Skip to main content
Download PDF

Clinicopathological features of HER2 positive metastatic colorectal cancer and survival analysis of anti-HER2 treatment

BMC Cancer volume 22, Article number: 355 (2022) Cite this article

Abstract

Background

We aimed to investigate response and prognostic factors in patients with human epidermal growth factor receptor 2 (HER2) positive metastatic colorectal cancer (mCRC) and compare the curative effect on patients who received different therapy regimens (including chemotherapy and chemotherapy combined with targeted drugs).

Methods

We retrospectively analyzed all HER2 positive mCRC patients treated at Peking University Cancer Hospital between September 2011 and February 2021. We divided 63 HER2 positive mCRC into group A and group B according to the use of trastuzumab or not. Besides, we assigned four subgroups according to the first-line therapies of KRAS/NRAS/BRAF WT patients. The Kaplan–Meier estimator was used to calculate PFS and OS. Univariable analysis and Cox proportional hazards models were used to analyze the association between clinicopathological features and survival outcomes.

Results

Among 63 patients, 54 (85.7%) were KRAS/NRAS/BRAF wild-type (WT). Univariate analysis showed that the male sex, primary lesions in the right colon, simultaneous metastasis, and unresectable primary lesions were significant risk factors for poor survival of HER2 positive mCRC (P < 0.05). Using Cox proportional hazards models, we found that the two factors of gender and resection of primary lesions were independent prognostic factors (P < 0.05). The median PFS and median OS of HER2-positive patients with mCRC who received first-line treatment were 8.4 months [95% confidence interval (CI): 5.0–11.7] and 48.2 months (95% CI: 23.5–72.8), respectively. The log-rank test revealed a significant difference in median OS survival between group A and group B (χ2 = 5.852, P = 0.016), and the two groups were divided according to the use or absence of trastuzumab treatment. In KRAS/NRAS/BRAF WT patients, there was a significant difference in median PFS and median OS between the fourth group patients (chemotherapy plus trastuzumab) and each of the other three groups (P < 0.05).

Conclusions

The two factors of gender and resection for primary lesion may be independent prognostic factors of advanced HER2 positive colorectal cancer patients. For patients with HER2-positive mCRC, patients in the chemotherapy combined with trastuzumab group have better efficacy than those without trastuzumab.

Peer Review reports

Introduction

According to a status report on the cancer burden worldwide in 2018, colorectal cancer (CRC) ranks third in incidence and second in mortality [1]. About 30–40% of CRC patients had metastatic disease at the time of initial presentation [2, 3]. A subset of mCRC driven by amplification or mutation of HER2 was detected using functional and genomic analyses of patient-derived xenografts. Amplification of HER2 only accounts for approximately 3% of CRC patients [4, 5], increasing up to 5% in KRAS exon 2 WT tumors and 5.2% in KRAS/BRAF WT patients at stage IV [6, 7]. As the success of targeted therapies fostered the development of specific and effective therapeutics for colorectal malignancies, we should pay more attention to CRC patients with rare mutations. Activation of HER2 is regulated through the heterodimerization with diverse ligand-bound receptors, and previous clinical studies suggest that HER2 and EGFR have causative and progressive roles in tumor development [8]. The antibody trastuzumab was developed as a means of blocking HER2 [9]. Trastuzumab can improve overall survival and progression-free survival in HER2-positive women with metastatic breast cancer. While the relevance of the HER2 therapeutic target has been established, its role as a biomarker for prognosis in CRC remains uncertain. Thus, the role of anti-HER2 targeted therapy in mCRC with HER2 overexpression needs further investigation. Herein, we described the clinicopathological characteristics and treatment outcomes of HER2-positive mCRC and evaluated which patient or tumor-related factors are associated with patient outcomes in a real-life setting.

Materials and methods

Study population

We retrospectively counted 2460 mCRC patients treated at Peking University Cancer Hospital from 01 September 2011 to 19 February 2021, of which 63 were HER2 positive patients. The study was approved by the Institutional Ethics Committee of Peking University Cancer Hospital and signed informed consent was obtained from each participant.

