Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, 08901, USA.
Rutgers Cancer Institute of New Jersey, 195 Little Albany St Room 3553, New Brunswick, NJ, USA.
Breast Cancer Res. 2021 Jan 13;23(1):7. doi: 10.1186/s13058-020-01385-5.
Invasive pleomorphic lobular carcinoma (PLC) of the breast is a subtype of invasive lobular cancer which compromises approximately 1% of all epithelial breast malignancies and is characterized by higher nuclear pleomorphism and poorer prognosis than classic invasive lobular cancer (ILC). Since PLC is more aggressive than classical ILC, we examined the underlying molecular alterations in this subtype of breast cancer to understand the possible benefit from targeted therapies.
In this study, we investigate the clinical characteristics and molecular alterations in 16 PLC from our institution. Additionally, we examined the clinical and genomic features in 31 PLC from the Cancer Genome Atlas (TCGA).
Overall, our analysis of PLC found that 28% had activating ERBB2 mutations, 21% had ERBB2 amplification, and 49% activating PIK3CA mutations. Among cases from our institution, we found 19% with activating ERBB2 mutations, 25% had ERBB2 amplification, and 38% with activating PIK3CA mutations. In data from TCGA, 32% had activating ERBB2 mutations, 19% had ERBB2 amplification, and 55% had activating PIK3CA mutations. While classic ILC in TCGA had similar percentages of PIK3CA alterations compared to PLC, activating ERBB2 alterations were exceedingly rare, with no activating ERBB2 mutations and only one case with ERBB2 amplification. Interestingly, in further examining TCGA data which included FGFR1 and PTEN, 94% of PLC had alterations in ERBB2, FGFR1, or the PI3K pathway.
Our results show a high frequency of ERBB2 and PIK3CA alterations in PLC and suggest all PLC should be tested for potential therapeutic targeting.
乳腺浸润性多形性小叶癌（PLC）是浸润性小叶癌的一种亚型，约占所有上皮性乳腺恶性肿瘤的 1%，其核异型性较高，预后较经典型浸润性小叶癌（ILC）差。由于 PLC 比经典型 ILC 更具侵袭性，我们研究了这种乳腺癌亚型的潜在分子改变，以了解靶向治疗的可能获益。
本研究我们分析了 16 例来自我们机构的 PLC 的临床特征和分子改变。此外，我们还研究了癌症基因组图谱（TCGA）中 31 例 PLC 的临床和基因组特征。
总的来说，我们对 PLC 的分析发现，28%的病例有激活的 ERBB2 突变，21%的病例有 ERBB2 扩增，49%的病例有激活的 PIK3CA 突变。在我们机构的病例中，我们发现 19%的病例有激活的 ERBB2 突变，25%的病例有 ERBB2 扩增，38%的病例有激活的 PIK3CA 突变。在 TCGA 的数据中，32%的病例有激活的 ERBB2 突变，19%的病例有 ERBB2 扩增，55%的病例有激活的 PIK3CA 突变。虽然 TCGA 中的经典型 ILC 与 PLC 相比，PIK3CA 改变的比例相似，但激活的 ERBB2 改变极为罕见，没有激活的 ERBB2 突变，只有一例 ERBB2 扩增。有趣的是，在进一步检查包括 FGFR1 和 PTEN 的 TCGA 数据时，94%的 PLC 存在 ERBB2、FGFR1 或 PI3K 通路的改变。
我们的研究结果表明 PLC 中 ERBB2 和 PIK3CA 改变的频率较高，提示所有 PLC 都应进行潜在治疗靶点的检测。
