Bone fractures among postmenopausal patients with endocrine-responsive early breast cancer treated with 5 years of letrozole or tamoxifen in the BIG 1-98 trial.
BACKGROUND
To compare the incidence and timing of bone fractures in postmenopausal women treated with 5 years of adjuvant tamoxifen or letrozole for endocrine-responsive early breast cancer in the Breast International Group (BIG) 1-98 trial.


METHODS
We evaluated 4895 patients allocated to 5 years of letrozole or tamoxifen in the BIG 1-98 trial who received at least some study medication (median follow-up 60.3 months). Bone fracture information (grade, cause, site) was collected every 6 months during trial treatment.


RESULTS
The incidence of bone fractures was higher among patients treated with letrozole [228 of 2448 women (9.3%)] versus tamoxifen [160 of 2447 women (6.5%)]. The wrist was the most common site of fracture in both treatment groups. Statistically significant risk factors for bone fractures during treatment included age, smoking history, osteoporosis at baseline, previous bone fracture, and previous hormone replacement therapy.


CONCLUSIONS
Consistent with other trials comparing aromatase inhibitors to tamoxifen, letrozole was associated with an increase in bone fractures. Benefits of superior disease control associated with letrozole and lower incidence of fracture with tamoxifen should be considered with the risk profile for individual patients.
Rabaglio
M
M
IBCSG Coordinating Center and Inselspital, Bern, Switzerland. Electronic address: manuela.rabaglio@ibcsg.org.
Sun
Z
Z
IBCSG Statistical Center, Dana-Farber Cancer Institute, Boston, MA.
Price
K N
KN
IBCSG Statistical Center and Frontier Science and Technology Research Foundation, Boston, MA, USA.
Castiglione-Gertsch
M
M
IBCSG Coordinating Center, Bern.
Hawle
H
H
IBCSG Coordinating Center, Bern.
Thürlimann
B
B
Senology Center of Eastern Switzerland and Swiss Group for Clinical Cancer Research (SAKK), Kantonsspital, St Gallen, Switzerland, Swiss Group for Clinical Cancer Research (SAKK).
Mouridsen
H
H
Danish Breast Cancer Cooperative Group, Rigshospitalet, Copenhagen, Denmark.
Campone
M
M
Institut du Cancer Nantes Atlantique, CLCC René Gauducheau, Saint Herblain, Fédération Nationale des Centres de Lutte Contre le Cancer, France.
Forbes
J F
JF
Australian New Zealand Breast Cancer Trials Group, University of Newcastle, Calvary Mater Newcastle, Newcastle, New South Wales, Australia.
Paridaens
R J
RJ
Department of Medical Oncology, University Hospital Gasthuisberg, Catholic University of Leuven, Leuven, Belgium.
Colleoni
M
M
Research Unit in Medical Senology, Department of Medicine, European Institute of Oncology, Milan, Italy.
Pienkowski
T
T
Cancer Center Maria Sklodowska-Curie Memorial Institute of Oncology, Warsaw, Poland.
Nogaret
J-M
JM
Department of Mammary and Pelvic Surgery, Jules Bordet Institute; Brussels, Belgium.
Láng
I
I
Department of Medical Oncology, National Institute of Oncology, Budapest, Hungary.
Smith
I
I
Breast Unit, The Royal Marsden Hospital, London, UK.
Gelber
R D
RD
IBCSG Statistical Center, Dana-Farber Cancer Institute, Harvard School of Public Health and Harvard Medical School, Boston, MA, USA.
Goldhirsch
A
A
Department of Medicine, European Institute of Oncology, Milan, Italy; Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
Coates
A S
AS
International Breast Cancer Study Group and University of Sydney, Sydney, New South Wales, Australia.
D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000150:complications* / Q000188:drug therapy; D004311:Double-Blind Method; D005260:Female; D050723:Fractures, Bone / Q000453:epidemiology* / Q000209:etiology; D006801:Humans; D015994:Incidence; D000077289:Letrozole; D008875:Middle Aged; D009570:Nitriles / Q000627:therapeutic use*; D017698:Postmenopause; D012307:Risk Factors; D013629:Tamoxifen / Q000627:therapeutic use*; D014230:Triazoles / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D009570:Nitriles; D014230:Triazoles; D013629:Tamoxifen; D000077289:Letrozole