The inclusion criteria for patients were as follows: 1) diagnosis of rectal or colon adenocarcinoma; 2) tumors must be HER2-positive; 3) at least one measurable target lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST); 4) good physical condition with an Eastern Cooperative Oncology Group score of 0 to 2; 5) no diseases of the heart, lung, liver, kidney, and no serious systemic diseases; 6) completed at least two cycles of treatment, including chemotherapy alone, trastuzumab combined with chemotherapy, bevacizumab combined with chemotherapy, or cetuximab combined with chemotherapy; 7) KRAS/NRAS/BRAF genes was detected in pathological samples of primary tumors or metastatic tumors.

HER2 positivity was defined as tumors with a HER2 score of 3+ in ≥50% of cells by immunohistochemistry (IHC), or a HER2 score of 2+ and a HER2:CEP17 ratio ≥ 2 in ≥50% of cells as determined by Fluorescence in Situ Hybridization (FISH). The molecular biomarkers included in the study were the KRAS, NRAS (exons 2, 3, and 4), and BRAF (V600E mutation allele) genes.

Study design

We divided 63 HER2 positive mCRC into group A and group B according to the use of trastuzumab or not. Group A used trastuzumab, while group B did not use trastuzumab. We further divided group A patients into four subgroups, the first-, second-, third-, and fourth-line treatments according to the application time of trastuzumab.

Additionally, we evaluated four subgroups of KRAS/NRAS/BRAF WT patients according to four different first-line therapies: group 1 for chemotherapy alone, group 2 for chemotherapy plus bevacizumab (anti-VEGF), group 3 for chemotherapy plus cetuximab (anti-EGFR), and group 4 for chemotherapy plus trastuzumab (anti-HER2).

Summary of treatments

In this study, patients mainly used single-agent chemotherapy, two-drug combination chemotherapy, and three-drug chemotherapy in each line of treatment. Some patients also used targeted drugs. The single-drug regimen mainly included capecitabine, tegafur, and raltitrexed. The two-drug combination chemotherapy regimens included irinotecan or oxaliplatin-based regimens, such as FOLFIRI, XELIRI, FOLFOX, and XELOX. The three-drug regimen included FOLFOXIRI and XELOXIRI. Targeted drugs mainly include trastuzumab, bevacizumab, and cetuximab.

Evaluation of treatment response

The tumor response was assessed according to Response Evaluation Criteria in Solid Tumors (RECIST, Version 1.1).

Statistical analysis

All data were analyzed using SPSS 26.0 software. Univariate analysis was performed using the log-rank test. Survival curves were generated using Kaplan-Meier estimates, differences between the curves were analyzed by log-rank tests. Multivariable Cox regression models were built for analysis of risk factors for survival outcomes. Statistical significance was set at a two-sided level of P < 0.05.

Results

Clinicopathological features and treatment response of HER2-positive mCRC

Sixty-three well-documented HER2-positive patients with mCRC were included in this study. The median patient age was 54 years (range, 27–78 yr). The median follow-up period was 23.7 (IQR 2.3–63.5) months. Patient pathological features are summarized in Table 1. The chemotherapy regimens in combination with the HER2-targeted treatment are summarized in Table 2. The chemotherapy regimens in KRAS/NRAS/BRAF WT patients of first-line therapies are summarized in Table 3. Treatment response evaluations in patients who received chemotherapy plus trastuzumab are summarized in Table 4.

Table 1 Characteristics of 63 HER2-positive mCRC
Full size table
Table 2 Summary of chemotherapy regimens in combination with the HER2-targeted drugs
Full size table
Table 3 Summary of regimens in 63 patients of first-line therapies
Full size table
Table 4 Treatment response evaluations in patients who received chemotherapy plus trastuzumab
Full size table

Adverse events

According to the Common Terminology Criteria for Adverse Events 3.0 (CTC 3.0), toxic side effects were classified into 1–4 grades. Most of the adverse events in this study were related to chemotherapy drugs. The common toxic side effects of each group are shown in Table 5.

