Omission of Surgery for Triple-negative Breast Cancer in Complete Response After Neoadjuvant Chemo-immunotherapy (WISH-OMICHIR)

Omission of Surgery for Triple-negative Breast Cancer in Complete Response Confirmed by MRI and Macrobiopsy After Neoadjuvant Chemo-immunotherapy: a Randomized, Multicenter Phase II Trial.

This clinical study aims to determine if skipping breast and axillary surgery could provide similar control of local and distant disease, with fewer complications and better quality of life, for triple-negative breast cancer patients in complete response after neoadjuvant chemo-immunotherapy.

Patients will be randomised into 2 groups :

• Control arm will receive the standard treatment, including surgery
• Experimental arm will receive the standard treatment, except surgery

Study Overview

• Status: Not yet recruiting
• Conditions: Triple Negative Breast Cancer; Non-Metastatic
• Intervention / Treatment: Procedure: Omission of surgery

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Carole Cagnot, Ph.D; Phone Number: 0147111891; Email: drci.promotion@curie.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Sex and age: Female, aged 18 years or older.
2. Histological type: Invasive breast carcinoma of no special type (NST).

3. Triple-negative phenotype, defined by:

   • Estrogen receptor (ER) < 10%,
   • Progesterone receptor (PR) < 10%,
   • HER2-negative status according to ASCO/CAP criteria (IHC score 0-1+, or 2+ without amplification by in situ hybridization).
4. High proliferation index: Ki-67 > 30%.
5. Primary tumor classified as T2, i.e. tumor size between 2 and 5 cm on imaging at diagnosis (mammography, ultrasound, and breast MRI).
6. No regional lymph node involvement or distant metastasis, confirmed by 18F-FDG PET-CT performed prior to neoadjuvant treatment.
7. Completion of the full neoadjuvant chemo-immunotherapy (NCIT) protocol according to the KEYNOTE-522 regimen (≥7 cycles including pembrolizumab).
8. Breast-conserving surgery deemed feasible based on the initial surgical assessment.
9. Radiological complete response (rCR) on post-NCIT breast MRI, associated with a negative vacuum-assisted biopsy (VAB) of the clip-marked tumor bed, confirming the absence of residual invasive or in situ disease.
10. Written informed consent obtained prior to any study-specific procedure.
11. Ability of the patient to comply with the protocol requirements and scheduled follow-up.
12. Affiliation with a national health insurance system, in accordance with French regulations.

Exclusion Criteria:

1. Presence of regional recurrence or metastatic disease at inclusion.
2. History of thoracic, breast, or regional lymph node irradiation, regardless of indication.
3. Invasive lobular carcinoma, excluded due to its different response profile and increased risk of multifocal residual disease.
4. Presence of ductal carcinoma in situ (DCIS) on diagnostic biopsy, or diffuse suspicious microcalcifications on mammography, precluding reliable assessment of complete response.
5. Bilateral breast cancer (except for localized and treated contralateral DCIS), or history of ipsilateral or contralateral invasive breast cancer.
6. Multifocal or multicentric disease detected on imaging (mammography, ultrasound, or breast MRI).
7. Skin involvement or inflammatory breast cancer, identified on imaging or clinical examination.

8. History of malignancy other than breast cancer, unless the disease has been in complete remission for ≥ 5 years and is considered at low risk of recurrence, with the exception of:

