Resistance to endocrine therapy in HR plus and/or HER2+breast cancer: the most promising predictive biomarkers

Autores da FMUP

• 

  Fernando Carlos De Landér Schmitt

  Autor

Participantes de fora da FMUP

• Miranda, F
• Prazeres, H
• Mendes, F
• Martins, D

Unidades de investigação

• Laboratório Associado RISE- Rede de Investigação em Saúde

  

  Investigador

  Fernando Carlos De Landér Schmitt

• Patologia

• RISE-Health

  

  Investigador

  Fernando Carlos De Landér Schmitt

Abstract

Breast cancer is the most common cancer in women. It is a heterogeneous disease, encompassing different biological subtypes that differ in histological features, outcomes, clinical behaviour and different molecular subtypes. Therapy has progressed substantially over the past years with a reduction both for locoregional and systemic therapy. Endocrine therapies have considerably reduced cancer recurrence and mortality. Despite the major diagnostic and therapeutic innovations, resistance to therapy has become a main challenge, especially in metastatic breast cancer, and became a major factor limiting the use of endocrine therapeutic agents in ER positive breast cancers. Approximately 50% of patients with ER positive metastatic disease achieve a complete or partial response with endocrine therapy. However, in the remaining patients, the benefit is limited due to resistance, intrinsic or acquired, resulting in disease progression and poor outcome. Tumour heterogeneity as well as acquired genetic changes and therapeutics pressure have been involved in the endocrine therapy resistance. Nowadays, targeted sequencing of genes involved in cancer has provided insights about genomic tumour evolution throughout treatment and resistance driver mutations. Several studies have described multiple alterations in receptor tyrosine kinases, signalling pathways such as Phosphoinositide-3-kinase-protein kinase B/Akt/mTOR (PI3K/Akt/mTOR) and Mitogen-activated protein kinase (MAPK), cell cycle machinery and their implications in endocrine treatment failure. One of the current concern in cancer is personalized therapy. The focus has been the discovery of new potentially predictive biomarkers capable to identify reliably the most appropriate therapy regimen and which patients will experience disease relapse. The major concern is also to avoid overtreatment/undertreatment and development of resistance. This review focuses on the most promising predictive biomarkers of resistance in estrogen receptor-positive breast cancer and the emerging role of circulating free-DNA as a powerful tool for longitudinal monitoring of tumour molecular profile throughout treatment.

© 2021. The Author(s), under exclusive licence to Springer Nature B.V.

Keywords

• Breast cancer; Resistance; Hormone therapy; Predictive; Biomarkers; Liquid biopsies