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Background: The effectiveness and safety of pyrotinib have been substantiated in human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer (BC). However, the role of pyrotinib as a single HER2 blockade in neoadjuvant setting among BC patients has not been studied. The objective of this study was to evaluate the efficacy and tolerability of pyrotinib plus taxanes as a novel neoadjuvant regimen in patients with HER2-positive early or locally advanced BC., Methods: In this single-arm exploratory phase II trial, patients with treatment-naïve HER2-positive BC (stage IIA-IIIC) received pyrotinib 400 mg once daily and taxanes [docetaxel 75 mg/m 2 or nanoparticle albumin-bound (nab)-paclitaxel 260 mg/m 2 every 3 weeks, or paclitaxel 80 mg/m 2 weekly] for a total of four 21-day cycles before surgery. Efficacy assessment was based on pathological and clinical measurements. The primary endpoint of this study was the total pathological complete response (tpCR) rate. The secondary endpoints included breast pCR (bpCR) rate, investigator-assessed objective response rate (ORR) and adverse events (AEs) profiles., Results: From 1 September 2021 to 30 December 2022, a total of 31 patients were enrolled. One patient was withdrawn due to unbearable skin rash after the second cycle of neoadjuvant therapy. The majority of the intention-to-treat (ITT) population was premenopausal (54.8%), had large tumors (90.3%) and metastatic nodes (58.1%) at diagnosis and hormone-receptor positive tumors (64.5%). Most participants used nab-paclitaxel (74.2%) and received mastectomy (67.7%) after neoadjuvant treatment. The tpCR and bpCR rates were 48.4% [95% confidence interval (CI): 30.8-66%] and 51.6% (95% CI: 34-69.2%), respectively. Grade ≥3 treatment-related AEs were observed in 16.1% (5/31) of the ITT population, including diarrhea (n=2, 6.5%), hand and foot numbness (n=1, 3.2%), loss of appetite (n=1, 3.2%), and skin rash (n=1, 3.2%). AE related dose reduction or pyrotinib interruption was not required., Conclusions: In female patients with HER2-positive non-metastatic BC, neoadjuvant pyrotinib monotherapy plus taxanes appears to show promising clinical benefit and controllable AEs [Chinese Clinical Trial Registry (ChiCTR2100050870)]. The long-term efficacy and safety of this regime warrant further verification., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-24-38/coif). The authors have no conflicts of interest to declare., (2024 Gland Surgery. All rights reserved.)

Background: The prognosis of patients who can achieve a complete response after neoadjuvant chemotherapy could be significantly improved. Thus, accurately predicting the efficacy of neoadjuvant chemotherapy is of great clinical significance. Currently, previous indicators such as neutrophil to lymphocyte ratio was poor in predicting the efficacy and prognosis of neoadjuvant chemotherapy in human epidermal growth factor receptor 2 (HER2) positive breast cancer patients., Methods: The data of 172 HER2 positive breast cancer patients admitted to the Nuclear 215 Hospital of Shaanxi Province from January 2015 to January 2017 were retrospectively collected. After neoadjuvant chemotherapy, the patients were divided into the complete response group (n=70) and the non-complete response group (n=102). The clinical characteristics and systemic immune-inflammation index (SII) levels of the two groups were compared. The patients were followed-up for 5 years post-surgery to observe whether recurrence or metastasis occurred after the operation by clinic visit combined with telephone calls., Results: The SII of the complete response group was significantly lower than that of the non-complete response group (587.43±175.97 vs. 821.82±231.58; P=0.000). The SII was valuable in predicting which HER2 positive breast cancer patients would fail to achieve a pathological complete response, and the area under the curve (AUC) was 0.773 [95% confidence interval (CI): 0.705-0.804; P=0.000]. A SII >755.10 was an adverse factor for HER2 positive breast cancer patients achieving a pathological complete response after neoadjuvant chemotherapy [P=0.000; relative risk (RR): 0.172 (95% CI: 0.082-0.358)]. The SII level was valuable in predicting recurrence within 5 years of surgery, and had an AUC of 0.828 (95% CI: 0.757-0.900; P=0.000). A SII >755.10 was a risk factor for recurrence within 5 years of surgery [P=0.001; RR: 4.945 (95% CI: 1.949-12.544)]. The SII level was valuable in predicting metastasis within 5 years of surgery, and had an AUC of 0.837 (95% CI: 0.756-0.917; P=0.000). A SII >755.10 was a risk factor for metastasis within 5 years of surgery [P=0.014, RR: 4.553 (95% CI: 1.362-15.220)]., Conclusions: The SII was associated with the prognosis and efficacy of neoadjuvant chemotherapy in HER2 positive breast cancer patients., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-23-55/coif). The authors have no conflicts of interest to declare., (2023 Gland Surgery. All rights reserved.)

