Is Pathologic Complete Response a Valid Surrogate Parameter of Treatment Efficacy in HER2 Positive Breast Cancer Patients Undergoing Primary Chemotherapy Plus Trastuzamab?

2005 ◽  
Vol 23 (31) ◽  
pp. 8130-8131 ◽  
Author(s):  
Alfredo Berruti ◽  
Daniele Generali ◽  
Maria Pia Brizzi ◽  
Mara Ardine ◽  
Luigi Dogliotti ◽  
...  
Breast Care ◽  
2019 ◽  
Vol 14 (6) ◽  
pp. 388-393
Author(s):  
Xinguang Wang ◽  
Yingjian He ◽  
Zhaoqing Fan ◽  
Tianfeng Wang ◽  
Yuntao Xie ◽  
...  

Background: We sought to investigate the incremental benefit of trastuzumab in patients with HER2-positive breast cancer who achieved a pathologic complete response (pCR) after neoadjuvant chemotherapy (NACT). Methods: The data of HER2-positive invasive breast cancer patients treated with NACT and achieving pCR were obtained from the institutional database. Patients were categorized according to trastuzumab administration. The Kaplan-Meier method and log-rank estimates were used to test the association between trastuzumab administration and survival. Univariate and multivariate Cox regressions were used to obtain hazard ratios. Results: Of 223 patients, 83 (37.2%) were treated with NACT without trastuzumab and 140 (62.8%) were treated with NACT plus trastuzumab for 1 year. After a median follow-up of 67 months, the trastuzumab group showed improved relapse-free survival compared with the no-trastuzumab group (95.7 vs. 87.8%, hazard ratio = 0.31, p = 0.028). No significant difference in distant disease-free survival or overall survival was observed (p = 0.250 and 0.432, respectively). Multivariate analysis identified endocrine therapy and trastuzumab administration to be associated with decreased risk of relapse (p = 0.018 and 0.030, respectively). Conclusion: The administration of trastuzumab should be considered standard treatment for HER2-positive patients who have achieved pCR after NACT alone.


Author(s):  
Ji Young You ◽  
Kyong Hwa Park ◽  
Eunsook Lee ◽  
Youngmee Kwon ◽  
Kyungtae Kim ◽  
...  

Background: We aimed to identify overexpressed genes or related pathways associated with good responses to anti-HER2 therapy and to suggest a model for predicting drug response in neoadjuvant therapy with trastuzumab in HER2-positive breast cancer patients. Methods: We recruited 64 women with breast cancer and categorized them into three groups according to anti-HER2 therapy response. RNA from twenty core needle biopsy paraffin-embedded tissues and four cultured cell was extracted, reverse transcribed, and subjected to microarray. The obtained data were analyzed using Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and database for annotation, visualization, and integrated discovery. Results: In total, 6,656 genes differentially expressed between trastuzumab-susceptible and trastuzumab-resistant cell lines (3,224 upregulated and 3,432 downregulated). Expression changes in 34 genes in several pathways were found to be related to the response to trastuzumab-containing treatment, interfering with adhesion to other cells or tissues (focal adhesion) and regulating extracellular matrix interactions and phagosome action. Thus, decreased tumor invasiveness and enhanced drug effects might be the mechanisms explaining the better drug response in complete response group. Conclusions: This multigene assay-based study provides insights into breast cancer signal transduction and the possible prediction of treatment response to targeted therapies such as trastuzumab.


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.


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