azzouz
F
F
Li
L
L
Robarge
J
J
Philips
S
S
Cao
D
D
Skaar
T C
TC
Rae
J M
JM
Storniolo
A M
AM
Flockhart
D A
DA
Hayes
D F
DF
Stearns
V
V
D015502:Absorptiometry, Photon; D000328:Adult; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D015519:Bone Density / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics; D047628:Estrogen Receptor alpha / Q000235:genetics*; D047629:Estrogen Receptor beta / Q000235:genetics; D005260:Female; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012042:Registries; D013629:Tamoxifen / Q000494:pharmacology*
D018931:Antineoplastic Agents, Hormonal; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D013629:Tamoxifen; D019389:Cytochrome P-450 CYP2D6