OPTImaL:Optimisation of Treatment for Patients With Low Stage Triple-negative Breast Cancer With High Stromal Tumor-infiltrating Lymphocytes

Inclusion Criteria:

• Female or male patients;

• >=18 years;

• Written informed consent;

• TNBC (defined as: invasive carcinoma; ER/PR expression 0-9%; Human Epidermal GrowthFactor Receptor 2 [HER2] negative [0, 1+ or 2+ on immunohistochemistry, without HER2amplification on in-situ hybridization]) on the diagnostic biopsy and the surgicalspecimen;

• Pathological stage I TNBC (according to the TNM staging 8th edition):

• pT1a/b/c (≤2 cm), confirmed by an invasive component of ≤2 cm on the surgicalspecimen (microinvasive disease [pT1mi, ≤1 mm) is not allowed);

• pN0, confirmed by absence of malignant cells in the sentinel lymph node or anyother lymph node after surgery (isolated tumor cells [N0(i+)] are not allowed);

• No evidence of nodal or distant metastases (cN0M0) on pre and/or postoperativeimaging examinations (performed following local/national guidelines, but mustinclude an 18F-fluorodeoxyglucose positron emission tomography/computed tomography [18F-FDG-PET/CT, at least from skull base to upper legs] or computed tomography [CT]of neck/chest/abdomen/pelvis [CT only if 18F-FDG-PET/CT would not be available; 18F-FDG-PET/CT mandatory in the Netherlands]);

• sTIL score of ≥50% for patients ≥40 years at the time of TNBC diagnosis and ≥75% forpatients <40 years at the time of TNBC diagnosis on an H&E FFPE tissue slide on thesurgical specimen, according to International Immuno-Oncology Biomarker WorkingGroup on Breast Cancer (formerly International TILs Working Group) guidelines, bylocal and central review

• Has undergone curative breast surgery (breast-conserving surgery or mastectomy andsurgical axillary staging [including at least sentinel lymph node procedure]);

• Absence of recurrence between curative breast surgery and expression of patientpreference;

• Eligible for radiotherapy (if indicated).

Exclusion Criteria:

• Prior disease history of invasive and/or non-invasive breast cancer, or ongoingtreatment for invasive and/or non-invasive breast cancer;

• Multifocal, multicentric or bilateral breast cancer at the time of screening;

• Administration of neoadjuvant systemic therapy;

• Presence of lymphovascular invasion on the diagnostic biopsy and/or the surgicalspecimen;

• Other invasive malignancy within 5 years prior to inclusion, with the exception ofade-quately treated non-melanoma skin cancer, localized cervical cancer, localizedand Gleason ≤6 prostate cancer;

• Uncontrolled severe illness or medical condition;

• Any psychological, familial, sociological or geographical condition potentiallyhampering compliance with the study protocol and follow-up schedule; thoseconditions should be assessed and discussed with the patient before the enrolment inthe in the trial.