13 Feb 2020

Genomic testing and the effect of pre-treatment with anti endocrine therapies

Genomic testing and the effect of pre-treatment with anti endocrine therapies

Patients with new primary breast cancer, who are treated with anti endocrine therapy prior to surgical resection, might still need genomic testing to assess if they would benefit from adjuvant chemotherapy after surgery.  The reasons for up-front anti endocrine therapy include downsizing an apparently low risk tumour to improve the likelihood of successful breast conserving surgery or to allow time for the patient to be treated for a different more pressing medical issue.  

Another scenario is the development of a new oestrogen responsive (ER positive) primary breast cancer in a woman currently taking an antioestrogen for a previous primary breast cancer; the interpretation of the recurrence score of the new cancer will need to take account of the effect of the (albeit ineffective) antioestrogen they have been taking.

In patients who have received primary antioestrogen treatment, genomic testing of tumour tissue for those meeting the criteria (ER positive, HER negative and lymph node negative) based on the surgical resection specimen can be misleading.  Small studies have shown a positive correlation between pre-treatment and post-treatment recurrence scores (RS) comparing the diagnostic core biopsy and resection specimens. However, none of the currently used genomic tests (Oncotype DX, Endopredict, Prosigna) are validated in the context of “up-front” primary endocrine therapy. 

The potential effect of antioestrogen upon the 21 gene assay Oncotype DX used by many breast units in UK, means that the RS should be interpreted with caution.  Where patients have had a course of planned antioestrogen prior to surgery, the diagnostic core biopsy should be used to assess the RS rather than the surgical resection specimen once the decision is taken at the multidisciplinary meeting that oncotype testing would help.