EUBREAST 25 (R) – INSPIRE Study – Inflammatory Breast Cancer Surgery: Preserving versus Radical Therapy

Principal Investigator

Sub-Principal Investigator

Steering Board

Assoc. prof. Oldřich Coufal, MD, PhD

Dr. Kerstin Pfister, Ulm University, Ulm, Germany

Dr. Jan Beneš, MD

Contact email:

info@eubreast.org

Summary:

Background and rationale

Over the past decades, surgical de-escalation in breast cancer has increasingly been adopted across a broad range of patients. However, patients with inflammatory breast cancer (IBC) have largely been excluded from pivotal studies evaluating less invasive surgical approaches. Consequently, mastectomy and axillary lymph node dissection (ALND) remain the standard surgical approach for patients with IBC, irrespective of their response to neoadjuvant therapy (NAT).

IBC represents one of the most aggressive subtypes of breast cancer and has traditionally been managed with multimodal therapy, including mastectomy and ALND. Unlike patients with other breast cancer subtypes, those with IBC have been systematically excluded from key prospective trials investigating less extensive breast and axillary surgery, including breast-conserving surgery (BCS), sentinel lymph node biopsy (SLNB), targeted lymph node biopsy (TLNB), and targeted axillary dissection (TAD).

Nevertheless, emerging evidence suggests that the extent of surgery required in IBC may warrant re-evaluation in selected patients. Analyses of large databases have shown no clear survival advantage associated with radical axillary surgery in patients with clinically node-negative IBC. Moreover, real-world series indicate that a substantial proportion of patients achieve a complete nodal response (ypN0) following NAT, particularly those with triple-negative or HER2-positive tumors. These findings raise concerns regarding potential axillary overtreatment and support further investigation into response-adapted surgical strategies.

Beyond axillary management, an excellent response to NAT may also prompt a re-evaluation of the extent of breast surgery in carefully selected patients. However, the oncological safety of breast-conserving approaches in IBC remains insufficiently established, and mastectomy continues to be the standard of care. Prospective studies are therefore needed to determine whether selected patients with IBC who achieve an excellent response to NAT may safely benefit from less extensive surgery of the breast and axilla. The INSPIRE study aims to address this knowledge gap by evaluating the potential for surgical de-escalation in both the breast and the axilla.

Study Milestones:

Step 1: Registry-based data analysis (Baden-Württemberg Cancer Registry)

Step 2: Registry-based data analysis (Consortium of German Cancer Registries)

Step 3: Prospective IBC arm of the AXSANA study (from Fall 2026 onwards)

Prizes and Presentations:

1. European Society of Surgical Oncology (ESSO) 2026 – Poster

De-escalation of Axillary Surgery in Inflammatory Breast Cancer: A New Clinical Era

Authors: J. Žatecký, O. Coufal, T. Kühn, I. Surovtsova, K. Pfister, K. Burtscher, P. Morakis

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2. Annual Congress of the German Society for Senology 2026 – Poster Award

Inflammatory Breast Cancer: Biology Matters More Than Phenotype – A Real-World Registry Study

Authors: I. Surovtsova, T. Kühn, J. Žatecký, K. Burtscher, K. Pfister, P. Morakis

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3. Brno Oncology Days 2026 – Oral Presentation

Inflammatory Breast Cancer – Is It Time for Conservative Axillary Surgery?

Authors: J. Žatecký, O. Coufal, T. Kühn, I. Surovtsova, K. Pfister, K. Burtscher, P. Morakis

Publications and related publications:

Žatecký, J., Coufal, O. De-escalation of Axillary Surgery in Inflammatory Breast Cancer: The Right Time is Coming. Ann Surg Oncol 32, 8555–8557 (2025). https://doi.org/10.1245/s10434-025-18356-9 (related)

https://link.springer.com/article/10.1245/s10434-025-18356-9