Background: Human epidermal growth factor receptor 2 (HER2) is a landmark protein in determining the targeted treatment of breast cancer (BC). However, the latest research shows that different intensity of HER2 protein expression levels in BC leads to different clinical characteristics, treatment, and prognosis, especially in HER2 low expression patients. Therefore, this study intends to analyze and compare the clinicopathologic features and prognosis of BC patients with low and zero HER2 expression from The Cancer Genome Atlas (TCGA) database and the data collected by our center., Methods: First, the BC dataset was downloaded from TCGA database, including 345 eligible and with complete clinical information BC patients, to compare the difference between HER2 low expression groups and HER2 zero expression groups and their correlation with estrogen receptor (ER) and progesterone receptor (PR) expression. Then, the clinicopathological data and follow-up of 405 patients with HER2 low expression and HER2 zero expression diagnosed with BC admitted to the Affiliated Hospital of Youjiang Medical University for Nationalities (YJMU) from January 2017 to December 2021 were collected to verify the consistency of the results of the two data sets., Results: Both the clinical samples and the TCGA data showed that the ER and PR rates were higher in the HER2 low expression group compared with the HER2 zero expression group. There were no significant differences in tumor size, lymph node metastasis, distant metastasis, and disease-free survival (DFS). In addition, the data analysis of 405 clinical samples also showed that the HER2 low expression group had a lower 3-year recurrence or metastasis rate compared with the HER2 zero expression group., Conclusions: Compared with HER2 zero expression, HER2 low patients express more ER and PR, and have less short-term recurrence and metastasis, but there is no obvious difference in DFS between the two groups., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-22-747/coif). The authors have no conflicts of interest to declare., (2023 Gland Surgery. All rights reserved.)

Background: Pyrotinib combined with capecitabine has been approved for the treatment of patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer in China. To date, the management of early-stage or locally advanced HER2-positive breast cancer in the clinic remains challenging. We conducted this trial to investigate the efficacy and safety of pyrotinib combined with capecitabine as neoadjuvant therapy (NAT) in elderly patients with HER2-positive breast cancer. Due to the stimulation of blood vessels by chemotherapy drugs, the elasticity of blood vessels in the elderly decreases, and then chemotherapy infusion is more likely to lead to phlebitis. Both pyrotinib and capecitabine can be taken to facilitate home treatment for elderly patients with HER2-positive breast cancer (BC)., Methods: From January 2020 to March 2021, patients aged between 70 and 81 years old with stage IIA-IIIB HER2-positive breast cancer were screened, enrolled, and assigned to receive six cycles of pyrotinib (320-400 mg, orally, once daily) plus capecitabine (1,250 mg/m 2 , orally, twice daily) on days 1-14 in every 21-day cycle. The primary endpoint was the objective response rate (ORR). Adverse events (AEs) were assessed in every neoadjuvant cycle. Surgery was performed after the last cycle, and the total pathological complete response (tpCR) was evaluated postoperatively., Results: Of the 23 patients enrolled, the ORR was 100% (23/23; 95% confidence intervals: 85 to 100). All patients underwent surgery with a tpCR rate of 43.5% (10/23; 95% confidence intervals: 23 to 66). The most common AE was diarrhea, occurring in 19 of 23 patients (82.6%); most of these patients sustained mild diarrhea (Grade 1 or Grade 2) and only three had moderate diarrhea (Grade 3). The incidences of other AEs, including weakness, loss of appetite, leukopenia, nausea, vomiting, hand-foot syndrome, etc., were low and the symptoms were mild. No severe AEs (Grade 4 or 5) were observed throughout the treatment., Conclusion: In our study, pyrotinib combined with capecitabine as neoadjuvant therapy in elderly women with HER2-positive breast cancer is safe and showed efficacy in this population, which may be widely used as a protocol for clinical neoadjuvant therapy., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-23-11/coif). The authors have no conflicts of interest to declare., (2023 Gland Surgery. All rights reserved.)

