Reduction of Neoadjuvant Treatment in Early Triple-Negative Breast Cancer

Prior treatment

• Relapse of a previous breast cancer.
• Any other malignancy within the previous 3 years, except for cancers considered adequately treated and at low risk of recurrence.
• Active autoimmune disease (e.g., inflammatory bowel disease, systemic lupus erythematosus, ankylosing spondylitis, scleroderma, multiple sclerosis, celiac disease, Wegener's granulomatosis) requiring systemic treatment within the previous 3 years (i.e., disease-modifying agents, corticosteroids, or immunosuppressive drugs).
• Prior treatment with systemic immunosuppressive medications (except physiologic replacement corticosteroids) within 30 days before the planned start of study treatment.
• Receipt of a live (attenuated) vaccine within 30 days before the planned start of study treatment.
• Active infection, including:
  • Tuberculosis (TB); Hepatitis B (known positive hepatitis B surface antigen \[HBsAg\]). Subjects with past or resolved HBV infection (defined by positive anti-HBc antibodies and negative HBsAg) are eligible; Hepatitis C. Subjects positive for anti-HCV antibodies are eligible only if HCV RNA is negative by polymerase chain reaction (PCR); Human immunodeficiency virus (HIV) infection. HIV-positive subjects are eligible if receiving treatment and having an undetectable viral load.
• Significant cardiovascular disease, including New York Heart Association (NYHA) Class II or higher heart disease, cardiomyopathy, acute inflammatory heart disease, myocardial infarction, transient ischemic attack (TIA), stroke within the previous 3 months, unstable arrhythmias, and/or unstable angina.
• Participation in another study involving one or more investigational medicinal products within 3 weeks before study entry (or within a period equivalent to 5 half-lives before the first dose of the study intervention). Participation in observational studies or long-term follow-up of other studies is permitted provided that no procedures likely to interfere with the interpretation of the present study results are performed.
• Prior systemic therapy or curative radiotherapy for the current breast cancer.

Other illness

• Metastatic disease at diagnosis.
• Bilateral breast cancer.
• Invasive breast adenocarcinoma with ER and PR \> 10% and/or HER2-positive disease.
• Ongoing acute urinary tract infection, pre-existing hemorrhagic cystitis, or known urinary tract obstruction.
• Known or suspected hypersensitivity, or severe allergy, to any active substance or excipient of the study drugs, including lactose.
• Any uncontrolled medical condition, neuropsychiatric disorder, or significant substance dependence that, in the opinion of the Principal Investigator, could interfere with study completion.

Other

• Pregnant or breastfeeding women, or women likely to become pregnant due to lack of effective contraception.
• Contraindication to MRI.
• Diagnosis of immunodeficiency.
• Vulnerable persons as defined under Article L.1121-6 of the French Public Health Code, adults under legal protection measures, or individuals unable to provide informed consent in accordance with Article L.1121-8 of the French Public Health Code.
• Current use of St. John's Wort (Hypericum perforatum).

• Male or female aged 18 years or older.
• Signed informed consent for study participation.
• Histologically and/or cytologically confirmed invasive triple-negative breast adenocarcinoma (ER and PR \< 10%, HER2-negative), documented on all tumor samples.
• Stage II disease: T2-T3N0M0 or T1-T2N1M0.
• Tumor-infiltrating lymphocytes (TILs) ≥ 30% on the initial biopsy (TILs will be assessed according to the recommendations of the International TILs Working Group 2014).
• Availability of tumor tissue samples.
• ECOG Performance Status ≤ 1.
• No contraindication to neoadjuvant chemotherapy or pembrolizumab.
• Adequate bone marrow function, defined as follows (laboratory assessments performed within 21 days prior to enrollment):
  • Absolute neutrophil count ≥ 1,500/μL (1.5 × 10⁹/L) Hemoglobin ≥ 10 g/dL Platelet count ≥ 100,000/μL (100 × 10⁹/L)
• Adequate hepatic function, defined as follows (laboratory assessments performed within 21 days prior to enrollment):
  • Total serum bilirubin ≤ 1.5 × ULN; for subjects with known Gilbert's syndrome, ≤ 3 × ULN is permitted AST (SGOT) ≤ 2.0 × ULN ALT (SGPT) ≤ 2.0 × ULN Alkaline phosphatase (ALP) ≤ 2.5 × ULN
• Adequate renal function, defined as follows (laboratory assessments performed within 21 days prior to enrollment):
  • Serum creatinine ≤ 1.5 × ULN or estimated glomerular filtration rate (eGFR) ≥ 40 mL/min/1.73 m²
• Left ventricular ejection fraction (LVEF) ≥ 50%, assessed by echocardiography. A routine LVEF assessment is acceptable if performed within 28 days prior to the start of screening.
• Adequate serum potassium, magnesium, and calcium levels (\> ULN).
• Negative serum pregnancy test at screening for subjects of childbearing potential.
• Women of childbearing potential must agree to use a highly effective method of contraception during the screening period, throughout study treatment, and for at least 7 months after the last administration of study treatment. It is strongly recommended that the male partner of a female participant also use a male condom with spermicide throughout this period.
• Affiliation with, or beneficiary of, a health insurance system.
• Ability to communicate and understand French without difficulty.