breast cancer and hormone receptor status
Last edited 08/2021 and last reviewed 08/2021
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 subsequent phosphorylation of intracellular tyrosine residues
leads to the recruitment of factors that transfer the signal from
the plasma membrane to the nucleus
- 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