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Genomic/transcriptomic signatures in breast cancer. A review of three prospective studies Volume 8, supplement 1, Janvier 2022

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Authors
1 Institut Paoli-Calmettes
Département d’oncologie médicale
232, bd Sainte Marguerite
BP 156
13273 Marseille cedex 09
France
2 Aix-Marseille Univ, Inserm, CNRS, Institut Paoli-Calmettes
CRCM — Laboratoire d’oncologie prédictive
232, bd Sainte Marguerite
BP 156
13273 Marseille cedex 09
France
* Tirés à part

Genomic signatures have been developed over the past 20 years for early HR+/HER2 breast cancer with two aims. First, their prognostic value provides additional information for physicians and patients about the risk of recurrence. Second, they can predict efficacy of cytotoxic chemotherapy and may assist physicians in choosing the best therapeutic option for each patient.

Phase III prospective randomised trials have been conducted in order to validate the clinical utility of genomic signatures, in particular to reduce adjuvant systemic therapy indications, and to decrease the administration of potentially toxic chemotherapies. These trials are called TAILORx (N = 10,273 patients with axillary lymph node-negative disease) and RxPONDER (N = 9,383 patients with between one and three metastatic axillary lymph nodes) for the Oncotype DX® assay, and MINDACT (N = 6,693 patients) for the MammaPrint® assay.

The de-escalation of adjuvant chemotherapy might be recommended for patients at high clinical risk and low genomic risk based on MammaPrint®. Based on the Oncotype DX® assay, adjuvant chemotherapy is not recommended for patients with a low or intermediate risk of recurrence (recurrence score [RS] below 25), except for young patients with an RS between 0 and 13, 14 and 25.

Both assays are also able to predict the efficacy of chemotherapy. The benefits of systemic cytotoxic therapies are observed in patients with high genomic risk, and in pre-menopausal patients with low to intermediate genomic risk.

Both tests have been validated by randomised prospective studies and are now part of routine treatment for HR+/HER2 patients, and should be more widely applied in order to guide therapeutic care more efficiently.