血浆ESR1突变检测有助于雌激素受体阳性晚期乳腺癌治疗选择
2016年5月31日，美国临床肿瘤学会《临床肿瘤学杂志》在线发表英国癌症研究所、皇家马斯登医院、美国托马斯杰弗逊大学、法国古斯塔夫·鲁西研究所、澳大利亚墨尔本大学、德国乳腺癌研究协作组、美国辉瑞的研究报告，通过分析SoFEA和PALOMA3两项研究，发现芳香酶抑制药治疗后进展后进行血浆ESR1突变检测，有助于进一步内分泌疗法的直接选择。
SoFEA研究：
有ESR1突变（PFS：氟维司群>依西美坦，P=0.02）
无ESR1突变（PFS：氟维司群≈依西美坦，P=0.77）
PALOMA3研究：
有ESR1突变（PFS：氟维司群＋帕泊昔布>氟维司群＋安慰剂，P=0.002）
无ESR1突变（PFS：氟维司群＋帕泊昔布>氟维司群＋安慰剂，P<0.001）
J Clin Oncol. 2016 Jun 6. [Epub ahead of print]
Plasma ESR1 Mutations and the Treatment of Estrogen Receptor-Positive Advanced Breast Cancer.
Charlotte Fribbens, Ben O’Leary, Lucy Kilburn, Sarah Hrebien, Isaac Garcia-Murillas, Matthew Beaney, Massimo Cristofanilli, Fabrice Andre, Sherene Loi, Sibylle Loibl, John Jiang, Cynthia Huang Bartlett, Maria Koehler, Mitch Dowsett, Judith M. Bliss, Stephen R.D. Johnston, Nicholas C. Turner.
Institute of Cancer Research; Royal Marsden Hospital; The Institute of Cancer Research Clinical Trials and Statistics Unit, London, UK; Thomas Jefferson University, Philadelphia, PA; Institut Gustave Roussy, Villejuif, France; University of Melbourne, Melbourne, Australia; German Breast Group, Neu-Isenburg, Germany; Pfizer, New York, NY.
PURPOSE: ESR1 mutations are selected by prior aromatase inhibitor (AI) therapy in advanced breast cancer. We assessed the impact of ESR1 mutations on sensitivity to standard therapies in two phase III randomized trials that represent the development of the current standard therapy for estrogen receptor–positive advanced breast cancer.
MATERIALS AND METHODS: In a prospective-retrospective analysis, we assessed ESR1 mutations in available archived baseline plasma from the SoFEA (Study of Faslodex Versus Exemestane With or Without Arimidex) trial, which compared exemestane with fulvestrant-containing regimens in patients with prior sensitivity to nonsteroidal AI and in baseline plasma from the PALOMA3 (Palbociclib Combined With Fulvestrant in Hormone Receptor–Positive HER2-Negative Metastatic Breast Cancer After Endocrine Failure) trial, which compared fulvestrant plus placebo with fulvestrant plus palbociclib in patients with progression after receiving prior endocrine therapy. ESR1 mutations were analyzed by multiplex digital polymerase chain reaction.
RESULTS: In SoFEA, ESR1 mutations were found in 39.1% of patients (63 of 161), of whom 49.1% (27 of 55) were polyclonal, with rates of mutation detection unaffected by delays in processing of archival plasma. Patients with ESR1 mutations had improved progression-free survival (PFS) after taking fulvestrant (n = 45) compared with exemestane (n = 18; hazard ratio [HR], 0.52; 95% CI, 0.30 to 0.92; P = .02), whereas patients with wild-type ESR1 had similar PFS after receiving either treatment (HR, 1.07; 95% CI, 0.68 to 1.67; P = .77). In PALOMA3, ESR1 mutations were found in the plasma of 25.3% of patients (91 of 360), of whom 28.6% (26 of 91) were polyclonal, with mutations associated with acquired resistance to prior AI. Fulvestrant plus palbociclib improved PFS compared with fulvestrant plus placebo in both ESR1 mutant (HR, 0.43; 95% CI, 0.25 to 0.74; P = .002) and ESR1 wild-type patients (HR, 0.49; 95% CI, 0.35 to 0.70; P < .001).
CONCLUSION: ESR1 mutation analysis in plasma after progression after prior AI therapy may help direct choice of further endocrine-based therapy. Additional confirmatory studies are required.
DOI: 10.1200/JCO.2016.67.3061