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Objective: To explore the difference in efficacy and safety of pyrotinib or lapatinib combined with chemotherapy in human epidermal growth factor receptor-2 (HER-2) positive breast cancer patients who failed the first-line trastuzumab-containing treatment., Methods: The present retrospective study included 164 HER-2 positive breast cancer patients admitted to our hospital. Among them, 68 cases received pyrotinib combined with chemotherapy after the failure of trastuzumab first-line treatment (pyrotinib group), and the other 96 cases received lapatinib combined chemotherapy (lapatinib group). The end of the follow-up time was set as June 1, 2020. The primary endpoint was progression free survival (PFS), and the secondary endpoints included best objective response rate (ORR) and safety., Results: Till the end of the follow-up, the best ORR (60.3% vs. 34.4%) in the pyrotinib group was significantly higher than that in the lapatinib group, and the median PFS (9.0 months vs. 6.2 months) was also largely prolonged (P<0.01). In addition, the median PFS of the patients with brain metastases in the pyrotinib group was 6.5 months, and was much longer that in the lapatinib group which wereth 3.5 months in length (P<0.05). Multivariate COX regression analysis showed that pyrotinib combined with chemotherapy (HR=0.653, P<0.05) was associated with longer PFS of patients, while the lapatinib group had a higher proportion of vomiting and hand foot syndrome than the pyrotinib group (P<0.05)., Conclusion: After the failure of first-line trastuzumab-containing treatment, combination of pyrotinib with chemotherapy has more significant short-term efficacy in HER-2 positive breast cancer patients than lapatinib combined with chemotherapy, especially in patients with brain metastasis., Competing Interests: None., (AJTR Copyright © 2021.)

Background: As a novel irreversible pan-ErbB inhibitor recently approved in China, pyrotinib has exhibited promising anticancer efficacy and acceptable safety profile in HER2-positive metastatic breast cancer (mBC). The aim of this retrospective study was to estimate the efficacy and safety of pyrotinib treatment in Chinese mBC patients., Methods: We retrospectively reviewed the real-world clinicopathological and treatment data of HER2-positive mBC patients receiving pyrotinib-based treatment from August 2018 to July 2019 in Qilu Hospital of Shandong University and other medical centers of Shandong Province in China., Results: A total of 64 patients treated with pyrotinib were included for analysis, and the median follow-up duration was 260 days (interquartile range, 199.0 to 339.0 days). Fifty-nine (92.2%) patients had been previously treated with trastuzumab and/or T-DM1, while 11 (17.2%) patients had been exposed to lapatinib. The objective response rate (ORR) of all patients was 73.4%, and the disease control rate (DCR) was 98.4%, with a clinical benefit rate (CBR) of 87.5%. Patients with exposure to lapatinib responded well to pyrotinib-based treatment, although the ORR was significantly lower compared with that of patients without exposure to lapatinib (44.1% vs 77.5%, p =0.037). Previous lapatinib exposure was negatively associated with the objective response of pyrotinib treatment (odds ratio [OR]=0.248, 95% confidence interval [CI] 0.063-0.970, p =0.045). The median progression-free survival (mPFS) for patients with previous lapatinib exposure and patients with visceral metastasis was 299 days (95% CI 240.1-357.9 days) and 359 days (95% CI 258.3-459.7 days), respectively. But the mPFS of the whole cohort has not been reached until the cut-off date. Cox multivariate analysis revealed that only visceral metastasis was an independent predictor of significantly shorter PFS ( p =0.041) but not previous exposure to lapatinib ( p =0.092). Diarrhea (28.1%), hand-foot syndrome (17.2%), and neutropenia (9.4%) were the most common grade 3 adverse events associated with pyrotinib treatment., Conclusion: Pyrotinib is highly beneficial to HER2-positive metastatic breast cancer patients, even in patients with previous lapatinib exposure. Pyrotinib is a feasible replacement of lapatinib in combination with chemotherapeutic drugs or as a monotherapy. Adverse effects are tolerable and easily manageable., Competing Interests: The authors report no conflicts of interest for this work., (© 2021 Sun et al.)

