Effects of tibolone and continuous combined hormone therapy on mammographic breast density and breast histochemical markers in postmenopausal women.
OBJECTIVE
To compare changes in mammographic density and the expression of markers of proliferation (Ki67) and apoptosis (Bcl-2) after 1 year of treatment with tibolone and continuous conjugated equine estrogens combined with medroxyprogesterone acetate (CEE-MPA).


METHODS
Comparative, randomized, evaluator-blinded study.


METHODS
City research hospital.


METHODS
Thirty-seven postmenopausal women.


METHODS
Tibolone (2.5 mg; n = 18) or continuous conjugated estrogens (0.625 mg) combined with medroxyprogesterone acetate (5 mg; n = 19) for 1 year.


METHODS
Mammographic density (BI-RADS density score), expression of immunohistochemical markers Ki67 and Bcl-2.


RESULTS
Mean breast density score decreased significantly from 2.22 to 1.67 in the tibolone group, compared with a significant increase in the CEE-MPA-treated group from 1.84 to 2.63. Ki67 expression decreased in 12 of 15, increased in 2 of 15, and remained unchanged in 1 of 15 subjects in the tibolone group, compared with 1 of 19, 15 of 19, and 3 of 19 subjects, respectively, in the CEE-MPA group. Bcl-2 expression decreased in 12 of 15, increased in 2 of 15, and remained unchanged in 1 of 15 subjects in the tibolone group, compared with 5 of 19, 9 of 19, and 5 of 19 subjects, respectively, in the CEE-MPA group.


CONCLUSIONS
One-year treatment with tibolone induced a decrease in breast density, with a reduction in proliferation and a stimulation of apoptosis, whereas 1-year treatment with CEE-MPA induced an increase in breast density, with stimulation of proliferation and inhibition of apoptosis, indicating that tibolone effects on the breast are different from those of CEE-MPA.
Valdivia
Isabel
I
Department of Obstetrics and Gynecology, University of Chile, Santiago, Chile. imvaldivia@entelchile.net
Campodónico
Italo
I
Tapia
Augusto
A
Capetillo
María
M
Espinoza
Arturo
A
Lavín
Pablo
P
D015415:Biomarkers / Q000032:analysis; D001940:Breast / Q000187:drug effects / Q000378:metabolism*; D004359:Drug Therapy, Combination; D004966:Estrogens, Conjugated (USP) / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism*; D008327:Mammography; D017258:Medroxyprogesterone Acetate / Q000627:therapeutic use*; D008875:Middle Aged; D009652:Norpregnenes / Q000627:therapeutic use*; D017698:Postmenopause; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D016037:Single-Blind Method
D015415:Biomarkers; D004966:Estrogens, Conjugated (USP); D019394:Ki-67 Antigen; D009652:Norpregnenes; D019253:Proto-Oncogene Proteins c-bcl-2; D017258:Medroxyprogesterone Acetate; C027385:tibolone