   • Treated carcinoma in situ of the cervix, endometrium, or colon,
   • Melanoma in situ,
   • Completely excised cutaneous basal cell or squamous cell carcinoma.
9. Severe or progressive non-malignant disease limiting life expectancy to less than 10 years, in the investigator's judgment.
10. Presence of a high-risk germline mutation predisposing to breast cancer (including BRCA1, BRCA2, or other identified predisposition genes).
11. Participation in another interventional clinical trial within 30 days prior to inclusion.
12. Current pregnancy or breastfeeding.
13. Cognitive impairment, psychiatric disorder, or social situation preventing valid informed consent or adequate understanding of the protocol, as assessed by the investigator.
14. Individuals deprived of liberty or under legal protection (guardianship, curatorship, or similar legal status), in accordance with applicable regulations.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental; standard care, except surgery	Procedure: Omission of surgery; Patients will not undergo breast and axillary surgery.
No Intervention: Control; standard care, including surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess invasive disease-free survival (iDFS)	Disease-free survival rate, taking into account the first occurrence of any of the following events : local or regional invasive recurrence, contralateral invasive breast cancer, distant metastasis, second primary cancer, death from any cause.	Within 36 months after randomisation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessing the locoregional recurrence-free interval (LRFI)	Number of months between randomization and the first occurrence of local or regional invasive recurrence (in the breast or regional lymph nodes)	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months
Assessing distant recurrence-free interval (DRFI)	Number of months between randomization and the first occurrence of distant metastases	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months
Assessing overall survival (OS)	Number of months between randomization and death, regardless of cause	From date of randomisation until the date of death, assessed up to 60 months
Assessing the adverse effects of macrobiopsy	Number of adverse events	Up to 30 days after macrobiopsy
Assessing the adverse effects of standard of care radiotherapy treatment	Number of grade ≥ 3 adverse events related to radiotherapy	From start of treatment through study completion, an average of 60 months
Assessing quality of life - EORTC QLQ-C30 Physical Functioning score	EORTC QLQ-C30 Physical Functioning score (0-100; higher = better)	Randomisation, month 6, month 12, month 18, month 24, month 30, month 36
Assessing quality of life - EORTC QLQ-C30 Fatigue score	EORTC QLQ-C30 Fatigue score (0-100; higher = worse)	Randomisation, month 6, month 12, month 18, month 24, month 30, month 36
Assessing quality of life - EORTC QLQ-C30 Global Health Status/Quality of Life score	EORTC QLQ-C30 Global Health Status/Quality of Life score (0-100; higher = better)	Randomisation, month 6, month 12, month 18, month 24, month 30, month 36
Assessing quality of life and aesthetic results - EORTC QLQ-BR42 Body Image score	EORTC QLQ-BR42 Body Image score (0-100; higher = better)	Randomisation, month 6, month 12, month 18, month 24, month 30, month 36
Assessing quality of life and aesthetic results - EORTC QLQ-BR42 Arm Symptoms score	EORTC QLQ-BR42 Arm Symptoms score (0-100; higher = worse)	Randomisation, month 6, month 12, month 18, month 24, month 30, month 36
Assessing quality of life and aesthetic results - EORTC QLQ-BR42 Future Perspective score	EORTC QLQ-BR42 Future Perspective score (0-100; higher = better)	Randomisation, month 6, month 12, month 18, month 24, month 30, month 36
Assessing the number of benign biopsies during follow-up	Number of benign biopsies of the breast or ipsilateral lymph nodes performed during follow-up	From date of randomisation until the date of new biopsy, assessed up to 60 months
Number of patients with residual disease not detected in the control arm	Evaluating the performance of MRI and macrobiopsy for predicting complete histologic response (pCR)	At surgery

Collaborators and Investigators

• Sponsor: Institut Curie
• Investigators: Principal Investigator: Toulsie Ramtohul, MD, Institut Curie

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): July 31, 2031
• Study Completion (Estimated): July 31, 2033

Study Registration Dates

• First Submitted: January 5, 2026
• First Submitted That Met QC Criteria: January 13, 2026
• First Posted (Actual): January 22, 2026

Study Record Updates

• Last Update Posted (Actual): January 22, 2026
• Last Update Submitted That Met QC Criteria: January 13, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms; Skin and Connective Tissue Diseases; Triple Negative Breast Neoplasms
• Other Study ID Numbers: IC 2025-05; 2025-A02926-43 (Other Identifier: ANSM)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Sponsor will share de-identified data sets. Documents generated under the project will be disseminated in accordance with Institut Curie policies
• IPD Sharing Time Frame: Data requests can be submitted starting 9 months after last article publication and will be made accessible for up to 12 months
• IPD Sharing Access Criteria: ccess to trial individual participant data can be requested by qualified researchers engaging in independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a data sharing agreement (DSA).
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No