Breast cancer and hormone receptor status

When clinicians manage breast cancer they consider various prognostic factors, including hormone receptor status and HER2 status

• hormone receptors include oestrogen receptors and progesterone receptors
• tumours that express either oestrogen receptors or progesterone receptors are commonly referred to as being hormone receptor positive
  • estimated that 60% and 80% of all breast cancers in premenopausal and postmenopausal women respectively are hormone receptor positive.
  • people with hormone receptor- positive breast cancer generally have a better prognosis than those with hormone-receptor-negative breast cancer
    
    
• tumours that overexpress the human epidermal growth factor receptor 2 (HER2) protein (HER2+) grow and divide more quickly, so women with HER2+ tumours generally have a worse prognosis than women with HER2 negative tumours
  • approximately 20-30% of people with metastatic breast cancer have HER2+ tumours, of which about 50% will also be hormone receptor positive

Aim of treatment in metastatic breast cancer is to palliate symptoms, prolong survival and maintain a good quality of life with minimal adverse

• choice of treatment depends on previous therapy, hormone receptor status, HER2 status and the extent of the disease

Notes:

• exposure to epidermal growth factor (EGF) leads to modifications in several aspects of the cellular behavior related to the development of cancer
• the overactivation of the human epidermal growth factor receptor (HERs), a family of tyrosine kinase receptors, leads to the development of cancer
• EGF binds to HER1 (also known as EGF receptor or ErbB1), which is the prototype of a family that includes three additional members:
  • HER2 (also known as neu or ErbB2), HER3 and HER4 (also known as ErbB3 and ErbB4, respectively)
  • the generation of HER homo- or hetero oligomers induces the activation of the intrinsic tyrosine kinase activity of the receptors
    • the subsequent phosphorylation of intracellular tyrosine residues leads to the recruitment of factors that transfer the signal from the plasma membrane to the nucleus
      • induces changes in the expression of genes that coordinately regulate proliferation, migration, adhesion, differentiation and apoptosis
  • the involvement of HER receptors, and particularly HER2, in the development of a variety of cancers, including breast tumors, has led the implementation of different therapeutic strategies
    • include monoclonal antibodies directed against the ectodomain of the receptors, such as Herceptin (also known as Trastuzumab), and small-molecule tyrosine kinase inhibitors (1)
    • Amplification of the HER2 gene (also known as ERBB2) is present in 10-20% of tumours in patients with early-stage breast cancer and is associated with aggressive cancers and an increased risk of disease recurrence
    • Trastuzumab, a humanised IgG1 monoclonal antibody that targets the extracellular domain of the HER2 protein, improves progression-free survival and overall survival when administered in combination with chemotherapy in HER2-positive metastatic breast cancer (3)
      • benefits are also seen with trastuzumab added to chemotherapy in non-metastatic breast cancer
      • adding trastuzumab to chemotherapy for early-stage, HER2-positive breast cancer reduces recurrence of, and mortality from, breast cancer by a third

Reference:

• 1)NICE (June 2012). Lapatinib or trastuzumab in combination with an aromatase inhibitor for the first-line treatment of metastatic hormonereceptor- positive breast cancer that overexpresses HER2
• 2) Baselga J, Norton L. Focus on breast cancer. Cancer Cell. 2002 May;1(4):319-22.
• 3) Early Breast Cancer Trialists' Collaborative group (EBCTCG).Trastuzumab for early-stage, HER2-positive breast cancer: a meta-analysis of 13864 women in seven randomised trials. Lancet Oncology 22(8):1139-1150, August 01, 2021