• A population pharmacokinetic model of pyrotinib was developed for the first time. • Montmorillonite coadministration can decrease pyrotinib's bioavailability by 50.3%. • Total protein and age have limited impact on the pharmacokinetic of pyrotinib. Pyrotinib, a new oral irreversible pan-ErbB tyrosine kinase inhibitor (TKI), has been approved in China for the treatment of HER2-positive advanced or metastatic breast cancer. This study aimed to conduct a population pharmacokinetics (PK) analysis of pyrotinib and to evaluate the impact of patient characteristics on pyrotinib's PK. A total of 1152 samples, provided by 59 adult female patients from two phase I clinical trials, were analyzed by nonlinear mixed-effects modeling. Monte Carlo simulation was conducted to assess impact of covariates on the exposure to pyrotinib. The PK of pyrotinib was adequately described by a one-compartment model with first-order absorption and elimination. Patient's age and total protein levels could affect pyrotinib's apparent volume of distribution, and concomitant use of montmorillonite could decrease the bioavailability of pyrotinib by 50.3%. No PK interactions were observed between capecitabine and pyrotinib. In this study, a population PK model of pyrotinib was developed to determine the influence of patient characteristics on the PK of pyrotinib. While patient age and total protein levels can significantly affect the apparent distribution volume of pyrotinib, the magnitude of the impact was limited, thus no dosage adjustment was recommended. Furthermore, concomitant use of montmorillonite for diarrhea needs to be taken with precaution. Image, graphical abstract [ABSTRACT FROM AUTHOR]

Human epidermal growth factor receptor 2 ( HER2 ) amplification or activating mutations are found in 1.6%-4% of non-small cell lung cancer (NSCLC). Pyrotinib has been reported to have better potency in NSCLC patients with HER2 exon 20 insertion (ex20ins) mutations; however, more clinical evidence is urgently needed to guide pyrotinib-based therapy in NSCLC with HER2 amplification or heterogeneous mutations. We retrospectively analyzed advanced NSCLC patients with HER2 amplification or mutations who were treated with pyrotinib-based therapy between September 25, 2018 and October 30, 2020 in our hospital. Molecular dynamics simulation was used to explore the bioactive conformation and binding mechanisms of pan- ErbB tyrosine kinase inhibitors (TKIs) including pyrotinib for different HER2 ex20ins variants. In this study, 79 eligible patients were included with 70 ex20ins variants, 6 missense mutations and 3 primary HER2 amplifications identified. A775&#95;G776insYVMA insertion was the most common observed subtype. The median progression-free survival (mPFS) was 5.8 (95% CI: 4.1-7.4) months. Use of pyrotinib-based therapy in first-/second-line settings showed a significantly better prognosis than that observed in third-line settings or above (mPFS: 9.1 vs. 4.4 months; P  = 0.0003). Compared with HER2 amplification and exon 20 non-YVMA insertion variants, patients with HER2 missense mutations had a visible mPFS benefit (12.2 vs. 6.8 vs. 5.2 months). Computational docking simulations revealed that pyrotinib failed to interact with the specific insertion variant P780&#95;Y781insGSP. These results indicated that pyrotinib-based therapy exhibited good anti-tumor activity and acceptable safety profile in HER2 -altered advanced NSCLC., (© 2021 Chinese National Cancer Center. Published by Elsevier B.V.)

Breast cancer patients with synchronous contralateral axillary lymph node metastasis (CAM) are very rare, and there is a lack of published treatment guidelines for this kind of patients. We presented a human epidermal growth factor receptor 2 (HER-2)-positive breast cancer case, who was diagnosed as CAM with primary trastuzumab resistance. In this case report, we describes a 47-year-old woman diagnosed with HER-2 positive breast cancer with regional lymph nodes metastasis. However, physical examination identified contralateral axillary lymph nodes, the auxiliary inspection did not assist in determining the nature of the right axillary lymph nodes, and there was no obvious mass in the right breast. Hence, we performed the core needle biopsy on the right axillary lymph node, which revealed the presence of metastatic breast adenocarcinoma. The patient received trastuzumab-based treatment, but this only afforded a progression-free survival of 5 months, owing to primary trastuzumab resistance. She was then successfully treated with pyrotinib, and the outcome was close to clinical complete response (CCR) with a progression-free survival of over 27 months thus far. This case report may help inform clinicians in the diagnosis of breast cancer with CAM and offer the treatment options in HER-2-positive metastasis breast cancer with primary trastuzumab resistance.

