Clinical Value of Next Generation Sequencing in Endocrine Therapy for Advanced Hormone Receptor Positive/HER-2 Negative Breast Cancer

Study Overview
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Brief Summary
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To determine the landscape of gene mutation before and after endocrine therapy, to search for molecular markers of endocrine therapy efficacy, and to explore the clinical value of using NGS detection of ctDNA to guide precise endocrine therapy in patients with advanced breast cancer. The primary endpoints were progression-free survival (PFS), and the secondary endpoints included overall survival time (OS), adverse events (AE), and severe adverse events (SAE).

Detailed Description
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Before treatment, the patients in the study group underwent NGS detection of ctDNA and formulated treatment plan according to the test results: 1) those with ESR1 mutation and who did not use fulvestrant before, preferred fulvestrant; 2) those with abnormal activation of PI3K/Akt/mTOR pathway signal, preferred mTOR inhibitor combined with endocrine therapy; 3) those with HER-2 sensitive point mutation, preferred anti-HER-2 therapy combined with endocrine therapy; 4) PDGFR mutation, preferential use of PDGFR inhibitors combined with endocrine therapy; 5) no significant gene mutation, making endocrine therapy plan according to the actual clinical situation. After 2 months of endocrine therapy, all patients underwent NGS detection of ctDNA, and the efficacy was evaluated according to RECIST v1.1 standard. If the efficacy evaluation is effective, continue the current treatment and re-evaluate the efficacy every two months; if the efficacy evaluation is ineffective (progress), then withdraw from this study. The vital signs, blood routine, liver and kidney functions and imaging examinations were examined at least every two months in the patients in the study group, and the curative effect was evaluated according to RECIST v1.1 standard.

Official Title
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Clinical Value of Next Generation Sequencing in Endocrine Therapy for Advanced Hormone Receptor Positive/HER-2 Negative Breast Cancer

Conditions
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Breast Neoplasm Female, Therapeutics, Mutation

Intervention / Treatment
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* Diagnostic Test: Next Generation Sequencing (NGS) detection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years, female； Pathologically and immunohistochemically confirmed ER-positive/HER-2-negative patients with advanced breast cancer； According to RECIST standard, lesions can be measured (primary lesion length > 1.0 cm or lymph node diameter > 1.5 cm)； Previous endocrine therapy resistance, preparation for second-or-above-line endocrine therapy； No visceral crisis； ECOG PS score: 0-2 points; Laboratory criteria: ① white blood cells were more than 4 x 109 /L, and neutrophil count (ANC) was more than 1.5 x 109 /L. ② platelet (>100 *109/L); hemoglobin (>10g/dL); serum creatinine (<1.5 *normal value) upper limit (ULN); aspartate aminotransferase (AST) (<2.5 *ULN); alanine aminotransferase (ALT) (<2.5 *ULN); total bilirubin (<1.5 *ULN); serum creatinine (<1.5 *ULN); the volunteers voluntarily joined the study, signed informed consent, and had good compliance and follow-up. Exclusion Criteria: Pregnant or lactation woman With mental disease With severe infection or active gastrointestinal ulcers With severe liver disease (such as cirrhosis), kidney disease, respiratory disease or diabetes taking part or participating in other clinical trials within one month.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NGS detection group<br>Before treatment, the patients in the study group underwent NGS detection of ctDNA and formulated endocrine treatment plan according to the test results. After 2 months of endocrine therapy, all patients underwent NGS detection of ctDNA, and the efficacy was evaluated according to RECIST v1.1 standard. | Diagnostic Test: Next Generation Sequencing (NGS) detection<br>* The NGS detection panel is designed by our team and covers genes that are clinically useful and have definite guiding significance for endocrine therapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) | From date of first use endocrine treatment until the date of first documented progression or date of death from any cause, whichever came first | up to 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) | Time from first use endocrine treatment to death | up to 60 months | 
| Adverse events (AEs) | Adverse events (AEs) and laboratory tests graded according to the NCI CTCAE (version 4.0) | up to 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast Neoplasm, Next Generation Sequencing, Endocrine Therapy