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

Prior treatment

• Participation in another interventional clinical trial within 30 days prior to inclusion.

Other illness

• 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.
• 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.
• 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).
• Cognitive impairment, psychiatric disorder, or social situation preventing valid informed consent or adequate understanding of the protocol, as assessed by the investigator.

Age

• 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.

Other

• Presence of ductal carcinoma in situ (DCIS) on diagnostic biopsy, or diffuse suspicious microcalcifications on mammography, precluding reliable assessment of complete response.
• Current pregnancy or breastfeeding.
• Individuals deprived of liberty or under legal protection (guardianship, curatorship, or similar legal status), in accordance with applicable regulations.

• 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.