Nottingham Breast Cancer Research Centre, University of Nottingham, Nottingham, UK.
School of Medicine, Royal Derby Hospital Centre, University of Nottingham, Uttoxeter Road, Derby, DE22 3DT, UK.
Breast Cancer Res Treat. 2021 Feb;185(3):647-655. doi: 10.1007/s10549-020-06023-4. Epub 2020 Nov 23.
Prediction of response to primary endocrine therapy (PET) in older women is based on measurement of oestrogen receptor (ER), progesterone receptor (PgR) and human epidermal growth factor (HER)-2. This study uses a unique method for construction of core needle biopsy (CNB) tissue microarray (TMA), to correlate expression of a panel of 17 biomarkers with clinical outcome, in patients receiving PET.
Over 37 years (1973-2010), 1758 older (≥ 70 years) women with operable primary breast cancer were managed in a single institution. Of these, 693 had sufficient good-quality CNB to construct TMA, of which 334 had ER-positive tumours treated by PET with a minimum of 6-month follow-up. A panel of biomarkers was measured by immunohistochemistry (ER, PgR, HER2, Ki-67, p53, CK5/6, CK 7/8, EGFR, BCL-2, MUC1, VEGF, LKB1, BRCA1, HER3, HER4, PTEN and AIB1). Expression of each biomarker was dichotomised into 'low' or 'high' based on breast cancer-specific survival (BCSS).
From the panel of biomarkers, multivariate analysis showed: High ER (p = 0.003) and PgR (p = 0.002) were associated with clinical benefit of PET at 6 months, as opposed to progressive disease. High ER (p = 0.0023), PgR (p < 0.001) and BCL-2 (p = 0.043) and low LKB1 (p = 0.022) were associated with longer time to progression. High PgR (p < 0.001) and low MUC1 (p = 0.021) were associated with better BCSS. Expression of other biomarkers did not show any significant correlation.
In addition to ER and PgR; MUC1, BCL-2 and LKB1 are important in determining the outcome of PET in this cohort.
预测老年女性对初始内分泌治疗（PET）的反应是基于雌激素受体（ER）、孕激素受体（PgR）和人表皮生长因子受体（HER）-2 的测定。本研究使用一种独特的方法构建核心针活检（CNB）组织微阵列（TMA），以评估一组 17 种生物标志物与接受 PET 治疗的患者的临床结果的相关性。
37 年来（1973-2010 年），在一家机构中对 1758 名年龄≥70 岁的可手术原发性乳腺癌老年女性进行了管理。其中，693 名患者有足够的高质量 CNB 构建 TMA，其中 334 名 ER 阳性肿瘤患者接受了 PET 治疗，随访时间至少为 6 个月。通过免疫组织化学（ER、PgR、HER2、Ki-67、p53、CK5/6、CK 7/8、EGFR、BCL-2、MUC1、VEGF、LKB1、BRCA1、HER3、HER4、PTEN 和 AIB1）测量了一组生物标志物。根据乳腺癌特异性生存（BCSS）将每个生物标志物的表达分为“低”或“高”。
在生物标志物中，多变量分析显示：高 ER（p=0.003）和 PgR（p=0.002）与 PET 治疗 6 个月时的临床获益相关，而不是进展性疾病。高 ER（p=0.0023）、PgR（p<0.001）和 BCL-2（p=0.043）和低 LKB1（p=0.022）与进展时间更长相关。高 PgR（p<0.001）和低 MUC1（p=0.021）与更好的 BCSS 相关。其他生物标志物的表达没有显示出任何显著相关性。
除了 ER 和 PgR 之外；MUC1、BCL-2 和 LKB1 在确定该队列中 PET 治疗结果方面也很重要。
