Fraga Teresa, de Sousa Maria João, Magalhães Joana, Basto Raquel, Paulo Judy, Bonito Nuno, Magalhães José Paulo, Figueiredo Paulo, Sousa Gabriela M
Medical Oncology, Instituto Português de Oncologia de Coimbra Francisco Gentil, Coimbra, PRT.
Medical Oncology, Centro Hospitalar Universitário do Porto, Porto, PRT.
Cureus. 2023 Jul 27;15(7):e42536. doi: 10.7759/cureus.42536. eCollection 2023 Jul.
Colorectal cancer (CRC) is the second-most deadly cancer worldwide. However, there remains a scarcity of precision treatments available for this type of cancer. Amplification or overexpression of human epidermal growth factor receptor 2 (HER2+) is a well-established therapeutic target in gastric and breast cancer. HER2 is positive in approximately 5% of CRC cases and has been implicated in resistance to therapy with anti-epidermal growth factor receptor antibodies. The aim of this study was to evaluate HER2 status in RAS and BRAF wild-type metastatic CRC (mCRC) and its correlation with survival outcomes.
A single-center retrospective analysis of RAS and BRAF wild-type mCRC patients undergoing systemic treatment was conducted from July 2014 to September 2020. Tissue HER2 status was determined by immunohistochemistry (IHC) and/or fluorescence in situ hybridization (FISH) and/or chromogenic in situ hybridization (CISH). HER2+ was defined as IHC3 (+) or IHC2 (+) through FISH or CISH (+).
Fifty-nine patients were included. The median age of all the included patients was 64 years (33-82). Four patients had HER2+ tumors (7%). Four patients had HER2+ tumors (7%). The majority of HER2+ mCRC cases were males (n=3) and left-sided CRC (n=3). All patients received FOLFIRI plus cetuximab as first-line treatment. At the median follow-up of 24.0 months, patients with HER2-negative mCRC presented with a median overall survival (mOS) of 39.4 months (95% confidence interval (CI) 32.7-46.0) and the four patients with HER2+ mCRC had a mOS of 20.4 months (95% CI; 9.5-31.3; p=0.07). In HER2-negative patients, the median PFS (mPFS) was 11.3 months (95% CI; 9.2-13.4) vsHER2-positive patients with a mPFS of 10.9 months (95% CI; 1.3-20.4; p=0.47).
To our knowledge, this is the first study reporting HER2+ in mCRC patients in a Portuguese population and the HER2+ rate was consistent with previous studies. Our study suggests that HER2+ may potentially be a marker that is able to predict poor prognosis in RAS and BRAF wild-type mCRC.
结直肠癌（CRC）是全球第二大致死性癌症。然而，针对这类癌症的精准治疗方法仍然匮乏。人表皮生长因子受体2（HER2+）的扩增或过表达是胃癌和乳腺癌中已确立的治疗靶点。HER2在约5%的CRC病例中呈阳性，并与抗表皮生长因子受体抗体治疗的耐药性有关。本研究的目的是评估RAS和BRAF野生型转移性结直肠癌（mCRC）中的HER2状态及其与生存结果的相关性。
对2014年7月至2020年9月接受全身治疗的RAS和BRAF野生型mCRC患者进行单中心回顾性分析。通过免疫组织化学（IHC）和/或荧光原位杂交（FISH）和/或显色原位杂交（CISH）确定组织HER2状态。HER2+定义为IHC3（+）或通过FISH或CISH（+）检测为IHC2（+）。
纳入59例患者。所有纳入患者的中位年龄为64岁（33 - 82岁）。4例患者的肿瘤为HER2+（7%）。大多数HER2+ mCRC病例为男性（n = 3）且为左侧结直肠癌（n = 3）。所有患者均接受FOLFIRI联合西妥昔单抗作为一线治疗。在中位随访24.0个月时，HER2阴性mCRC患者的中位总生存期（mOS）为39.4个月（95%置信区间（CI）32.7 - 46.0），4例HER2+ mCRC患者的mOS为20.4个月（95% CI；9.5 - 31.3；p = 0.07）。在HER2阴性患者中，中位无进展生存期（mPFS）为11.3个月（95% CI；9.2 - 13.4），而HER2阳性患者的mPFS为10.9个月（95% CI；1.3 - 20.4；p = 0.47）。
据我们所知，这是第一项报道葡萄牙人群中mCRC患者HER2+情况的研究，HER2+率与先前研究一致。我们的研究表明，HER2+可能潜在地是一种能够预测RAS和BRAF野生型mCRC预后不良的标志物。