Table 5 Toxic side effects in each group of KRAS/NRAS/BRAF WT patients (N)
Full size table

Survival analysis

The final follow-up for all patients occurred on 19 February 2021. All 63 patients (100%) fulfilled the follow-up criteria, and 25 patients (39.7%) died during the follow-up period because of the progression of the disease. Male, primary lesions in the right colon, simultaneous metastasis, and unresectable primary lesions may be significant risk factors for poor survival in our univariate analysis (Table 6). When multivariate analysis with Cox regression was performed, we found that the two factors of gender and resection for primary lesion may be independent prognostic factors (Table 7).

Table 6 Univariate survival analyses of patients according to various clinicopathological variables
Full size table
Table 7 Multivariate Cox model analyses of prognostic factors
Full size table

The median PFS among all 63 patients with the first-line treatment was 8.4 months [95% CI: 5.0–11.7] and the median OS was 48.2 months (95% CI: 23.5–72.8) with the first-line treatment (Fig. 1). The log-rank test revealed a significant difference in median OS survival between group A (treated with trastuzumab) and B (not treated with trastuzumab) (χ2 = 5.852, P = 0.016) (Fig. 2). There is no significant difference in survival between patients in the first-line treatment group and patients in the second-line and subsequent-line treatment groups (P = 0.203). The differences in survival between patients of the first-, second-, third-, and fourth-line treatment groups were not significant. The corresponding Kaplan-Meier analyses are depicted in Fig. 3.

Fig. 1
figure 1

Kaplan–Meier curves of PFS and OS in patients with the first-line treatment

Full size image
Fig. 2
figure 2

Kaplan–Meier curves of OS in patients who received chemotherapy with or without trastuzumab

Full size image
Fig. 3
figure 3

Kaplan–Meier curves of overall survival in patients who received chemotherapy plus trastuzumab at different lines

Full size image

The median PFS time of KRAS/NRAS/BRAF WT patients with mCRC treated with four different first-line therapies were 6.3 months (95% CI: 2.1–10.5) in group 1 (chemotherapy alone), 8.4 months (95% CI: 6.5–10.2) in group 2 (bevacizumab plus chemotherapy), 6.7 months (95% CI: 1.6–11.8) in group 3 (cetuximab plus chemotherapy), and PFS was not reached in group 4 (trastuzumab plus chemotherapy). The median OS was 41.9 months (95% CI: 28.4–55.4) in group 1 and 50.0 months (95% CI: 3.9–95.9) in group 3. However, OS in group 2 and group 4 was not reached. The log-rank test revealed a significant difference in median PFS survival between group 1 and group 4 (χ2 = 6.308, P = 0.012), group 2 and group 4 (χ2 = 5.021, P = 0.025), group 3 and group 4 (χ2 = 5.302, P = 0.021), respectively. However, there was no significant difference in the median OS between these four groups (P > 0.05 for each comparison). The corresponding Kaplan-Meier analyses are depicted in Fig. 4.

Fig. 4
figure 4

Kaplan–Meier curves of PFS and OS in KRAS/NRAS/BRAF WT patients according to four different first-line therapies

Full size image

Discussion

Herein, among 63 HER2-positive mCRC patients, 54 (85.7%) were KRAS/NRAS/BRAF WT. The primary tumor site was left-sided in 88.9% of patients. This suggests that overexpression of HER2 is more likely to occur in patients with left hemicolorectal cancer and KRAS/NRAS/BRAF WT colorectal cancer. Some previous CRC studies have reported that primary location and KRAS status are related to the amplification of HER2. A previous study retrospectively assessed the prevalence and putative clinicopathological significance of HER2/neu overexpression/amplification in a series of 1645 CRC samples. HER2/neu-positive tumors tended to be more frequent in colon sigmoideum/ rectum than in the ascending/descending colon (18 vs. 6) [10]. In the HERACLES trial, among 27 patients with HER2-positive mCRC, 23 were rectal (7) and distal colon (16), and 4 were proximal colon cancer [6]. In a meta-analysis of mCRC including 1914 stage II-III patients and 1342 stage IV patients, HER2-overexpression was associated with the WT KRAS/BRAF status, where 5.2% of cases showed WT KRAS/BRAF versus only 1.0% containing mutated tumors (P < 0.0001) in stage IV and 2.1% versus 0.2% in stage II–III tumors (P = 0.01), respectively [7].

