Weak ER pos HER2 neg Breast CA and breast CA which lost ER expression
Research type
Research Study
Full title
Molecular Analysis of Weakly Oestrogen Receptor Positive (ER 3-5/8) HER2 negative Breast Cancer and breast cancer which has lost Oestrogen Receptor (ER) expression
IRAS ID
300221
Contact name
Alicia Okines
Contact email
Sponsor organisation
The Royal Marsden NHS Foundation Trust
Duration of Study in the UK
0 years, 9 months, 1 days
Research summary
Based on whether breast cancer cells express oestrogen receptors (ER), progesterone receptors (PR) and the HER2 receptor, breast cancer is classified as:
I. ER positive HER2 negative breast cancer;
II. HER2 positive breast cancer or;
III. Triple Negative Breast Cancer (TNBC).
The method to determine if breast cancer cells express oestrogen receptors (ER) is based on the intensity of staining and the percentage of positively stained cells.
ER 0-2/8 (<1%) is treated as ER negative. ER 6-8/8 (≥ 10%) is ER strongly positive.
ER weakly positive HER2 negative breast cancers, with ER scores of 3-5/8 (1-10%) are currently treated as ER-positive HER2 negative disease. However, increasing evidence suggests that ER weakly positive HER2 negative breast cancers have a similar pattern of gene expression, and similar clinical outcomes as TNBC, a more aggressive sub-type of breast cancer.
In recent years, standard treatments for ER positive HER2 negative and TNBC have diverged markedly in the past 5 years, and immunotherapy is now an option for patients with TNBC, if the TNBC cells express a protein called PDL1.
It is unknown what percentage of patients with ER weakly positive HER2 negative breast cancer cells express PD-L1, which may predict response to immunotherapy treatments for these patients who are currently unable to access this treatment.
Sometimes when breast cancer relapses, it can change type, sometimes losing expression of the oestrogen receptor and will be classified as TNBC. It is unclear from other studies whether this TNBC is the same or different to the cancers which never had oestrogen expression. It is also unknown what percentage of these patients with TNBC who had previous ER-positive breast cancer cells express PD-L1.
The study aims to molecularly characterise weakly ER positive HER2 negative breast cancers and TNBC that have developed following an ER-positive early breast cancer to determine the dominant molecular sub-types of these groups and the percentage of patient samples that are positive for PD-L1.
The study will use previously collected tissue from patients who have signed consent to additional research being undertaken on their tissue.
Ultimately the study aims to inform future clinical trials of immunotherapy for these groups of patients.REC name
HSC REC A
REC reference
24/NI/0012
Date of REC Opinion
8 Jan 2024
REC opinion
Favourable Opinion