Chandran Elias A, Kennedy Ian
Department of Medical Oncology, Waikato Hospital, Hamilton, New Zealand.
J Immunother Precis Oncol. 2020 May 18;3(3):133-136. doi: 10.36401/JIPO-20-5. eCollection 2020 Aug.
mutations resulting in disinhibition of the phosphoinositide 3-kinase (PI3K) pathway are present in approximately a third of estrogen receptor (ER)-positive breast cancer. Recent clinical trials of PI3K inhibition in -mutated metastatic breast cancer have shown improvement in progression-free survival of up to 11 months. We report a 68-year-old woman with metastatic ER-positive breast cancer with mutation who despite having disease progression after four lines of endocrine therapy (ET) attained a complete response (CR) after subsequent addition of a PI3K inhibitor. Remarkably, her CR is still maintained at 5 years. We believe this may be due to the co-occurrence of an mutation, which increases sensitivity to PI3K inhibition. Our case demonstrates restoration of sensitivity to ET by additional inhibition of PI3K, which resulted in exceptional disease response, far exceeding the expected duration. Hence, we believe that PI3K inhibition in addition to ET should be considered in patients with simultaneous and mutations.
导致磷酸肌醇3-激酶（PI3K）信号通路去抑制的突变存在于约三分之一的雌激素受体（ER）阳性乳腺癌中。近期针对PI3K突变的转移性乳腺癌进行的PI3K抑制临床试验显示，无进展生存期改善长达11个月。我们报告了一名68岁患有转移性ER阳性乳腺癌且存在PIK3CA突变的女性，尽管在接受四线内分泌治疗（ET）后疾病进展，但在随后添加PI3K抑制剂后获得了完全缓解（CR）。值得注意的是，她的CR在5年后仍得以维持。我们认为这可能是由于同时发生了TP53突变，该突变增加了对PI3K抑制的敏感性。我们的病例表明，通过额外抑制PI3K可恢复对ET的敏感性，从而产生了异常的疾病反应，远远超过预期持续时间。因此，我们认为对于同时存在PIK3CA和TP53突变的患者，除ET外还应考虑使用PI3K抑制剂。