Human epidermal growth factor receptor 2 (HER2) is an important driver gene and prognostic indicator of breast cancer and also a key predictor of HER2-targeted therapies. The emerging anti-HER2 drugs have greatly changed the diagnosis and treatment modalities of breast cancer and dramatically improved the prognosis of HER2-positive breast cancer patients. To optimize the treatment of HER2 breast cancer an update of expert consensus on HER2 positive breast cancer was made to adjust the different recommendation levels from early stage to metastatic stage. Meanwhile, antibody-drug conjugate (ADC) like trastuzumab deruxtecan (T-Dxd) has been shown to have great efficacy in HER2-positive and HER2 low expression breast cancer patients. Clinically, on the basis of the original definition for HER2-negative breast cancer, patients with HER2 immunohistochemistry (IHC) 1+ or IHC 2+ and in-situ hybridization (ISH)-negative are defined as low HER2 expression (HER2-low). As both the low expression and the positive expression of the HER2 protein is clinically significant for disease treatment and prognosis, we added a new chapter of HER2 low to recommend a proper regimen for this kind of patients. In this consensus, we also talk about the importance of clinical research, real world evidence, biosimilars and so on. In addition, the whole-course management of HER2 breast cancer is even more critical during pandemic of coronavirus disease 2019 (COVID-19). An approach that gives preference to "low-toxicity regimens and oral preparations" are also recommended., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tbcr.amegroups.com/article/view/10.21037/tbcr-22-48/coif). XW serves as an unpaid editorial member of Translational Breast Cancer Research from December 2020 to November 2022. SSW, CG, FJ, YY, QZ, ES and JW serve as the unpaid editorial members of Translational Breast Cancer Research from March 2022 to April 2024. SW and YL serve as the unpaid editorial members of Translational Breast Cancer Research from May 2021 to April 2023. JL serves as an unpaid Managing Editor of Translational Breast Cancer Research from November 2019 to October 2024. ZJ serves as the Editor-in-Chief of Translational Breast Cancer Research. The other authors have no conflicts of interest to declare., (2022 Translational Breast Cancer Research. All rights reserved.)

Background: This study sought to estimate the prognostic effect of intratumoral heterogeneity (ITH) and Yes-associated protein 1 (YAP1) intensity in human epidermal growth factor receptor 2 (HER2) positive breast cancer patients. We also investigated individualized adjuvant therapy for YAP1-sufficient patients and HER2 heterogeneous patients., Methods: The relationship between prognostic outcomes and clinicopathological variables in 1,650 retrieved breast cancer patients was evaluated. The HER2 intensity and YAP1 expression in HER2-ITH and non-ITH (NITH) patients were also estimated. All patients were followed-up, regardless of whether or not they received intensive treatment, to explore individualized adjuvant therapy for YAP1-sufficient patients and HER2 heterogeneous patients., Results: Over-expression and nuclear localization of YAP1 were significant in HER2-ITH patients. The over-expression of YAP1 and the presence of ITH affected the prognosis of HER2 positive patients. YAP1 intensity and lymph nodes metastases was more obviously affected the survival of HER2-ITH patients, while the prognosis of NITH patients were correlated with clinical Tumor-Node-Metastasis (cTNM) stage and lymph-vascular space invasion (LVSI) status. HER2-NITH patients and YAP1-insufficient patients benefited from a combination of Trastuzumab and Pertuzumab/Lapatinib, while Capecitabine significantly decreased the relapse risk of ITH patients and YAP1-sufficient patients., Conclusions: YAP1 overexpression and nuclear localization was usually observed in HER2-ITH patients. For HER2-NITH patients, an advanced stage of cTNM and LVSI status increased the recurrent risk, and intensified Pertuzumab or Lapatinib treatment (combination with Trastuzumab) improved their survival. For HER2-ITH patients, the overexpression of YAP1 and pathological lymph nodes (pLN) metastases increased recurrent risk, and intensified Capecitabine treatment improved their survival. YAP1 overexpression contributed to a poor prognostic outcome, especially when HER2 signal intensity was insufficient., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-22-52/coif). The authors have no conflicts of interest to declare., (2022 Gland Surgery. All rights reserved.)

