Effect of long-term treatment with raloxifene on mammary density in postmenopausal women.
OBJECTIVE
To evaluate in a group of postmenopausal women the effects of long-term raloxifene treatment on breast density using a digitized analysis of mammograms and on insulinlike growth factor-1 (IGF-1), insulinlike growth factor binding protein-3 (IGFBP-3), and sex hormone-binding globulin (SHBG) plasma levels.


METHODS
Seventy healthy postmenopausal women with normal body weight were enrolled in this study and were divided into two groups based on their bone status, evaluated by dual-energy x-ray at the lumbar spine (L2-4). Fifty women (chronological age 52.4 +/- 4.1 y, menopausal age 42.1 +/- 3.9 y), in whom the L2-4 T score was less than -2.5 SD, were treated with raloxifene HCl 60 mg/day orally for 2 years. The other 20 women (chronological age 53.6 +/- 3.5 y, age at menopause 43.1 +/- 3.6 y), in whom the L2-4 T score ranged between -1 and -2.5 SD, were enrolled as controls. All 70 women received calcium (1 g/d orally) and cholecalciferol (880 UI/d orally) supplementation. Moreover, all women followed a normocaloric and personalized diet. All women had mammography at baseline and after 2 years of therapy. The mammographic images on traditional support (radiography) were acquired by using a film scanner and were then elaborated by means of ad hoc software. Moreover, assessments of IGF-1, IGFBP-3, and SHBG plasma levels were obtained at baseline and after 24 months.


RESULTS
After 24 months of therapy, there was a significant variation in the raloxifene-treated group with respect to baseline in the distribution of gray classes of radiographic images. In particular, an attenuation of graphic trace with a reduction of the areas with the lowest and most elevated gray classes was observed. In the control group, no significant variations of graphic traces were observed. Moreover, raloxifene treatment significantly reduced IGF-1 and increased IGFBP-3 and SHBG plasma levels at 24 months. During follow-up, IGF-1, IGFPB-3, and SHBG levels did not change significantly in the control group.


CONCLUSIONS
Long-term treatment with raloxifene in a population of postmenopausal women is able to reduce breast density. Such an effect could perhaps explain the reduction in the incidence of mammary carcinoma observed in the Multiple Outcomes of Raloxifene Evaluation study probably due to the direct antiestrogenic activity of raloxifene on mammalian tissue and/or its indirect activity increasing SHBG levels or modifying the IGF-1/IGFBP-3 ratio.
Lasco
Antonino
A
Department of Internal Medicine, Azienda Ospedaliera Universitaria Messina, Messina, Italy. alasco@unime.it
Gaudio
Agostino
A
Morini
Elisa
E
Morabito
Nancy
N
Nicita-Mauro
Claudio
C
Catalano
Antonino
A
Denuzzo
Giulia
G
Sansotta
Carlo
C
Xourafa
Anastasia
A
Macrì
Ilaria
I
Frisina
Nicola
N
D015502:Absorptiometry, Photon; D000328:Adult; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001940:Breast / Q000187:drug effects* / Q000473:pathology; D001943:Breast Neoplasms / Q000517:prevention & control; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood / Q000187:drug effects; D007334:Insulin-Like Growth Factor I / Q000187:drug effects; D008159:Lumbar Vertebrae; D008327:Mammography; D008875:Middle Aged; D017698:Postmenopause; D020849:Raloxifene Hydrochloride / Q000008:administration & dosage / Q000494:pharmacology*; D020845:Selective Estrogen Receptor Modulators / Q000008:administration & dosage / Q000494:pharmacology*; D012738:Sex Hormone-Binding Globulin / Q000187:drug effects
D050071:Bone Density Conservation Agents; D018972:Insulin-Like Growth Factor Binding Protein 3; D020845:Selective Estrogen Receptor Modulators; D012738:Sex Hormone-Binding Globulin; D020849:Raloxifene Hydrochloride; D007334:Insulin-Like Growth Factor I