Pyrotinib (PYR) is a pan-HER kinase inhibitor that inhibits signaling via the RAS/RAF/MEK/MAPK and PI3K/AKT pathways. In this study, we aimed to investigate the antitumor efficacy of pyrotinib combined with adriamycin (ADM) and explore its mechanisms on HER2 + breast cancer. We investigated the effects of PYR and ADM on breast cancer in vitro and in vivo . MTT assay, Wound-healing, and transwell invasion assays were used to determine the effects of PYR, ADM or PYR combined with ADM on cell proliferation, migration, and invasion of SK-BR-3 and AU565 cells in vitro . Cell apoptosis and cycle were detected through flow cytometry. In vivo , xenograft models were established to test the effect of PYR, ADM, or the combined therapy on the nude mice. Western blotting was performed to assess the expression of Akt, p-Akt, p-65, p-p65, and FOXC1. The results indicated that PYR and ADM significantly inhibited the proliferation, migration, and invasion of SK-BR-3 and AU565 cells, and the inhibitory rate of the combination group was higher than each monotherapy group. PYR induced G1 phase cell-cycle arrest, while ADM induced G2 phase arrest, while the combination group induced G2 phase arrest. The combined treatment showed synergistic anticancer activities. Moreover, PYR significantly downregulated the expression of p-Akt, p-p65, and FOXC1. In clinical settings, PYR also exerts satisfactory efficacy against breast cancer. These findings suggest that the combination of PYR and ADM shows synergistic effects both in vitro and in vivo . PYR suppresses the proliferation, migration, and invasion of breast cancers through down-regulation of the Akt/p65/FOXC1 pathway., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wang, Deng, Chen, Xu, Hu, Kong, Liang, Yuan, Li and Wang.)

Background: HER2 transmembrane domain (TMD) mutation has been reported as a rare driver mutation associated with advanced stage disease and a poor prognosis in patients with lung adenocarcinoma (LUAD). We aimed to comprehensively profile the genetic landscape and treatment response information of HER2 TMD-mutant LUAD., Methods: An in-house database of 7,812 LUAD patients was screened for mutation prevalence. A multi-center cohort of 16 HER2 V659E-mutant patients and an external cohort of 38 HER2 -mutant patients from cBioPortal with overall survival (OS) data were analyzed. Eight patients from the in-house cohort were included in the real-world study of treatment response. Molecular docking simulation and binding affinity prediction were performed., Results: In Chinese LUAD, the prevalence of HER2 TMD mutation was 0.18% (14/7,812), and 0.14% (11/7,812) for the HER2 V659E mutation. The most recurrent co-alteration was TP53 mutation (n=4, 25%) and HER2 amplification (n=2, 12.5%). TMD-mutant patients were diagnosed at more advance stages (P<0.001) and had poorer OS (median OS 10.0 vs. 61.6 months, HR =7.9, 95% CI: 1.0-61.0, P<0.001) than non-TMD mutations. The overall response rate of targeted therapy, chemo-based therapy, and immunotherapy was 57.1%, 22.2%, and 0%, respectively. We postulated to challenge the resistance of tyrosine kinase inhibitor (TKI) with another with stronger binding energy to HER2 and supported the conclusion with a successful case. Additionally, we demonstrated a three-month response to the off-label use of pyrotinib in fifth-line therapy., Conclusions: Comapred with non-TMD mtuations, HER2 TMD mutation is a rare driver mutation with poorer prognosis in LUAD. Targeted therapy is the dominant choice for patients harboring this targetable mutation and longer OS could possibly be achieved through rechallenge with TKI of stronger binding affinity. Response to fifth-line pyrotinib was observed., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tlcr-21-107). Dr. JY, Dr. BL, Dr. HHZ, and Dr. JZ report personal fees from Burning Rock Biotechnology Co. Ltd. during the conduct of the study. Dr. NXL reports grants from National Key Research and Development Program of China, Beijing Health Promotion Association, grants from Beijing Natural Science Foundation, Major projects of the Beijing Municipal Science and Technology Commission, and Beijing Dongcheng District Science and Technology Commission Excellent Talents Project, during the conduct of the study. The other authors have no conflicts of interest to declare., (2021 Translational Lung Cancer Research. All rights reserved.)