Objective: The purpose of this article review is to discuss the current adjuvant approach for human epidermal growth factor receptor 2 (HER2) gene amplification or overexpression inflammatory breast cancer (IBC), as well as promising therapies to improve the prognosis of these patients, with the main focus on the high risk setting of patients with residual disease after neoadjuvant therapy., Background: IBC is a rare and very aggressive form of breast cancer. HER2+ is more frequent in IBC than in non-IBC. A combined multimodality therapy is essential for better outcomes in non-metastatic HER2+ IBC patients, including neoadjuvant chemotherapy, with dual HER2 blockade, local therapy with surgery and radiotherapy, and adjuvant systemic therapy, which is defined on the basis of pathological response and hormone receptor (HR) status. Dual HER2 blockade with trastuzumab and pertuzumab combined to neoadjuvant chemotherapy improved the pathological complete response (pCR) rate. However, HER+ IBC patients with residual disease at surgery have a high risk of recurrence and death., Methods: A comprehensive review was conducted through Medline/PubMed database, ClinicalTrials.gov, and conference abstracts., Conclusions: Escalation of adjuvant therapy for patients with HER2+ IBC with residual invasive disease after neoadjuvant therapy is recommended. Adjuvant ado-trastuzumab emtansine and neratinib, for HR+ disease, are the most recent advances in this setting, with a clinically meaningful improvement in invasive disease-free survival (iDFS). Despite the clinical advances, reducing the risk of central nervous system recurrence remains an unmet need. Several promising clinical trials are ongoing to improve patients' prognosis in this high-risk of recurrence setting.

Background: Gastric cancer (GC) is one of the most malignant diseases and threatens the health of individuals across the globe. Hitherto, the identification of prognosis risk stratification on GC has mainly depended on the TNM staging, but owing to its inaccuracy and incompleteness, the prognostic value it offers remains controversial in the current clinical setting. Thus, an effective prognostic model for GC after radical gastrectomy is still needed., Methods: Patients with pathologically confirmed GC who underwent radical gastrectomy from 2 different centers were retrospectively enrolled into a training and the validation cohort, respectively. The least absolute shrinkage and selection operator (LASSO) algorithm was applied to select variables among multiple factors, including clinical characteristics, pathological parameters, and surgery- and treatment-related indicators. The multivariate Cox regression method was used to establish the model to predict 1-, 2-, and 3-year survival. Both internal and external validations of the nomogram were then completed in terms of discrimination, calibration, and clinical utility. Finally, prognostic risk stratification of GC was conducted with X-tile software., Results: A total of 1,424 patients with GC were eligible in this study, including 1,010 in the training cohort and 414 in the validation cohort. Seven indicators were selected by LASSO to develop the nomogram, including the number of positive lymph nodes, tumor size, adjacent organ invasion, vascular invasion, the level of carbohydrate antigen 125 (CA 125), depth of invasion, and human epidermal growth factor receptor 2 (HER2) status. The nomogram demonstrated a robust predictive capacity with favorable accuracy, discrimination, and clinical utility both in the internal and external validations. Moreover, we divided the population into 3 risk groups of survival according to the cutoff points generated by X-tile, and in this way, the nomogram was further improved into a risk-stratified prognosis model., Conclusions: We have developed a prognostic risk stratification nomogram for GC patients after radical gastrectomy with 7 available indicators that may guide clinical practice and help facilitate tailored decision-making, thus avoiding overtreatment or undertreatment and improving communication between clinicians and patients., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/atm-21-6359). The authors have no conflicts of interest to declare., (2021 Annals of Translational Medicine. All rights reserved.)

