A genomic predictor of response and survival following taxane-anthracycline chemotherapy for invasive breast cancer.
A genomic predictor of response and survival following taxane-anthracycline chemotherapy for invasive breast cancer.
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DOI：
10.1001/jama.2011.593
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发表时间：
2011-05-11
期刊：
影响因子：
--
通讯作者：
Symmans WF
中科院分区：
文献类型：
--
作者：
Hatzis C;Pusztai L;Valero V;Booser DJ;Esserman L;Lluch A;Vidaurre T;Holmes F;Souchon E;Wang H;Martin M;Cotrina J;Gomez H;Hubbard R;Chacón JI;Ferrer-Lozano J;Dyer R;Buxton M;Gong Y;Wu Y;Ibrahim N;Andreopoulou E;Ueno NT;Hunt K;Yang W;Nazario A;DeMichele A;O'Shaughnessy J;Hortobagyi GN;Symmans WF
准确预测哪些人从标准治疗中获得生存益处的概率高（或不高），对于个体化癌症治疗策略至关重要。
开发一种针对新诊断的浸润性乳腺癌化疗反应和生存的预测因子。
从新诊断的乳腺癌（310例患者）的基因表达微阵列中，开发针对新辅助化疗耐药性和反应性的不同预测特征（根据雌激素受体（ER）状态分层）。然后利用以下特征组合预测乳腺癌治疗敏感性：1）对内分泌治疗的敏感性，2）化疗耐药性，3）化疗敏感性。进行独立验证（198例患者），并与其他已报道的化疗反应基因组预测因子进行比较。
一项前瞻性多中心研究，用于开发和测试新辅助化疗的基因组预测因子。
新诊断的HER2阴性乳腺癌采用含紫杉烷和蒽环类药物序贯方案的化疗，然后进行内分泌治疗（如果激素受体阳性）。
如果预测为治疗敏感，在中位随访（3年）时的无远处复发生存率（DRFS）以及绝对风险降低（ARR，两个预测组的DRFS差异）及其95%置信区间（CI）。
在独立验证队列中的患者（99%为临床II - III期），被预测为治疗敏感的（占总数的28%），其无远处复发生存率为92%（CI 85 - 100），与其他患者相比有生存益处（绝对风险降低（ARR）18%；CI 6 - 28）。如果乳腺癌雌激素受体阳性（30%预测为敏感，无远处复发生存率为97%，CI 91 - 100；ARR 11%，CI 0.1 - 21）或雌激素受体阴性（26%预测为敏感，无远处复发生存率为83%，CI 68 - 100；ARR 26%，CI 4 - 28），预测是准确的，并且在调整相关临床病理特征后的多变量分析中具有显著性。其他基因组预测因子如果预测对化疗有反应，反而显示出生存更差的情况。
一种结合雌激素受体状态、预测的化疗耐药性、预测的化疗敏感性和预测的内分泌敏感性的基因组预测因子，能够准确识别出紫杉烷 - 蒽环类化疗后有生存益处的患者。
Accurate prediction of who will (or won’t) have high probability of survival benefit from standard treatments is fundamental for individualized cancer treatment strategies. To develop a predictor of response and survival from chemotherapy for newly diagnosed invasive breast cancer. Development of different predictive signatures for resistance and response to neoadjuvant chemotherapy (stratified according to estrogen receptor (ER) status) from gene expression microarrays of newly diagnosed breast cancer (310 patients). Then prediction of breast cancer treatment-sensitivity using the combination of signatures for: 1) sensitivity to endocrine therapy, 2) chemo-resistance, and 3) chemo-sensitivity. Independent validation (198 patients) and comparison with other reported genomic predictors of chemotherapy response. Prospective multicenter study to develop and test genomic predictors for neoadjuvant chemotherapy. Newly diagnosed HER2-negative breast cancer treated with chemotherapy containing sequential taxane and anthracycline-based regimens then endocrine therapy (if hormone receptor-positive). Distant relapse-free survival (DRFS) if predicted treatment-sensitive and absolute risk reduction (ARR, difference in DRFS of the two predicted groups) at median follow-up (3 years), and their 95% confidence intervals (CI). Patients in the independent validation cohort (99% clinical Stage II–III) who were predicted to be treatment-sensitive (28% of total) had DRFS of 92% (CI 85–100) and survival benefit compared to others (absolute risk reduction (ARR) 18%; CI 6–28). Predictions were accurate if breast cancer was ER-positive (30% predicted sensitive, DRFS 97%, CI 91–100; ARR 11%, CI 0.1–21) or ER-negative (26% predicted sensitive, DRFS 83%, CI 68–100; ARR 26%, CI 4–28), and were significant in multivariate analysis after adjusting for relevant clinical-pathologic characteristics. Other genomic predictors showed paradoxically worse survival if predicted to be responsive to chemotherapy. A genomic predictor combining ER status, predicted chemo-resistance, predicted chemo-sensitivity, and predicted endocrine sensitivity accurately identified patients with survival benefit following taxane-anthracycline chemotherapy.
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影响因子：
168.9
作者：
Wang, YX;Klijn, JGM;Foekens, JA
通讯作者：
Foekens, JA
DOI：
10.1158/1078-0432.ccr-09-2247
发表时间：
2010-01-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Lee JK;Coutant C;Kim YC;Qi Y;Theodorescu D;Symmans WF;Baggerly K;Rouzier R;Pusztai L
通讯作者：
Pusztai L
影响因子：
6.2
作者：
Symmans, WF;Ayers, M;Pusztai, L
通讯作者：
Pusztai, L
影响因子：
45.3
作者：
Liedtke, Cornelia;Mazouni, Chafika;Pusztai, Lajos
通讯作者：
Pusztai, Lajos
影响因子：
45.3
作者：
Symmans, W. Fraser;Peintinger, Florentia;Pusztai, Lajos
通讯作者：
Pusztai, Lajos