Zoledronic acid combined with adjuvant endocrine therapy of tamoxifen versus anastrozol plus ovarian function suppression in premenopausal early breast cancer: final analysis of the Austrian Breast and Colorectal Cancer Study Group Trial 12.
BACKGROUND
Zoledronic acid (ZOL) plus adjuvant endocrine therapy significantly improved disease-free survival (DFS) at 48- and 62-month follow-up in the ABCSG-12 trial. We present efficacy results of a final additional analysis after 94.4 months.


METHODS
Patients were premenopausal women who had undergone primary surgery for stage I/II estrogen-receptor-positive and/or progesterone-receptor-positive breast cancer with <10 positive lymph nodes, and were scheduled for standard goserelin therapy. All 1803 patients received goserelin (3.6 mg every 28 days) and were randomized to tamoxifen (20 mg/days) or anastrozole (1 mg/days), both with or without ZOL (4 mg every 6 months) for 3 years. The primary end point was DFS; recurrence-free survival and overall survival (OS) were secondary end points.


RESULTS
After 94.4-month median follow-up (range, 0-114 months), relative risks of disease progression [hazard ratio (HR) = 0.77; 95% confidence interval (CI) 0.60-0.99; P = 0.042] and of death (HR = 0.66; 95% CI 0.43-1.02; P = 0.064) are still reduced by ZOL although no longer significant at the predefined significance level. Overall, 251 DFS events and 86 deaths were reported. Absolute risk reductions with ZOL were 3.4% for DFS and 2.2% for OS. There was no DFS difference between tamoxifen alone versus anastrozole alone, but there was a pronounced higher risk of death for anastrozole-treated patients (HR = 1.63; 95% CI 1.05-1.45; P = 0.030). Treatments were generally well tolerated, with no reports of renal failure or osteonecrosis of the jaw.


CONCLUSIONS
These final results from ABCSG 12 suggest that twice-yearly ZOL enhances the efficacy of adjuvant endocrine treatment, and this benefit is maintained long-term.


BACKGROUND
NCT00295646 (http://www.clinicaltrials.gov/ct2/results?term=00295646).
Department of Surgery and Comprehensive Cancer Center, Medical University of Vienna, Vienna michael.gnant@meduniwien.ac.at.
M
M
Gnant
Department of Internal Medicine III, Paracelsus Medical University Salzburg, Salzburg.
B
B
Mlineritsch
Clinical Department of Oncology, Medical University of Graz, Graz.
H
H
Stoeger
Clinical Department of Oncology, Medical University of Graz, Graz.
G
G
Luschin-Ebengreuth
Department of General and Visceral Surgery, Hospital of the Sisters of Charity, Linz.
M
M
Knauer
Department of Internal Medicine III, Paracelsus Medical University Salzburg, Salzburg.
M
M
Moik
Department of Surgery and Comprehensive Cancer Center, Medical University of Vienna, Vienna.
R
R
Jakesz
Department of Surgery and Comprehensive Cancer Center, Medical University of Vienna, Vienna.
M
M
Seifert
Department of Gynecology and Obstetrics, Medical University of Innsbruck, Innsbruck, Austria.
S
S
Taucher
Clinical Department of Oncology, Medical University of Graz, Graz.
V
V
Bjelic-Radisic
Clinical Department of Oncology, Medical University of Graz, Graz.
M
M
Balic
Gynecology and Obstetrics Clinic, University of Schleswig-Holstein, Kiel.
H
H
Eidtmann
Gynecology and Gynecological Oncology, IOZ-München, Munich, Germany.
W
W
Eiermann
Department of Surgery and Comprehensive Cancer Center, Medical University of Vienna, Vienna.
G
G
Steger
Department of Surgery, Wiener Neustadt Hospital, Wiener Neustadt.
W
W
Kwasny
Department of Surgery and Comprehensive Cancer Center, Medical University of Vienna, Vienna.
P
P
Dubsky
Department of Surgery, Hanusch Hospital, Vienna.
U
U
Selim
Department of Surgery and Comprehensive Cancer Center, Medical University of Vienna, Vienna.
F
F
Fitzal
Center of Hematology and Medical Oncology, General Hospital Linz, Linz.
G
G
Hochreiner
Department of Surgery, Practice of Dr Wette, Sankt Veit an der Glan.
V
V
Wette
Hospital Hietzing, Vienna.
P
P
Sevelda
Clinical Department of Oncology, Medical University of Graz, Graz.
F
F
Ploner
Department of Surgery and Comprehensive Cancer Center, Medical University of Vienna, Vienna.
R
R
Bartsch
Department of Statistics, Austrian Breast and Colorectal Cancer Study Group, Vienna, Austria.
C
C
Fesl
Department of Internal Medicine III, Paracelsus Medical University Salzburg, Salzburg.
R
R
Greil
D000328:Adult; D000077384:Anastrozole; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D050071:Bone Density Conservation Agents / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality; D004164:Diphosphonates / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D017273:Goserelin / Q000008:administration & dosage; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009570:Nitriles / Q000008:administration & dosage; D017697:Premenopause; D013629:Tamoxifen / Q000008:administration & dosage; D014230:Triazoles / Q000008:administration & dosage; D000077211:Zoledronic Acid
D018931:Antineoplastic Agents, Hormonal; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D009570:Nitriles; D014230:Triazoles; D013629:Tamoxifen; D017273:Goserelin; D000077384:Anastrozole; D000077211:Zoledronic Acid
LHRH agonists; anastrozol; bisphosphonates; early breast cancer; tamoxifen; zoledronic acid