在一项早期乳腺癌前瞻性试验中，由70基因和80基因组合特征确定的与年龄无关的术前化疗敏感性及5年预后
Age-Independent Preoperative Chemosensitivity and 5-Year Outcome Determined by Combined 70- and 80-Gene Signature in a Prospective Trial in Early-Stage Breast Cancer.
作者信息
Whitworth Pat, Beitsch Peter D, Pellicane James V, Baron Paul L, Lee Laura A, Dul Carrie L, Nash Charles H, Murray Mary K, Richards Paul D, Gittleman Mark, Budway Raye, Rahman Rakhshanda Layeequr, Kelemen Pond, Dooley William C, Rock David T, Cowan Ken, Lesnikoski Beth-Ann, Barone Julie L, Ashikari Andrew Y, Dupree Beth, Wang Shiyu, Menicucci Andrea R, Yoder Erin B, Finn Christine, Corcoran Kate, Blumencranz Lisa E, Audeh William
机构信息
Nashville Breast Center, Nashville, TN, USA.
Targeted Medical Education, Cupertino, CA, USA.
出版信息
Ann Surg Oncol. 2022 Apr 4;29(7):4141-52. doi: 10.1245/s10434-022-11666-2.
BACKGROUND
The Neoadjuvant Breast Symphony Trial (NBRST) demonstrated the 70-gene risk of distant recurrence signature, MammaPrint, and the 80-gene molecular subtyping signature, BluePrint, precisely determined preoperative pathological complete response (pCR) in breast cancer patients. We report 5-year follow-up results in addition to an exploratory analysis by age and menopausal status.
METHODS
The observational, prospective NBRST (NCT01479101) included 954 early-stage breast cancer patients aged 18-90 years who received neoadjuvant chemotherapy and had clinical and genomic data available. Chemosensitivity and 5-year distant metastasis-free survival (DMFS) and overall survival (OS) were assessed. In a post hoc subanalysis, results were stratified by age (≤ 50 vs. > 50 years) and menopausal status in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) tumors.
RESULTS
MammaPrint and BluePrint further classified 23% of tumors to a different subtype compared with immunohistochemistry, with more precise correspondence to pCR rates. Five-year DMFS and OS were highest in MammaPrint Low Risk, Luminal A-type and HER2-type tumors, and lowest in MammaPrint High Risk, Luminal B-type and Basal-type tumors. There was no significant difference in chemosensitivity between younger and older patients with Low-Risk (2.2% vs. 3.8%; p = 0.64) or High-Risk tumors (14.5% vs. 11.5%; p = 0.42), or within each BluePrint subtype; this was similar when stratifying by menopausal status. The 5-year outcomes were comparable by age or menopausal status for each molecular subtype.
CONCLUSION
Intrinsic preoperative chemosensitivity and long-term outcomes were precisely determined by BluePrint and MammaPrint regardless of patient age, supporting the utility of these assays to inform treatment and surgical decisions in early-stage breast cancer.
背景
新辅助乳腺癌交响乐试验（NBRST）表明，70基因远处复发风险特征检测MammaPrint和80基因分子亚型特征检测BluePrint能够准确判定乳腺癌患者术前病理完全缓解（pCR）情况。我们报告了5年随访结果，并按年龄和绝经状态进行了探索性分析。
方法
前瞻性观察性NBRST（NCT01479101）纳入了954例年龄在18至90岁之间接受新辅助化疗且有临床和基因组数据的早期乳腺癌患者。评估化疗敏感性以及5年无远处转移生存期（DMFS）和总生存期（OS）。在事后亚组分析中，对激素受体阳性/人表皮生长因子受体2阴性（HR+/HER2-）肿瘤患者按年龄（≤50岁与>50岁）和绝经状态进行分层分析。
结果
与免疫组化相比，MammaPrint和BluePrint将23%的肿瘤进一步分类为不同亚型，与pCR率的对应关系更精确。5年DMFS和OS在MammaPrint低风险、管腔A型和HER2型肿瘤中最高，在MammaPrint高风险、管腔B型和基底型肿瘤中最低。低风险（2.2%对3.8%；p = 0.64）或高风险肿瘤（14.5%对11.5%；p = 0.42）的年轻和老年患者之间，或各BluePrint亚型内，化疗敏感性无显著差异；按绝经状态分层时情况类似。各分子亚型的5年结局在年龄或绝经状态方面具有可比性。
结论
无论患者年龄如何，BluePrint和MammaPrint均可准确判定术前内在化疗敏感性和长期结局，支持这些检测方法在早期乳腺癌治疗和手术决策中的应用价值。
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