Skipping surgery or radiotherapy for some women with HER2-positive or triple-negative early breast cancer
Omission of Local Therapies in Women Patients With HER2-positive or Triple-negative Breast Cancer: A Two Arm, Phase 2, Non-inferiority Trial for Surveillance in Maximum Responders to Neoadjuvant Systemic Therapy
This trial tests whether women with early HER2-positive or triple-negative breast cancer who have an excellent response to neoadjuvant therapy can safely skip surgery or skip radiotherapy.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 152 (estimated) |
| Ages | 18 Years and up |
| Sex | Female |
| Sponsor | Fondazione IRCCS Istituto Nazionale dei Tumori, Milano Academic / other |
| Locations | 1 site (Milan) |
| Trial ID | NCT06938724 on ClinicalTrials.gov |
What this trial studies
This is a phase 2, prospective, non-randomized non-inferiority trial with two parallel arms testing omission of local therapies in highly selected responders to neoadjuvant systemic treatment. Each arm uses a two-stage group-sequential design with 76 patients per arm and an interim futility analysis after 43 patients reviewed by an independent DSMC. Arm A will offer omission of surgery in unifocal T1-2 N0 M0 patients demonstrating maximal response (managed with whole-breast irradiation only), while Arm B will offer omission of radiotherapy for patients with confirmed complete pathological response after conservative surgery. The trial enrolls adult women with unifocal HER2-positive or triple-negative T1-2 N0-1 M0 breast cancer treated at a single Italian cancer center.
Who should consider this trial
Good fit: Women aged 18 or older with unifocal T1-2 N0-1 M0 HER2-positive or triple-negative breast cancer who achieve maximal clinical or complete pathological response after neoadjuvant systemic therapy and are planned for breast-conserving management.
Not a fit: Patients with residual invasive disease or DCIS, bilateral synchronous cancers, recent other malignancies, known high‑risk germline mutations (BRCA1/2, PALB2, TP53), or those unable to adhere to regular follow‑up are unlikely to benefit.
Why it matters
Potential benefit: If successful, eligible patients might avoid surgery or radiotherapy and their short- and long-term side effects while maintaining cancer control.
How similar studies have performed: Smaller pilot and observational series suggest de-escalation of local therapy may be feasible in highly selected responders, but robust randomized evidence is still limited.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * Women ≥ 18y. * Initial diagnosis of unifocal HER2-positive (regardless of HR status) or Triple-negative (HR positivity lower than 10% is allowed) T1-2, N0-1, M0 breast cancer. * Treated with neoadjuvant systemic treatment according to the center recommendations. * Maximum responders and/or complete pathological response proved by surgery. * Scheduled for breast conservation. * Giving specific informed consent. Exclusion Criteria: * One of the inclusion criteria missed. * Residual ductal carcinoma in situ (DCIS) at VABB and/or surgery. * Bilateral synchronous breast cancer. * Previous malignancy within 5 years. * BRCA1-2, PALB2 or p53 proven mutation carrier (VUS are exclusion criteria as well). * Patients unable to perform regular follow up.
Where this trial is running
Milan
- Fondazione IRCCS Istituto Nazionale Tumori Milano — Milan, Italy (Recruiting)
Study contacts
- Principal investigator: Massimiliano Gennaro, MD — Fondazione IRCCS Istituto Nazionale Tumori Milan
- Study coordinator: Massimiliano Gennaro, MD
- Email: massimiliano.gennaro@istitutotumori.mi.it
- Phone: +390223903246
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.