Grizzi Giulia, Ghidini Michele, Botticelli Andrea, Tomasello Gianluca, Ghidini Antonio, Grossi Francesco, Fusco Nicola, Cabiddu Mary, Savio Tommaso, Petrelli Fausto
Oncology Unit, Oncology Department, ASST of Cremona, Cremona, Italy.
Oncology Unit, Internal Medicine Department, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Cancer Manag Res. 2020 Jan 30;12:675-686. doi: 10.2147/CMAR.S202965. eCollection 2020.
Neoadjuvant hormonal therapy (NEO-HT) is a possible treatment option for breast cancer (BC) patient with estrogen receptor positive (ER+) and HER2 negative (HER2-) disease. The absence of solid data on the type of drugs to be used and duration of treatment as well as lack of clear evidence of effectiveness of NEO-HT compared to chemotherapy (CT) reserve its use for patients with old age or frail conditions. However, the low pathologic complete response rate (pCR) obtained with tamoxifen or aromatase inhibitors (AIs) alone does not make NEO-HT as a suitable option for the neoadjuvant treatment of HR+ HER2-. The use of the cyclin-dependent kinase 4 and 6 (CDK 4/6) inhibitors palbociclib, ribociclib and abemaciclib of the mammalian target of rapamycin (mTOR) inhibitor everolimus and of the phosphoinositide 3 kinase (PI3K) inhibitor taselisib together with endocrine therapy (ET) has become a standard in advanced breast cancer, showing clinical effectiveness and significantly prolonging median progression-free survival compared to ET only. In the early phase disease, the use of ET together with CDK 4/6, mTOR and PI3K inhibitors is still investigational. Data from recent studies are promising even though less impressive than in metastatic setting. In this context, the use of genomic-transcriptomic tools (such as ONCOTYPE, PAM50) and the identification of novel biomarkers (ESR1, PI3Kca, PDGF-R) on tissue or with liquid biopsy could help to select patient prone to respond to endocrine-combined therapy and able to achieve pCR. With our review, we aimed at evaluating the current state of the art in the treatment of locally advanced breast cancer with NEO-HT.
新辅助激素疗法（NEO-HT）是雌激素受体阳性（ER+）且人表皮生长因子受体2阴性（HER2-）的乳腺癌（BC）患者的一种可能的治疗选择。关于所使用药物类型和治疗持续时间缺乏确凿数据，以及与化疗（CT）相比缺乏新辅助激素疗法有效性的确切证据，这使得该疗法仅适用于老年或身体虚弱的患者。然而，单独使用他莫昔芬或芳香化酶抑制剂（AI）获得的低病理完全缓解率（pCR）并不使新辅助激素疗法成为HR+ HER2-新辅助治疗的合适选择。细胞周期蛋白依赖性激酶4和6（CDK 4/6）抑制剂哌柏西利、瑞博西尼和阿贝西利、哺乳动物雷帕霉素靶蛋白（mTOR）抑制剂依维莫司以及磷酸肌醇3激酶（PI3K）抑制剂塔西利单抗与内分泌治疗（ET）联合使用已成为晚期乳腺癌的标准治疗方法，与单纯内分泌治疗相比，显示出临床有效性并显著延长了中位无进展生存期。在疾病早期阶段，内分泌治疗与CDK 4/6、mTOR和PI3K抑制剂联合使用仍在研究中。尽管近期研究数据不如转移性疾病中那么令人印象深刻，但仍很有前景。在此背景下，使用基因组转录组工具（如ONCOTYPE、PAM50）以及在组织或液体活检中鉴定新型生物标志物（ESR1、PI3Kca、PDGF-R）有助于选择易于对内分泌联合治疗产生反应并能够实现pCR的患者。通过我们的综述，旨在评估新辅助激素疗法治疗局部晚期乳腺癌的当前技术水平。
