Three out of four patients with metastatic breast cancer would be candidates for targeted therapy

It is possible to increase the detection of potentially treatable genomic alterations in patients with metastatic breast cancer. This is shown by the HOPE study, by the SOLTI group, which was presented at the congress held by the European Society of Medical Oncology (ESMO 2023) in Madrid.

The data presented by Tomás Pascual, researcher of the aforementioned work, oncologist at the Hospital Clínic of Barcelona and scientific director of SOLTI at ESMO 2023 and which correspond to the analysis of more than 50% of the 600 (356 so far) patients included in the study , show that 75% of the patients analyzed have genomic alterations in their tumor and, therefore, that they may have potential targeted treatment.

Before carrying out the aforementioned study, only 15% of women knew about these alterations, which shows that thanks to the screening carried out at HOPE, the detection of alterations has multiplied by 5.

This is the first national clinical trial – whose inclusion has been led by patients with metastatic breast cancer – that demonstrates the benefit of offering access to tumor sequencing techniques and thus extending precision oncology throughout the territory.

Increased detection

Through the use of sequencing tests to detect mutations or biomarkers, both in blood and tumor tissue, carried out in the context of HOPE, the number of patients who now have information that could help them guide their oncological treatment has multiplied by 5..

The work also indicates that the use of sequencing tests to detect mutations or biomarkers in blood and tissue has made it possible to increase the detection of potentially treatable genomic alterations in the included patients by 60 percentage points, from 15% to 75%.

Pascual points out that the genomic alterations mentioned have been detected in various subgroups of breast cancer, including HER2+, triple negative and luminal disease (RH+/HER2-).. “In the HOPE study, we did not limit participation to patients with a specific disease subgroup, which allowed us to obtain results representative of the entire breast cancer patient population.”

It also mentions as relevant that 77.4% of the study participants had luminal disease, which makes “the genomic alterations present in this subgroup especially significant in our findings.”

In his opinion, it is important to highlight that the focus of HOPE is to collect 'real-life' data, which means that “our conclusions are based on the daily clinical experience of breast cancer patients.”. “The proportions of patients in each disease subgroup that we observed in our study closely reflect the true prevalence of these subtypes in the general population.”

The SOLTI team continues to actively research to better understand the genomic alterations in each subgroup of patients.. “In future publications, we plan to share detailed information on the genomic alterations most detected in each of the patient subgroups, which will allow us to deepen our knowledge and further improve personalized treatment for women with breast cancer.”

Although not all disorders currently have targeted treatment available or in widespread use, the HOPE data “constitute a decisive step, since without knowing them they could never be treated in an individualized way.”

Current and future custom arsenal

Regarding the current and future therapeutic arsenal for these genomic alterations in metastatic breast, the researcher points out that there are currently specific treatments aimed at the identified genomic alterations.. In this sense, this study has been essential to personalize therapy more effectively.

“Specifically, patients with luminal disease have benefited from PI3K inhibitors, thanks to the detection of alterations in their tumor DNA that were previously unknown.. Additionally, in a smaller number of cases, some patients have received PARP inhibitors, AKT, and other targeted treatments.. And all this has been possible thanks to the identification of key biomarkers.”

On the horizon, new therapies are emerging, such as the SERD family, which are proving “to be effective and could be implemented in the near future in patients with mutations in the ESR1 gene.”

He emphasizes that the 'most exciting' thing is that this discovery not only has immediate implications, but also opens doors to promising future therapies.

“The revelation of these biomarkers not only improves the precision of current treatments, but also paves the way for ongoing research.”. Furthermore, understanding these genomic alterations opens doors to future advances.. “Patients who have them may have the opportunity to participate in clinical trials exploring more specific, targeted therapies.”

These advances therefore highlight the importance of continued research in the field of metastatic breast cancer.. “As we better understand the genomic complexities of the disease, we are better equipped to develop more effective therapies and significantly improve the survival and quality of life of affected patients.”

The clinical benefits of knowledge of genomic alterations have profound and positive implications for patients, both in terms of greater survival, less toxicity, and greater quality of life.

First, this knowledge provides the possibility of receiving specific and targeted treatments, which, compared to standard therapies such as chemotherapy, are usually associated with fewer side effects.

Access in equity: worrying reality

“This not only improves the quality of life of patients by reducing toxicity and discomfort associated with the treatment, but also allows greater adherence to it, essential for its effectiveness.”. Furthermore, the possibility of avoiding or postponing the administration of chemotherapy, a traditionally intensive option with considerable long-term side effects, has a significant impact on the quality of life of patients with advanced breast cancer who can have very long survivals.” .

At this time, technological advances are produced and applied to research very quickly.. But equitable access to these advances does not follow the same pace.. “Currently, unfortunately, not all women with metastatic breast cancer have equitable access to genomic analysis in our country. “Inequality in access to these diagnostic tools is a worrying reality.”

In his opinion, in Spain, disparities are evident in the health services coverage of the autonomous communities, where access to genomic diagnostic tools varies considerably.. “Even within a community, larger hospitals, especially those dedicated to research, tend to have access to more advanced diagnostic technologies compared to other hospitals.”

Thus, it highlights another of the notable points of the HOPE study: it has provided concrete evidence that it is possible to implement a molecular screening program at the state level that prioritizes equity among patients.

“However, for this equity to be a reality for all affected women, it is essential that authorities demonstrate a genuine will to overcome these barriers.. The implementation of solid policies is required to guarantee access to precision medicine for all citizens, regardless of their geographic location or socioeconomic level.. Only with an inclusive approach and a real commitment can we overcome these disparities and provide all patients with the care and treatment they deserve,” says the scientific director of SOLTI.

Women, drivers of their process

HOPE is the first clinical trial in which patients requested their own participation and, also, through a mobile app.

Unlike conventional clinical studies, the active role of patients is a key element of HOPE: through a mobile application that launches an individual journey for the molecular characterization and integration of clinical data. Furthermore, their involvement in the monitoring phase has been decisive in obtaining the results.

The patients, points out Tomás Pascual, “have been the cornerstone of the development of the HOPE study in several significant dimensions”. Not only have they been beneficiaries of this study, but they have been essential co-creators of it and have been part of the study's steering committee.. “Their active participation and valuable contribution have promoted scientific research and have allowed many patients to better understand their history and different therapeutic options.”

Individually, the patients have been “fundamental in each stage of the process.”. “HOPE has adopted a patient-centered approach, meaning that patients themselves have registered and provided detailed clinical information as well as essential biological samples for genomic analyses.”

This level of active participation, often even without the direct support of their doctors, represents “a significant paradigm shift in clinical research.”. “It has given them a leading role in the management of their disease and has encouraged their training to be active participants in making future decisions regarding their treatment.”