Impact of BRCA Mutation Status on Outcome and Response to Neoadjuvant Chemotherapy (NACT) in Triple-negative Breast Cancer (TNBC) Patients.
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 136
- 试验地点
- 1
- 主要终点
- pathologic complete response (pCR) rate
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Retrospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
结局指标
主要结局
pathologic complete response (pCR) rate
时间窗: 1 month
pCR rate of TNBC patients receiving NACT according to germline BRCA mutational status.
次要结局
- Overall Survival (OS)(1 month)
- Event Free Survival (EFS)(1 month)