Third generation PAM50-based genomic test: more precisely predicting response to anti-cancer therapy

Published today in the journal Clinical Cancer Research, results from an international multi-center study led by Aleix Prat, Principal Investigator of VHIO´s Translational Genomics Group, Head of the Medical Oncology Service at the Hospital Clínic de Barcelona, and Group Leader of Translational Genomics and Targeted Therapies against Solid Tumors of the August Pi i Sunyer Biomedical Research Institute (IDIBAPS), evidence the predictive capacity of a new genomic test in gauging the response of hormone-receptor-positive (HR+) breast cancer patients to chemotherapy.

Carried out in collaboration with colleagues at various hospital across Spain as well as researchers belonging to the Spanish Breast Cancer Research Group (GEICAM), the Lineberger Comprehensive Cancer Center (University of North Carolina, USA), the Royal Marsden Foundation Trust (London, UK), and the University of Edinburgh CRUK Center (Scotland), this study analyzed the genomic makeup of tumors from over 2000 patients with hormone sensitive breast cancer across 8 different clinical sites. These molecular insights have led to the development and validation of a third generation PAM50-Prosigna genomic test that can more precisely predict the sensitivity of these tumors to treatment with chemotherapy and hormone therapy.

This novel Prosigna test builds on previous progress at second-generation level (PAM50-derived subtype classifier and risk model), in predicting the survival of patients with HR+ breast cancer which has in turn significantly better-guided treatment decisions concerning the administration of chemotherapeutic-based therapy. It is thanks to this third generation discovery that response can now be calculated for these patients with intermediate risk of their respective cancer returning within the first ten years – representing a third of all patients undergoing second generation genomic testing. The Hospital Clínic de Barcelona will be the first hospital at global level to implement this very latest predictor assay aimed at rendering cancer treatment and care more precise for an increasing number of patients.

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Source: Hospital Clínic de Barcelona

Hospital Clínic will implement a new genomic test to predict response to treatment in breast cancer

Researchers from Hospital Clínic and IDIBAPS lead an international study in which they have developed a genomic test to predict the response to chemotherapy in breast cancer. Hospital Clínic of Barcelona will be the first hospital in the world to implement this third generation test. This test is based on the data produced by the second-generation test PAM50, and for which Hospital Clínic is one of the reference centers.

The article, published today in the journal Clinical Cancer Research, has been coordinated by Dr. Aleix Prat, Head of the Clinical Oncology Department at Hospital Clínic, the Translational genomics and targeted therapeutics in solid tumors research team at IDIBAPS and the Translational Genomics group of the Vall d’Hebron Institute of Oncology (VHIO). The study has involved several hospitals in Spain within the GEICAM breast cancer co-operative group, researchers from the University of North Carolina (USA), the Royal Marsden Foundation Trust in London, the University of Otago (New Zealand) and The University of Edinburgh (Scotland).

About 70% of breast cancers are hormone-sensitive. However, this group is very heterogeneous from a clinical and biological point of view. In the past few years, the incorporation of second generation genomic tests into clinical practice has allowed the identification of a group of patients at low risk of relapse who do not need chemotherapy and another group at high risk, who do need it. In contrast, the benefit of chemotherapy in the group of intermediate-risk patients is uncertain.

The team led by Dr. Aleix Prat has analyzed the genomic data of more than 2,000 tumors of patients with breast cancer treated in 8 clinical trials. With these molecular data and complex bioinformatic tools they have discovered and validated a new third generation genomic test that is able to better detect the sensitivity of tumors to chemotherapy treatment than current second generation tests. This new test is based on the analysis of the data produced by the second generation genomic test known as PAM50.

“The second-generation genomic tests that we are currently using can predict the survival of patients with hormone-sensitive breast cancer and this information is useful for making decisions about the need to indicate chemotherapy. With this new third generation test we have taken a step forward and now we can directly predict the benefit to be gained from chemotherapy, as well as with the hormone therapy”, explains Dr. Prat.

In addition, this test is especially useful in a subgroup of breast cancer patients who have an intermediate risk of relapse during the first 10 years of follow-up and who account for one-third of patients in which the second-generation test is used. “This is the most difficult group to treat because, at the moment, the most suitable therapeutic option has not been established. In this context, the test helps us to choose one treatment, the other, or both“, explains Dr. Prat. “This new genomic test brings us closer to personalized or precision medicine; that is, it provides more detailed information about the benefits and risks of chemotherapy and hormone therapy. This information also helps to empower patients in making decisions about their treatment”, he concludes. The new test will be implemented in clinical practice at Hospital Clínic of Barcelona before the end of this year.



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