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Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
Published on: March 20, 2020
Precision medicine for metastatic breast cancer--limitations and solutions
Monica Arnedos1, Cecile Vicier2, Sherene Loi3
1Department of Medical Oncology, Gustave Roussy and Université Paris Sud, 94800 Villejuif, France.
Abstract:
The development of precision medicine for the management of metastatic breast cancer is an appealing concept; however, major scientific and logistical challenges hinder its implementation in the clinic. The identification of driver mutational events remains the biggest challenge, because, with the few exceptions of ER, HER2, PIK3CA and AKT1, no validated oncogenic drivers of breast cancer exist. The development of bioinformatic tools to help identify driver mutations, together with assessment of pathway activation and dependency should help resolve this issue in the future. The occurrence of secondary resistance, such as ESR1 mutations, following endocrine therapy poses a further challenge. Ultra-deep sequencing and monitoring of circulating tumour DNA (ctDNA) could permit early detection of the genetic events underlying resistance and inform on combination therapy approaches. Beside these scientific challenges, logistical and operational issues are a major limitation to the development of precision medicine. For example, the low incidence of most candidate genomic alterations hinders randomized trials, as the number of patients to be screened would be too high. We discuss these limitations and the solutions, which include scaling-up the number of patients screened for identifying a genomic alteration, the clustering of genomic alterations into pathways, and the development of personalized medicine trials.
Insights
Precision medicine for metastatic breast cancer faces challenges in identifying driver mutations and overcoming resistance. Solutions involve advanced bioinformatics, circulating tumor DNA analysis, and novel clinical trial designs for personalized therapies.
Area of Science:
- Oncology
- Genomics
- Translational Medicine
Background:
- Precision medicine offers tailored treatment for metastatic breast cancer but faces significant hurdles.
- Identifying specific oncogenic drivers beyond ER, HER2, PIK3CA, and AKT1 remains a major obstacle.
Purpose of the Study:
- To discuss the scientific and logistical challenges in implementing precision medicine for metastatic breast cancer.
- To explore potential solutions for overcoming these barriers and advancing personalized treatment strategies.
Main Methods:
- Review of current limitations in identifying driver mutations and resistance mechanisms.
- Discussion of bioinformatic tools for pathway analysis and circulating tumor DNA (ctDNA) for resistance detection.
- Exploration of strategies for clinical trial design, including patient screening and genomic alteration clustering.
Main Results:
- Lack of validated oncogenic drivers and acquired resistance (e.g., ESR1 mutations) are key scientific challenges.
- Logistical issues, such as low incidence of specific genomic alterations, impede randomized trials.
- Ultra-deep sequencing and ctDNA monitoring show promise for early resistance detection and guiding combination therapies.
Conclusions:
- Advancements in bioinformatics and ctDNA analysis are crucial for identifying drivers and resistance.
- Innovative clinical trial designs, like personalized medicine trials and pathway-based approaches, are needed to overcome logistical barriers.
- Addressing these challenges will facilitate the clinical implementation of precision medicine for metastatic breast cancer.
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