In univariate analysis, although the sample size was small, it was found that males, primary lesions of the right colon, simultaneous metastasis and unresectable primary lesions may be important risk factors for low survival. Previous retrospective studies on patients with HER2-positive mCRC are relatively lacking. We will continue to collect data from HER2-positive mCRC patients for analysis and further confirmation of the results.

The outcomes of anti-HER2 agents in mCRC are uncertain during the last decade. Ramanathan et al. reported a phase II study of treatment with trastuzumab combined with irinotecan in nine advanced CRC patients overexpressing HER2. 11 of 138 (8.0%) screened tumors (2+ in 5 and 3+ in 6 patients) detected HER2/neu overexpression via IHC. Among 7 evaluable patients, 5 (71%) achieved a partial response to the treatment with trastuzumab and irinotecan. This study further found that irinotecan did not alter the pharmacokinetic activity and effects of trastuzumab. However, the low rate of HER-2/neu overexpression in advanced CRC patients restricted further investigation and caused the premature termination of the study [11]. From Fig. 2 in this study, it can be seen that for patients with HER2-positive mCRC, patients in the chemotherapy combined with trastuzumab group have better efficacy than those without trastuzumab. This result has potential significance for clinical practice. At the same time, it can be seen from Fig. 4 that in the first-line treatment of KRAS/NRAS/BRAF WT patients, chemotherapy combined with trastuzumab seems to be more effective than the regimens of chemotherapy with bevacizumab, chemotherapy with cetuximab, or chemotherapy alone. However, because the sample size of the fourth group is too small, we hope to continue to expand the sample size for further analysis.

In addition, the median PFS of group 3 (cetuximab plus chemotherapy) was shorter compared to that of group 2 (bevacizumab plus chemotherapy) in KRAS/NRAS/BRAF WT mCRC with first-line treatment (6.7 versus 8.4 months). Although not statistically significant, HER2/neu-positive mCRC displayed a tendency to reduce progression-free survival. HER2 amplification as a negative predictor of the response to cetuximab was also proposed in earlier studies [12, 13]. In a retrospective clinical series, Yonesaka et al. evaluated 233 cetuximab-treated patients for the clinical impact of HER2 amplification [14]. Compared to patients without HER2-amplified tumors, those with HER2-amplified tumors exhibited significantly shorter durations for PFS (89 vs. 149 days) and OS (307 vs. 515 days) [14]. Another study analyzing the relationship between HER2 amplification and the efficacy of anti-EGFR monoclonal antibody therapy in RAS and BRAF WT mCRC patients showed that anti-EGFR agent-treated HER2-positive patients (n = 79) showed worsened outcomes compared to patients lacking the anti-EGFR treatment (ORR, 31.2% vs. 46.9%, P = 0.031; PFS, 5.7 months vs. 7 months, P = 0.087) [15].

In patients with HER2-positive mCRC treated with trastuzumab, although the survival rate of patients in the first-line treatment group was not significantly different from that of patients in the second-line and subsequent treatment groups, However, it can be seen from Fig. 3 that the efficacy of the first-line treatment group has a better trend than that of the second-line and subsequent treatment groups. Due to the small sample size, we hope to expand the sample size in the future to further clarify whether the early application of anti-HER2 drugs will achieve better efficacy.

The prognostic role of HER2 in mCRC remained uncertain until now. In this study, the median PFS of each group was shorter than that reported in previous studies. 1.6% of cases were found to be HER2/neu positive in a previous study that examined 1645 cases of primary colorectal carcinoma [10]. Furthermore, this study revealed that HER2/neu positivity was significantly correlated with advanced lymph node metastases and Union for International Cancer Control (UICC) stages [10]. Concerning long-term implications, HER2/neu-positive colorectal carcinomas are significantly correlated with reduced OS [16]. These results indicated that there may be a negative prognostic association between HER2 amplification and the KRAS/NRAS/BRAF WT status in advanced CRC patients undergoing first-line treatment.