Background: To compare the efficacy and safety of pyrotinib and trastuzumab emtansine (T-DM1) in patients who experienced disease progression on trastuzumab and lapatinib treatment., Methods: This was a real-world study that included cases of metastatic breast cancer (MBC) with trastuzumab and lapatinib failure. One group of patients received pyrotinib monotherapy or combination therapy, whereas the other group received T-DM1 monotherapy. The primary study endpoint was progression-free survival (PFS); secondary endpoints were the objective response rate (ORR), clinical benefit rate (CBR) and safety., Results: Between January 2013 and November 2019, 105 patients were enrolled in the pyrotinib group (n=55) or T-DM1 group (n=50). The median PFS was 6.0 months (95% CI, 4.7 to 7.3 months) with pyrotinib and 4.2 months (95% CI, 3.6 to 4.8 months) with T-DM1 (P=0.044). ORR values were 16.3% and 20.0% in the pyrotinib and T-DM1 groups, respectively (P=0.629); CBR values were 45.5% and 40.0% in the pyrotinib and T-DM1 groups, respectively (P=0.573). Subgroup analysis of those benefitting from lapatinib revealed a median PFS of 8.1 months (95% CI, 4.8 to 11.4 months) in the pyrotinib group, whereas that of the T-DM1 group was 4.4 months (95% CI, 3.8 to 5.0 months, P=0.013). Moreover, the median PFS of patients without liver metastases was 6.9 months (95% CI, 3.7 to 10.1 months) in the pyrotinib group and 4.1 months (95% CI, 3.1 to 5.1 months) in the T-DM1 group (P=0.010). The main common adverse events (AEs) were diarrhea (98.2%) and nausea (49.1%) in the pyrotinib group and thrombocytopenia (42.0%) and nausea (40.0%) in the T-DM1 group. The percentages of grade 3 to 4 AEs in the pyrotinib and T-DM1 groups were 34.5% and 40.0%, respectively., Conclusions: The results of this study suggest that patients with HER2-positive MBC with trastuzumab and lapatinib failure can benefit from subsequent pyrotinib treatment and tolerate this treatment well, especially those who have benefited from previous lapatinib treatment or those who have no liver metastasis., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-20-4054). The authors have no conflicts of interest to declare., (2021 Annals of Translational Medicine. All rights reserved.)

Background: Several human epidermal growth factor receptor 2 (HER2)-targeted regimens (anti-HER2 target agent combined chemotherapy) have been introduced for the treatment of HER2-positive locally advanced or metastatic breast cancer progressed after trastuzumab. We therefore conducted a network meta-analysis to compare and rank HER2-targeted regimens in this population after trastuzumab therapy., Methods: The electronic databases of PubMed, EmBase, Cochrane Central Register of Controlled Trials, and the websites of http://clinicaltrials.gov/ (US NIH) were systematically searched for published and unpublished randomized controlled trials (RCTs) from their inception to October, 2020. Nine treatment regimens were eligible to be included in this analysis. The primary outcomes were overall response rate (ORR), progression-free survival (PFS) and overall survival (OS), while the secondary outcomes were grade ≥3 adverse events., Results: A total of 2,104 citations were identified and 12 RCTs comprising 3,769 patients were selected for final analysis. For HER2 positive unresectable, locally advanced or metastatic patients progressed after trastuzumab therapy pyrotinib plus capecitabine ranked the highest surface under the cumulative ranking area (SUCRA) in PFS, ORR and its SUCRA in OS was higher than Trastuzumab emtansine (T-DM1). T-DM1 plus atezolizumab, pyrotinib plus capecitabine, and pertuzumab plus trastuzumab plus capecitabine had comparable SUCRA in OS (76.1% vs. 74.5% vs. 71.2%). Six of included studies reported any grade ≥3 adverse events, the prevalence of any grade ≥3 adverse events in lapatinib plus capecitabine (353/683), T-DM1 (213/558), trastuzumab plus capecitabine (130/218), pertuzumab plus trastuzumab plus capecitabine (118/228), pyrotinib plus capecitabine (220/384), T-DM1 plus atezolizumab (43/132) and capecitabine (24/94) were 51.7%, 38.2%, 59.6%, 51.8%, 57.3%, 32.6% and 25.5%, respectively. Specific adverse event characteristics related to different HER2-targeted regimens need to be well known ahead and managed during the therapy., Conclusions: The results indicated that for HER2 positive breast cancer with previous trastuzumab therapy pyrotinib plus capecitabine was probably more efficacious in PFS and ORR. T-DM1 plus atezolizumab, pyrotinib plus capecitabine and pertuzumab plus trastuzumab plus capecitabine have comparable effect on OS improvement and all of them were likely better than T-DM1. The risk of grade ≥3 adverse events for specific treatment regimens were also provided., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-20-5149). The authors have no conflicts of interest to declare., (2020 Annals of Translational Medicine. All rights reserved.)

