Adjuvant capecitabine-containing chemotherapy benefit and homologous recombination deficiency in early-stage triple-negative breast cancer patients.
Adjuvant capecitabine-containing chemotherapy benefit and homologous recombination deficiency in early-stage triple-negative breast cancer patients.
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早期三阴性乳腺癌患者的辅助卡皮替滨化学疗法的益处和同源重组缺乏症。
DOI：
10.1038/s41416-022-01711-y
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发表时间：
2022-06
影响因子：
8.8
通讯作者：
Linn, Sabine C.
中科院分区：
文献类型：
--
作者：
de Boo, Leonora W.;Jozwiak, Katarzyna;Joensuu, Heikki;Lindman, Henrik;Lauttia, Susanna;Opdam, Mark;van Steenis, Charlaine;Brugman, Wim;Kluin, Roelof J. C.;Schouten, Philip C.;Kok, Marleen;Nederlof, Petra M.;Hauptmann, Michael;Linn, Sabine C.
在一些随机试验和荟萃分析中，在早期三阴性乳腺癌 (TNBC) 患者的标准化疗中添加辅助卡培他滨可以提高生存率。然而，许多患者并没有受益。我们评估了类似 BRCA1 的 DNA 拷贝数特征（表明同源重组缺陷），作为 FinXX 试验 TNBC 亚组中卡培他滨获益的预测生物标志物。早期TNBC患者被随机分配接受含卡培他滨辅助化疗（TX + CEX：卡培他滨-多西他赛，随后环磷酰胺-表阿霉素-卡培他滨）和常规化疗（T + CEF：多西他赛，随后环磷酰胺-表阿霉素-氟尿嘧啶）。使用已建立的 DNA 比较基因组杂交算法，根据低覆盖率全基因组下一代测序数据确定肿瘤 BRCA1 样状态。对于 129/202 (63.9%) 的患者，可以确定 BRCA1 样状态，这主要是由于缺乏组织。在中位随访 10.7 年期间，发生 35 例复发和 32 例死亡。与68名（52.7%）BRCA1样肿瘤患者（HR 0.66，95% CI 0.24-1.81）相比，61名（47.3%）名非BRCA1样肿瘤患者（HR 0.23，95% CI 0.08-0.70）添加卡培他滨似乎更能提高无复发生存率（P-相互作用 = 0.17）。根据我们的数据，非 BRCA1 样 TNBC 患者似乎受益于在辅助化疗中添加卡培他滨。患有 BRCA1 样 TNBC 的患者也可能受益。需要进一步的研究来定义 BRCA1 样 TNBC 患者中可能无法从卡培他滨辅助治疗中获益的亚组。
The addition of adjuvant capecitabine to standard chemotherapy of early-stage triple-negative breast cancer (TNBC) patients has improved survival in a few randomised trials and in meta-analyses. However, many patients did not benefit. We evaluated the BRCA1-like DNA copy number signature, indicative of homologous recombination deficiency, as a predictive biomarker for capecitabine benefit in the TNBC subgroup of the FinXX trial. Early-stage TNBC patients were randomised between adjuvant capecitabine-containing (TX + CEX: capecitabine-docetaxel, followed by cyclophosphamide-epirubicin-capecitabine) and conventional chemotherapy (T + CEF: docetaxel, followed by cyclophosphamide-epirubicin-fluorouracil). Tumour BRCA1-like status was determined on low-coverage, whole genome next-generation sequencing data using an established DNA comparative genomic hybridisation algorithm. For 129/202 (63.9%) patients the BRCA1-like status could be determined, mostly due to lack of tissue. During a median follow-up of 10.7 years, 35 recurrences and 32 deaths occurred. Addition of capecitabine appears to improve recurrence-free survival more among 61 (47.3%) patients with non-BRCA1-like tumours (HR 0.23, 95% CI 0.08–0.70) compared to 68 (52.7%) patients with BRCA1-like tumours (HR 0.66, 95% CI 0.24–1.81) (P-interaction = 0.17). Based on our data, patients with non-BRCA1-like TNBC appear to benefit from the addition of capecitabine to adjuvant chemotherapy. Patients with BRCA1-like TNBC may also benefit. Additional research is needed to define the subgroup within BRCA1-like TNBC patients who may not benefit from adjuvant capecitabine.
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影响因子：
45.3
作者：
Joensuu, Heikki;Kellokumpu-Lehtinen, Pirkko-Liisa;Lindman, Henrik
通讯作者：
Lindman, Henrik
DOI：
10.1073/pnas.0807297105
发表时间：
2008-09-30
影响因子：
11.1
作者：
Anderson, Ericka L.;Baltus, Andrew E.;Page, David C.
通讯作者：
Page, David C.
影响因子：
8.8
作者：
Lips EH;Mulder L;Oonk A;van der Kolk LE;Hogervorst FB;Imholz AL;Wesseling J;Rodenhuis S;Nederlof PM
通讯作者：
Nederlof PM
影响因子：
7.3
作者：
Barber, Louise J.;Sandhu, Shahneen;Ashworth, Alan
通讯作者：
Ashworth, Alan
影响因子：
45.3
作者：
Denduluri, Neelima;Chavez-MacGregor, Mariana;Giordano, Sharon H.
通讯作者：
Giordano, Sharon H.