Human epidermal growth factor receptor 2 (HER2), as a receptor tyrosine kinase of EGF receptor family, whose mutation is often associated with even if less frequency but poor prognosis and shorter survival in pulmonary malignant tumor. HER2 status include mutation, overexpression, amplification and also some rare genotypes, detected by next generation sequencing (NGS), immunohistochemistry (IHC), and also fluorescence in situ hybridization (FISH). Different genotypes represent different therapeutic targets and indicate different clinical prognosis concluded by previous studies. Unfortunately, no standard guidelines for first-line treatment are widely recognized, and current therapeutic schedules include chemotherapy, radiotherapy, targeted therapy, and immunotherapy. Especially for patients with advanced metastasis, chemotherapy is based as a systemic therapy using studies of breast cancer or EGFR-positive lung adenocarcinoma as a template. Studies already explored treatment including EGFR tyrosine kinase inhibitors (TKIs) such as gefitinib and afatinib, and also trastuzumab and its conjugation like HER2-targeted antibody-drug conjugate trastuzumab emtansine (T-DM1) and conjugate trastuzumab deruxtecan (T-DXd). Also, he researches explored combination therapy with chemotherapy and TKIs or monoclonal antibodies. This review describes commonly used therapies for HER2-positive/HER2-overexpression patients and general relationship between genotypes of HER2, drug selection and final prognosis in order to provide suggestions for future diagnosis and treatment., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jtd-20-3265). The authors have no conflicts of interest to declare., (2021 Journal of Thoracic Disease. All rights reserved.)

Esophageal and gastric adenocarcinomas are frequently diagnosed at an advanced stage and have a dismal prognosis. Even in patients with potentially curative cancer, nearly 50% will develop recurrent disease despite aggressive treatments. A number of biomarkers currently guide treatment decisions for patients with esophageal and gastric adenocarcinoma and include human epidermal growth factor receptor 2 (HER2) amplification, mismatch repair deficiency/microsatellite instability (dMMR/MSI-H) and program death-ligand 1 (PD-L1) expression. This review will focus on the function, testing and FDA-approved targeted therapies for HER2, dMMR/MSI-H and PD-L1. In addition, a number of novel targets in esophageal and gastric cancer are being studied in clinical trials. Neurotrophic-tropomyosin receptor kinase (NTRK), claudin-18 (CLDN18)/Rho GTPase activating protein 26 ( ARHGAP26 ) gene fusion, fibroblast growth factor receptor (FGFR), lymphocyte-activation gene 3 (LAG3) and T cell immunoglobulin and mucin-domain containing-3 (TIM3) will be briefly reviewed. Despite several biomarkers used in the selection of treatment therapies, treatment outcomes remain poor. Future research efforts will focus on the identification of new biomarkers, moving existing biomarkers into earlier lines of therapy, and evaluating new combinations of existing biomarkers and therapies., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare., (2020 Translational Gastroenterology and Hepatology. All rights reserved.)

Background: Treatment strategies for various subtypes of breast cancer (BC) are different based on their distinct molecular characteristics. Therefore, it is very important to identify key differentially expressed genes (DEGs) between ER-positive/HER2-negative BC and ER-negative/HER2-negative BC., Methods: Gene expression profiles of GSE22093 and GSE23988 were obtained from the Gene Expression Omnibus database. There were 74 ER-positive/HER2-negative BC tissues and 85 ER-negative/HER2-negative BC tissues in the two profile datasets. DEGs between ER-positive/HER2-negative tissues and ER-negative/HER2-negative BC tissues were identified by the GEO2R tool. The common DEGs among the two datasets were detected with Venn software online. Next, we made use of the Database for Annotation, Visualization and Integrated Discovery to analyze enriched Kyoto Encyclopedia of Gene and Genome (KEGG) pathways and gene ontology terms. Then, the protein-protein interactions (PPIs) of these DEGs were visualized by Cytoscape with the Search Tool for the Retrieval of Interacting Genes. Of the proteins in the PPI network, Molecular Complex Detection plug-in analysis identified nine core upregulated genes and one core downregulated gene. UALCAN and Gene Expression Profiling Interactive Analysis were applied to determine the expression of these 10 genes in BC. Furthermore, for the analysis of overall survival among those genes, the Kaplan-Meier method was implemented., Results: Ninety-three common DEGs (63 upregulated and 30 downregulated) were identified. KEGG pathway enrichment analysis showed that upregulated DEGs were particularly enriched in the progesterone-mediated oocyte maturation pathway. In addition, PGR might be a prognostic biomarker for ER-positive/HER2-negative BC. CCND1 is a poor prognostic biomarker for ER-positive/HER2-negative BC and ER-negative/HER2-negative BC. Moreover, TFF1, AGR2 and EGFR might be predictive biomarkers of node metastasis in ER-positive/HER2-negative BC and ER-negative/HER2-negative BC., Conclusions: CCND1, AGR2, PGR, TFF1 and EGFR are the key DEGs between ER-positive/HER2-negative BC and ER-negative/HER2-negative BC. Further studies are required to confirm the functions of the identified genes., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/gs.2020.03.40). The authors have no conflicts of interest to declare., (2020 Gland Surgery. All rights reserved.)

