Triple-Negative Breast Cancer
Conditions
Keywords
BRCA1/2, Neoadjuvant chemotherapy, Platinum agents, Triple-Negative Breast Ccancer
Brief summary
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.
Detailed description
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.
Interventions
GENETICBRCA1/2 genetic testing
All patients will undergo genetic testing for BRCA 1 and BRCA 2 germline mutations, employing next generation sequencing (NGS) techniques.
Sponsors
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| pathologic complete response (pCR) rate | 1 month | pCR rate of TNBC patients receiving NACT according to germline BRCA mutational status. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Event Free Survival (EFS) | 1 month | EFS of TNBC patients receiving NACT according to germline BRCA mutational status. |
| Overall Survival (OS) | 1 month | OS of TNBC patients receiving NACT according to germline BRCA mutational status. |
Countries
Italy
Outcome results
None listed