Division of Medical Oncology, Department of Medical and Surgical Sciences for Children and Adults, University Hospital of Modena, 41125 Modena, Italy.
Division of Medical Oncology, Department of Oncology and Hematology, University Hospital of Modena, 41125 Modena, Italy.
Int J Mol Sci. 2022 Jun 25;23(13):7079. doi: 10.3390/ijms23137079.
Endocrine therapy (ET), associated with CDK 4/6 inhibitors, represents the first choice of treatment for HR+/HER2- metastatic breast cancer (mBC). Primary or secondary endocrine resistance could develop; however validated biomarkers capable of predicting such a conditions are not available. Several studies have shown that HR+/HER2- mBC comprises five intrinsic subtypes. The purpose of this systematic review was to analyze the potential correlations between intrinsic subtype, efficacy of treatment, and patient outcome. Five papers that analyzed the intrinsic subtype with PAM50 assay in patients (pts) with HR+/HER2- mBC treated with ET (alone or in combination) within seven phase III clinical trials (EGF30008, BOLERO-2, PALOMA-2,3, MONALEESA-2,3,7) were identified. Non-luminal subtypes are more frequent in endocrine-resistant pts and in metastatic sites (vs. primary tumors), have less benefit from ET, and worse prognosis. Among these, HER2-enriched subtypes are similar to HER2+ tumors and benefit from the addition of anti-HER2 agents (lapatinib) and, for less clear reasons, of ribociclib (unconfirmed data for palbociclib and everolimus). Basal-like subtypes are similar to triple-negative tumors, making them more sensitive to chemotherapy. The intrinsic subtype is also not static but can vary over time with the evolution of the disease. Currently, the intrinsic subtype does not play a decisive role in the choice of treatment in clinical practice, but has potential prognostic and predictive value that should be further investigated.
内分泌治疗（ET）联合 CDK4/6 抑制剂是 HR+/HER2-转移性乳腺癌（mBC）的首选治疗方法。可能会出现原发性或继发性内分泌耐药；但是，目前还没有可用的能够预测这种情况的验证性生物标志物。多项研究表明，HR+/HER2- mBC 包含五个固有亚型。本系统评价的目的是分析固有亚型、治疗效果和患者结局之间的潜在相关性。共确定了 5 篇分析 HR+/HER2- mBC 患者固有亚型的论文，这些患者接受了 ET（单独或联合使用）治疗，且纳入了 7 项 III 期临床试验（EGF30008、BOLERO-2、PALOMA-2、3、MONALEESA-2、3、7），这些研究均使用了 PAM50 检测。在内分泌耐药患者和转移性部位（与原发性肿瘤相比）中，非腔面亚型更为常见，对 ET 的获益较小，预后更差。在这些亚型中，HER2 富集亚型与 HER2+肿瘤相似，并且受益于添加抗 HER2 药物（拉帕替尼），且（原因不太明确）还受益于 ribociclib（对于 palbociclib 和 everolimus，数据未经证实）。基底样亚型与三阴性肿瘤相似，使其对化疗更敏感。固有亚型也不是静态的，而是随着疾病的进展而发生变化。目前，固有亚型在临床实践中对治疗选择没有决定性作用，但具有潜在的预后和预测价值，应进一步研究。
