小肿瘤四阴性乳腺癌术后化疗长期结局

　　由于缺乏随机对照研究数据，各个国际指南对病理确诊肿瘤大小不超过2厘米、腋窝淋巴结阴性、雌激素受体阴性、孕激素受体阴性、HER2阴性早期乳腺癌术后辅助化疗的推荐意见不同。

　　2020年6月14日，欧洲癌症治疗研究组织、欧洲癌症组织、欧洲乳腺癌专科医师学会《欧洲癌症杂志》在线发表荷兰癌症研究所、阿姆斯特丹圣母医院、乌得勒支大学医疗中心、荷兰综合癌症组织、特温特大学的研究报告，对荷兰全国小肿瘤四阴性乳腺癌术后辅助化疗的长期生存结局进行了分析。

　　该人群回顾研究根据荷兰癌症登记数据库确定2005～2016年荷兰全国诊断为小肿瘤四阴性乳腺癌的全部患者共计4366例，获取患者特征、肿瘤特征和治疗特征。从荷兰统计局获取患者的死亡日期和原因。通过多因素比例风险分析回归模型，对入组时年龄、肿瘤大小、肿瘤分级、原发肿瘤局部治疗方法、腋窝淋巴结孤立肿瘤细胞、组织学类型等其他影响因素进行校正后，分析术后辅助化疗与乳腺癌相关生存和总生存的相关性，并通过倾向评分加权进行敏感性分析。

　　结果，其中病理确诊肿瘤大小：

• 0.1～0.5厘米：284例（ 6.5%）

• 0.5～1.0厘米：923例（21.1%）

• 1.0～2.0厘米：3159例（72.4%）

　　术后辅助化疗患者占53%，与术后未化疗患者相比：

• 年龄较小

• 肿瘤较大

• 肿瘤分级较高

　　中位随访8.2年（四分位：5.8～10.9）期间，死亡671例（15.4%），其中死于乳腺癌311例（7.1%）。

　　对其他影响因素进行校正后，化疗与未化疗相比，乳腺癌死亡风险显著减少35%（校正后风险比：0.65，95%置信区间：0.48～0.89，P<0.001）。

　　肿瘤越大，化疗与未化疗相比，效果越显著（P=0.02）

• 0.1～0.5厘米：乳腺癌死亡风险相似（校正后风险比：4.28，95%置信区间：1.12～16.44）

• 0.5～1.0厘米：乳腺癌死亡风险相似（校正后风险比：1.12，95%置信区间：0.51～2.49）

• 1.0～2.0厘米：乳腺癌死亡风险低40%（校正后风险比：0.60，95%置信区间：0.43～0.82）

　　总生存与乳腺癌相关生存结果一致，倾向评分加权分析也证实了初步分析结果。

　　因此，该研究结果表明，术后辅助化疗与未化疗相比，小肿瘤四阴性乳腺癌患者的乳腺癌相关生存和总生存长期结局显著较好，尤其对于肿瘤大小1.0～2.0厘米的患者。

Eur J Cancer. 2020 Jun 14;135:66-74.

Adjuvant chemotherapy in small node-negative triple-negative breast cancer.

Tessa G. Steenbruggen, Erik van Werkhoven, Mette S. van Ramshorst, Vincent O. Dezentjé, Marleen Kok, Sabine C. Linn, Sabine Siesling, Gabe S. Sonke.

The Netherlands Cancer Institute, Amsterdam, the Netherlands; Onze Lieve Vrouwe Gasthuis, Amsterdam, the Netherlands; University Medical Center Utrecht, Utrecht, the Netherlands; Netherlands Comprehensive Cancer Organisation, Utrecht, the Netherlands; University of Twente, Enschede, the Netherlands.

HIGHLIGHTS

• Recommendations on adjuvant chemotherapy in pT1N0M0 TNBC differ among guidelines.

• Adjuvant chemotherapy is associated with better breast cancer-specific survival and overall survival in pT1N0M0 TNBC.

• The association of chemotherapy with a better outcome was most pronounced in pT1c tumours (hazard ratio 0.60, 0.43-0.82).

BACKGROUND: Recommendations on adjuvant chemotherapy in pT1N0M0 triple-negative breast cancer (TNBC) differ among international guidelines owing to lack of randomized trial data. We evaluated associations of adjuvant chemotherapy with a long-term outcome in a population-based cohort of pT1N0M0 TNBC.

METHODS: All patients diagnosed with pT1N0M0 TNBC in the Netherlands between 2005 and 2016 were identified from the Netherlands Cancer Registry. Patient, tumour and treatment characteristics were recorded. The date and cause of death were obtained from Statistics Netherlands. We used multivariable Cox regression models to evaluate associations of adjuvant chemotherapy with breast cancer-specific survival (BCSS) and overall survival (OS), adjusted for baseline characteristics and performed sensitivity analyses using propensity score (PS) weighting.

RESULTS: We identified 4366 patients: 284 with pT1a, 923 with pT1b and 3159 with pT1c tumours. Adjuvant chemotherapy was administered in 53% of patients. Patients receiving chemotherapy had more unfavourable baseline characteristics including younger age, larger tumours and higher tumour grade. At 8.2 years median follow-up (interquartile range = 5.8-10.9), 671 patients had died, of whom 311 because of breast cancer. After adjustment for baseline characteristics, chemotherapy was associated with improved BCSS (adjusted hazard ratio [aHR] = 0.65; 95% confidence interval [CI] = 0.48-0.89). The effect of chemotherapy differed by tumour size (pT1a: aHR = 4.28, 95% CI = 1.12-16.44; pT1b: aHR = 1.12, 95% CI = 0.51-2.49; pT1c: aHR = 0.60, 95% CI = 0.43-0.82; p interaction = 0.02). Findings for OS were in line with BCSS results. PS-weighting analysis confirmed the results of the primary analysis.

CONCLUSIONS: Adjuvant chemotherapy is associated with better BCSS and OS in pT1N0M0 TNBC. Better outcome is most evident in pT1c tumours and may not outweigh harm in pT1a/pT1b tumours.

KEYWORDS: Adjuvant chemotherapy, Triple-negative breast cancer, Axillary lymph node-negative

DOI: 10.1016/j.ejca.2020.04.033