Breast cancer outcome in relation to bone mineral density and bisphosphonate use: a sub-study of the DATA trial

Irene E. G. van Hellemond; Carolien H. Smorenburg; Petronella G. M. Peer; Astrid C. P. Swinkels; Caroline M. Seynaeve; Maurice J. C. van der Sangen; Judith R. Kroep; Hiltje de Graaf; Aafke H. Honkoop; Frans L. G. Erdkamp; Franchette W. P. J. van den Berkmortel; Wilfred K. de Roos; Sabine C. Linn; Alexander L. T. Imholz; Maaike de Boer; Vivianne C. G. Tjan-Heijnen; Dutch Breast Canc Res Grp BOOG

doi:10.1007/s10549-020-05567-9

Breast cancer outcome in relation to bone mineral density and bisphosphonate use: a sub-study of the DATA trial

Irene E. G. van Hellemond, Carolien H. Smorenburg, Petronella G. M. Peer, Astrid C. P. Swinkels, Caroline M. Seynaeve, Maurice J. C. van der Sangen, Judith R. Kroep, Hiltje de Graaf, Aafke H. Honkoop, Frans L. G. Erdkamp, Franchette W. P. J. van den Berkmortel, Wilfred K. de Roos, Sabine C. Linn, Alexander L. T. Imholz, Maaike de Boer, Vivianne C. G. Tjan-Heijnen^*, Dutch Breast Canc Res Grp BOOG

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Purpose The phase III DATA study compared 6 and 3 years of adjuvant anastrozole following 2-3 years of tamoxifen in postmenopausal breast cancer patients. This pre-planned side-study assessed the relationship between a reduced bone mineral density (BMD) and distant recurrence-free survival (DRFS), and evaluated the effect of bisphosphonates on DRFS. Methods We selected all patients with a BMD measurement within 3 years after randomisation (landmark) without any DRFS events. Kaplan-Meier methods and Cox proportional hazards models were used for analyses. Results Of 1860 eligible patients, 1142 had a DEXA scan before the landmark. The BMD was normal in 436 (38.2%) and showed osteopenia in 565 (49.5%) and osteoporosis in 141 (12.3%) patients. After a median follow-up of 5.0 years from the landmark, neither osteopenia nor osteoporosis (compared with normal BMD) were associated with DRFS in both the 6-year [osteopenia HR 0.82 (95% CI 0.45-1.49), osteoporosis HR 1.10 (95% CI 0.26-4.67)] and the 3-year arm [osteopenia HR 0.75 (95% CI 0.40-1.42), osteoporosis HR 1.86 (95% CI 0.43-8.01)]. Moreover, bisphosphonate use did not impact DRFS. Conclusion No association was observed between a reduced BMD and DRFS. Neither did we observe an impact of bisphosphonates on DRFS.

Original language	English
Pages (from-to)	675-685
Number of pages	11
Journal	Breast Cancer Research and Treatment
Volume	180
Issue number	3
DOIs	https://doi.org/10.1007/s10549-020-05567-9
Publication status	Published - Apr 2020

Keywords

Breast cancer
Tamoxifen
Aromatase inhibitor
Bone health
Osteoporosis
Bisphosphonates
Survival
Bone metastases
Distant recurrence-free survival
ZOLEDRONIC ACID
POSTMENOPAUSAL WOMEN
IN-VITRO
THERAPY
CELLS
RISK
CHEMOTHERAPY
METASTASIS
MECHANISMS
CLODRONATE

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van Hellemond, I. E. G., Smorenburg, C. H., Peer, P. G. M., Swinkels, A. C. P., Seynaeve, C. M., van der Sangen, M. J. C., Kroep, J. R., de Graaf, H., Honkoop, A. H., Erdkamp, F. L. G., van den Berkmortel, F. W. P. J., de Roos, W. K., Linn, S. C., Imholz, A. L. T., de Boer, M., Tjan-Heijnen, V. C. G., & Dutch Breast Canc Res Grp BOOG (2020). Breast cancer outcome in relation to bone mineral density and bisphosphonate use: a sub-study of the DATA trial. Breast Cancer Research and Treatment, 180(3), 675-685. https://doi.org/10.1007/s10549-020-05567-9

