Hilbers Florentine S, Poncet Coralie, Tryfonidis Konstantinos, Viale Giuseppe, Delaloge Suzette, Pierga Jean-Yves, Brain Etienne G C, Rubio Isabel T, Thompson Alastair M, Rutgers Emiel J T, Piccart Martine J, van 't Veer Laura J, Cardoso Fatima
Department of Molecular Pathology, Netherlands Cancer Institute, Amsterdam, Netherlands.
European Organization for Research and Treatment of Cancer- EORTC Headquarters, Brussels, Belgium.
NPJ Breast Cancer. 2024 Nov 2;10(1):97. doi: 10.1038/s41523-024-00670-2.
Small, hormone receptor-positive (HR+), HER2-negative (HER2-), lymph node-negative breast cancers are associated with relatively low rates of disease recurrence and have therefore been underrepresented in clinical trials assessing the effects of systemic therapy. Consequently, it remains uncertain if this patient population derives benefit from these treatments. For this exploratory analysis, we selected MINDACT (NCT00433589) patients with a HR+, HER2-, T1ab (≤1 cm) tumor and negative lymph nodes. Patients with discordant clinical risk and MammaPrint genomic risk classification were randmomized to receive chemotherapy based on either the clinical or the genomic risk assessment. Endocrine therapy treatment was based on local guidelines. 715/6693 (10.7%) MINDACT patients had HR+, HER2-, T1abN0 breast cancer and were included in this analysis. All were clinically low-risk, 124/715 (17.3%) were genomic high-risk. For genomic high-risk tumors, 8-year distant metastasis-free survival (DMFS) was 92.9% (95% CI 86.2-96.4%) compared to 95.0% (95% CI 92.8-96.6%) for genomic low-risk tumors. For genomic high-risk tumors treated with or without chemotherapy, 8-year DMFS was 89.2% (95% CI 73.6-95.8%) and 94.1% (95% CI 82.9-98.1%), respectively. For genomic low-risk tumors, the 8-year DMFS and disease-free survival (DFS) were 96.1% (95% CI 93.4-97.6%) and 89.3% (95% CI 85.5-92.2%) when treated with endocrine therapy and 92.9% (95% CI 87.9-95.9%) and 79.4% (95% CI 72.5-84.8%) without. In conclusion, although the number of randomized patients is small, patients with small, genomic high-risk breast cancer did not seem to derive benefit from chemotherapy. Endocrine therapy was associated with improved outcomes even in genomic low-risk breast cancers.
肿瘤较小、激素受体阳性（HR+）、人表皮生长因子受体2阴性（HER2-）、无淋巴结转移的乳腺癌疾病复发率相对较低，因此在评估全身治疗效果的临床试验中代表性不足。因此，尚不确定这一患者群体是否能从这些治疗中获益。在这项探索性分析中，我们选取了MINDACT（NCT00433589）研究中HR+、HER2-、T1ab（≤1 cm）肿瘤且无淋巴结转移的患者。临床风险与MammaPrint基因风险分类不一致的患者被随机分配，根据临床或基因风险评估接受化疗。内分泌治疗依据当地指南进行。715/6693（10.7%）例MINDACT研究患者患有HR+、HER2-、T1abN0乳腺癌，并纳入本分析。所有患者临床风险均为低风险，其中124/715（17.3%）为基因高风险。对于基因高风险肿瘤，8年无远处转移生存率（DMFS）为92.9%（95%CI 86.2-96.4%），而基因低风险肿瘤为95.0%（95%CI 92.8-96.6%）。对于接受或未接受化疗的基因高风险肿瘤，8年DMFS分别为89.2%（95%CI 73.6-95.8%）和94.1%（95%CI 82.9-98.1%）。对于基因低风险肿瘤，接受内分泌治疗时8年DMFS和无病生存率（DFS）分别为96.1%（95%CI 93.4-97.6%）和89.3%（95%CI 85.5-92.2%），未接受内分泌治疗时分别为92.9%（95%CI 87.9-95.9%）和79.4%（95%CI 72.5-84.8%）。总之，尽管随机分组的患者数量较少，但基因高风险的小乳腺癌患者似乎未从化疗中获益。即使在基因低风险的乳腺癌中，内分泌治疗也与更好的预后相关。
