5-year follow-up of a randomized controlled trial of immediate versus delayed zoledronic acid for the prevention of bone loss in postmenopausal women with breast cancer starting letrozole after tamoxifen: N03CC (Alliance) trial.
BACKGROUND
Postmenopausal women with breast cancer receiving aromatase inhibitors are at an increased risk of bone loss. The current study was undertaken to determine whether upfront versus delayed treatment with zoledronic acid (ZA) impacted bone loss. This report described the 5-year follow-up results.


METHODS
A total of 551 postmenopausal women with breast cancer who completed tamoxifen treatment and were undergoing daily letrozole treatment were randomized to either upfront (274 patients) or delayed (277 patients) ZA at a dose of 4 mg intravenously every 6 months. In the patients on the delayed treatment arm, ZA was initiated for a postbaseline bone mineral density T-score of <-2.0 or fracture.


RESULTS
The incidence of a 5% decrease in the total lumbar spine bone mineral density at 5 years was 10.2% in the upfront treatment arm versus 41.2% in the delayed treatment arm (P<.0001). A total of 41 patients in the delayed treatment arm were eventually started on ZA. With the exception of increased NCI Common Toxicity Criteria (CTC) grade 1/2 elevated creatinine and fever in the patients treated on the upfront arm and cerebrovascular ischemia among those in the delayed treatment arm, there were no significant differences observed between arms with respect to the most common adverse events of arthralgia and back pain. Osteoporosis occurred less frequently in the upfront treatment arm (2 vs 8 cumulative cases), although this difference was not found to be statistically significant. Bone fractures occurred in 24 patients in the upfront treatment arm versus 25 patients in the delayed treatment arm.


CONCLUSIONS
Immediate treatment with ZA prevented bone loss compared with delayed treatment in postmenopausal women receiving letrozole and these differences were maintained at 5 years. The incidence of osteoporosis or fractures was not found to be significantly different between treatment arms.
Division of Medical Oncology, Washington University School of Medicine, St. Louis, Missouri.
Nina D
ND
Wagner-Johnston
Alliance Statistics and Data Center, Mayo Clinic, Rochester, Minnesota.
Jeff A
JA
Sloan
Alliance Statistics and Data Center, Mayo Clinic, Rochester, Minnesota.
Heshan
H
Liu
Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota.
Ann E
AE
Kearns
Department of Hematology/Oncology, Mayo Clinic Florida, Jacksonville, Florida.
Stephanie L
SL
Hines
Alliance Statistics and Data Center, Mayo Clinic, Rochester, Minnesota.
Suneetha
S
Puttabasavaiah
Wichita Community Clinical Oncology Program, Wichita, Kansas.
Shaker R
SR
Dakhil
Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota.
Jacqueline M
JM
Lafky
Department of Hematology/Oncology, Mayo Clinic Florida, Jacksonville, Florida.
Edith A
EA
Perez
Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota.
Charles L
CL
Loprinzi
D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018567:Breast Neoplasms, Male / Q000188:drug therapy / Q000453:epidemiology; D017024:Chemotherapy, Adjuvant; D004164:Diphosphonates / Q000008:administration & dosage* / Q000009:adverse effects; D018450:Disease Progression; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage* / Q000009:adverse effects; D000077289:Letrozole; D008297:Male; D008875:Middle Aged; D009570:Nitriles / Q000627:therapeutic use*; D015663:Osteoporosis, Postmenopausal / Q000517:prevention & control*; D017698:Postmenopause; D013629:Tamoxifen / Q000627:therapeutic use*; D014230:Triazoles / Q000627:therapeutic use*; D000077211:Zoledronic Acid
D000970:Antineoplastic Agents; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D009570:Nitriles; D014230:Triazoles; D013629:Tamoxifen; D000077211:Zoledronic Acid; D000077289:Letrozole
bone loss; breast cancer; letrozole; postmenopausal; tamoxifen; zoledronic acid