The overexpression or amplification of HER2 has been observed in a significant proportion of both gastric cancer (GC) and breast cancer (BC) cases. Pyrotinib is an irreversible dual (EGFR/HER2) tyrosine kinase inhibitor (TKI), newly evaluated for the treatment of HER2‑overexpressing cancer types. As radiotherapy (RT) serves a crucial role in controlling the local recurrence of GC and BC, the present study investigated the impact of pyrotinib on the irradiation response. The current results demonstrated that pyrotinib enhanced the radiosensitivity of HER2‑overexpressing GC and BC cells in vitro and in vivo. In both NCI‑N87 and SKBR3 cells, pyrotinib suppressed the irradiation‑induced HER2 nuclear transport. Furthermore, pyrotinib increased DNA damage induced by irradiation in both cancer cell lines. Pyrotinib also enhanced the cytotoxicity of docetaxel, which may provide a novel strategy for potential drug combinations. Thus, pyrotinib is a promising irradiation sensitizer in patients with HER2‑overexpressing GC and BC. The present results provide a theoretical foundation for further clinical evaluation of pyrotinib.

Purpose: Pyrotinib is a newly-developed irreversible pan-ErbB receptor tyrosine kinase inhibitor. This study reported the first real-world data of pyrotinib-based therapy in metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC), focusing on efficacy in lapatinib-treated patients and in brain metastasis., Materials and Methods: One hundred thirteen patients with metastatic HER2-positive BC treated with pyrotinib-based therapy in Fudan University Shanghai Cancer Center under non-clinical trial settings from September 1, 2018 to March 1, 2019 were included., Results: Over half patients have received more than two lines of systematic therapy and exposed to two or more kinds of anti-HER2 agents. Most patients received a combined therapy, commonly of pyrotinib plus capecitabine, or vinorelbine or trastuzumab. Median progression-free survival (PFS) was 6.3 months (range, 5.54 to 7.06 months) and objective response rate (ORR) was 29.5%, with two patients (1.9%) achieving complete response. Lapatinib-naïve patients had significantly longer PFS than lapatinib-treated patients (9.0 months vs. 5.4 months, p=0.001). ORR for lapatinib-treated patients was 23.2%. Thirty-one of 113 patients have brain metastasis. Median PFS was 6.7 months and intracranial ORR was 28%. For patients without concurrent radiotherapy and/or brain surgery, the ORR was very low (6.3%). But for patients receiving concurrent radiotherapy and/or brain surgery, the ORR was 66.7%, and three patients achieved complete response. Most common adverse event was diarrhea., Conclusion: Pyrotinib-based therapy demonstrated promising effects in metastatic HER2-positive BC and showed activity in lapatinib-treated patients. For patients with brain metastasis, pyrotinib-based regimen without radiotherapy showed limited efficacy, but when combined with radiotherapy it showed promising intracranial control.

Patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer inevitably progressed after a short response to initial trastuzumab treatment, suggesting a possibility of acquired-resistance to trastuzumab. Pyrotinib, an irreversible pan-ErbB receptor tyrosine kinase inhibitor (TKI), has been reported as an effective and safe drug for the treatment of HER2-positive relapsed or metastatic breast cancer. Pyrotinib combined with capecitabine is widely used to treat HER2-positive metastatic breast cancer in patients who have been previously treated with anthracyclines, taxanes, and trastuzumab. However, the efficacy of pyrotinib combined with other chemotherapy drugs is still unclear. Here we report pyrotinib combined with carboplatin in treating a patient with HER2-positive relapsed breast cancer who had acquired resistance to trastuzumab. The patient received three cycles of treatments of pyrotinib (400 mg, orally once per day, days 1-21) combined with carboplatin (600 mg, iv drip, day 1, cycled every 21 days). The patient showed an excellent response to the therapy, including faded rashes on the skin of her breast, no obvious signs of recurrence from the breast magnetic resonance imaging (MRI), decreased skin thickness and cord shadow of the right breast, unchanged degree of right pleural effusion, and no enlarged LN. The patient had a stable disease time of more than four months. Our case provides evidence for the feasibility and efficacy of pyrotinib with carboplatin in treating patients with HER2-positive relapsed or metastatic breast cancer who may develop resistance to trastuzumab.

