Impact of BRCA Mutation Status on Outcome and Response to Neoadjuvant Chemotherapy (NACT) in Triple-negative Breast Cancer (TNBC) Patients.
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Triple-Negative Breast Cancer
- Sponsor
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS
- Enrollment
- 136
- Locations
- 1
- Primary Endpoint
- pathologic complete response (pCR) rate
- Status
- Completed
- Last Updated
- 3 years ago
Overview
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.
Investigators
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.
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.
Outcomes
Primary Outcomes
pathologic complete response (pCR) rate
Time Frame: 1 month
pCR rate of TNBC patients receiving NACT according to germline BRCA mutational status.
Secondary Outcomes
- Overall Survival (OS)(1 month)
- Event Free Survival (EFS)(1 month)