@article{2f0fee3edbff4362abac30381524a4b9,

title = "Breast cancer outcome in relation to bone mineral density and bisphosphonate use: a sub-study of the DATA trial",

abstract = "Purpose The phase III DATA study compared 6 and 3 years of adjuvant anastrozole following 2-3 years of tamoxifen in postmenopausal breast cancer patients. This pre-planned side-study assessed the relationship between a reduced bone mineral density (BMD) and distant recurrence-free survival (DRFS), and evaluated the effect of bisphosphonates on DRFS. Methods We selected all patients with a BMD measurement within 3 years after randomisation (landmark) without any DRFS events. Kaplan-Meier methods and Cox proportional hazards models were used for analyses. Results Of 1860 eligible patients, 1142 had a DEXA scan before the landmark. The BMD was normal in 436 (38.2%) and showed osteopenia in 565 (49.5%) and osteoporosis in 141 (12.3%) patients. After a median follow-up of 5.0 years from the landmark, neither osteopenia nor osteoporosis (compared with normal BMD) were associated with DRFS in both the 6-year [osteopenia HR 0.82 (95% CI 0.45-1.49), osteoporosis HR 1.10 (95% CI 0.26-4.67)] and the 3-year arm [osteopenia HR 0.75 (95% CI 0.40-1.42), osteoporosis HR 1.86 (95% CI 0.43-8.01)]. Moreover, bisphosphonate use did not impact DRFS. Conclusion No association was observed between a reduced BMD and DRFS. Neither did we observe an impact of bisphosphonates on DRFS.",

keywords = "Breast cancer, Tamoxifen, Aromatase inhibitor, Bone health, Osteoporosis, Bisphosphonates, Survival, Bone metastases, Distant recurrence-free survival, ZOLEDRONIC ACID, POSTMENOPAUSAL WOMEN, IN-VITRO, THERAPY, CELLS, RISK, CHEMOTHERAPY, METASTASIS, MECHANISMS, CLODRONATE",

author = "{van Hellemond}, {Irene E. G.} and Smorenburg, {Carolien H.} and Peer, {Petronella G. M.} and Swinkels, {Astrid C. P.} and Seynaeve, {Caroline M.} and {van der Sangen}, {Maurice J. C.} and Kroep, {Judith R.} and {de Graaf}, Hiltje and Honkoop, {Aafke H.} and Erdkamp, {Frans L. G.} and {van den Berkmortel}, {Franchette W. P. J.} and {de Roos}, {Wilfred K.} and Linn, {Sabine C.} and Imholz, {Alexander L. T.} and {de Boer}, Maaike and Tjan-Heijnen, {Vivianne C. G.} and {Dutch Breast Canc Res Grp BOOG}",

note = "Funding Information: This study was funded by AstraZeneca NL, ClinicalTrials.gov number, NCT00301457. Funding Information: IEGvH, SCL and ACPS report institutional grants from AstraZeneca during the conduct of the study. MdB reports research grants from Roche, Eisai, Novartis, Pfizer, and Lily during the conduct of the study; and consultation/speakers fee from Roche, Novartis, and Pfizer. VCGT-H reports consultant/advisory role to Pfizer, Lily, and Novartis, and grants to the institute for research from AstraZeneca, Roche, Novartis, Pfizer, and Lilly during the conduct of the study. FWPJvdB, FLGE, HdG, AH, ALTI, JRK, PGMP, WKdR, MJCvdS, CMS, CHS declare no conflicts of interests. Funding Information: We thank Wim A.J.G. Lemmens, Bianca Schalk, and Ton de Haan for their assistance with performing the statistical analyses. Publisher Copyright: {\textcopyright} 2020, The Author(s).",

year = "2020",

month = apr,

doi = "10.1007/s10549-020-05567-9",

language = "English",

volume = "180",

pages = "675--685",

journal = "Breast Cancer Research and Treatment",

issn = "0167-6806",

publisher = "Springer, Cham",

number = "3",

}

van Hellemond, IEG, Smorenburg, CH, Peer, PGM, Swinkels, ACP, Seynaeve, CM, van der Sangen, MJC, Kroep, JR, de Graaf, H, Honkoop, AH, Erdkamp, FLG, van den Berkmortel, FWPJ, de Roos, WK, Linn, SC, Imholz, ALT, de Boer, M , Tjan-Heijnen, VCG & Dutch Breast Canc Res Grp BOOG 2020, 'Breast cancer outcome in relation to bone mineral density and bisphosphonate use: a sub-study of the DATA trial', Breast Cancer Research and Treatment, vol. 180, no. 3, pp. 675-685. https://doi.org/10.1007/s10549-020-05567-9

TY - JOUR

T1 - Breast cancer outcome in relation to bone mineral density and bisphosphonate use

T2 - a sub-study of the DATA trial

AU - van Hellemond, Irene E. G.

AU - Smorenburg, Carolien H.

AU - Peer, Petronella G. M.

AU - Swinkels, Astrid C. P.

AU - Seynaeve, Caroline M.

AU - van der Sangen, Maurice J. C.

AU - Kroep, Judith R.

AU - de Graaf, Hiltje

AU - Honkoop, Aafke H.

AU - Erdkamp, Frans L. G.

AU - van den Berkmortel, Franchette W. P. J.

AU - de Roos, Wilfred K.

AU - Linn, Sabine C.