Background: Pyrotinib, an irreversible pan-ERBB inhibitor, has shown promising antitumour activity, and acceptable tolerability. This research was conducted to evaluate the actual use and effectiveness of pyrotinib in China, therefore, contributed to solve the problem of real-world data scarcity. Methods: In this retrospective study, 168 patients who received pyrotinib treatment for HER2-positive metastatic breast cancer (MBC) in Hunan Province from June 2018 to August 2019 were included. Progression-free survival (PFS), tumor mutation burden (TMB), and drug-related adverse events (AEs) after pyrotinib administration were analyzed. Results: The median PFS (mPFS) time in the 168 participants was 8.07 months. The mPFS times in patients with pyrotinib in second-line therapy ( n = 65) and third-or-higher-line therapy ( n = 94) were 8.10 months and 7.60 months, respectively. Patients with brain metastases achieved 8.80 months mPFS time. In patients with pyrotinib in third-or-higher-line therapy, patients who had previously used lapatinib still got efficacy but showed a shorter mPFS time (6.43 months) than patients who had not (8.37 months). TMB was measured in 28 patients, K-M curve ( P = 0.0024) and Multivariate Cox analysis ( P = 0.0176) showed a significant negative association between TMB and PFS. Diarrhea occurred in 98.2% of participants (in any grade) and 19.6% in grade 3-4 AEs. Conclusion: Pyrotinib is highly beneficial to second-or-higher-line patients or HER2-positive MBC patients with brain metastases. Pyrotinib seems to be a feasible strategy both in combination of chemotherapeutic drugs or as a replacement of lapatinib if diseases progressed. TMB could be a potential predictor for evaluating pyrotinib's effectiveness in HER2-positive MBC., (Copyright © 2020 Chen, Ouyang, Anwar, Xie, Wang, Fan, Qian, Chen, Zhou, Guo, Gu, Ding, Yang, Liu, Deng, Xiao, Li, Wang, Zeng, Hu, Zhou, Qiu, Wang, Weng, Liu, Li, Tang, Wang, Zhang, Dai, Tang, Wu, Xiao, Li, Liu, Li, Yi and Ouyang.)

Radiation therapy is a widely used treatment for esophageal cancer. However, radiation resistance might result in a poor prognosis. Overexpression of HER2 has been related to adaptive radiation resistance. Pyrotinib is a HER2 inhibitor that shows an anti-tumor effect in breast cancer. The present study aims to explore the influence of pyrotinib combined with radiotherapy on HER2-positive esophageal cancer cells and explore the underlying mechanism. We screened two cell lines (TE-1 and KYSE30) that highly express HER2 from several human esophageal cancer cell lines. Cells were treated with pyrotinib or/and radiation. Cell proliferation, cell cycle distribution, and cell migration were measured. The protein levels involved in cell cycle and DNA repair were measured by Western blot. Results showed that pyrotinib inhibited HER2 activation and exerted an anti-proliferative effect in TE-1 and KYSE30 cells. Furthermore, it enhanced the anti-proliferative effect of radiation in these two cell lines. These effects might be via inhibiting HER2 phosphorylation, inducing G0/G1 arrest, and reducing EMT and DNA repair. Our results indicated that pyrotinib sensitivitied HER2 positive esophageal cancer cells to radiation treatment through various mechanisms. These findings may provide a new therapeutic strategy for treating HER2 positive esophageal cancer., (© 2020 The Author(s).)

The incidence of breast cancer ranks first among female malignant tumors that affect women's health. Epidermal growth factor receptor (EGFR) family overexpression, especially human epidermal receptor2 (HER2), features prominently in breast cancer with a significant relation to poor prognosis. Currently, specific monoclonal antibodies and tyrosine kinase inhibitors (TKIs) are the two HER2 targeting strategies that have successfully improved the prognosis of patients with HER2-positive breast cancer. This paper focuses on three officially approved TKIs for HER2 breast cancer, namely, lapatinib, neratinib and pyrotinib, and systematically reviews the mechanism, safety, efficacy and resistance of these TKIs., Competing Interests: None., (AJCR Copyright © 2019.)