Abstract：
OBJECTIVE: To investigate potential differences in pathological complete response (pCR) rates and overall survival (OS) between HER2-low and HER2-zero patients with early-stage hormone receptor (HR)-positive and triple-negative breast cancer (TNBC), in the neoadjuvant chemotherapy setting.
METHODS: We identified early-stage invasive HER2-negative BC patients who received neoadjuvant chemotherapy diagnosed between 2010 and 2018 in the National Cancer Database. HER2-low was defined by immunohistochemistry (IHC) 1+ or 2+ with negative in situ hybridization, and HER2-zero by IHC0. All the methods were applied separately in the HR-positive and TNBC cohorts. Logistic regression was used to estimate the association of HER2 status with pCR (i.e. ypT0/Tis and ypN0). Kaplan-Meier method and Cox proportional hazards model were applied to estimate the association of HER2 status with OS. Inverse probability weighting and/or multivariable regression were applied to all analyses.
RESULTS: For HR-positive patients, 70.9% (n = 17,934) were HER2-low, whereas 51.1% (n = 10,238) of TNBC patients were HER2-low. For both HR-positive and TNBC cohorts, HER2-low status was significantly associated with lower pCR rates [HR-positive: 5.0% vs. 6.7%; weighted odds ratio (OR) = 0.81 (95% CI: 0.72-0.91), p < 0.001; TNBC: 21.6% vs. 24.4%; weighted OR = 0.91 (95% CI: 0.85-0.98), p = 0.007] and improved OS [HR-positive: weighted hazard ratio = 0.85 (95% CI: 0.79-0.91), p < 0.001; TNBC: weighted hazard ratio = 0.91 (95% CI: 0.86-0.96), p < 0.001]. HER2-low status was associated with favorable OS among patients not achieving pCR [HR-positive: adjusted hazard ratio = 0.83 (95% CI: 0.77-0.89), p < 0.001; TNBC: adjusted hazard ratio = 0.88 (95% CI 0.83-0.94), p < 0.001], while no significant difference in OS was observed in patients who achieved pCR [HR-positive: adjusted hazard ratio = 1.00 (95% CI: 0.61-1.63), p > 0.99; TNBC: adjusted hazard ratio = 1.11 (95% CI: 0.85-1.45), p = 0.44].
CONCLUSIONS: In both early-stage HR-positive and TNBC patients, HER2-low status was associated with lower pCR rates. HER2-zero status might be considered an adverse prognostic factor for OS in patients not achieving pCR.
METHODS: We identified early-stage invasive HER2-negative BC patients who received neoadjuvant chemotherapy diagnosed between 2010 and 2018 in the National Cancer Database. HER2-low was defined by immunohistochemistry (IHC) 1+ or 2+ with negative in situ hybridization, and HER2-zero by IHC0. All the methods were applied separately in the HR-positive and TNBC cohorts. Logistic regression was used to estimate the association of HER2 status with pCR (i.e. ypT0/Tis and ypN0). Kaplan-Meier method and Cox proportional hazards model were applied to estimate the association of HER2 status with OS. Inverse probability weighting and/or multivariable regression were applied to all analyses.
RESULTS: For HR-positive patients, 70.9% (n = 17,934) were HER2-low, whereas 51.1% (n = 10,238) of TNBC patients were HER2-low. For both HR-positive and TNBC cohorts, HER2-low status was significantly associated with lower pCR rates [HR-positive: 5.0% vs. 6.7%; weighted odds ratio (OR) = 0.81 (95% CI: 0.72-0.91), p < 0.001; TNBC: 21.6% vs. 24.4%; weighted OR = 0.91 (95% CI: 0.85-0.98), p = 0.007] and improved OS [HR-positive: weighted hazard ratio = 0.85 (95% CI: 0.79-0.91), p < 0.001; TNBC: weighted hazard ratio = 0.91 (95% CI: 0.86-0.96), p < 0.001]. HER2-low status was associated with favorable OS among patients not achieving pCR [HR-positive: adjusted hazard ratio = 0.83 (95% CI: 0.77-0.89), p < 0.001; TNBC: adjusted hazard ratio = 0.88 (95% CI 0.83-0.94), p < 0.001], while no significant difference in OS was observed in patients who achieved pCR [HR-positive: adjusted hazard ratio = 1.00 (95% CI: 0.61-1.63), p > 0.99; TNBC: adjusted hazard ratio = 1.11 (95% CI: 0.85-1.45), p = 0.44].
