演題抄録

臓器別シンポジウム

開催概要
開催回
第58回・2020年・京都
 

進行再発乳癌におけるホルモン療法および抗HER2療法の耐性化機序とその克服

演題番号 : SY20-1

[筆頭演者]
高野 利実:1 

1:がん研究会有明病院・乳腺内科

 

For metastatic breast cancer (MBC), chemotherapy, endocrine therapy, and molecular-targeted therapy have been widely used, and there remain many clinical questions on optimal use of these drugs. To establish optimal sequence of treatment, we have to elucidate mechanisms of drug resistance and find strategies to overcome it.
In patients with HER2-negative, estrogen receptor-positive MBC, endocrine therapy is routinely used as monotherapy or combination therapy with molecular-targeted agents. Many molecular-targeted agents such as CDK4/6 inhibitors, mTOR inhibitors, PI3K inhibitors, Akt inhibitors, and HDAC inhibitors have been studied in combination with endocrine therapy. To discuss optimal sequence of endocrine therapy, we should consider the mechanisms of resistance to both endocrine therapy and molecular-targeted agents. ESR1 mutations are known to cause resistance to aromatase inhibitors, and many other biomarkers have also been studied in this field. Recent hot topic is the acquired resistance to CDK4/6 inhibitors, and some biomarkers have been suggested to cause the resistance; Rb, cycline E1, CDK2, CDK6, PIK3CA mutations, and so on.
In patients with HER2-positive MBC, anti-HER2 agents such as trastuzumab, lapatinib, pertuzumab, trastuzumab emtansine (T-DM1), and trastuzumab deruxtecan are used. Even though these anti-HER2 agents have certainly prolonged overall survival in patients with HER2-positive MBC, most diseases progress during treatments. Some biomarkers have been suggested to play a role in intrinsic or acquired resistance; HER2 expression, HER dimerization, HER2 gene alterations, ADCC activities, and PI3K/Akt/mTOR pathway alterations including PIK3CA mutations. New anti-HER2 agents including HER2-TKIs, HER2-MAbs, and HER2-ADCs, and new combinations of anti-HER2 agents and other molecular-targeted drugs are under development to overcome the resistance.
In this session, I will also overview clinical trials conducted to overcome the resistance.

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