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

Официальное название

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.

Обзор

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

Вмешательства

• Процедура Omission of surgery
  Patients will not undergo breast and axillary surgery.

Первичные конечные точки

• Assess invasive disease-free survival (iDFS) [Срок оценки: Within 36 months after randomisation]

Вторичные конечные точки (12)

• Assessing the locoregional recurrence-free interval (LRFI) [Срок оценки: 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) [Срок оценки: 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) [Срок оценки: From date of randomisation until the date of death, assessed up to 60 months]
• Assessing the adverse effects of macrobiopsy [Срок оценки: Up to 30 days after macrobiopsy]
• Assessing the adverse effects of standard of care radiotherapy treatment [Срок оценки: From start of treatment through study completion, an average of 60 months]
• Assessing quality of life - EORTC QLQ-C30 Physical Functioning score [Срок оценки: Randomisation, month 6, month 12, month 18, month 24, month 30, month 36]
• Assessing quality of life - EORTC QLQ-C30 Fatigue score [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: Randomisation, month 6, month 12, month 18, month 24, month 30, month 36]
• Assessing the number of benign biopsies during follow-up [Срок оценки: From date of randomisation until the date of new biopsy, assessed up to 60 months]

Критерии участия

Критерии включения

• Sex and age: Female, aged 18 years or older.
• Histological type: Invasive breast carcinoma of no special type (NST).
• 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).
• High proliferation index: Ki-67 > 30%.
• Primary tumor classified as T2, i.e. tumor size between 2 and 5 cm on imaging at diagnosis (mammography, ultrasound, and breast MRI).
• No regional lymph node involvement or distant metastasis, confirmed by 18F-FDG PET-CT performed prior to neoadjuvant treatment.
• Completion of the full neoadjuvant chemo-immunotherapy (NCIT) protocol according to the KEYNOTE-522 regimen (≥7 cycles including pembrolizumab).
• Breast-conserving surgery deemed feasible based on the initial surgical assessment.
• 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.
• Written informed consent obtained prior to any study-specific procedure.
• Ability of the patient to comply with the protocol requirements and scheduled follow-up.
• Affiliation with a national health insurance system, in accordance with French regulations.

Критерии исключения

• Presence of regional recurrence or metastatic disease at inclusion.
• History of thoracic, breast, or regional lymph node irradiation, regardless of indication.
• Invasive lobular carcinoma, excluded due to its different response profile and increased risk of multifocal residual disease.
• Presence of ductal carcinoma in situ (DCIS) on diagnostic biopsy, or diffuse suspicious microcalcifications on mammography, precluding reliable assessment of complete response.
• Bilateral breast cancer (except for localized and treated contralateral DCIS), or history of ipsilateral or contralateral invasive breast cancer.
• Multifocal or multicentric disease detected on imaging (mammography, ultrasound, or breast MRI).
• Skin involvement or inflammatory breast cancer, identified on imaging or clinical examination.
• 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.
• Severe or progressive non-malignant disease limiting life expectancy to less than 10 years, in the investigator's judgment.
• Presence of a high-risk germline mutation predisposing to breast cancer (including BRCA1, BRCA2, or other identified predisposition genes).
• Participation in another interventional clinical trial within 30 days prior to inclusion.
• Current pregnancy or breastfeeding.
• Cognitive impairment, psychiatric disorder, or social situation preventing valid informed consent or adequate understanding of the protocol, as assessed by the investigator.
• Individuals deprived of liberty or under legal protection (guardianship, curatorship, or similar legal status), in accordance with applicable regulations.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Франция · 4 центра

• Centre Georges-François Leclerc — Dijon
• Institut Curie-Paris — Paris
• Hôpital Tenon — Paris
• Institut Curie Saint-Cloud — Saint-Cloud

Идентификаторы

NCT: NCT07357948 · IC 2025-05 · 2025-A02926-43

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