老年早期三阴性乳腺癌化疗总生存结局
众所周知，对于早期三阴性乳腺癌年轻女性，术前化疗或术后化疗已被证实可显著延长生存时间。不过，对于早期三阴性乳腺癌老年女性，合并症较多，自然生存时间相对有限，难以开展前瞻随机对照研究，术前化疗或术后化疗的生存获益证据极少，故有必要对历史数据进行回顾分析。不过，回顾分析难以避免选择偏倚，例如选择化疗的患者通常年轻、合并症较少、肿瘤较大、分级较高、淋巴结转移较多，选择不化疗的患者通常高龄、合并症较多、肿瘤较小、分级较低、淋巴结转移较多。
2020年12月1日，英国《柳叶刀》肿瘤学分册正式发表美国佛罗里达MD安德森癌症中心、德克萨斯大学MD安德森癌症中心、宾夕法尼亚阿宾顿杰斐逊医疗中心、瑞典哥德堡大学萨赫尔格雷斯卡医院的研究报告，探讨了局部治疗＋化疗对早期三阴性乳腺癌老年女性总生存结局的影响。
该大样本回顾研究利用美国外科医师学会癌症委员会和美国癌症学会的全国癌症数据库，对2004年1月1日～2014年12月31日确诊I～III期三阴性乳腺浸润癌经手术治疗的年龄≥70岁女性进行回顾分析。剔除T1aN0M0期乳腺癌以及雌激素受体状态、孕激素受体状态或HER2状态数据不全的患者。为了减少回顾研究的选择偏倚，故将患者分为三组：被推荐但未化疗者、接受化疗者、不推荐也未化疗者。主要结局为总生存。通过倾向评分匹配和多因素比例风险回归模型，对年龄、肿瘤大小、肿瘤分级、淋巴结状态、合并症评分等其他影响因素进行匹配和校正，以最大程度地减少选择偏倚。
结果，1万6062例三阴性乳腺癌女性符合分析条件，中位随访38.3个月（四分位：20.7～46.1，范围：0～138.0，95%置信区间：37.8～38.7）。
全部患者的5年总生存率为62.3%（95%置信区间：59.7～64.4）。
三组患者的5年总生存率显著不同（合并对数秩P<0.0001）
接受化疗：68.5%（95%置信区间：66.4～70.6）
被推荐但未化疗：61.1%（95%置信区间：59.0～63.2）
不推荐也未化疗：53.7%（95%置信区间：51.8～55.8）
对1884对倾向评分匹配患者进行单因素分析，接受化疗与被推荐但未化疗相比，总死亡风险减少15%（风险比：085，95%置信区间：0.74～0.96，P=0.012）。
对1884对倾向评分匹配患者进行多因素比例风险回归模型分析，对年龄、肿瘤大小、肿瘤分级、淋巴结状态、合并症评分等其他影响因素进行匹配和校正后，接受化疗与被推荐但未化疗相比，总死亡风险减少31%（风险比：0.69，95%置信区间：0.60～0.80，P<0.0001）。
对倾向评分匹配患者进行分层后，接受化疗与被推荐但未化疗相比：
淋巴结阴性女性：总死亡风险减少20%（风险比：0.80，95%置信区间：0.66～0.97，P=0.007）
淋巴结阳性女性：总死亡风险减少24%（风险比：0.76，95%置信区间：0.64～0.91，P=0.006）
合并症评分>0分：总死亡风险减少26%（风险比：0.74，95%置信区间：0.59～0.94，P=0.013）
因此，该研究结果表明，对年龄≥70岁的早期三阴性乳腺癌女性，无论淋巴结状态或合并症评分如何，都应该考虑化疗。
对此，意大利米兰大学欧洲癌症研究院发表同期评论：早期三阴性乳腺癌老年患者化疗的用途。
Lancet Oncol. 2020 Dec;21(12):1611-1619.
Addition of chemotherapy to local therapy in women aged 70 years or older with triple-negative breast cancer: a propensity-matched analysis.
Jennifer A Crozier, Todd A Pezzi, Caitlin Hodge, Slavica Janeva, Beth-Ann Lesnikoski, Laila Samiian, Amanda Devereaux, William Hammond, Riccardo A Audisio, Christopher M Pezzi.
Baptist MD Anderson Cancer Center, Jacksonville, FL, USA; University of Texas MD Anderson Cancer Center, Houston, TX, USA; Abington-Jefferson Health, Abington, PA, USA; Sahlgrenska University Hospital, Gothenburg, Sweden.
BACKGROUND: There is a scarcity of data exploring the benefits of adjuvant or neoadjuvant chemotherapy in the treatment of breast cancer in older women. We aimed to explore the effect of adding chemotherapy to local therapy on overall survival in older women with triple-negative breast cancer.
METHODS: For this propensity-matched analysis, we used data from the National Cancer Database, a joint project of the Commission on Cancer of the American College of Surgeons and the American Cancer Society. We included data from women aged 70 years or older with surgically treated, American Joint Committee on Cancer (AJCC) Stage I-III invasive triple-negative breast cancer diagnosed from 2004 to 2014. Patients with T1aN0M0 disease and those with incomplete data on oestrogen receptor status, progesterone receptor status, or HER2 status were excluded. To reduce bias, patients were subdivided into three groups: those who were recommended chemotherapy but did not receive it; those who received chemotherapy; and those for whom chemotherapy was not recommended and not given. The primary outcome was overall survival. Multivariate Cox regression analysis and propensity score matching were done to minimise bias.
FINDINGS: Between Jan 1, 2004, and Dec, 31, 2014, 16062 women with triple-negative breast cancer in the database met the inclusion criteria for this analysis. Median follow-up was 38.3 months (IQR 20.7-46.1, range 0-138.0; 95% CI 37.8-38.7). Collectively, the 5-year overall survival estimate of the 16062 patients in the study cohort was 62.3% (95% CI 59.7-64.4). 5-year estimated overall survival was 68.5% (95% CI 66.4-70.6) for patients receiving chemotherapy, 61.1% (59.0-63.2) for patients recommended but not given chemotherapy, and 53.7% (51.8-55.8) for patients not recommended chemotherapy and not given chemotherapy (pooled log rank p<0.0001). Multivariate Cox regression analysis of a propensity score-matched sample comparing those who received chemotherapy with those who were recommended but not given chemotherapy (n=1884 matched pairs) identified improved overall survival with chemotherapy (hazard ratio [HR] 0.69 [95% CI 0.60-0.80]; p<0.0001). After stratifying the propensity score matching sample, this benefit persisted for node-negative women (HR 0.80 [95% CI 0.66-0.97]; p=0.007), node-positive women (0.76 [0.64-0.91]; p=0.006), and those with a comorbidity score greater than 0 (HR 0.74 [95% CI 0.59-0.94]; p=0.013).
INTERPRETATION: These data support consideration of chemotherapy in the treatment of women aged 70 years or older with triple-negative breast cancer.
DOI: 10.1016/S1470-2045(20)30538-6
Lancet Oncol. 2020 Dec;21(12):1543-1545.
Use of chemotherapy in elderly patients with early-stage triple-negative breast cancer.
Giuseppe Curigliano, Gabriella Pravettoni.
European Institute of Oncology, IRCCS, Milan, Italy; University of Milan, Milan, Italy.
DOI: 10.1016/S1470-2045(20)30694-X