October is Australia’s Breast Cancer Awareness month
27 September 2023
We spoke with Dr Amardeep Gilhotra about SA Pathology research aimed at developing a scoring system for enhancing precision reporting of HER2 low cases as newer targeted breast cancer treatments emerge.
Amar is a senior consultant in Anatomical Pathology with special interest in the diagnosis of breast cancers. New treatments for breast cancers are continually being adopted into clinical practice.
Many new treatments are targeted for use in specific subsets of breast cancers, subsets characterised by the expression of a particular protein or presence of a particular genetic profile. The introduction of targeted treatments has an impact on pathology, as a clinician will need a diagnosis of breast cancer and a detailed analysis of the cancer to enable a targeted treatment to be prescribed.
One of the first targeted drugs for breast cancer was Herceptin. Herceptin is used to treat breast cancers that overexpress HER2 (the Human Epidermal growth factor Receptor 2), and specifically those cancers that overexpress HER2 because multiple copies of the HER2 gene are present in the cancer cells. HER2 expression in a cancer promotes rapid growth.
To identify the approximately 15% of patients eligible for Herceptin, the pathologist assesses the intensity of HER2 expression by the cancer cells, grading them on a 4-point scale from no expression to high expression. Highly expressing cancers (2+ and 3+) are further analysed for the presence of multiple gene copies. Patients with cancers that express low levels of HER2 (0 and 1+) or higher levels but without multiple gene copies (2+NA) are not eligible for Herceptin treatment.
Recently, a new antibody drug conjugate has been developed that targets breast cancers that express lower levels of HER2 (1+, 2+NA). HER2 low cancers comprise 55% of all breast cancers, opening a targeted treatment option for many more breast cancer patients.
In the future the pathologist will need to confidently and accurately differentiate between cancers with low expression and no expression of HER2, and that is not an easy call to make. If the pathologist makes the wrong call, it will impact the patient negatively – over-treating those with no HER2 expression or under-treating those with low HER2 expression.
Amar is a member of The Australian HER2 Low Concordance Study team, comprising a group of 9 experienced breast pathologists from 8 laboratories across Australia, led by SA Pathology’s Professor Gelareh Farshid. The consortium has joined forces to establish an expert consensus of how to identify a HER2 low cancer accurately every time.
The group members scored a set of breast cancer samples stained for HER2 as either 0 or 1+ and reviewed their findings, discussing the features that led to scoring, identified the pitfalls, established consensus scores and are now validating their approach with a test set of cases, aiming for a very high concordance in reporting these cases. An evaluation of AI assisted scoring is also planned.
Success will lead to explicit HER2 low- focused scoring guidelines and a national Quality Assurance Program for training pathologists across Australia.
More importantly, this program, led out of SA Pathology, will ensure all pathology services in Australia are prepared for testing once the new treatment is widely available, leading to immediate benefit of patients.
No doubt the team will then begin work on the next diagnostic challenge.
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