Background: Although trastuzumab has been shown to be beneficial for treating patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer, information regarding its benefits is limited to very low-risk cases with tumours ≤1 cm and without lymphatic metastases (pT1abN0). The present meta-analysis integrates information from literature and determines the benefit of trastuzumab in pT1abN0, HER2-positive breast cancer patients., Methods: PubMed, MEDLINE, and EMBASE databases were searched for studies published before Sep 30, 2019. Our primary endpoint was tumor recurrence, whether provided as overall or distant recurrences., Results: Seven studies involving 1,181 patients with pT1abN0, HER2-positive breast cancer were included in the systemic review. The median follow-up periods ranged from 37 to 78 months. The patients in the trastuzumab arm had generally inferior profiles such as higher rate of T1b, grade 3, and hormone negative cases, among available studies. Concomitant chemotherapy was more commonly applied in the trastuzumab arm (75-100% vs. 0-42%), and the hormone therapy application was similar in both arms (20-66%). In a pooled analysis of seven available studies, patients treated with trastuzumab had less overall recurrence relative to controls, with an odds ratio of 0.201 [95% confidence interval (CI): 0.100-0.404, P<0.001]. Five studies were available for a pooled analysis of distant recurrence. Although the results were not significant (P=0.115), distant recurrence did not occur in 237 patients treated with trastuzumab, but did occur in 16 out of 436 control patients. The odds ratio for distant recurrence was 0.328 (95% CI: 0.082-1.311)., Conclusions: The adjuvant treatment including trastuzumab was shown to reduce overall recurrence. Distant recurrence may also be reduced, as it did not occur among the 237 patients who underwent trastuzumab treatment., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare., (2020 Annals of Translational Medicine. All rights reserved.)

Human epidermal growth factor receptor 2 (HER2) mutation and amplification are distinct molecular targets in lung cancer, but the specific targeted therapy for their coexistence is undetermined. Personalized targeted therapy is based on mutation type, with different mutations requiring different treatment. A 64-year-old Chinese woman was diagnosed with advanced lung adenocarcinoma. She was determined as having insertion mutations in exon 20 of the HER2 gene (c.2326G > TTGT) by the amplification refractory mutation system (ARMS) and HER2 gene amplification (HER2/CEP17 ratio 2.6) by fluorescence in situ hybridization (FISH). Thereafter, she was treated with afatinib as first-line therapy, to which she responded. After 2 months, the tumor lesion decreased in size. Computed tomography (CT) follow-up showed stable lung lesions, although she later developed multiple brain metastases and subsequently died of brain failure. Lung adenocarcinoma with coexistent HER2 mutation and amplification is relatively uncommon and has no reported cases on targeted therapy. This case was important because it showed effective response to afatinib and provides evidence to help clinicians identify the therapeutic regimen for such patients.

Though most patients with breast cancer are cured, there are still many patients progressed to metastatic breast cancer (MBC) and some are diagnosed as MBC. Human epidermal growth factor receptor 2 (HER2) is positive in about 20% all breast cancer patients and considered as a poor prognostic factor. The advent of ant-HER2 therapy has prominently prolonged the time of disease progression and survival for HER2-positive MBC patients. This review summarizes the advance in anti-HER2 therapy in HER2-positive MBC according to the phase III clinical trials, and briefly discusses some new agents and anti-HER2 therapy for HER2 low-or non-expression breast cancer patients.

