Published in:
Open Access
01-12-2022 | Breast Cancer | Research
Relationship between ER expression by IHC or mRNA with Ki67 response to aromatase inhibition: a POETIC study
Authors:
Elena Lopez-Knowles, Simone Detre, Margaret Hills, Eugene F. Schuster, Maggie C. U. Cheang, Holly Tovey, Lucy S. Kilburn, Judith M. Bliss, John Robertson, Elizabeth Mallon, Anthony Skene, Abigail Evans, Ian Smith, Mitch Dowsett
Published in:
Breast Cancer Research
|
Issue 1/2022
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Abstract
Background
In clinical practice, oestrogen receptor (ER) analysis is almost entirely by immunohistochemistry (IHC). ASCO/CAP recommends cut-offs of < 1% (negative) and 1–10% (low) cells positive. There is uncertainty whether patients with ER low tumours benefit from endocrine therapy. We aimed to assess IHC and mRNA cut-points for ER versus biological response of primary breast cancer to 2 weeks’ aromatase inhibitor treatment as measured by change in Ki67.
Methods
Cases were selected from the aromatase inhibitor treatment group of POETIC. We selected the 15% with the poorest Ki67 response (PR, < 40% Ki67 suppression, n = 230) and a random 30% of the remainder categorised as intermediate (IR, 40–79% Ki67 suppression, n = 150) and good-responders (GR, ≥ 80% Ki67 suppression, n = 230) from HER2 − group. All HER2 + cases available were selected irrespective of their response category (n = 317). ER expression was measured by IHC and qPCR.
Results
ER IHC was available from 515 HER2 − and 186 HER2 + tumours and ER qPCR from 367 HER2 − and 171 HER2 + tumours. Ninety-one percentage of patients with ER IHC < 10% were PRs with similar rates in HER2 − and HER2 + cases. At or above ER IHC 10% substantial numbers of patients showed IR or GR. Similar proportions of patients were defined by cut-points of ER IHC < 10% and ER mRNA < 5 units. In addition, loss of PgR expression altered ER anti-proliferation response with 92% of PgR − cases with ER IHC < 40% being PRs.
Conclusions
There was little responsiveness at IHC < 10% and no distinction between < 1% and 1–10% cells positive. Similar separation of PRs from IR/GRs was achieved by IHC and mRNA.