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BRCA状态可预测三阴性乳腺癌新辅助化疗期间对含紫杉烷方案的耐药性。

BRCAness predicts resistance to taxane-containing regimens in triple negative breast cancer during neoadjuvant chemotherapy.

作者信息

Akashi-Tanaka Sadako, Watanabe Chie, Takamaru Tomoko, Kuwayama Takashi, Ikeda Murasaki, Ohyama Hiroto, Mori Miki, Yoshida Reiko, Hashimoto Rikako, Terumasa Sawada, Enokido Katsutoshi, Hirota Yuko, Okuyama Hiromi, Nakamura Seigo

机构信息

Department of Breast Surgical Oncology, Showa University School of Medicine, Tokyo, Japan.

Department of Breast Surgical Oncology, Showa University School of Medicine, Tokyo, Japan.

出版信息

Clin Breast Cancer. 2015 Feb;15(1):80-5. doi: 10.1016/j.clbc.2014.08.003. Epub 2014 Sep 28.

Abstract

BACKGROUND

To provide optimal treatment of heterogeneous triple negative breast cancer (TNBC), we need biomarkers that can predict the chemotherapy response.

PATIENTS AND METHODS

We retrospectively investigated BRCAness in 73 patients with breast cancer who had been treated with taxane- and/or anthracycline-based neoadjuvant chemotherapy (NAC). Using multiplex, ligation-dependent probe amplification on formalin-fixed core needle biopsy (CNB) specimens before NAC and surgical specimens after NAC. BRCAness status was assessed with the assessor unaware of the clinical information.

RESULTS

We obtained 45 CNB and 60 surgical specimens from the 73 patients. Of the 45 CNB specimens, 17 had BRCAness (38.6% of all subtypes). Of the 23 TNBC CNB specimens, 14 had BRCAness (61% of TNBC cases). The clinical response rates were significantly lower for BRCAness than for non-BRCAness tumors, both for all tumors (58.8% vs. 89.3%, P = .03) and for TNBC (50% vs. 100%, P = .02). All tumors that progressed with taxane therapy had BRCAness. Of the patients with TNBC, those with non-BRCAness cancer had pathologic complete responses significantly more often than did those with BRCAness tumors (77.8% vs. 14.3%, P = .007). After NAC, the clinical response rates were significant lower for BRCAness than for non-BRCAness tumors in all subtypes (P = .002) and in TNBC cases (P = .008). After a median follow-up of 26.4 months, 6 patients-all with BRCAness-had developed recurrence. Patients with BRCAness had shorter progression-free survival than did those with non- BRCAness (P = .049).

CONCLUSION

Identifying BRCAness can help predict the response to taxane, and changing regimens for BRCAness TNBC might improve patient survival. A larger prospective study is needed to further clarify this issue.

摘要

背景

为了对异质性三阴性乳腺癌(TNBC)进行最佳治疗,我们需要能够预测化疗反应的生物标志物。

患者与方法

我们回顾性研究了73例接受紫杉烷和/或蒽环类药物新辅助化疗(NAC)的乳腺癌患者的BRCAness状态。在NAC前使用多重连接依赖探针扩增技术检测福尔马林固定的粗针穿刺活检(CNB)标本,NAC后检测手术标本。由不知道临床信息的评估者评估BRCAness状态。

结果

我们从73例患者中获得了45份CNB标本和60份手术标本。在45份CNB标本中,17份具有BRCAness(占所有亚型的38.6%)。在23份TNBC的CNB标本中,14份具有BRCAness(占TNBC病例的61%)。BRCAness肿瘤的临床缓解率显著低于非BRCAness肿瘤,所有肿瘤均如此(58.8%对89.3%,P = .03),TNBC也是如此(50%对100%,P = .02)。所有接受紫杉烷治疗后病情进展的肿瘤均具有BRCAness。在TNBC患者中,非BRCAness癌症患者的病理完全缓解率显著高于BRCAness肿瘤患者(77.8%对14.3%,P = .007)。NAC后,所有亚型中BRCAness肿瘤的临床缓解率显著低于非BRCAness肿瘤(P = .002),TNBC病例中也是如此(P = .008)。中位随访26.4个月后,6例患者——均为BRCAness患者——出现复发。BRCAness患者的无进展生存期短于非BRCAness患者(P = .049)。

结论

识别BRCAness有助于预测对紫杉烷的反应,改变BRCAness TNBC的治疗方案可能会提高患者生存率。需要进行更大规模的前瞻性研究以进一步阐明这一问题。

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