Effect of tibolone on breast cancer cell proliferation in postmenopausal ER+ patients: results from STEM trial.
OBJECTIVE
Tibolone is a selective tissue estrogenic activity regulator, approved for the treatment of vasomotor symptoms in postmenopausal women. We have done an exploratory, double-blind, randomized, placebo-controlled pilot trial to investigate the tissue-specific effects of 2.5 mg tibolone on breast cancer in postmenopausal women, in particular on tissue proliferation (STEM, Study of Tibolone Effects on Mamma carcinoma tissue).


METHODS
Postmenopausal women with initially stage I/II, estrogen receptor-positive (ER+) primary breast cancer, were randomly assigned to 14 days of placebo or 2.5 mg/d tibolone. Core biopsies of the primary tumor were obtained before and after treatment. Ki-67 and apoptosis index were analyzed in baseline and corresponding posttreatment specimen.


RESULTS
Of 102 enrolled patients, 95 had evaluable data. Baseline characteristics were comparable between both treatment groups. Breast cancer cases are mainly invasive (99%), stage I or II (42% and 50% respectively), and ER+ (99%). Median intratumoral Ki-67 expression at baseline was 13.0% in the tibolone group and 17.8% in the placebo group, and decreased to 12.0% after 14 days of tibolone while increasing to 19.0% in the placebo group. This change from baseline was not significantly different between tibolone and placebo (Wilcoxon test; P=0.17). A significant difference was observed between the treatment groups when the median change from baseline apoptosis index was compared between the treatment groups (tibolone, 0.0%; placebo, +0.3%; Wilcoxon test; P=0.031). The incidence of adverse effects was comparable.


CONCLUSIONS
In ER+ breast tumors, 2.5 mg/d tibolone given for 14 days has no significant effect on tumor cell proliferation.
Kubista
Ernst
E
Division of Special Gynecology, Medical University of Vienna, Vienna, Austria.
Planellas Gomez
Juan V M
JV
Dowsett
Mitch
M
Foidart
Jean-Michel
JM
Pohlodek
Kamil
K
Serreyn
Rudolphe
R
Nechushkin
Michail
M
Manikhas
Alexey G
AG
Semiglazov
Victor F
VF
Hageluken
Cornelius C M
CC
Singer
Christian F
CF
D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology* / Q000601:surgery; D002455:Cell Division / Q000187:drug effects; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D008875:Middle Aged; D009652:Norpregnenes / Q000009:adverse effects / Q000627:therapeutic use*; D010919:Placebos; D017698:Postmenopause; D012449:Safety
D018931:Antineoplastic Agents, Hormonal; D009652:Norpregnenes; D010919:Placebos; C027385:tibolone