NordicTrip, a Translational Study of Preoperative Chemotherapy in TNBC

Inclusion Criteria:

1. Signed written informed consent approved by the Ethical Review Board (IRB).

2. Age ≥ 18 to < 76 years.

3. Histologically confirmed unilateral adenocarcinoma of the breast where neoadjuvantchemotherapy followed by definitive surgery is planned.

4. Node positive disease (N1-3) or if clinically N0 Tumor size >20 mm. When decidingT-stage the following hierarchy applies,

5. MRI

6. Ultrasound

7. Mammography

8. Clinical examination

9. ER negative tumor defined by at least one the following:

10. ER < 1% cells positive by immunohistochemistry (IHC) or ER ≤ 10% cells positiveby IHC and basal-like subtype using gene expression analysis

11. ER < 10% cells positive by IHC and PgR < 10% cells positive by IHC

12. HER2-normal tumor defined according to applicable national guidelines

13. Consent for germline mutation screening for BRCA1, BRCA2 and other inherited breastcancer associated genes.

14. WHO performance status 0 or 1.

15. Negative pregnancy test in women of childbearing potential (premenopausal or <12months of amenorrhea post-menopause and who have not undergone surgicalsterilization).

16. Willingness of female patients of childbearing potential, male patients, and theirsexual partners to use an effective means of contraception during the treatmentperiod and at least 6 months thereafter.

17. Willingness by the patient to undergo treatment and study related proceduresaccording to the protocol.

Exclusion Criteria:

1. Clinical or radiological signs of metastatic disease.

2. History of other malignancy within the last 5 years, except for carcinoma in situ ofthe cervix or non-melanoma skin cancer.

3. Previous chemotherapy for cancer or other malignant disease.

4. Charlson comorbidity index, excluding score for malignancy: (CCI) > 2, Comment: Inpatients 70-75 a CCI = 3 is allowed, see appendix B.

5. Inadequate organ function, suggested by the following laboratory results: a Absolute neutrophil count < 1,5 x 109/L b Platelet count < 100 x 109/L c Hemoglobin < 90 g/L d Total bilirubin greater than the upper limit of normal (ULN) unless the patienthas documented Gilbert´s syndrome e ASAT (SGOT) and/or ALAT (SGPT) > 2,5 x ULN f ASAT (SGOT) and/or ALAT (SGPT) > 1,5 x ULN with concurrent serum alkalinephosphatase (ALP) > 2,5 x ULN g Serum creatinine clearance < 50 ml/min

6. Concurrent peripheral neuropathy of grade 3 or greater (NCI-CTCAE, Version 5.0).

7. Patient who is actively breast feeding.

8. Assessed by the Investigator to be unable or unwilling to comply with therequirements of the protocol.

9. Patients with known deficiency of the DPD-enzyme who completely lack DPD.