Lund University and Skåne University Hospital, Department of Clinical Sciences, Lund, Division of Oncology and Pathology, Lund, Sweden. Department of Plastic and Reconstructive Surgery, Skåne University Hospital, Malmö, Sweden.
Lund University and Skåne University Hospital, Department of Clinical Sciences, Lund, Division of Oncology and Pathology, Lund, Sweden. Department of Oncology, Skåne University Hospital, Lund, Sweden.
Clin Cancer Res. 2015 Aug 15;21(16):3640-50. doi: 10.1158/1078-0432.CCR-14-2564. Epub 2015 Apr 22.
To evaluate whether tumor androgen receptor (AR) expression was prognostic and/or predictive for endocrine treatment alone or in combination with estrogen receptor (ER). The AR has been hypothesized to have differential prognostic roles in breast cancer depending on tumor ER status, and to influence endocrine treatment response.
A population-based prospective cohort of 1,026 patients diagnosed with primary invasive breast cancer in Lund, Sweden, between 2002 and 2012 was followed until June 2014. Associations between immunohistochemical AR expression in tumor tissue microarrays, patient and tumor characteristics, and AR genotypes were analyzed. Disease-free survival (DFS) by AR status, and combined ER/AR status was assessed in various treatment groups.
AR expression was assessable in 913 tumors. AR(+) tumors (85.0%) were associated with higher age (P = 0.036) and favorable tumor characteristics. The AR(+) status was a prognostic marker for DFS (LogRank P = 0.025). There was an interaction between AR and ER expression with respect to prognosis (adjusted P(interaction) ≤ 0.024). Tumors with discordant hormone receptor expressions (ER(+)AR(-) or ER(-)AR(+)) demonstrated worse prognosis compared with concordant tumor expressions (ER(+)AR(+) or ER(-)AR(-)) in multivariable models [adjusted HRs (95% confidence intervals); ≥ 1.99 (1.28-3.10), P ≤ 0.002]. ER(+)AR(-) indicated early treatment failure with aromatase inhibitors (AI) among chemonaïve patients aged 50 or older.
Prediction of breast cancer prognosis and treatment response was improved by combining AR and ER status. AR negativity predicted early treatment failure with AI but not tamoxifen, a finding that warrants confirmation in a randomized setting. Patients may benefit from anti-androgens or selective AR modulators.
评估肿瘤雄激素受体 (AR) 的表达是否对单独使用内分泌治疗或与雌激素受体 (ER) 联合治疗具有预后和/或预测价值。AR 被假设在乳腺癌中具有不同的预后作用，取决于肿瘤 ER 状态，并影响内分泌治疗反应。
在 2002 年至 2012 年期间，在瑞典隆德诊断为原发性浸润性乳腺癌的 1026 例患者中进行了一项基于人群的前瞻性队列研究，并随访至 2014 年 6 月。分析了肿瘤组织微阵列中免疫组织化学 AR 表达、患者和肿瘤特征以及 AR 基因型之间的关联。根据 AR 状态和 ER/AR 状态评估各种治疗组的无病生存 (DFS)。
可评估 913 例肿瘤的 AR 表达。AR(+)肿瘤 (85.0%) 与较高的年龄 (P = 0.036) 和有利的肿瘤特征相关。AR(+)状态是 DFS 的预后标志物 (LogRank P = 0.025)。AR 与 ER 表达之间存在预后的相互作用 (调整后的 P(interaction) ≤ 0.024)。激素受体表达不一致的肿瘤 (ER(+)AR(-) 或 ER(-)AR(+)) 在多变量模型中表现出比一致肿瘤表达 (ER(+)AR(+) 或 ER(-)AR(-))更差的预后 [调整后的 HRs (95%置信区间)；≥1.99 (1.28-3.10)，P ≤ 0.002]。对于 50 岁或以上的化疗初治患者，ER(+)AR(-) 提示使用芳香化酶抑制剂 (AI) 治疗早期失败。
结合 AR 和 ER 状态可改善乳腺癌预后和治疗反应的预测。AR 阴性预测 AI 治疗的早期失败，但不预测他莫昔芬治疗的早期失败，这一发现需要在随机研究中得到证实。患者可能受益于抗雄激素或选择性 AR 调节剂。
