Breast Cancer, Hormone Receptor-positive Breast Cancer, Hormone Therapy
Conditions
Keywords
CDK4, 6 inhibitor, Neoadjuvant therapy, Hormone therapy, Hormone Receptor-positive Breast Cancer
Brief summary
The 3 FDA-approved CDK4, 6 inhibitors, palbociclib, ribociclib, and abemciclib, all provided progression-free survival benefits when combined with endocrine therapy in advanced ER+/HER2- breast cancer. But, not all of them provided overall survival benefit in the same setting. One of the proposed mechanisms that influence the overall survival difference is from the different influence of the 3 CDK4, 6 inhibitors on tumor microenvironment and/ or immune system. However, there was no head-to-head comparison of the 3 CDK4, 6 inhibitors in the same study. Neoadjuvant therapy provides a window to obtain tissue samples before treatment, during treatment, and after treatment. We aim to compare the immune modulation effects of palbociclib, ribociclib, and abemaciclib with letrozole in neoadjuvant treatment for ER+/HER2- early breast cancer.
Detailed description
The 3 FDA-approved CDK4, 6 inhibitors, palbociclib, ribociclib, and abemciclib, all provided progression-free survival benefits when combined with endocrine therapy in advanced ER+/HER2- breast cancer. But, not all of them provided overall survival benefit in the same setting. One of the proposed mechanisms that influence the overall survival difference is from the different influence of the 3 CDK4, 6 inhibitors on tumor microenvironment and/ or immune system. However, there was no head-to-head comparison of the 3 CDK4, 6 inhibitors in the same study. Neoadjuvant therapy provides a window to obtain tissue samples before treatment, during treatment, and after treatment. We aim to compare the immune modulation effects of palbociclib, ribociclib, and abemaciclib with letrozole in neoadjuvant treatment for ER+/HER2- early breast cancer. We will collect tumor tissue, blood, and stool samples prospectively before treatment, at 2 weeks after treatment, and after 12 weeks of treatment at the time of surgery. Immune modulation effects will be compared between 3 treatment groups from breast tumor RNAseq analysis.
Interventions
DRUGPalbociclib
CDK4, 6 inhibitor
DRUGRibociclib
CDK4, 6 inhibitor
DRUGAbemaciclib
CDK4, 6 inhibitor
DRUGLetrozole
Endocrine therapy
Sponsors
National Taiwan University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Female patients aged ≥ 20 years old at the time of informed consent. * Patient has a histologically and/or cytologically confirmed diagnosis of estrogen-receptor positive and/or progesterone receptor positive breast cancer based on the most recently analyzed tissue sample and all tested by local laboratory. with estrogen receptor positive (\>10%) on IHC staining and HER2 negative (IHC 0+/1+, or IHC 2+ plus FISH negative) * Stage II to III * With adequate organ function * ECOG 0-1
Exclusion criteria
* Pregnant or nursing (lactating) women * Women of child-bearing potential unless using highly effective methods of contraception during study drug dosing and for 12 months post-dosing * Patients with active systemic infections or known to have AIDS or to test positive for HIV antibody at Screening * Any other disease or condition that could interfere with participation in the study according to the study protocol, or with the ability of the patients to cooperate and comply with the study procedures.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The expression of immune-related signature change after different CDK4/6 inhibitor treatments by RNAseq | Through study completion, an average of 3 years | Characterization of RNAseq from serial tumor biopsy samples |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adverse events | 4 months | According to CTCAE 4.03 |
Countries
Taiwan
Contacts
Primary ContactYen-Shen Lu, MD, PhD
Outcome results
None listed