scholarly journals ANTI-HER2 ANTIBODIES IN COMBINATION WITH CHEMOTHERAPY OR CHEMOTHERAPY-FREE REGIMENS TARGETING HER2-POSITIVE BREAST CANCER: A SYSTEMATIC REVIEW

2020 ◽  
Vol 20 (2) ◽  
pp. 285-306
Author(s):  
Siti Muhamad Nur Husna ◽  
Faezahtul Arbaeyah Hussain ◽  
Maya Mazuwin Yahya ◽  
Anne Dyhl-Polk ◽  
Kah Keng Wong

Breast cancer is the leading cause of cancer-related death in female worldwide. Human epidermal growth factor receptor 2 (HER2) amplification is observed in approximately 20% of breast cancer cases and is associated with poor clinical outcomes. Dual HER2 blockade without chemotherapy represents an attractive therapeutic approach, and it remains unresolved if anti-HER2 therapeutic antibodies are sufficient to replace chemotherapy regimens. In this review, we discuss the approved therapeutic monoclonal antibodies (pertuzumab and trastuzumab) and antibody-drug conjugate (trastuzumab emtansine or T-DM1) for the treatment of HER2-positive breast cancer patients. In summary, phase II and III clinical trials have demonstrated that dual HER2 blockade (pertuzumab and trastuzumab) plus chemotherapy regimens confer better efficacy compared with dual HER2 blockade alone, or anti-HER2 antibody monotherapy, in HER2-positive breast cancer patients. Dual HER2 blockade (pertuzumab and trastuzumab) combined with chemotherapies (5-fluorouracil, epirubicin, cyclophosphamide and docetaxel) yield superior response. Moreover, dual HER2 blockade (T-DM1 and pertuzumab) in combination with docetaxel represents a promising treatment regimen containing T-DM1. Ongoing clinical trials are assessing the optimal chemotherapy of choice with anti-HER2 antibodies combinations. In conclusion, improved outcomes are attributable to selection for the optimal chemotherapy regimen in combination with anti-HER2 antibodies instead of replacing chemotherapy altogether with the current line of anti-HER2 therapeutic antibodies.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e12610-e12610
Author(s):  
Qiyun Shi ◽  
Juncheng Xuhong ◽  
Jia Ge ◽  
Feng Liu ◽  
Yang Lan ◽  
...  

e12610 Background: Our previous study reported a good efficacy and safety of pyrotinib combined with trastuzumab neoadjuvant treatment in human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients. We further explored the potential biomarkers for the efficacy of pyrotinib combined with trastuzumab neoadjuvant treatment in HER2-positive breast cancer patients. Methods: To date, a total of 96 patients with early-stage breast cancer were enrolled for the neoadjuvant pyrotinib combined with trastuzumab treatment clinical trial (ChiCTR1900022293). By the method of 425 genes next-generation sequencing (NGS), the genomic characteristics of them were evaluated for the potential correlation with postoperative pathological complete response (pCR). Results: Among the cohort of 96 cases, a total of 32 patients have completed the whole therapy as well as final surgery and acquired qualified sequencing analysis report, and 18 of them achieved total pCR. The most frequently mutated driver genes were TP53 (75%), PIK3CA (44%), NBN (9%), RUNX1 (9%), FANCD2 (9%), ATRX (9%), MAP3K1 (9%) and NF1 (9%), respectively. In terms of somatic copy number alterations, the most frequent alterations are gain or amplification of ERBB2 (63%), MYC (22%), CCND1 (19%), CDK12 (16%) and FGF19 (16%), respectively. The median tumor mutation burden (TMB) of the 36 patients was 4.23 mut/Mb (0.00-29.61). Compared with pCR populations, non-pCR populations had significantly higher median TMB (5.29 vs 3.17 mut/Mb, P = 0.025). In addition, the pCR rate of patients with wild-type PIK3CA is significantly higher than that of patients with mutated PIK3CA (88.9% vs 14.3%, P < 0.001). Conclusions: Preliminary results suggested that HER2-positive breast cancer patients with higher TMB and activating mutations in PIK3CA are less likely to benefit from pyrotinib combined with trastuzumab neoadjuvant therapy, which need larger sample size to validate. *Qiyun Shi and Juncheng Xuhong contributed equally. #Co-corresponding author (Dr. Jun Jiang, [email protected]; Dr. Xiaowei Qi, [email protected]). Clinical trial information: ChiCTR1900022293.


2021 ◽  
pp. 107815522110055
Author(s):  
Amsalu Degu ◽  
Asha Yussuf

Background The incidence of human epidermal growth factor receptor 2 (HER 2) positive breast cancers is rapidly rising worldwide. Although there have been many studies on HER 2 breast cancer treatment and management in recent years, there is a lack of comprehensive reports on the treatment outcomes and disparities within the available literature. Hence, this review aimed to determine the treatment outcomes and their associated factors among patients with HER2-positive breast cancer. Methods A computer-based systematic literature search was conducted using PubMed, EMBASE, and Google scholar databases of articles published from 2000 to 2020. The following key terms (HER 2 positive breast cancer, predictor, determinant, associated factor) and Medical Subject Headings (MeSH) terms (breast neoplasms, treatment outcome, and risk factors) were used to search the English language published articles. Results In most studies, trastuzumab was the most commonly used treatment regimen used in combination with chemotherapeutic agents. Generally, most of the studies (15 studies) showed that the overall survival outcome was relatively higher after treatment among HER2 positive breast cancer patients. Nonetheless, two studies showed that the absence of significant change in the overall survival despite adequate treatment was given to the study participants. In addition, three studies demonstrated a partial response after treating HER2-positive breast cancer patients. Conclusion Generally, the overall survival outcome was relatively higher after treatment among HER2 positive breast cancer patients. The addition of trastuzumab in most of the studies has shown improvement in the overall survival and the disease-free survival rate of the study patients.


Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3540
Author(s):  
Hamid Maadi ◽  
Mohammad Hasan Soheilifar ◽  
Won-Shik Choi ◽  
Abdolvahab Moshtaghian ◽  
Zhixiang Wang

Trastuzumab as a first HER2-targeted therapy for the treatment of HER2-positive breast cancer patients was introduced in 1998. Although trastuzumab has opened a new avenue to treat patients with HER2-positive breast cancer and other types of cancer, some patients are not responsive or become resistant to this treatment. So far, several mechanisms have been suggested for the mode of action of trastuzumab; however, the findings regarding these mechanisms are controversial. In this review, we aimed to provide a detailed insight into the various mechanisms of action of trastuzumab.


Breast Care ◽  
2021 ◽  
pp. 1-7
Author(s):  
Christoph Suppan ◽  
Daniel Steiner ◽  
Eva Valentina Klocker ◽  
Florian Posch ◽  
Elisabeth Henzinger ◽  
...  

<b><i>Background:</i></b> The addition of trastuzumab to standard chemotherapy has improved survival in patients with HER2-positive breast cancer in neoadjuvant, adjuvant, and metastatic settings. In higher tumor stages, the addition of pertuzumab is now a standard of care and associated with a favorable toxicity profile. We evaluated the safety and efficacy of the trastuzumab biosimilar SB3 in combination with pertuzumab in HER2-positive breast cancer patients. <b><i>Methods:</i></b> Seventy-eight patients with HER2-positive breast cancer treated at the Division of Oncology at the Medical University of Graz were included. Summary measures are reported as medians (25th to 75th percentile) for continuous variables and as absolute frequencies (%) for count data. <b><i>Results:</i></b> Thirty-five patients received a median of 4 (3–7) cycles of trastuzumab biosimilar SB3 plus pertuzumab. All patients had a normal baseline left ventricular ejection fraction (LVEF; &#x3e;50%) prior to the initiation of SB3 plus pertuzumab treatment with a median LVEF of 60% (60–65). Twenty-one patients had a median absolute LVEF decline of 1% (–5 to 0). Two patients (5.7%) had a LVEF reduction ≤50%, but none ≥10%. There were no unexpected adverse events. Twenty-two of 35 patients (63%) were treated with trastuzumab biosimilar SB3 and pertuzumab in the neoadjuvant setting and 11 patients (50%) achieved a pathological complete response. The safety and the efficacy in this setting was comparable to the trastuzumab plus pertuzumab combination in neoadjuvantly treated matched samples. <b><i>Conclusion:</i></b> In this series of HER2-positive breast cancer patients, the combination of SB3 plus pertuzumab was consistent with the known safety and efficacy profile of trastuzumab and pertuzumab combination.


2021 ◽  
Author(s):  
Gloria Tuwei ◽  
Amsalu Degu

Abstract Background: For several years, HER2-positive breast cancer was associated with poor outcomes and higher mortality rates than other breast cancer subtypes. Nevertheless, the advent of Trastuzumab has significantly changed the treatment paradigm of HER2-positive breast cancer. However, it is not an affordable treatment option in sub-Saharan African countries. Besides, there was a lack of comprehensive data about the survival outcomes of HER2-positive breast cancer patients in our setting. Hence, the present study aimed to determine the survival outcomes among HER2-positive breast cancer patients at the Oncology Department of Kenyatta National Hospital.Methods: A hospital-based retrospective cohort design was used to evaluate the survival outcomes, and associated factors among patients with HER2-positive breast cancer admitted between 2015 and 2019 at Kenyatta National Hospital. A total of 50 eligible HER2-positive breast cancer patients were included in the study. In the pre-designed data abstraction tool, the data were collected by reviewing the medical records of the patients. The data were entered and analyzed using the Statistical Package for the Social Sciences version 27 software. The mean survival time was estimated using Kaplan Meier survival analysis. Cox regression analysis was employed to estimate the predictors of mortality among HER2-positive breast cancer patients.Results: The study showed that the overall survival rate was 30%, with a significant decrease in the percentage survival rate across the five years. More than half of the study participants (26, 52%) showed cancer progression during the last follow-up period. The present study showed that the mean cancer-specific survival rate among the study patients was 26.74±18.395 months. The study showed that the mean survival time of patients aged below 60 years (32.513 months), without co-morbidities (34.40 months), and the early stage of the disease (50.639 months) was higher than their counterparts. Multivariate cox-regression analysis revealed that advanced stage (AHR=13.1, 95% CI=2.6-66.6, P=0.002 and distant metastasis (AHR=15.0, 95% CI=3.6-62.8, P≤0.001) were the significant predictors of mortality among HER2 positive breast cancer patients.Conclusions: The overall survival rate of HER 2 positive breast cancer was 30%. Advanced stage and distant metastasis were the significant predictors of mortality among HER2-positive breast cancer patients.


2020 ◽  
Vol 31 ◽  
pp. S332
Author(s):  
M. Lopez ◽  
C. Minguito Carazo ◽  
I. Delgado Sillero ◽  
M. Rojas Piedra ◽  
B. Távara Silva ◽  
...  

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