In the last decades, progress in the field of science and medicine has led to the incursion of new and innovative therapies to treat breast cancer. The wide range of possibilities in this new medical era offers patients multiple treatment options, and physicians face a challenging scenario in selecting the optimal one.
In this context, precision or personalized oncology emerged as a revolutionary approach designed to customize disease prevention and treatment based on the characteristics of each patient.
Precision oncology considers the disease's genetics, which can influence how a person responds to treatments. The goal is to optimize cancer treatment to be more effective and efficient by targeting interventions to individuals who will benefit most, meanwhile reducing the risk of side effects and avoiding the use of ineffective treatments. In simpler words, its goal is to deliver the right cancer treatment to the right patient at the right dose and time.
Precision oncology is based on genetic mutations as the foundation of cancer development.
Specific genes in the tumor-forming cells, when altered, can lead to cancer progression and development. These genes serve as biological markers or biomarkers that help to predict how the cancer will evolve and respond to a specific treatment. Genomics is the scientific discipline that analyzes this large set of genes to draw conclusions on treatment selection.
The American Society of Clinical Oncology (ASCO) and other tumor-specific societies provide updated guidelines with gene lists involved in tumor development that can be used in precision oncology.
Understanding how cancer will evolve in an individualized patient is critical for selecting the best treatment. Precision oncology empowers clinicians to make evidence-based decisions on treatment selection and patients to face therapy with confidence and trust.
The progress in accurate breast cancer treatment has been remarkable over recent years, mainly because of the subdivision into different subtypes of breast cancer and their treatment platforms based on biomarker characterization.
Biomarkers are cell sensors that capture signals from outside the cells. In cancer cells, the number of these sensors is superior to that in regular cells; they are overexpressed, increasing the number of signals they receive. Due to these signals, cancer cells grow uncontrollably, contributing to tumor development. Specifically, on breast cancer cells, these sensors are the progesterone receptor (PR), the estrogen receptor (ER), and the human epidermal growth factor receptor 2 (HER2).
The receptors serve as therapeutic targets, classifying breast cancer types and tailoring their treatment. However, the next step for improving outcomes for patients with breast cancer is to refine subsets and treatments based on additional informational content such as the ones provided by the characterization of genomics.
HER2-positive breast cancer, which means that the HER2 receptor is overexpressed, affects 1 in 5 women diagnosed with this disease. Every 4 minutes, 3 patients are diagnosed worldwide, since HER2+ breast cancer affects 390,000 women annually.
It is a clinically and biologically heterogeneous condition that shows differences among patients. This heterogeneity implies that not all of them respond the same way to the treatment, so there is a chance to refine the treatment in every clinical case. Some patients still experience a recurrence despite current therapies. In contrast, others will be cured with less intense chemotherapy or no systemic treatment, reducing adverse effects that directly impact the quality of life.
Precision oncology through diagnostic assays offers the possibility to refine cancer treatment, guiding the selection of the most appropriate one for every clinical case. These tests analyze the expression of multiple genes in a tumor sample to provide information about the cancer's characteristics, potential behavior, and how it might respond to specific treatments.
Can patients with HER2+ breast cancer benefit from the diagnostic assays in tailoring their treatment?
HER2DX is the first genomic tool to optimize HER2-positive breast cancer treatment, improving patients' quality of life without compromising its results.
HER2DX, developed by Reveal Genomics, is a minimally invasive diagnostic assay based on artificial intelligence that analyzes 27 genes involved in 4 key biological processes that lead to tumor development. It combines this information with 2 clinically used parameters: tumor size and the involvement of lymph nodes. This information is integrated into an artificial intelligence algorithm that provides scores to predict disease evolution and guide treatment choices.
This tool has already been validated in over 2,000 patients and included in the Spanish Society of Medical Oncologists (SEOM) guidelines as a useful clinical tool. The diverse scores provided by HER2DX have been validated in retrospective clinical studies, a type of research that looks back at existing records and patient data to identify patterns, correlations, and outcomes. These have been performed in 8 datasets, showing their potential in identifying patients likely to respond to treatment and improving outcomes.
Besides retrospective validation, prospective studies are needed to observe future outcomes, further confirm findings, establish cause-and-effect relationships, and provide reliable and robust evidence for medical practice and guidelines.
The DEFINITIVE project, a prospective clinical trial funded by the European Commission, aims to demonstrate that a personalized treatment guided by HER2DX improves patients’ quality of life without affecting the outcome and survival rates, validating its clinical effectiveness.
The importance of the DEFINITIVE assay, a 5-year international phase III prospective clinical trial conducted over 44 centers in 7 European and associated countries, lies in its comprehensive approach to evaluating the HER2DX® diagnostic test in HER2-positive early breast cancer. This study involves 304 patients with stage II to IIIA HER2-positive breast cancer who have not received prior treatment. It is designed to compare outcomes between two groups:
By comparing the two groups, the study aims to demonstrate that treatment guided by HER2DX results is not only safe and efficient but also tailored to the individual patient’s genetic profile. This personalized approach is expected to improve the overall quality of life for patients by minimizing unnecessary treatments and their associated side effects. Besides, the study will compare the outcomes related to reducing costs for healthcare systems between the two groups.
Positive results will support the broader implementation of HER2DX in clinical practice, promoting personalized and cost-effective treatment for patients with HER2-positive breast cancer.
The DEFINITIVE project, along with HER2DX retrospective clinical evidence and inclusion in clinical guidelines, is a big step towards its implementation by healthcare systems at regional, national, and European levels. It will turn precision oncology into a reality, empowering healthcare professionals and patients toward personalized treatment.
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