Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Clin Cancer Res. 2022 Jul 1;28(13):2878-2889. doi: 10.1158/1078-0432.CCR-21-3100.
Metaplastic breast cancer (MpBC) is a rare subtype of breast cancer that is commonly triple-negative and poorly responsive to neoadjuvant therapy in retrospective studies.
To better define clinical outcomes and correlates of response, we analyzed the rate of pathologic complete response (pCR) to neoadjuvant therapy, survival outcomes, and genomic and transcriptomic profiles of the pretreatment tumors in a prospective clinical trial (NCT02276443). A total of 211 patients with triple-negative breast cancer (TNBC), including 39 with MpBC, received doxorubicin-cyclophosphamide-based neoadjuvant therapy.
Although not meeting the threshold for statistical significance, patients with MpBCs were less likely to experience a pCR (23% vs. 40%; P = 0.07), had shorter event-free survival (29.4 vs. 32.2 months, P = 0.15), metastasis-free survival (30.3 vs. 32.4 months, P = 0.22); and overall survival (32.6 vs. 34.3 months, P = 0.21). This heterogeneity is mirrored in the molecular profiling. Mutations in PI3KCA (23% vs. 9%, P = 0.07) and its pathway (41% vs. 18%, P = 0.02) were frequently observed and enriched in MpBCs. The gene expression profiles of each histologically defined subtype were distinguishable and characterized by distinctive gene signatures. Among nonmetaplastic (non-Mp) TNBCs, 10% possessed a metaplastic-like gene expression signature and had pCR rates and survival outcomes similar to MpBC.
Further investigations will determine if metaplastic-like tumors should be treated more similarly to MpBC in the clinic. The 23% pCR rate in this study suggests that patients with MpBC should be considered for NAT. To improve this rate, a pathway analysis predicted enrichment of histone deacetylase (HDAC) and RTK/MAPK pathways in MpBC, which may serve as new targetable vulnerabilities.
化生性乳腺癌（MpBC）是一种罕见的乳腺癌亚型，在回顾性研究中，它通常是三阴性的，对新辅助治疗反应不佳。
为了更好地定义临床结果和反应相关性，我们分析了前瞻性临床试验（NCT02276443）中接受蒽环类药物联合环磷酰胺新辅助治疗的 211 例三阴性乳腺癌（TNBC）患者的病理完全缓解（pCR）率、生存结果以及预处理肿瘤的基因组和转录组特征。包括 39 例 MpBC 患者在内的 211 例 TNBC 患者接受了多柔比星-环磷酰胺为基础的新辅助治疗。
尽管没有达到统计学意义的阈值，但 MpBC 患者的 pCR 率较低（23%对 40%；P=0.07），无事件生存率（29.4 对 32.2 个月，P=0.15）、无转移生存率（30.3 对 32.4 个月，P=0.22）和总生存率（32.6 对 34.3 个月，P=0.21）较短。这种异质性反映在分子谱分析中。PI3KCA 突变（23%对 9%，P=0.07）及其通路（41%对 18%，P=0.02）在 MpBC 中频繁观察到且富集。每种组织学定义的亚型的基因表达谱都是可区分的，并具有独特的基因特征。在非化生性（非-Mp）TNBC 中，10%具有化生性样基因表达特征，pCR 率和生存结果与 MpBC 相似。
进一步的研究将确定在临床上是否应该更类似于 MpBC 来治疗化生性样肿瘤。本研究中 23%的 pCR 率表明，MpBC 患者应考虑接受新辅助治疗。为了提高这一比率，通路分析预测 MpBC 中组蛋白去乙酰化酶（HDAC）和 RTK/MAPK 通路的富集，这可能成为新的靶向弱点。
