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Published on: July 25, 2020
Molecular Profile and Matched Targeted Therapy for Advanced Breast Cancer Patients
Rosa Falcone1, Pasquale Lombardi1, Marco Filetti1,2
1Phase 1 Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy.
Abstract:
(1) Background: Precision oncology is opening new treatment opportunities for patients suffering from solid tumors. In the last two decades, the advent of CDK4/6 inhibitors, immunotherapy, and antibody-drug conjugates (ADC) improved survival outcomes for advanced or metastatic breast cancers (BC). Nevertheless, some patients progress to approved therapies and still maintain good clinical conditions. (2) Methods: With the aim to estimate the accrual rate to experimental precision oncology treatments, we collected molecular and clinical characteristics of BC patients evaluated at Phase 1 Unit of Fondazione Policlinico Gemelli. Clinical data were retrieved from hospital records. Molecular analysis was performed using Next-Generation Sequencing (NGS) FoundationOne CDx on tissue or blood. (3) Results: Among the 38 BC patients referred to our unit, 35 completed the genomic analysis. All patients were female with advanced (mean number of metastatic sites: 3, range 1-6) BC. Median age at our evaluation was 52 (IQR, 48-59). ECOG PS was good in 97% of the study population, although heavily pre-treated (median number of systemic treatments: 5, IQR 3-7). Half of referred patients were HR+/HER2- BC, with 39% triple negative breast cancer (TNBC). NGS testing was performed on relapsed disease among most (71%) participants, in particular lymph nodes and soft tissue. Liquid biopsy was requested in 23% of cases. The median time from sample collection to NGS testing was 1 month and from diagnosis 54 months. The median value of mutations, VUS, and TMB were 6, 11, and 5, respectively. TP53, PIK3CA, BRCA2, ESR1, and RAD21 were the genes with the highest number of molecular alterations. In 5 patients (14%), the molecular analysis was helpful to assign targeted therapy in the context of clinical trials with a median progression-free survival of 5 months. (4) Conclusions: HR+/HER2- and TNBC were the most frequent subtypes referred for NGS testing. Tissue biopsy of relapsed disease was feasible in 71% of cases. The molecular analysis offered a new treatment opportunity in 14% of patients. The real benefit of these treatments remains to be evaluated in larger cohorts.
Insights
Precision oncology treatments offer new hope for advanced breast cancer (BC) patients. Genomic analysis identified targeted therapy opportunities for 14% of heavily pre-treated patients, improving outcomes.
Area of Science:
- Oncology
- Genomics
- Clinical Trials
Background:
- Precision oncology advances, including CDK4/6 inhibitors, immunotherapy, and antibody-drug conjugates (ADCs), have improved outcomes for advanced breast cancer (BC).
- Despite therapeutic progress, some patients with advanced or metastatic BC experience disease progression while maintaining good clinical status, necessitating novel treatment strategies.
- The study addresses the need to understand patient accrual and molecular profiles for experimental precision oncology treatments in advanced BC.
Purpose of the Study:
- To estimate the accrual rate of patients with advanced breast cancer (BC) into experimental precision oncology treatments.
- To collect and analyze molecular and clinical characteristics of BC patients evaluated at a Phase 1 Unit.
- To assess the utility of Next-Generation Sequencing (NGS) in identifying targeted therapy opportunities for heavily pre-treated BC patients.
Main Methods:
- Retrospective collection of molecular and clinical data from 38 advanced breast cancer (BC) patients evaluated at a Phase 1 Unit.
- Genomic analysis performed using Next-Generation Sequencing (NGS) FoundationOne CDx on tissue or blood samples.
- Clinical data retrieval from hospital records, including patient demographics, disease stage, treatment history, and genomic alterations.
Main Results:
- Genomic analysis was completed for 35 out of 38 referred BC patients, all female with advanced disease (median 3 metastatic sites).
- The majority of patients were heavily pre-treated (median 5 prior systemic treatments) with good performance status (97% ECOG PS 0-1).
- Next-Generation Sequencing (NGS) identified actionable molecular alterations in 14% of patients, leading to targeted therapy assignment in clinical trials with a median progression-free survival of 5 months. Key altered genes included TP53, PIK3CA, BRCA2, ESR1, and RAD21.
Conclusions:
- Hormone receptor-positive/HER2-negative (HR+/HER2-) and triple-negative breast cancer (TNBC) were the most frequent subtypes referred for NGS testing.
- Tissue biopsy of relapsed disease was feasible in 71% of cases, with liquid biopsy utilized in 23%.
- Molecular analysis via NGS provided new targeted treatment opportunities for a subset of advanced breast cancer patients, though further evaluation in larger cohorts is warranted.
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