Background: The aberrant status of target genes and their associations with clinicopathologic characteristics are still unclear in primary lung adenocarcinoma., Methods: The common mutations and translocations of nine target genes were evaluated in 1,247 specimens of surgically-resected primary lung adenocarcinoma. Immunohistochemistry was used to analyze the expressions of programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) in 731 specimens. The frequency of the aberrations and their associations with clinicopathologic characteristics were analyzed., Results: Overall, 952 (76.3%) of 1,247 patients harbored at least one target mutation or translocation: epidermal growth factor receptor ( EGFR ) (729, 58.5%), v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog ( KRAS ) (83, 6.7%), human epidermal growth factor receptor 2 ( HER2 ) (82, 6.6%), anaplastic lymphoma kinase ( ALK) (23, 1.8%), phosphoinositide-3-kinase catalytic alpha polypeptide ( PIK3CA ) (20, 1.6%), Ret proto-oncogene RET (15, 1.2%), ROS proto-oncogene 1 receptor tyrosine kinase ( ROS1 ) (12, 1.0%), B-raf proto-oncogene ( BRAF ) (9, 0.7%), neuroblastoma RAS viral (v-ras) oncogene homolog ( NRAS ) (3, 0.2%). Fourteen (1.9%) of 731 patients were PD-1 positive and 95 (13.0%) were PD-L1 positive in tumor cells. In men and smokers, there were more frequent KRAS mutations (both P<0.001) and PD-L1 positive tumors (P<0.001, P=0.005, respectively), and less frequent EGFR mutations (P=0.049, <0.001, respectively). In ground-glass opacity (GGO) or ground-glass nodules (GGN), there were more HER2 (P=0.033) but less EGFR (P=0.025) and PIK3CA mutations (P=0.012), and ALK translocations (P=0.014). EGFR (P<0.001), KRAS mutations (P=0.004) and PD-L1 positive tumors (P=0.046) were more frequent in older patients, while HER2 (P<0.001), ALK (P=0.005) and ROS1 aberrations (P=0.044) were less frequent. Invasive mucinous adenocarcinoma was significantly associated with KRAS and ALK aberrations (both P<0.001), while solid predominant adenocarcinoma was associated with ROS1 translocations (P=0.036) and PD-L1 expression (P<0.001). KRAS, HER2, and ALK aberrations were scarce in patients with EGFR mutations (all P<0.001), while PD-L1 positive tumors positively correlated with ALK translocations (P=0.031) and negatively correlated with HER2 mutations (P=0.019)., Conclusions: Most patients with primary lung adenocarcinoma harbored target gene aberrations. The frequency of each alteration differed in patients depending on clinicopathologic characteristics., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Human epidermal growth factor receptor 2 (HER2)-targeted therapies have revolutionized the treatment of HER2-positive breast cancer, both in the metastatic and early stage settings. While trastuzumab and lapatinib had been the mainstays of treatment in combination with chemotherapy, innate and acquired resistance to these therapies occur. More recently, two additional HER2-directed therapies have been approved for HER2-positive breast cancer. Pertuzumab is a humanized monoclonal antibody that binds to the extracellular portion of the receptor on a domain distinct from the binding site of trastuzumab. The addition of pertuzumab to trastuzumab results in synergistic tumor cell inhibition and has been shown to significantly improve clinical outcomes for patients with HER2-positive metastatic breast cancer (MBC) compared to trastuzumab plus chemotherapy alone. In addition, ado-trastuzumab emtansine (T-DM1), a novel antibody-drug conjugate linking trastuzumab with the cytotoxic maytansinoid, DM1, is an effective treatment for HER2-positive breast cancer that has progressed on other HER2-directed therapies. Both pertuzumab and T-DM1 are relatively well tolerated. This review presents the mechanisms of action as well as phase I, II and III clinical data describing the safety and efficacy of pertuzumab and T-DM1 for HER2-positive breast cancer.