These two conditions suggest resistance to HER2 in breast cancer

Issuing time:2018-10-23 00:00

Metastatic breast cancer lacks effective treatment, and is still a difficult problem in the field of breast cancer treatment.Her2 (human epidermal growth factor receptor-2) -positive breast cancer accounts for about one-third of all breast cancer patients. 20-30%, the prognosis is better Her2 Patients with negative breast cancer were even worse.


Peripheral blood circulating tumor  DNA (ctDNA) detection is one of the methods of liquid biopsy, as a non-invasive tumor detection technology has been in clinical application for many years.Ctdna Is a small molecule secreted from tumor tissue into the peripheral blood. DNA  Fragments, with the characterization of tumor-specific gene changes. Most of the research is based on analysis Ctdna One or more genetic mutations are used to monitor disease progression, but feasible criteria have not been identified to guide clinical practice.


Peking Union Medical College Hospital, Chinese Academy of Medical Sciences MAF The team conducted a clinical study aimed at assessing the likelihood of passing the sequence Ctdna Sequencing analysis of breast cancer resistance Her2 The feasibility of treating drug resistance.The study was included in the study  18. Example Her2 Patients with positive metastatic breast cancer who received oral anti Her1 / 2 Tyrosinase inhibitor therapy (clinical trial No. Nct01937689), during which a total of 52. Four plasma samples.Analysis of Blood of Breast Cancer Patients with Gene Targeting Capture Second Generation Sequencing  CtDNA.


stay  18. Example Her2 Among patients with positive metastatic breast cancer  14. One patient presented with a progressive event, and 14. Among the patients with progression 6. One patient was primary drug resistant.Before and after breast cancer treatment Ctdna Than we found, HER2  Gene amplification in primary drug resistant patients (4 / 6, 66.7%).The study also found that TP53 Gene ( 3 / 6 ),  50.0 % ) and  PI3K / mTOR  Pathway genes (3 / 6, 50.0%) mutation was also the main marker of primary drug resistance in breast cancer patients.


The results show that, if breast cancer patients have the following conditions that indicate resistance Her2 Resistance to treatment:


1. Persistent or recurrent peripheral blood  Her2 Amplification;


2. TP53 / PIK3CA / MOTOR / PTEN  The mutations in the related resistance genes range from zero to one or an increase    20 percent.


And CT The dynamics of breast cancer patients were analyzed according to predetermined criteria  Ctdna Can monitor the patient's resistance (sensitivity 85.7%, specificity 55.0%).In addition, dynamic Ctdna The monitoring standards are still there  Her2 Positive metastatic breast cancer plays an important role in the prognosis.


To sum up, the longitudinal gene Ctdna Sequencing can be used to monitor metastatic breast cancer resistance Her2 Treatment of drug resistance and anti-metastatic breast cancer  Her2 Precision therapy provides guidance.


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