Christian F. Singer MD; 2025 SABCS: Denosumab Bone Protection in ER-Positive Early Breast Cancer Brings Added Benefit with Progesterone Receptor Positive Tumors: ABCSG 18 Study Findings

Denosumab Bone Protection in ER-Positive Early Breast Cancer Brings Added Benefit with Progesterone Receptor Positive Tumors: ABCSG 18 Study Findings

An interview with:

Christian F Singer MD, Professor of Clinical-Translational Gynecological Oncology, Medical University of Vienna, Austria

SAN ANTONIO, USA—Post-menopausal women treated with denosumab to give bone protection along with their aromatase inhibitor hormone therapy did better if their tumors tested positive for the progesterone receptor as well as for the estrogen receptor.  This is according to finding from the ABCSG 18 Study (of the Austrian Breast and Colorectal Cancer Study Group).

The research was reported at the 2025 San Antonio Breast Cancer Symposium by Christian Singer MD, Professor of Clinical-Translational Gynecological Oncology at the Medical University of Vienna, Austria.  The Audio Journal of Oncology’s Peter Goodwin called to see him at his poster to find out more:

AUDIO JOURNAL OF ONCOLOGY: Christian F. Singer MD

IN: [GOODWIN] “We are at the San Antonio ..…..

OUT ……..Journal of Oncology, I’m Peter Goodwin.   7:22secs

ABSTRACT:

Authors:

Singer1, D. Hlauschek2, D. Egle3, A. Reiner4, G. G. Steger5, G. Huber6, R. Greil7, G. Rinnerthaler8, F. Fitzal9, C. Brunner3, C. Suppan8, G. Pfeiler1, S. P. Gampenrieder7, M. Seifert1, S. Kacerovsky-Strobl10, C. Deutschmann1, K. Wimmer11, M. Balic12, R. Jakesz5, C. Fesl2, H. Fohler13, M. Gnant5;

Institutions:

1Department of Gynecology and Obstetrics, Medical University of Vienna, Vienna, AUSTRIA, 2Statistics Department, Austrian Breast and Colorectal Cancer Study Group (ABCSG), Vienna, AUSTRIA, 3Department of Obstetrics and Gynecology, Medical University of Innsbruck, Innsbruck, AUSTRIA, 4Institut für Klinische Pathologie, Molekularpathologie und Mikrobiologie, Klinik Donaustadt, Vienna, AUSTRIA, 5Comprehensive Cancer Center, Medical University of Vienna, Vienna, AUSTRIA, 6Ordination Dr. Huber, Breast Center Carinthia, St. Veit/Glan, AUSTRIA, 7Department of Internal Medicine III, Oncologic Center, Salzburg Cancer Research Institute, Paracelsus Medical University, Salzburg, AUSTRIA, 8Division of Clinical Oncology, Department of Internal Medicine, Medical University of Graz, Graz, AUSTRIA, 9Department of Surgery and Breast Health Center, Hanusch Hospital, Vienna, AUSTRIA, 10Department of Surgery, Klinikum Donaustadt, Vienna, AUSTRIA, 11Division of General Surgery, Department of Surgery, Medical University of Vienna, Vienna, AUSTRIA, 12Division of Oncology, University of Pittsburgh Medical School, Hillmans Cancer Center, Pittburgh, PA, 13Management, Austrian Breast and Colorectal Cancer Study Group (ABCSG), Vienna, AUSTRIA.

Title:

The improved long-term outcome in denosumab-treated postmenopausal women with early luminal breast cancer in ABCSG 18 is driven by progesterone receptor (PR)-positive tumors.

Background:

The biological effects of progesterone are mediated through the RANK/RANK-ligand system, which promotes tumor growth and malignant behavior in breast cancer models. In the large prospective, double-blind, placebo-controlled, phase 3 ABCSG 18 trial we have demonstrated that the addition of the RANK ligand denosumab dramatically reduces fractures compared to placebo, but also improves disease-free survival (DFS), and overall survival (OS) in aromatase inhibitor-treated postmenopausal patients with early luminal breast cancer.

Patients and Methods:

Tumor histological grade, as well as immunohistochemically quantified Ki-67, estrogen receptor (ER), and progesterone receptor (PR) data were collected from 2,026 patients. ER and PR were assessed according to the Allred score and considered positive if ≥3. Disease-free survival (DFS), distant recurrence-free (DRFS), and overall survival (OS) data were prospectively collected during a median follow-up (FU) of 8.1 years as part of the ABCSG 18 study. Cox Models were used to evaluate the association with outcome.

Results:

Overall, luminal A-like tumors had a better DFS, DRFS, and OS than luminal B-like tumors, but PR expression per se was not prognostic in this large prospective clinical trial. Patients with PR positive tumors, however, who were treated with denosumab, enjoyed a considerably better long-term outcome than patients who had been randomized to the placebo arm (HR for DFS: 0.80; 95% CI 0.65-0.98; HR for DRFS: 0.68; 95% CI 0.51-0.90; HR for OS 0.63; 95% CI 0.46-0.88). In contrast, in patients with PR-negative tumors, no differences in long-term outcomes between the denosumab or placebo arm of the trial were observed (HR for DFS: 0.87; 95% CI 0.46-1.64; HR for DRFS: 1.19; 95% CI 0.53-2.66; HR for OS 0.99; 95% CI 0.37-2.65). While the HR for DFS in denosumab vs placebo patients remained stable with increasing Allred scores, HRs for DRFS and OS improved with increasing Allred scores, thereby suggesting that the efficacy of denosumab depends on the degree of intra-tumoral PR expression.

Conclusion:

Our results indicate that the long-term outcome benefit for adjuvant denosumab in this large prospective randomized placebo-controlled trial is driven by patients with PR-positive tumors. The disruption of PR signaling, either via PR antagonization or by RANKL inhibition, could therefore be a promising therapeutic strategy in luminal breast cancer.

260119 Christian F. Singer MD A J Oncology

From:

SABCS 2025 Wednesday Dec. 10 Poster 5:00 pm