Although the US FDA has not approved any anti-HER2 therapies for the treatment of mCRC so far, the first-generation anti-HER2 molecules such as trastuzumab (Herceptin), lapatinib (Tykerb) and Pertuzumab (Perjeta) Has become the subject of many studies. In preclinical therapeutic trials, Bertotti et al. genetically characterized a large xenograft cohort of mCRC samples (“xenopatients”) to reveal new oncoprotein targets and factors that contribute to therapeutic responses [13]. Patient-derived mCRC xenografts exhibiting HER2 amplification were sensitive to pertuzumab or cetuximab HER2 inhibition in combination with lapatinib, but treatment with pertuzumab alone or in combination with cetuximab had no effect [13]. These data support the development of clinical methods that target HER2 amplification in mCRC. HERACLES-A, a multicentre, open-label, phase II trial, aimed to provide proof of concept for the antitumor activity of trastuzumab and lapatinib in HER2-positive CRC patients [6]. Adult patients possessing the WT KRAS exon 2 (codons 12 and 13) and HER2-positive refractory mCRC were enrolled into a standard of care protocol including cetuximab or panitumumab. IHC and FISH were used to verify patient HER2 status using established CRC-specific diagnostic criteria. Of 914 patients with WT KRAS exon 2 (codons 12 and 13) mCRC, and 48 patients (5%) with HER2-positive tumors were identified. Among 27 evaluable patients, one, seven, and 12 patients exhibited a complete response, a partial response, and stable disease, respectively. The ORR was 30% and the median OS was 46 weeks. HERACLES-B, a single-arm phase II trial, assessed the efficacy of combined pertuzumab and trastuzumab emtansine (T-DM1) treatment [17]. Among 31 evaluable patients, three and 21 patients exhibited a partial response and disease stabilization, respectively. Finally, the phase IIa multiple basket study MyPathway assessed the activity of a combination of pertuzumab and trastuzumab in HER2-amplified mCRC patients [18]. Among 57 patients with HER2-amplified mCRC, only one patient showed a complete response and 17 had partial responses. Thus, 18 (32%) patients in total achieved a marked response, but further work is needed to develop drugs and drug combinations effective against HER2-amplified mCRC. Dual HER2 inhibition with trastuzumab plus lapatinib or pertuzumab has shown promising preliminary anti-tumoral efficacy in RAS wild-type mCRC. For a limited subgroup (around 5%) of mCRC patients refractory to chemotherapy drugs and anti-EGFR-targeted drugs such as cetuximab and panitumumab, targeting HER2 represents an additional but valuable therapeutic strategy. When applying HER2 blockers in this situation, studies have shown that dual HER2 blockers have advantages [19].

In conclusion, the anti-HER2 targeting drug (trastuzumab) combined with chemotherapy achieved a better therapeutic effect in comparison to other agents in this study, especially in the first and second-line treatment for advanced HER2 positive colorectal cancer. From this retrospective analysis, it can be seen that anti-HER-2 targeted therapy has achieved good results in patients with HER-2 positive colorectal cancer, and it is worthy of further prospective randomized controlled studies.

Availability of data and materials

All data generated or analysed during this study are included in this published article.

References

  1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424. https://doi.org/10.3322/caac.21492 Epub 2018 Sep 12. Erratum in: CA Cancer J Clin. 2020;70(4):313. PMID: 30207593.

    Article  PubMed  Google Scholar 

  2. Jiang X, Yuan YP, Xu DT, Zhang B, Liu YL. Influences of diagnostic modes on an early diagnosis of colorectal cancer. Zhonghua Yi Xue Za Zhi. 2011;91(41):2886–90 Chinese. PMID: 22333606.

    PubMed  Google Scholar 

  3. Moreno CC, Mittal PK, Sullivan PS, Rutherford R, Staley CA, Cardona K, et al. Colorectal Cancer initial diagnosis: screening colonoscopy, diagnostic colonoscopy, or emergent surgery, and tumor stage and size at initial presentation. Clin Colorectal Cancer. 2016;15(1):67–73. https://doi.org/10.1016/j.clcc.2015.07.004 Epub 2015 Jul 29. PMID: 26602596.