CONCLUSIONS: In both early-stage HR-positive and TNBC patients, HER2-low status was associated with lower pCR rates. HER2-zero status might be considered an adverse prognostic factor for OS in patients not achieving pCR.
摘要：
目的：探讨早期激素受体（HR）阳性和三阴性乳腺癌（TNBC）的低HER2和零HER2患者病理完全缓解（pCR）率和总生存期（OS）的潜在差异。在新辅助化疗环境中。
方法：我们在国家癌症数据库中确定了2010年至2018年期间接受新辅助化疗的早期侵袭性HER2阴性BC患者。低HER2通过免疫组织化学（IHC）1+或2+定义，原位杂交阴性，和HER2-零通过IHC0。所有方法分别应用于HR阳性和TNBC队列。使用逻辑回归来估计HER2状态与pCR(即ypT0/Tis和ypN0)的关联。采用Kaplan-Meier法和Cox比例风险模型评估HER2状态与OS的相关性。将逆概率加权和/或多变量回归应用于所有分析。
结果：对于HR阳性患者，70.9%（n=17,934）为低HER2，而51.1%(n=10,238)的TNBC患者HER2低。对于HR阳性和TNBC队列，低HER2状态与较低的pCR率显着相关[HR阳性：5.0％vs.6.7%；加权比值比(OR)=0.81(95%CI：0.72-0.91)，p<0.001；TNBC：21.6%vs.24.4%；加权OR=0.91（95%CI：0.85-0.98），p=0.007]和改进的OS[HR-positive：加权风险比=0.85(95%CI：0.79-0.91)，p<0.001；TNBC：加权风险比=0.91（95%CI：0.86-0.96），p<0.001]。在未达到pCR的患者中，HER2低状态与良好的OS相关[HR-positive:调整后的风险比=0.83(95%CI:0.77-0.89)，p<0.001；TNBC：调整后的风险比=0.88（95%CI0.83-0.94），p<0.001],而在达到pCR[HR阳性：调整后的风险比=1.00（95％CI：0.61-1.63）的患者中，OS没有显着差异，p>0.99；TNBC：调整后的危险比=1.11(95%CI：0.85-1.45)，p=0.44]。
结论：在早期HR阳性和TNBC患者中，低HER2状态与较低的pCR率相关。在未达到pCR的患者中，HER2-零状态可能被认为是OS的不良预后因素。
方法：我们在国家癌症数据库中确定了2010年至2018年期间接受新辅助化疗的早期侵袭性HER2阴性BC患者。低HER2通过免疫组织化学（IHC）1+或2+定义，原位杂交阴性，和HER2-零通过IHC0。所有方法分别应用于HR阳性和TNBC队列。使用逻辑回归来估计HER2状态与pCR(即ypT0/Tis和ypN0)的关联。采用Kaplan-Meier法和Cox比例风险模型评估HER2状态与OS的相关性。将逆概率加权和/或多变量回归应用于所有分析。
结果：对于HR阳性患者，70.9%（n=17,934）为低HER2，而51.1%(n=10,238)的TNBC患者HER2低。对于HR阳性和TNBC队列，低HER2状态与较低的pCR率显着相关[HR阳性：5.0％vs.6.7%；加权比值比(OR)=0.81(95%CI：0.72-0.91)，p<0.001；TNBC：21.6%vs.24.4%；加权OR=0.91（95%CI：0.85-0.98），p=0.007]和改进的OS[HR-positive：加权风险比=0.85(95%CI：0.79-0.91)，p<0.001；TNBC：加权风险比=0.91（95%CI：0.86-0.96），p<0.001]。在未达到pCR的患者中，HER2低状态与良好的OS相关[HR-positive:调整后的风险比=0.83(95%CI:0.77-0.89)，p<0.001；TNBC：调整后的风险比=0.88（95%CI0.83-0.94），p<0.001],而在达到pCR[HR阳性：调整后的风险比=1.00（95％CI：0.61-1.63）的患者中，OS没有显着差异，p>0.99；TNBC：调整后的危险比=1.11(95%CI：0.85-1.45)，p=0.44]。
结论：在早期HR阳性和TNBC患者中，低HER2状态与较低的pCR率相关。在未达到pCR的患者中，HER2-零状态可能被认为是OS的不良预后因素。
