Clinical and molecular biomarkers for prediction of endocrine response after short preoperative endocrine therapy in the WSG ADAPT-HR+/HER2- and ADAPTcycle trials (N = 7914).

We investigated predictors of ET response in the West German Study Group (WSG) ADAPT-HR+/HER2- and ADAPTcycle trials.

我们在西德研究组（WSG）ADAPT-HR+/HER2-和ADAPTcycle试验中研究了内分泌治疗反应的预测因素。

patients_and_methods

ET response (Ki67 ≤10%) after 2- to 4-week standard ET, recurrence score (RS), and nodal status were used for treatment allocation.

在2至4周的标准内分泌治疗（ET）后，内分泌治疗反应（Ki67 ≤10%）、复发评分（RS）和淋巴结状态被用于治疗分配。

In ADAPT-HR+/HER2-, patients at high clinical risk received ET alone if N0-1 and RS 0-11 or RS 12-25 and ET response.

在ADAPT-HR+/HER2-的患者中，如果临床风险高，N0-1和RS 0-11或RS 12-25且内分泌治疗反应良好，则仅接受内分泌治疗。

In ADAPTcycle, N0-1 patients with RS > 25 and ET response and those with RS < 25 and e.g. ET nonresponse, N2-3 patients with RS ≤ 25 and ET response, were randomly assigned to receive (neo)adjuvant chemotherapy or aromatase inhibitor (AI)+ribociclib.

在ADAPTcycle研究中，N0-1期患者若复发评分（RS）>25且内分泌治疗（ET）有效，或者RS<25且ET无效，以及N2-3期患者若RS≤25且ET有效，被随机分配接受（新）辅助化疗或芳香酶抑制剂（AI）+ribociclib治疗。

Predictors of ET response were identified through multivariable logistic regression models.

通过多变量逻辑回归模型确定了ET反应的预测因素。

Results

Three thousand six hundred seventy-five patients from the ADAPT-HR+/HER2- cohort (≤50 years and premenopausal, ≤50 years: N = 1250; >50 years or postmenopausal, >50 years: N = 2425) and 4239 from the ADAPTcycle screening cohort (≤50 years: N = 1336; >50 years: N = 2903) were analyzed.

分析了来自ADAPT-HR+/HER2-队列的3675名患者（≤50岁且为绝经前，≤50岁：N = 1250；>50岁或为绝经后，>50岁：N = 2425）和来自ADAPTcycle筛查队列的4239名患者（≤50岁：N = 1336；>50岁：N = 2903）。

ET response rates were higher after AI (ADAPT-HR+/HER2-/ADAPTcycle: 81.4%/76.7%) versus tamoxifen (ADAPT-HR+/HER2-/ADAPTcycle: 40.1%/34.7%) in both age groups, with further improvement by ovarian function suppression (OFS) in premenopausal patients.

在两个年龄组中，芳香化酶抑制剂（AI）治疗后的内分泌治疗（ET）反应率（ADAPT-HR+/HER2-/ADAPTcycle：81.4%/76.7%）均高于他莫昔芬（ADAPT-HR+/HER2-/ADAPTcycle：40.1%/34.7%），并且在绝经前患者中，通过卵巢功能抑制（OFS）进一步提高了反应率。

Premenopausal patients with GnRH plus AI had similar ET response rates as postmenopausal patients.

使用GnRH联合AI的绝经前患者与绝经后患者的内分泌治疗（ET）反应率相似。

ET response predictors included AI use (plus OFS in premenopausal), age >50 years, lower RS and baseline Ki67 levels, and higher expression of estrogen receptor (by immunohistochemistry) and HER2 (by Oncotype DX™).

内分泌治疗（ET）反应的预测因素包括使用芳香化酶抑制剂（绝经前患者还需加用卵巢功能抑制剂OFS），年龄>50岁，较低的复发评分（RS）和基线Ki67水平，以及雌激素受体（通过免疫组化）和HER2（通过Oncotype DX™）的高表达。

In ADAPT-HR+/HER2-, 5-year distant disease-free survival in ET responders was markedly higher than in nonresponders and also in chemotherapy-treated N0-1 patients with RS > 25 (87.0 versus 80.7%), and it was only slightly lower than that in the RS 12-25 group.

在ADAPT-HR+/HER2-研究中，内分泌治疗（ET）反应者的5年远处无病生存率显著高于非反应者，也高于接受化疗的N0-1期患者且复发评分（RS）>25（87.0%对比80.7%），并且仅略低于RS 12-25组的生存率。

Conclusions

We observed similar ET response rates in two large phase III trials.

我们在两项大型III期试验中观察到相似的内分泌治疗反应率。

Postmenopausal patients (mostly receiving AI) had higher ET response rates than younger patients.

绝经后患者（大多数接受芳香酶抑制剂治疗）的内分泌治疗反应率高于年轻患者。

However, young patients with GnRH+AI had ET response rates comparable with those of postmenopausal patients, suggesting that therapy rather than biology accounts for the difference.

然而，接受GnRH+AI治疗的年轻患者与绝经后患者的内分泌治疗反应率相当，这表明差异可能是由于治疗方式而非生物学因素所致。

Combining ET response and gene expression assessment could help more patients with luminal eBC avoid chemotherapy.

结合内分泌治疗反应和基因表达评估可能帮助更多的具有腔内表型的早期乳腺癌患者避免化疗。