  4. Kavanagh DO, Chambers G, O'Grady L, Barry KM, Waldron RP, Bennani F, et al. Is overexpression of HER-2 a predictor of prognosis in colorectal cancer? BMC Cancer. 2009;1(9):1. https://doi.org/10.1186/1471-2407-9-1 PMID: 19118499; PMCID: PMC2648993.

  5. Ross JS, Fakih M, Ali SM, Elvin JA, Schrock AB, Suh J, et al. Targeting HER2 in colorectal cancer: The landscape of amplification and short variant mutations in ERBB2 and ERBB3. Cancer. 2018;124(7):1358–73. https://doi.org/10.1002/cncr.31125 Epub 2018 Jan 16. PMID: 29338072; PMCID: PMC5900732.

  6. Sartore-Bianchi A, Trusolino L, Martino C, Bencardino K, Lonardi S, Bergamo F, et al. Dual-targeted therapy with trastuzumab and lapatinib in treatment-refractory, KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer (HERACLES): a proof-of-concept, multicentre, open-label, phase 2 trial. Lancet Oncol. 2016;17(6):738–46. https://doi.org/10.1016/S1470-2045(16)00150-9. Epub 2016 Apr 20. Erratum in: Lancet Oncol. 2016(10):e420. PMID: 27108243.

  7. Richman SD, Southward K, Chambers P, Cross D, Barrett J, Hemmings G, et al. HER2 overexpression and amplification as a potential therapeutic target in colorectal cancer: analysis of 3256 patients enrolled in the QUASAR, FOCUS and PICCOLO colorectal cancer trials. J Pathol. 2016;238(4):562–70. https://doi.org/10.1002/path.4679 Epub 2016 Jan 29. PMID: 26690310; PMCID: PMC4785607.

  8. Hynes NE, Lane HA. ERBB receptors and cancer: the complexity of targeted inhibitors. Nat Rev Cancer. 2005;5(5):341–54. https://doi.org/10.1038/nrc1609 Erratum in: Nat Rev Cancer 2005;5(7):580. PMID: 15864276.

  9. Coussens L, Yang-Feng TL, Liao YC, Chen E, Gray A, McGrath J, et al. Tyrosine kinase receptor with extensive homology to EGF receptor shares chromosomal location with neu oncogene. Science. 1985;230(4730):1132–9. https://doi.org/10.1126/science.2999974 PMID: 2999974.

  10. Ingold Heppner B, Behrens HM, Balschun K, Haag J, Krüger S, Becker T, et al. HER2/neu testing in primary colorectal carcinoma. Br J Cancer. 2014;111(10):1977–84. https://doi.org/10.1038/bjc.2014.483 Epub 2014 Sep 11. PMID: 25211663; PMCID: PMC4229629.

  11. Ramanathan RK, Hwang JJ, Zamboni WC, Sinicrope FA, Safran H, Wong MK, et al. Low overexpression of HER-2/neu in advanced colorectal cancer limits the usefulness of trastuzumab (Herceptin) and irinotecan as therapy. A phase II trial. Cancer Invest. 2004;22(6):858–65. https://doi.org/10.1081/cnv-200039645 PMID: 15641483.

  12. Bertotti A, Papp E, Jones S, Adleff V, Anagnostou V, Lupo B, et al. The genomic landscape of response to EGFR blockade in colorectal cancer. Nature. 2015;526(7572):263–7. https://doi.org/10.1038/nature14969 Epub 2015 Sep 30. PMID: 26416732; PMCID: PMC4878148.

  13. Bertotti A, Migliardi G, Galimi F, Sassi F, Torti D, Isella C, et al. A molecularly annotated platform of patient-derived xenografts (“xenopatients”) identifies HER2 as an effective therapeutic target in cetuximab-resistant colorectal cancer. Cancer Discov. 2011;1(6):508–23. https://doi.org/10.1158/2159-8290.CD-11-0109 Epub 2011 Sep 2. PMID: 22586653.

