The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, UK.
Ralph Lauren Centre for Breast Cancer Research, Royal Marsden Hospital, London, UK.
Breast Cancer Res. 2022 Sep 12;24(1):61. doi: 10.1186/s13058-022-01556-6.
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.
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.
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.
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.
在临床实践中，雌激素受体（ER）分析几乎完全依赖免疫组织化学（IHC）。ASCO/CAP 建议将截断值设为<1%（阴性）和 1-10%（低）细胞阳性。目前还不确定 ER 低肿瘤患者是否受益于内分泌治疗。我们旨在评估 ER 的 IHC 和 mRNA 截断值与原发性乳腺癌对 2 周芳香化酶抑制剂治疗的生物学反应之间的关系，该反应通过 Ki67 的变化来衡量。
从 POETIC 的芳香化酶抑制剂治疗组中选择病例。我们选择 Ki67 反应最差的 15%（PR，<40%Ki67 抑制，n=230）和剩余的随机 30%（IR，40-79%Ki67 抑制，n=150）和良好反应者（GR，≥80%Ki67 抑制，n=230）的 HER2-组。从 HER2+组中选择了所有可用的 HER2+病例，无论其反应类别如何（n=317）。通过 IHC 和 qPCR 测量 ER 表达。
HER2-组有 515 例和 HER2+组有 186 例可获得 ER IHC，HER2-组有 367 例和 HER2+组有 171 例可获得 ER qPCR。91%的 ER IHC<10%的患者为 PR，HER2-和 HER2+病例的比例相似。在 ER IHC 达到或超过 10%时，有相当数量的患者表现为 IR 或 GR。通过 ER IHC<10%和 ER mRNA<5 单位的截断值，也有类似比例的患者被定义为这两种情况。此外，PgR 表达的丧失改变了 ER 的抗增殖反应，92%的 ER IHC<40%的 PgR-病例为 PR。
在 ER IHC<10%时反应性较低，而<1%和 1-10%细胞阳性之间没有区别。通过 IHC 和 mRNA 也可以实现 PR 与 IR/GR 的类似分离。
