Genetic Pathology Evaluation Centre, Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
Canadian Cancer Trials Group, Queen's University, Kingston, Ontario, Canada.
Clin Cancer Res. 2021 Dec 1;27(23):6570-6579. doi: 10.1158/1078-0432.CCR-21-1942. Epub 2021 Oct 6.
Accurate IHC biomarkers incorporating nestin positivity or inositol polyphosphate-4-phosphate (INPP4B) loss have recently been optimized to identify the basal-like intrinsic breast cancer subtype regardless of estrogen, progesterone, or Her2 status. We examined the predictive capacity of these basal biomarkers in the CCTG MA.5 chemotherapy and MA.12 endocrine therapy trials.
Formalin-fixed paraffin embedded blocks of primary tumors from patients randomized in the two trials were used to build tissue microarrays. IHC staining for nestin and INPP4B followed published methods and REMARK criteria. A prespecified statistical plan tested the hypothesis that patients with basal breast cancer (nestin or INPP4B) would not benefit from anthracycline substitution in MA.5 or from tamoxifen in MA.12.
Nestin positivity or INPP4B loss was observed in 110/453 (24%) interpretable samples from MA.5 and 47/366 (13%) from MA.12, and was associated with high grade, younger age, estrogen receptor negativity, triple-negative, core basal, and PAM50 basal-like subtypes. In the MA.5 trial, patients assigned as basal experienced lower benefit from anthracycline versus nonanthracycline adjuvant chemotherapy [HR, 1.49; 95% confidence interval (CI), 0.72-3.10] when compared with non-basal (nestin and INPP4B) cases where there was a higher benefit from anthracyclines (HR, 0.75; 95% CI, 0.54-1.04; = 0.01). In the MA.12 trial, patients assigned as basal did not demonstrate a benefit from adjuvant tamoxifen versus placebo (HR, 0.48; 95% CI, 0.12-1.86; = 0.29), whereas nonbasal cases displayed significant benefit (HR, 0.66; 95% CI, 0.45-0.98; = 0.04), although the interaction test was not significant.
The nestin/INPP4B IHC panel identifies women with basal breast cancers who benefit from nonanthracycline chemotherapy but not endocrine adjuvant treatments.
最近，通过整合巢蛋白阳性或肌醇多磷酸-4-磷酸（INPP4B）缺失的免疫组织化学（IHC）生物标志物，已成功优化了用于鉴定基底样固有乳腺癌亚型的方法，无论雌激素、孕激素或 Her2 状态如何。我们在 CCTG MA.5 化疗和 MA.12 内分泌治疗试验中检验了这些基底生物标志物的预测能力。
使用来自两个试验中随机分组患者的福尔马林固定石蜡包埋原发肿瘤块，构建组织微阵列。巢蛋白和 INPP4B 的 IHC 染色遵循已发表的方法和 REMARK 标准。一个预先设定的统计方案检验了如下假设：在 MA.5 中，接受蒽环类药物替代治疗或在 MA.12 中接受他莫昔芬治疗的基底样乳腺癌（巢蛋白阳性或 INPP4B 缺失）患者不会获益。
在 MA.5 中，110/453（24%）可解释样本中观察到巢蛋白阳性或 INPP4B 缺失，而在 MA.12 中为 47/366（13%），且与高级别、年轻、雌激素受体阴性、三阴性、核心基底和 PAM50 基底样亚型相关。在 MA.5 试验中，与非基底（巢蛋白和 INPP4B）病例相比，接受蒽环类药物与非蒽环类药物辅助化疗的患者，被分配为基底样的患者获益更低[风险比（HR），1.49；95%置信区间（CI），0.72-3.10]，而非基底病例则从蒽环类药物中获益更高（HR，0.75；95%CI，0.54-1.04； = 0.01）。在 MA.12 试验中，与安慰剂相比，被分配为基底样的患者接受辅助他莫昔芬治疗并未获益（HR，0.48；95%CI，0.12-1.86； = 0.29），而非基底病例则显示出显著获益（HR，0.66；95%CI，0.45-0.98； = 0.04），尽管交互检验无统计学意义。
巢蛋白/INPP4B IHC 面板可鉴定出受益于非蒽环类化疗而非内分泌辅助治疗的基底样乳腺癌女性。
