BRCA and NACT in TNBC Patients

The goal of this observational study is to evaluate data from patients with triple-negative breast cancer (TNBC) treated with neoadjuvant chemotherapy (NACT) in order to better define the impact of germline BRCA1/2 (gBRCA1/2) mutation status on outcomes in this patient population.

The aims of the study are:

* To evaluate the rate of pathologic complete response (pCR) in patients with locally advanced TNBC who performed NACT, in relation to the mutational status of gBRCA.
* To evaluate Evaluate Event Free survival (EFS) and Overall Survival (OS) in this patients population.

Triple-negative breast cancer (TNBC) is characterized by earlier recurrence and shorter survival compared with other types of breast cancer. Moreover, approximately 15 to 25% of all TNBC patients harbor germline BRCA (gBRCA) 1/2 mutations, which confer a more aggressive phenotype. However, TNBC seems to be particularly sensitive to chemotherapy, the so-called 'triple negative paradox'. Therefore, Neoadjuvant chemotherapy (NACT) is currently considered the preferred approach for early-stage TNBC. BRCA status has also been studied as a predictive biomarker of response to platinum compounds. Although several randomized trials investigated the addition of carboplatin to standard NACT in early-stage TNBC, the role of BRCA status remains unclear. In this retrospective analysis, data from 136 consecutive patients with Stage I-III TNBC who received standard NACT, with or without the addition of carboplatin, will be evaluated in order to define clinical features and outcomes in BRCA 1/2 mutation carriers and non-carrier controls.

Eligibility Criteria:
Inclusion Criteria:

* Written informed consent.
* Age older than 18 years.
* Unilateral or bilateral primary carcinoma of the breast, confirmed histologically by core biopsy.
* Tumor lesion in the breast with a palpable size of ≥ 2 cm and/or ≥ 1.5 cm by ultrasound or magnetic resonance imaging (MRI). In case of inflammatory carcinoma, the extent of inflammation can be used as measurable lesion.
* American Joint Commission on Cancer stage II or III invasive breast cancer.
* Known estrogen (ER)- and progesterone (PgR)-receptor negative tumors.
* Known HER-2/neu negative tumors, defined as IHC 1+/2+ or SISH not amplified.
* Patients suitable for neoadjuvant chemotherapy
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤2 or Karnowsky performance status index at least 80%.
* Normal cardiac function must be confirmed by ECG and cardiac ultrasound (LVEF or shortening fraction) within 1 month prior to registration.
* Laboratory requirements:

  * Hematology: Absolute neutrophil count (ANC) ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L, Hemoglobin ≥ 10 g/dL.
  * Hepatic function: Total bilirubin \< 1 x UNL, ASAT (SGOT) and ALAT (SGPT)≤ 2.5 x UNL, Alkaline phosphatase ≤ 5 UNL. Patients with ASAT and / or ALAT \> 1.5 x UNL associated with alkaline phosphatase \> 2.5 x UNL are not eligible for the study.
  * Renal function: Creatinine ≤ 2 mg/dL, \< 1,25 UNL (or the calculated creatinine clearance ≥ 60 mL/min).
* Paraffin tumor tissue block made available.
* Availability to provide the set up of the histological preparations for molecular analysis.
* Negative pregnancy test (urine or serum).
* Patients must be available and compliant for treatment and follow-up.

Exclusion Criteria:

* Patients candidate for adjuvant chemotherapy.
* Evidence of distant metastasis.
* Prior chemotherapy for any malignancy.
* Prior radiation therapy for breast cancer.
* Pregnant or lactating patients.
* Inadequate general condition.
* Previous malignant disease.
* Known or suspected congestive heart failure (\>NYHA I) and/or coronary heart disease, angina pectoris requiring antianginal medication, previous history of myocardial infarction, evidence of transmural infarction on ECG, un- or poorly controlled arterial hypertension, rhythm abnormalities requiring permanent treatment, clinically significant valvular heart disease.
* History of significant neurological or psychiatric disorders that would prohibit the understanding and giving of informed consent.