Abstract P4-14-11: No impact of osteoporosis or bisphosphonate use for osteoporosis on breast cancer outcome: A sub-study of the DATA trial
Authors: van Hellemond IE , Smorenburg CH , Peer PG , Swinkels AC , Seynaeve CM , van der Sangen MJ , Kroep JR , de Graaf H , Honkoop AH , Erdkamp FL , van den Berkmortel FW , de Roos WK , Linn SC , Imholz AL , de Boer M , Tjan-Heijnen VC 
Published: May 2019

Abstract
Background:
The phase III DATA study (NCT00301457) investigates the efficacy of 6 versus 3 years of adjuvant anastrozole after an initial 2-3 year treatment with tamoxifen in postmenopausal women with breast cancer. A reduced bone mineral density (BMD) is associated with a lower risk of breast cancer. Bisphosphonates as adjuvant therapy in postmenopausal patients have been shown to prevent (distant) breast cancer recurrences. In this planned side-study of the DATA trial we assessed the relationship between osteoporosis and distant recurrence free survival (DRFS), and evaluated the effect of bisphosphonate use for reduced BMD in general on DRFS.
Methods:
Decisions on BMD measurements and bisphosphonate use in the DATA study were left to the treating physician. We registered all BMD measurements and start of bisphosphonate-use. BMD was measured by a dual-energy x-ray absorptiometry (DEXA) scan of the lumbar spine/hip. We used a landmark of 3 years beyond the start of anastrozole, to create 3 different groups by BMD values based on DEXA scans made before the landmark and before a DRFS event (normal T score &gt;-1.0, osteopenia T score &lt;-1.0, osteoporosis T score &lt;-2.5). Kaplan Meier methodology was used for analyzing the DRFS for these groups. The events ending a period of DRFS were defined according to the STEEP criteria. For analyzing the relationship between bisphosphonate use and DRFS, overall bisphosphonate use was integrated as a time dependent covariate.
Results:
Of the 1860 DATA patients, 1142 (65.5% in the 6-year arm and 62.9% in the 3-year arm) had a DEXA scan within the first 3 years after randomization. A normal BMD was diagnosed in 436 (38.2%) patients, osteopenia in 565 (49.5%), and osteoporosis in 141 (12.3%). Of the latter group, 112 (80.9%) used bisphosphonates. In the total study population (n=1860), bisphosphonates were overall used over time before a DRFS event in 226 patients (24.2%) in the 6-year arm and 201 patients (21.7%) in the 3-year arm. During the study, only 46 patients used bisphosphonates without a diagnosis of osteopenia/osteoporosis.
After a median follow up of 5.0 years from the landmark (interquartile range 4.3-5.7), osteoporosis (n=141) did not have a significant impact on DRFS when compared with the group without osteoporosis (normal/osteopenia (n=1001)) (HR 1.19, p=0.24 in the 6-year arm and HR=0.79, P=0.56 in the 3-year arm, P interaction=0.45). Neither when compared with only the group with a normal BMD (n=436) (HR=1.15, p=0.72 in the 6-year arm and HR=0.67, p=0.34 in the 3-year arm, P interaction=0.35).
Within the group with osteoporosis, bisphosphonate use did not lead to a better DRFS (HR=1.47, P=0.72 in the 6-year arm and HR 0.65, P=0.61 in the 3-year arm, P interaction=0.55). Bisphosphonate use in general was also not associated with DRFS (HR 1.31, P=0.13 in the 6-year arm and HR 0.88, P=0.52 in the 3-year arm, P interaction=0.14).
Conclusion:
In this DATA sub-study, we observed no association between the presence of osteoporosis before the landmark of 3 years after the start of anastrozole and DRFS. However, as most patients with early osteoporosis also were treated with bisphosphonates this may have influenced the results. At the conference additional analyses will be presented.
Citation Format: van Hellemond IE, Smorenburg CH, Peer PG, Swinkels AC, Seynaeve CM, van der Sangen MJ, Kroep JR, de Graaf H, Honkoop AH, Erdkamp FL, van den Berkmortel FW, de Roos WK, Linn SC, Imholz AL, de Boer M, Tjan-Heijnen VC. No impact of osteoporosis or bisphosphonate use for osteoporosis on breast cancer outcome: A sub-study of the DATA trial [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-14-11.