Supplementary Material for: Do we need the anthracyclines for elderly patients with triple negative breast cancer?

Objectives
Triple-negative breast cancer (TNBC) requires chemotherapy-based systemic treatment which is usually anthracycline-based (AB). The cardiotoxicity of AB regimens is especially relevant in the elderly population. Therefore, we retrospectively compared survival and toxicity between elderly patients with early TNBC receiving anthracycline-based or anthracycline-free (AF) adjuvant chemotherapy to evaluate whether elderly patients with TNBC could be spared anthracycline-related toxicity without compromising survival.

Methods
The study population comprised 221 women with TNBC older than 65 years from the SUCCESS A and SUCCESS C studies, who underwent primary surgery and received either AB (3x fluorouracil-epirubicin-cyclophosphamide followed by 3x docetaxel) or AF (6x docetaxel-cyclophosphamide) adjuvant chemotherapy according to a standardized protocol. The two groups were compared regarding clinicopathological parameters (pT, pN, grading, histological subtype, type of surgery, adjuvant radiotherapy) and side effects using chi-square tests, and regarding survival (overall survival, invasive disease-free survival, breast-cancer specific survival, distant disease-free survival) using log-rank tests and cox regressions.

Results
There was no significant difference between the two groups regarding any of the clinicopathological parameters and no significant difference was observed in survival parameters. However, elderly patients with the AB regime had significantly more often grade 3 or 4 adverse events (75.2% vs 50.6%, p < 0.001) during adjuvant chemotherapy than patients with the AF regimen.

Conclusion
In our retrospective analysis of SUCCESS A and C trial, the use of AF chemotherapy in elderly patients with TNBC was associated with similar survival rates but less toxicity compared to AB chemotherapy. Further randomized controlled trials with AF regimen focussing on elderly patients with TNBC are necessary to confirm our results.

目标
三阴性乳腺癌（Triple-negative breast cancer, TNBC）需接受基于化疗的全身治疗，通常为蒽环类药物（anthracycline-based, AB）方案。AB方案的心脏毒性在老年人群中尤为突出。因此，我们回顾性比较了接受AB或无蒽环类药物（anthracycline-free, AF）辅助化疗的早期TNBC老年患者的生存情况与毒性反应，以评估TNBC老年患者是否可在不影响生存的前提下避免蒽环类药物相关毒性。

方法
研究人群包括来自SUCCESS A和SUCCESS C研究的221名65岁以上TNBC女性患者，她们均接受了初始手术，并根据标准化方案接受AB（3周期氟尿嘧啶-表柔比星-环磷酰胺，随后3周期多西他赛）或AF（6周期多西他赛-环磷酰胺）辅助化疗。采用卡方检验（chi-square test）比较两组的临床病理参数（pT、pN、分级、组织学亚型、手术类型、辅助放疗）及副作用；采用对数秩检验（log-rank test）和Cox回归（Cox regression）比较生存指标（总生存期、浸润性无病生存期、乳腺癌特异性生存期、远处无病生存期）。

结果
两组在所有临床病理参数方面均无显著差异，生存指标亦无显著差异。然而，接受AB方案的老年患者在辅助化疗期间发生3级或4级不良事件的比例显著更高（75.2% vs 50.6%，p < 0.001）。

结论
在对SUCCESS A和C试验的回顾性分析中，与AB化疗相比，老年TNBC患者使用AF化疗的生存率相似，但毒性更低。需进一步开展针对老年TNBC患者的AF方案随机对照试验以验证我们的结果。