Bone-Induced HER2 Promotes Secondary Metastasis in HR+/HER2- Breast Cancer

Rahat Alam^#^{1

2

3}, Anna Reva^#^{1

2

3}, David G Edwards^{4

5

6}, Bree M Lege^{4

6

7}, Laura S Munoz-Arcos⁸, Carolina Reduzzi⁸, Swarnima Singh^{1

2

3}, Xiaoxin Hao^{4

5

6}, Yi-Hsuan Wu^{4

5

6}, Zeru Tian⁹, Laura M Natalee^{5

6}, Gargi Damle^{1

2}, Deniz Demircioglu^{1

2}, Yixian Wang⁹, Ling Wu^{4

5

6}, Elisabetta Molteni⁸, Dan Hasson^{1

2}, Bora Lim¹⁰, Zbigniew Gugala¹¹, Jerry E Chipuk^{1

2

3}, Julie E Lang¹², Joseph A Sparano^{1

2

3}, Chonghui Cheng^{4

6

7}, Massimo Cristofanilli⁸, Han Xiao⁹, Xiang H-F Zhang^{4

5

6

13}, Igor L Bado^{1

2

3}

Affiliations

¹ Icahn School of Medicine, Mount Sinai, New York, New York.
² Tisch Cancer Institute, Mount Sinai, New York, New York.
³ Department of Oncological Sciences, Mount Sinai, New York, New York.
⁴ Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas.
⁵ Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas.
⁶ Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas.
⁷ Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas.
⁸ Division of Hematology-Oncology, Department of Medicine, Weill Cornell Medicine, New York, New York.
⁹ Department of Chemistry, Rice University, Houston, Texas.
¹⁰ Division of Cancer Medicine, MD Anderson, Department of Breast Medical Oncology, Houston, Texas.
¹¹ Department of Orthopedic Surgery and Rehabilitation, University of Texas Medical Branch, Galveston, Texas.
¹² Division of Breast Cancer, Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.
¹³ McNair Medical Institute, Baylor College of Medicine, Houston, Texas.

^# Contributed equally.

PMID: 39835789
PMCID: PMC11964846 (available on 2025-10-02)
DOI: 10.1158/2159-8290.CD-23-0543

Bone-Induced HER2 Promotes Secondary Metastasis in HR+/HER2- Breast Cancer

Rahat Alam et al. Cancer Discov. 2025.

. 2025 Apr 2;15(4):818-837.

doi: 10.1158/2159-8290.CD-23-0543.

Authors

Affiliations

¹ Icahn School of Medicine, Mount Sinai, New York, New York.
² Tisch Cancer Institute, Mount Sinai, New York, New York.
³ Department of Oncological Sciences, Mount Sinai, New York, New York.
⁴ Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas.
⁵ Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas.
⁶ Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas.
⁷ Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas.
⁸ Division of Hematology-Oncology, Department of Medicine, Weill Cornell Medicine, New York, New York.
⁹ Department of Chemistry, Rice University, Houston, Texas.
¹⁰ Division of Cancer Medicine, MD Anderson, Department of Breast Medical Oncology, Houston, Texas.
¹¹ Department of Orthopedic Surgery and Rehabilitation, University of Texas Medical Branch, Galveston, Texas.
¹² Division of Breast Cancer, Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.
¹³ McNair Medical Institute, Baylor College of Medicine, Houston, Texas.

^# Contributed equally.

PMID: 39835789
PMCID: PMC11964846 (available on 2025-10-02)
DOI: 10.1158/2159-8290.CD-23-0543

Abstract

Given the urgent need for alternative strategies to block metastasis progression, we demonstrate that blocking HER2-mediated secondary metastasis improves clinical outcome and establish HER2 as a biomarker for bone metastasis in patients with initial HR+/HER2- breast cancer, which represents ∼70% of all cases.

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Conflict of interest statement

The authors declare no potential conflicts of interest.

References

1. Paterson AHG, Anderson SJ, Lembersky BC, Fehrenbacher L, Falkson CI, King KM, et al. Oral clodronate for adjuvant treatment of operable breast cancer (National Surgical Adjuvant Breast and Bowel Project protocol B-34): A multicentre, placebo-controlled, randomised trial. Lancet Oncol 2012;13:734–42. - PMC - PubMed
1. Gnant M, Mlineritsch B, Stoeger H, Luschin-Ebengreuth G, Knauer M, Moik M, et al. 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. Annals of Oncology 2015;26:313–20. - PubMed
1. Von Minckwitz G, Möbus V, Schneeweiss A, Huober J, Thomssen C, Untch M, et al. German adjuvant intergroup node-positive study: A phase III trial to compare oral ibandronate versus observation in patients with high-risk early breast cancer. Journal of Clinical Oncology 2013;31:3531–9. - PubMed
1. Coleman R, Powles T, Paterson A, Gnant M, Anderson S, Diel I, et al. Adjuvant bisphosphonate treatment in early breast cancer: meta-analyses of individual patient data from randomised trials. Lancet. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Open Access article distributed under the terms of CC BY; 2015;386:1353–61. - PubMed
1. Coleman R, De Boer R, Eidtmann H, Llombart A, Davidson N, Neven P, et al. Zoledronic acid (zoledronate) for postmenopausal women with early breast cancer receiving adjuvant letrozole (ZO-FAST study): Final 60-month results. Annals of Oncology 2013;24:398–405. - PubMed

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Bone-Induced HER2 Promotes Secondary Metastasis in HR+/HER2- Breast Cancer

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Bone-Induced HER2 Promotes Secondary Metastasis in HR+/HER2- Breast Cancer

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