Light-Bright: BRCA and NACT in TNBC Patients
Study Details
Study Description
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:
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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.
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To evaluate Evaluate Event Free survival (EFS) and Overall Survival (OS) in this patients population.
Condition or Disease | Intervention/Treatment | Phase |
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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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Women with early triple negative breast cancer who received neoadjuvant chemotherapy.
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Genetic: BRCA1/2 genetic testing
All patients will undergo genetic testing for BRCA 1 and BRCA 2 germline mutations, employing next generation sequencing (NGS) techniques.
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Outcome Measures
Primary Outcome Measures
- pathologic complete response (pCR) rate [1 month]
pCR rate of TNBC patients receiving NACT according to germline BRCA mutational status.
Secondary Outcome Measures
- 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.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Written informed consent.
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Age older than 18 years.
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Unilateral or bilateral primary carcinoma of the breast, confirmed histologically by core biopsy.
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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.
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American Joint Commission on Cancer stage II or III invasive breast cancer.
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Known estrogen (ER)- and progesterone (PgR)-receptor negative tumors.
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Known HER-2/neu negative tumors, defined as IHC 1+/2+ or SISH not amplified.
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Patients suitable for neoadjuvant chemotherapy
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Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤2 or Karnowsky performance status index at least 80%.
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Normal cardiac function must be confirmed by ECG and cardiac ultrasound (LVEF or shortening fraction) within 1 month prior to registration.
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Laboratory requirements:
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Hematology: Absolute neutrophil count (ANC) ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L, Hemoglobin ≥ 10 g/dL.
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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.
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Renal function: Creatinine ≤ 2 mg/dL, < 1,25 UNL (or the calculated creatinine clearance ≥ 60 mL/min).
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Paraffin tumor tissue block made available.
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Availability to provide the set up of the histological preparations for molecular analysis.
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Negative pregnancy test (urine or serum).
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Patients must be available and compliant for treatment and follow-up.
Exclusion Criteria:
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Patients candidate for adjuvant chemotherapy.
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Evidence of distant metastasis.
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Prior chemotherapy for any malignancy.
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Prior radiation therapy for breast cancer.
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Pregnant or lactating patients.
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Inadequate general condition.
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Previous malignant disease.
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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.
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History of significant neurological or psychiatric disorders that would prohibit the understanding and giving of informed consent.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Fondazione Policlinico Universitario Agostino Gemelli IRCCS | Rome | RM | Italy | 00168 |
Sponsors and Collaborators
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 5111