Dynamic Monitoring of HER2 and ctDNA Specific Mutations in Patients With Recurrent or Metastatic Breast Cancer by Digital PCR
Dynamic Monitoring of HER2 and ctDNA Specific Mutations in Patients With Recurrent or Metastatic Breast Cancer by Digital PCR
This was a prospective, single-center clinical study. The study was designed to investigate
 the relationship between plasma HER2 amplification or specific mutations abundance and
 clinical response in patients with recurrent or metastatic breast cancer.
Patients were divided into two groups according to ctDNA HER2 amplification status by dPCR
 method. Group A consisted of patients with positive HER2 amplification at the time of
 enrollment. Plasma HER2 amplification status was measured by dPCR during dynamic monitoring.
 GroupB consists of patients with negative HER2 amplification when enrolled. Plasma samples
 were collected before treatment and breast cancer hotspot mutations were detected with NGS,
 According to the NGS test results, patient's specific mutations were analyzed and selected,
 which and plasma HER2 amplification status were measured by dPCR during dynamic monitoring.

 The study was designed to investigate the relationship between plasma HER2 amplification or
 specific mutations abundance and imaging assessment in patients with recurrent or metastatic
 breast cancer. And also to investigate the proportion of predicting in advance the treatment
 efficacy of recurrent or metastatic breast cancer by plasma HER2 ctDNA, as well as the median
 time difference between predicted clinical efficacy by changes in abundance of plasma HER2
 amplification specific mutations and medical imaging evaluation in patients.

 The study only focus on ctDNA detection and does not involve any interventions.
Inclusion Criteria:

 1. Confirmed by pathology and/or histology/cytology as breast cancer;

 2. Patients with recurrent or metastatic breast cancer who are 18 to 75 years old, not
 limited to the first relapse or metastasis;

 3. There are evaluable tumor lesions;

 4. Physical strength: ECOG score 0-1;

 5. The expected survival period is more than 3 months;

 6. Agree to be collected tissue specimen;

 7. The patient has no major organ dysfunction, agrees and can implement a treatment plan
 based on the patient's condition.

 8. Voluntary enrollment, good compliance, can be followed up and observed.

 Exclusion Criteria:

 1. Severe vital organs (heart, liver, kidney) dysfunction; clinically significant heart
 disease, classified by New York Heart Association (NYHA) as grade III-IV heart failure
 or more severe congestive heart failure or severe Arrhythmia requiring drug
 intervention; uncontrolled angina, uncontrolled arrhythmia or uncontrollable
 hypertension, electrocardiogram (ECG)-confirmed myocardial infarction within 6 months;

 2. Have a history of organ transplantation, splenectomy;

 3. Patients with other malignancies, except cured non-melanoma skin cancer, cervical
 carcinoma in situ, or other tumors that have been cured for at least 5 years;

 4. Moderate or severe renal impairment [creatinine clearance equal to or lower than
 50ml/min (calculated according to Cockroft and Gault equations)], or serum creatinine
 > normal upper limit (ULN); pulmonary function test FEV1 < 50% of estimated value;

 5. Parallel surgical treatment of other diseases is required;

 6. Patients who are pregnant or breast-feeding (women of childbearing age need to be
 examined for pregnancy); women of childbearing age must take contraceptive measures
 that the investigator considers effective;

 7. Patients with or showing signs of disseminated spongiform encephalopathy or family
 members have the disease;

 8. In the active period of other acute infectious diseases or chronic infectious
 diseases;

 9. Have uncontrolled epilepsy, central nervous system disease or a history of mental
 disorders;

 10. People with disabilities or with no legal capacity or legal capacity is limited;

 11. Those who received a research medication or formulation/treatment (ie, participated in
 other trials) within 4 weeks prior to enrollment;

 12. Other situations when the investigators believe that patients should not participate
 in this trial.

 Quitting criteria:

 1. The patient suffers from other diseases and needs to be immediately taken to other
 therapists, and is no longer suitable for sampling test;

 2. Diagnosis of encephalitis and other inflammatory neuropathies;

 3. After the enrollment, it is clearly determined that the subject does not meet the
 requirements of the subject;

 4. The investigator believes that the withdrawal of the trial is in the best interest of
 the subject;

 5. Pregnancy;

 6. Poor compliance, two consecutive failures to accept testing as planned;

 7. The patient him/herself or the researcher believes that it is medically required to be
 withdrawn from the study.

 8. For subjects who discontinued the study early, the reason for the early withdrawal
 should be recorded, and the time of the last visit should be recorded, and the
 inspection items at the time of early termination of the study should be completed in
 the last visit as much as possible.