Leon-Ferre Roberto A, Dimitroff K, Yau C, Giridhar K V, Mukhtar R, Hirst G, Hylton N, Perlmutter J, DeMichele A, Yee D, van 't Veer L, Rugo H, Symmans W F, Goetz M P, Esserman L, Boughey J C
Mayo Clinic Comprehensive Cancer Center, Rochester, MN, USA.
Department of Oncology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
Breast Cancer Res. 2025 Jun 23;27(1):115. doi: 10.1186/s13058-025-02070-1.
Operable triple-negative (TNBC) and HER2-positive breast cancer are often treated with neoadjuvant systemic therapy (NAST). NAST response is highly prognostic, with pathologic complete response (pCR) being associated with low risk of recurrence or death. In contrast, residual disease (RD) after NAST is associated with higher risks and is an indication for escalated postoperative therapy. Recent studies suggest that tumor (T) size and nodal (N) status at diagnosis influence clinical outcomes independent of NAST response. We evaluated the impact of initial clinical stage on clinical outcomes according to response to NAST in I-SPY2.
Patients with stage II or III TNBC or HER2-positive breast cancer treated on the I-SPY2 trial (NCT01042379) with required data on clinical T size and N status prior to NAST, residual cancer burden (RCB) index, recurrence and survival were included. Survival outcomes, including event-free (EFS), distant recurrence-free (DRFS), and overall survival (OS), were assessed using multivariable Cox proportional hazard models.
Among 1,033 patients (TNBC: 638, HER2-positive: 395), the median follow-up was 4.4 years (range 0.3-10.2). 47% achieved pCR (TNBC: 44%, HER2-positive: 51%). Smaller baseline T size, but not N status, was associated with higher pCR rates. However, in those not achieving pCR, RCB class was correlated with both baseline T size and N status in TNBC, and with baseline N status (but not T size) in HER2-positive. Among patients with RD, larger baseline T size was independently associated with worse EFS and DRFS in TNBC and HER2-positive, and with OS in TNBC; while N status was associated with EFS and DRFS in TNBC on univariate analysis only. We did not identify an association between baseline T size or N status and outcomes in patients achieving pCR.
Tumor size at diagnosis remained an independent prognostic factor in patients with TNBC and HER2-positive breast cancer with RD after NAST. In contrast, patients achieving pCR had excellent outcomes regardless of initial disease extent, supporting the relevance of pCR as a surrogate endpoint in breast cancer.
I-SPY 2 TRIAL beginning December 31, 2009: Neoadjuvant and Personalized Adaptive Novel Agents to Treat Breast Cancer (I-SPY 2), NCT01042379.
可手术切除的三阴性（TNBC）和人表皮生长因子受体2（HER2）阳性乳腺癌通常采用新辅助全身治疗（NAST）。NAST反应具有高度预后价值，病理完全缓解（pCR）与低复发或死亡风险相关。相比之下，NAST后的残留疾病（RD）与更高风险相关，是强化术后治疗的指征。最近的研究表明，诊断时的肿瘤（T）大小和淋巴结（N）状态独立于NAST反应影响临床结局。我们在I-SPY2研究中评估了初始临床分期对根据NAST反应的临床结局的影响。
纳入在I-SPY2试验（NCT01042379）中接受治疗的II期或III期TNBC或HER2阳性乳腺癌患者，这些患者具有NAST前临床T大小和N状态、残留癌负担（RCB）指数、复发和生存的所需数据。使用多变量Cox比例风险模型评估生存结局，包括无事件生存（EFS）、远处无复发生存（DRFS）和总生存（OS）。
在1033例患者中（TNBC：638例，HER2阳性：395例），中位随访时间为4.4年（范围0.3 - 10.2年）。47%的患者达到pCR（TNBC：44%，HER2阳性：51%）。基线T大小较小而非N状态与较高的pCR率相关。然而，在未达到pCR的患者中，TNBC的RCB分级与基线T大小和N状态均相关，而HER2阳性患者中与基线N状态（而非T大小）相关。在有RD的患者中，基线T大小较大在TNBC和HER2阳性患者中与较差的EFS和DRFS独立相关，在TNBC中与OS相关；而N状态仅在单变量分析中与TNBC的EFS和DRFS相关。我们未发现基线T大小或N状态与达到pCR的患者结局之间存在关联。
诊断时的肿瘤大小在NAST后有RD的TNBC和HER2阳性乳腺癌患者中仍然是一个独立的预后因素。相比之下，达到pCR的患者无论初始疾病范围如何都有良好的结局，支持pCR作为乳腺癌替代终点的相关性。
I-SPY 2试验于2009年12月31日开始：新辅助和个性化适应性新型药物治疗乳腺癌（I-SPY 2），NCT01042379。
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