  14. Yonesaka K, Zejnullahu K, Okamoto I, Satoh T, Cappuzzo F, Souglakos J, et al. Activation of ERBB2 signaling causes resistance to the EGFR-directed therapeutic antibody cetuximab. Sci Transl Med. 2011;3(99):99ra86. https://doi.org/10.1126/scitranslmed.3002442. PMID: 21900593; PMCID: PMC3268675.

  15. Sartore-Bianchi A, Amatu A, Porcu L, Ghezzi S, Lonardi S, Leone F, et al. HER2 positivity predicts unresponsiveness to EGFR-targeted treatment in metastatic colorectal cancer. Oncologist. 2019;24(10):1395–402. https://doi.org/10.1634/theoncologist.2018-0785 Epub 2019 Apr 5. PMID: 30952821; PMCID: PMC6795149.

  16. Wang XY, Zheng ZX, Sun Y, Bai YH, Shi YF, Zhou LX, et al. Significance of HER2 protein expression and HER2 gene amplification in colorectal adenocarcinomas. World J Gastrointest Oncol. 2019;11(4):335–47. https://doi.org/10.4251/wjgo.v11.i4.335 PMID: 31040898; PMCID: PMC6475672.

  17. Sartore-Bianchi A, Lonardi S, Martino C, Fenocchio E, Tosi F, Ghezzi S, et al. Pertuzumab and trastuzumab emtansine in patients with HER2-amplified metastatic colorectal cancer: the phase II HERACLES-B trial. ESMO Open. 2020;5(5):e000911. https://doi.org/10.1136/esmoopen-2020-000911 PMID: 32988996; PMCID: PMC7523198.

  18. Meric-Bernstam F, Hurwitz H, KPS R, McWilliams RR, Fakih M, VanderWalde A, et al. Pertuzumab plus trastuzumab for HER2-amplified metastatic colorectal cancer (MyPathway): an updated report from a multicentre, open-label, phase 2a, multiple basket study. Lancet Oncol. 2019;20(4):518–30. https://doi.org/10.1016/S1470-2045(18)30904-5 Epub 2019 Mar 8. PMID: 30857956; PMCID: PMC6781620.

  19. Bitar L, Zouein J, Haddad FG, Eid R, Kourie HR. HER2 in metastatic colorectal cancer: a new to target to remember. Biomark Med. 2021;15(2):133–6. https://doi.org/10.2217/bmm-2020-0491 Epub 2021 Jan 14. PMID: 33442995.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

Not applicable.

Funding

This work was supported by Beijing Hospitals Authority Clinical Medicine Development of Special Funding Support, code: (ZYLX202116).

Author information

Authors and Affiliations

  1. Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Fu-Cheng Road 52, Hai-Dian District, Beijing, 100142, China

    Liu Yang, Wenfei Li, Zhihao Lu, Ming Lu, Jun Zhou, Zhi Peng, Xiaotian Zhang, Xicheng Wang, Lin Shen & Jian Li

  2. Department of oncology, People’s Hospital of Zhongmu, Zhengzhou, 451450, Henan Province, China

    Liu Yang

Authors
  1. Liu Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wenfei Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zhihao Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ming Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jun Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Zhi Peng
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Xiaotian Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Xicheng Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Lin Shen
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Jian Li
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Liu Yang performed the data analyses and wrote the manuscript. Jian Li contributed significantly to analysis and manuscript preparation. Zhihao Lu, Wenfei Li, Ming Lu, Jun Zhou, Zhi Peng, Xiaotian Zhang, Xicheng Wang, and Lin Shen helped perform the analysis with constructive discussions. The author(s) read and approved the final manuscript.

Corresponding author

Correspondence to Jian Li.

Ethics declarations

Ethics approval and consent to participate

The experimental protocol was established according to the ethical guidelines of the Helsinki Declaration and was approved by the Human Ethics Committee of Peking University Cancer Hospital. Written informed consent was obtained from individual or guardian participants.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yang, L., Li, W., Lu, Z. et al. Clinicopathological features of HER2 positive metastatic colorectal cancer and survival analysis of anti-HER2 treatment. BMC Cancer 22, 355 (2022). https://doi.org/10.1186/s12885-022-09447-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s12885-022-09447-x

Keywords

BMC Cancer

ISSN: 1471-2407

Contact us