BRCA and NACT in TNBC Patients (Light-Bright)

Impact of BRCA Mutation Status on Outcome and Response to Neoadjuvant Chemotherapy (NACT) in Triple-negative Breast Cancer (TNBC) Patients.

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.

Study Overview

• Status: Completed
• Conditions: Triple-Negative Breast Cancer
• Intervention / Treatment: Genetic: BRCA1/2 genetic testing

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 Type: Observational
• Enrollment (Actual): 136

Contacts and Locations

Study Locations

• Italy
  • RM
    • Rome, RM, Italy, 00168
      • Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Women with early triple negative breast cancer, suitable for neoadjuvant chemotherapy achieving and not achieving pCR.

Description

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 Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Women with early triple negative breast cancer who received neoadjuvant chemotherapy.	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pathologic complete response (pCR) rate	pCR rate of TNBC patients receiving NACT according to germline BRCA mutational status.	1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event Free Survival (EFS)	EFS of TNBC patients receiving NACT according to germline BRCA mutational status.	1 month
Overall Survival (OS)	OS of TNBC patients receiving NACT according to germline BRCA mutational status.	1 month

Collaborators and Investigators

• Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Publications and helpful links

General Publications

• Pavese F, Capoluongo ED, Muratore M, Minucci A, Santonocito C, Fuso P, Concolino P, Di Stasio E, Carbognin L, Tiberi G, Garganese G, Corrado G, Di Leone A, Generali D, Fragomeni SM, D'Angelo T, Franceschini G, Masetti R, Fabi A, Mule A, Santoro A, Belli P, Tortora G, Scambia G, Paris I. BRCA Mutation Status in Triple-Negative Breast Cancer Patients Treated with Neoadjuvant Chemotherapy: A Pivotal Role for Treatment Decision-Making. Cancers (Basel). 2022 Sep 21;14(19):4571. doi: 10.3390/cancers14194571.

Study record dates

Study Major Dates

• Study Start (Actual): January 2, 2013
• Primary Completion (Actual): October 1, 2022
• Study Completion (Actual): October 1, 2022

Study Registration Dates

• First Submitted: February 20, 2023
• First Submitted That Met QC Criteria: February 20, 2023
• First Posted (Actual): March 2, 2023

Study Record Updates

• Last Update Posted (Actual): March 2, 2023
• Last Update Submitted That Met QC Criteria: February 20, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Neoadjuvant chemotherapy; BRCA1/2; Platinum agents; Triple-Negative Breast Ccancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Triple Negative Breast Neoplasms
• Other Study ID Numbers: 5111

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No