【原】转移性乳腺癌雌激素受体编码基因发生突变相关临床病理学特征分析

　　雌激素受体α编码基因（ESR1）突变是雌激素受体阳性转移性乳腺癌对内分泌治疗耐药的重要机制。不过，与转移性乳腺癌ESR1突变相关的临床病理学特征尚不明确。

　　2018年8月2日，美国乳腺癌研究基金会和英国《自然》旗下《乳腺癌》在线发表哈佛大学医学院达纳法伯癌症研究所、贝斯以色列女执事医疗中心的研究报告，分析了转移性乳腺癌ESR1发生突变相关的临床病理学特征。

　　该研究收集了155例转移性乳腺癌患者的血浆和详细临床数据，通过液滴数字聚合酶链反应（ddPCR）对循环游离脱氧核糖核酸（cfDNA）检测了最常见的ESR1突变和对照基因PIK3CA突变。

　　结果发现，雌激素受体阳性HER2阴性乳腺癌患者113例（73%），其中检测到ESR1突变患者34例（30%）。

• ESR1突变发生率与原发病变的病理学特征或远处复发时间无相关性。

• ESR1突变发生率与既往芳香酶抑制剂术后辅助治疗或转移治疗有显著相关性。

• ESR1突变发生率还与既往氟维司群治疗呈正相关。

• 相反，CDK4/6抑制剂治疗后ESR1突变发生率较低。

• PIK3CA突变发生率与上述全身治疗无显著相关性。

　　因此，该研究结果证实，在芳香酶抑制剂术后辅助治疗和转移治疗的选择压力下，ESR1容易发生突变，并且对于雌激素受体阳性乳腺癌术后辅助治疗和转移治疗的优化具有重要意义。

NPJ Breast Cancer. 2018 Aug 2;4:22.

Unraveling the clinicopathological features driving the emergence of ESR1 mutations in metastatic breast cancer.

Yanan Kuang, Bilal Siddiqui, Jiani Hu, Matthew Pun, MacIntosh Cornwell, Gilles Buchwalter, Melissa E. Hughes, Nikhil Wagle, Paul Kirschmeier, Pasi A. Janne, Cloud P. Paweletz, Nancy U. Lin, Ian E. Krop, William T. Barry, Eric P. Winer, Myles Brown, Rinath Jeselsohn.

Dana-Farber Cancer Institute, Boston, MA, USA; Beth Israel Deaconess Medical Center, Boston, MA, USA.

ESR1 mutations were recently found to be an important mechanism of endocrine resistance in ER-positive (ER+) metastatic breast cancer. To determine the clinicopathological features driving the emergence of the ESR1 mutations we studied plasma cfDNA and detailed clinical data collected from patients with metastatic breast cancer. Droplet Digital PCR was performed for the detection of the most common ESR1 mutations and PIK3CA mutations. Among the patients with ER+/HER2- disease, ESR1 mutations were detected in 30% of the patients. There were no associations between the pathological features of the primary disease or time to distant recurrence and the emergence of ESR1 mutations in metastatic disease. The prevalence of the ESR1 mutations was significantly associated with prior treatment with an aromatase inhibitor in the adjuvant or metastatic setting. The prevalence of the ESR1 mutations was also positively associated with prior fulvestrant treatment. Conversely, the prevalence of ESR1 mutations was lower after treatment with a CDK4/6 inhibitor. There were no significant associations between specific systemic treatments and the prevalence of PIK3CA mutations. These results support the evolution of the ESR1 mutations under the selective pressure of treatment with aromatase inhibitors in the adjuvant and metastatic settings and have important implications in the optimization of adjuvant and metastatic treatment in ER+ breast cancer.

DOI: 10.1038/s41523-018-0075-5