AU - Imholz, Alexander L. T.

AU - de Boer, Maaike

AU - Tjan-Heijnen, Vivianne C. G.

AU - Dutch Breast Canc Res Grp BOOG

N1 - Funding Information: This study was funded by AstraZeneca NL, ClinicalTrials.gov number, NCT00301457. Funding Information: IEGvH, SCL and ACPS report institutional grants from AstraZeneca during the conduct of the study. MdB reports research grants from Roche, Eisai, Novartis, Pfizer, and Lily during the conduct of the study; and consultation/speakers fee from Roche, Novartis, and Pfizer. VCGT-H reports consultant/advisory role to Pfizer, Lily, and Novartis, and grants to the institute for research from AstraZeneca, Roche, Novartis, Pfizer, and Lilly during the conduct of the study. FWPJvdB, FLGE, HdG, AH, ALTI, JRK, PGMP, WKdR, MJCvdS, CMS, CHS declare no conflicts of interests. Funding Information: We thank Wim A.J.G. Lemmens, Bianca Schalk, and Ton de Haan for their assistance with performing the statistical analyses. Publisher Copyright: © 2020, The Author(s).

PY - 2020/4

Y1 - 2020/4

N2 - Purpose The phase III DATA study compared 6 and 3 years of adjuvant anastrozole following 2-3 years of tamoxifen in postmenopausal breast cancer patients. This pre-planned side-study assessed the relationship between a reduced bone mineral density (BMD) and distant recurrence-free survival (DRFS), and evaluated the effect of bisphosphonates on DRFS. Methods We selected all patients with a BMD measurement within 3 years after randomisation (landmark) without any DRFS events. Kaplan-Meier methods and Cox proportional hazards models were used for analyses. Results Of 1860 eligible patients, 1142 had a DEXA scan before the landmark. The BMD was normal in 436 (38.2%) and showed osteopenia in 565 (49.5%) and osteoporosis in 141 (12.3%) patients. After a median follow-up of 5.0 years from the landmark, neither osteopenia nor osteoporosis (compared with normal BMD) were associated with DRFS in both the 6-year [osteopenia HR 0.82 (95% CI 0.45-1.49), osteoporosis HR 1.10 (95% CI 0.26-4.67)] and the 3-year arm [osteopenia HR 0.75 (95% CI 0.40-1.42), osteoporosis HR 1.86 (95% CI 0.43-8.01)]. Moreover, bisphosphonate use did not impact DRFS. Conclusion No association was observed between a reduced BMD and DRFS. Neither did we observe an impact of bisphosphonates on DRFS.

AB - Purpose The phase III DATA study compared 6 and 3 years of adjuvant anastrozole following 2-3 years of tamoxifen in postmenopausal breast cancer patients. This pre-planned side-study assessed the relationship between a reduced bone mineral density (BMD) and distant recurrence-free survival (DRFS), and evaluated the effect of bisphosphonates on DRFS. Methods We selected all patients with a BMD measurement within 3 years after randomisation (landmark) without any DRFS events. Kaplan-Meier methods and Cox proportional hazards models were used for analyses. Results Of 1860 eligible patients, 1142 had a DEXA scan before the landmark. The BMD was normal in 436 (38.2%) and showed osteopenia in 565 (49.5%) and osteoporosis in 141 (12.3%) patients. After a median follow-up of 5.0 years from the landmark, neither osteopenia nor osteoporosis (compared with normal BMD) were associated with DRFS in both the 6-year [osteopenia HR 0.82 (95% CI 0.45-1.49), osteoporosis HR 1.10 (95% CI 0.26-4.67)] and the 3-year arm [osteopenia HR 0.75 (95% CI 0.40-1.42), osteoporosis HR 1.86 (95% CI 0.43-8.01)]. Moreover, bisphosphonate use did not impact DRFS. Conclusion No association was observed between a reduced BMD and DRFS. Neither did we observe an impact of bisphosphonates on DRFS.

KW - Breast cancer

KW - Tamoxifen

KW - Aromatase inhibitor

KW - Bone health

KW - Osteoporosis

KW - Bisphosphonates

KW - Survival

KW - Bone metastases

KW - Distant recurrence-free survival

KW - ZOLEDRONIC ACID

KW - POSTMENOPAUSAL WOMEN

KW - IN-VITRO

KW - THERAPY

KW - CELLS

KW - RISK

KW - CHEMOTHERAPY

KW - METASTASIS

KW - MECHANISMS

KW - CLODRONATE

U2 - 10.1007/s10549-020-05567-9

DO - 10.1007/s10549-020-05567-9

M3 - Article

C2 - 32124136

SN - 0167-6806

VL - 180

SP - 675

EP - 685

JO - Breast Cancer Research and Treatment

JF - Breast Cancer Research and Treatment

IS - 3

ER -