title: Influence of adjuvant tamoxifen treatment on bone mineral density and bone turnover markers in postmenopausal breast cancer patients in Japan.
abstract: The effect of adjuvant tamoxifen treatment on bone mineral density (BMD) and bone turnover markers was studied in postmenopausal breast cancer patients. The relationship of tamoxifen's effect with the genetic polymorphisms of estrogen receptor (ER)-alpha and ER-beta gene was also studied. Twenty-one postmenopausal breast cancer patients were given tamoxifen (20 mg/day) as the adjuvant treatment after the surgery. BMD of the lumbar supine (dual emission X-rays absorptiometry) and bone resorption (deoxypyridinoline, aminoterminal telopeptide of type I collagen, and carboxyterminal telopeptide of type I collagen) and formation (propeptide of type I procollagen, osteocalcin, and bone-specific alkaline phosphatase) markers were examined at baseline (before the surgery), 6 and 12 months after the start of tamoxifen treatment. Genetic polymorphisms analyzed were TA dinucleotide repeats polymorphism in the promoter region and PvuII and XbaI restriction fragment length polymorphism for the ER-alpha gene and the CA dinucleotide repeats polymorphism in the intron 5 for the ER-beta gene. Tamoxifen significantly increased BMD of the lumbar spine at both 6 (P<0.01) and 12 months (P<0.01) after the start of tamoxifen as compared with that at baseline. The mean percent increase in BMD was 3.3% at 6 months and 2.7% at 12 months. All bone resorption and formation markers significantly decreased at both 6 and 12 months. Among the four genetic polymorphisms studied, only ER-beta CA repeat polymorphism was found to be significantly associated with BMD at 12 months, i.e. BMD of the 21 CA repeats allele carriers was significantly higher than that of the non-carriers (P=0.025). These results suggest that tamoxifen increases BMD of the lumbar supine by reducing the bone turnover in postmenopausal breast cancer patients, and this bone restoring effect of tamoxifen is more marked in ER-beta 21 CA repeats allele carriers than non-carriers.
authors.affiliation: Department of Surgical Oncology, Osaka University Medical School, 2-2 E-10 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Kohri
authors.initials: K
authors.lastname: Yoneda
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Tanji
authors.forename: Noriko
authors.initials: N
authors.lastname: Ikeda
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Miyoshi
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Taguchi
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Tamaki
authors.forename: Shinzaburo
authors.initials: S
authors.lastname: Noguchi
mesh_terms: D000367:Age Factors; D000368:Aged; D000483:Alleles; D015519:Bone Density / Q000187:drug effects*; D001862:Bone Resorption; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D017024:Chemotherapy, Adjuvant; D047628:Estrogen Receptor alpha; D005260:Female; D005838:Genotype; D006801:Humans; D007564:Japan; D008875:Middle Aged; D011110:Polymorphism, Genetic; D017698:Postmenopause; D011960:Receptors, Estrogen / Q000235:genetics; D013629:Tamoxifen / Q000627:therapeutic use*; D013997:Time Factors
chemical_list: D047628:Estrogen Receptor alpha; D011960:Receptors, Estrogen; D013629:Tamoxifen