MRI-guided early surgery and reduced chemotherapy for stage II–III triple-negative breast cancer

Inclusion Criteria:

* Patient is eligible per physician's discretion for the KEYNOTE-522 regimen (Neoadjuvant paclitaxel-carboplatin-doxorubicin-cyclophosphamide-pembrolizumab)
* Signed written informed consent
* Histologically confirmed primary infiltrating breast cancer with estrogen receptor expression \<1%, Progesterone receptor expression \<1%, and without overexpression and/or amplification of HER2 according to ASCO/CAP 2013 guideline (locally assessed)
* T2-3N0, T1-3N1 disease according to TNM-staging (8th edition, AJCC).
* Nodal status must be examined by ultrasound and fine-needle aspiration or core biopsy in case of suspicious lymph nodes.
* No evidence of distant metastases (Stage IV disease) on FDG-PET performed within 35 days of enrollment.
* Age ≥18
* WHO performance status ≤ 2
* Visible breast tumor on contrast enhanced MRI (no minimal longest diameter required)
* MRI breast must be performed within 35 days prior to registration
* Patients with a history of autoimmune disease are eligible for the study per treating physician's discretion.
* Laboratory requirements - within 21 days prior to enrollment:

  * Adequate bone marrow function (ANC ≥1.5 x 109/l, platelets ≥100 x 109/l)
  * Adequate hepatic function (ALT, AST and bilirubin ≤2.5 times upper limit of normal)
  * Subjects with Gilbert's syndrome may have a total bilirubin ≥2.5 × the ULN range, if no evidence of biliary obstruction exists;
  * Adequate renal function: creatinine clearance \>50 ml/min estimated using the Cockcroft-Gault equation, or based on a 24-hour urine collection measurement
  * LVEF ≥50% measured by echocardiography
* Women of childbearing potential and men must agree to remain abstinent (refrain from heterosexual intercourse) or use adequate contraceptive methods (failure rate of \<1% per year,) during treatment and for at least 6 months after the last dose of pembrolizumab. A woman is considered to be of childbearing potential if she is post-menarcheal, has not reached a postmenopausal state (≥12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus). Examples of contraceptive methods with a failure rate of \<1% per year include bilateral tubal ligation, male sterilization, established, proper use of hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices (IUDs), and copper IUDs. Women who are not postmenopausal (≥12 months of non-therapy-induced amenorrhea) or surgically sterile must have a negative β-HCG serum or urine pregnancy test result.

Exclusion Criteria:

* Concurrent breastfeeding
* Concurrent contralateral or ipsilateral non-TNBC second primary infiltrating breast cancer. Contralateral or ipsilateral TNBC second primary infiltrating breast cancer or DCIS is allowed.
* Concurrent anti-cancer treatment or another investigational drug
* Any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
* Patients who have a history of a second malignancy are eligible, provided the malignancy has been adequately treated, there is no ongoing treatment for the second malignancy, and overall principal investigator (PI) approval is obtained.
* Has undergone excisional biopsy of the primary tumor, and/or axillary lymph node dissection prior to study treatment.
* Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study intervention.
* History or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that might confound the results of the study or interfere with the participant's ability to cooperate with the requirements of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator.