Advanced breast cancer, liquid biopsy for evaluation of Esr1 mutations
An integrated approach to neoplasia with liquid biopsy can assure patients firstly thanks to a dedicated fund and then with the inclusion in the Essential Levels of Care of a correct diagnosis and appropriate therapy: the proposals of a Consensus with oncologists and anatomo-pathologists
by Umberto Malapelle *, Giuseppe Curigliano **, Carmine Pinto ***
Key points
The analysis of epidemiological data on advanced breast cancer (Cma) - 'locally advanced' (stage III) and 'metastatic' (stage IV) - shows that about 37.000 women live in Italy with this neoplasm in an aggressive form: the percentage of patients diagnosed with de novo metastatic disease is 6-7%, while it is estimated that 20-30% of tumour cases initially diagnosed at an early stage will undergo subsequent recurrence and systemic spread ("Linee guida Carcinoma Mammario Avanzato, 2023" Aiom).
With reference to the morphological classification of breast cancer lesions supplemented with the determination of the receptor profile of the neoplasm, HRpositive/HER2negative (HR+/HER2-) tumours are estimated in 70% of these patients.
NGS Platforms and Esmo Recommendations
The spread of next-generation gene sequencing (NGS) platforms has contributed substantially to the development of new therapeutic pathways closely dependent on the spread of new biomarkers that play a key role in defining the choice of the most appropriate treatment in relation to the molecular aspects of the malignancy.
The 2024 recommendations of the European Society for Medical Oncology (Esmo), which regulate the use of NGS platforms in clinical practice, indicate as mandated the genotyping of the following biomarkers in HR+/HER2- CMA patients: PIK3CA and ESR1 mutations (estimated prevalence for both alterations 30-40%), PTEN and ATK1 mutations, with prevalence data in 7% and 5% of cases, respectively. Furthermore, germline BRCA 1-2 test profiling (4%), which plays a strategic role in both hereditary genetic risk management and familial prevention, should be performed in all metastatic patients who have not been evaluated in the early stages of disease.
Liquid biopsy and ESR1 activating mutations
This term commonly refers to the collection of peripheral venous blood to perform genomic characterisation analyses of neoplasia. In clinical practice, circulating tumour-derived nucleic acids (ctDNA) - which represent a small fraction (3x10-9 molecules/ml blood) of the free nucleic acids in the circulatory stream (cfDNA) released by physiological cell turnover processes - become the target of molecular investigation. The search for molecular alterations of clinical interest is carried out from cfDNA using highly sensitive technologies, such as digital PCR (dPCR) and NGS, which make it possible to detect any mutations present in the tumour fraction.
