BRCA and NACT in TNBC Patients

Completed

• Conditions: Triple-Negative Breast Cancer
• Interventions: Genetic: BRCA1/2 genetic testing

• Registration Number: NCT05750719
• Lead Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS

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.

Study Timeline

• Study Start: 2013-01-02
• Primary Completion: 2022-10-01
• Study Completion: 2022-10-01
• Status Verified: 2023-02
• Study First Submitted: 2023-02-20
• Study First Submitted QC: 2023-02-20
• Last Update Submitted: 2023-02-20
• Study First Posted: 2023-03-02
• Last Update Posted: 2023-03-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 136

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.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Women with early triple negative breast cancer who received neoadjuvant chemotherapy.	BRCA1/2 genetic testing	-

Primary Outcome Measures

Name	Time	Method
pathologic complete response (pCR) rate	1 month	pCR rate of TNBC patients receiving NACT according to germline BRCA mutational status.

Secondary Outcome Measures

Name	Time	Method
Overall Survival (OS)	1 month	OS of TNBC patients receiving NACT according to germline BRCA mutational status.
Event Free Survival (EFS)	1 month	EFS of TNBC patients receiving NACT according to germline BRCA mutational status.

Trial Locations

Locations (1)

Fondazione Policlinico Universitario Agostino Gemelli IRCCS; 🇮🇹 Rome, RM, Italy