A Study of the Gut Microbiome in Hormone Receptor-positive HER2-negative Breast Cancer Treated With CDK4/6 Inhibitors

Summary

Ciclibiome is a prospective study including BC patients starting treatment with a CDK4/6 inhibitor (in the metastatic and in the adjuvant setting). This study will focus on the interplay between the gut microbiome (its composition and evolution during treatment), circulating immune, metabolic and cytokine biomarkers (before and during treatment), and response outcomes to the CDK4/6 inhibitor. The main aim of the study is to highlight the existence of a microbial, immune and/or metabolic biomarker of response to CDK4/6 inhibition in BC, assessable by a stool or blood sample examination. Ultimately, this will allow to study new potential combination partners for CDK4/6 inhibitors in escalation trials for poor prognosis patients.

Eligibility

\* Cohort of metastatic HR-positive HER2-negative breast cancer :

Inclusion Criteria:

Patients that respond to each of these criteria can be included :

* Diagnosis of previously untreated HR+ HER2- advanced breast cancer (defined as locally advanced and unresectable, or metastatic). HR+ defined as positive estrogen receptors as per local laboratory testing. HER2- defined as negative ISH test or an IHC status of 0 or 1+ as per local laboratory testing.
* Planned first-line treatment with an endocrine therapy (aromatase inhibitor or fulvestrant) and a CDK4/6i.
* Male or female ≥ 18 years of age at the time the informed consent is signed.
* Being able to provide written informed consent.
* Patients with a history of early breast cancer are allowed providing systemic therapy (including adjuvant endocrine therapy) was discontinued more than 6 months ago.
* Patients are willing and able to comply with the protocol for the duration of the study including sample collection.
* Paraffin-embedded tumor tissue available at diagnosis of metastatic disease (inclusion to be discussed if not available).

Exclusion Criteria:

Patients who respond to any of these criteria are excluded :

* Administration of the CDK4/6i already started.
* Concurrent or previous non breast-related malignancy in the last 3 years prior to the start of the study treatment (with the exception of a history of adequately treated cervical carcinoma in situ or non-melanoma skin cancer).
* Treatment or chronic prevention of an infection through oral or intravenous antibiotic administered less than 1 month ago. History of unique antibiotic administration as prophylaxis for an invasive procedure is allowed.
* Active disease requiring treatment with an immunomodulatory agent. Low dose oral corticosteroids (equivalent to 8 mg or less of prednisone) or topical corticosteroids are allowed.
* Serological positivity for human immunodeficiency virus (HIV) or hepatitis C (HCV).
* Known active hepatitis.
* Active inflammatory bowel disease or documented malabsorption.
* Alcohol consumption (\>3 glasses/day).

  * Cohort of early HR-positive HER2-negative breast cancer at high risk of relapse :

Inclusion criteria :

Patients that respond to each of these criteria can be included :

* Early HR+ HER2- node-positive breast cancer considered at high risk of relapse (≥ 4 positive lymph nodes, or 1-3 positive lymph nodes and either or both grade 3 or tumor size \> 5 cm). HR+ defined as positive estrogen receptors as per local laboratory testing. HER2- defined as negative ISH test or an IHC status of 0 or 1+ as per local laboratory testing.
* Planned adjuvant treatment with a CDK4/6i, in combination with an endocrine therapy (aromatase inhibitor or tamoxifen, with or without LHRH agonists).
* Male or female ≥ 18 years of age at the time the informed consent is signed.
* Being able to provide written informed consent.
* Patients are willing and able to comply with the protocol for the duration of the study including sample collection.
* Paraffin-embedded tumor tissue available at diagnosis of the disease or at surgical resection (inclusion to be discussed if not available).

Exclusion criteria :

Patients who respond to any of these criteria are excluded :

* Administration of the CDK4/6i already started. Ongoing administration of the endocrine therapy before study inclusion is allowed.
* Concurrent or previous non breast-related malignancy in the last 3 years prior to the start of the study treatment (with the exception of a history of adequately treated cervical carcinoma in situ or non-melanoma skin cancer).
* Treatment or chronic prevention of an infection through oral or intravenous antibiotic administered less than 1 month ago. History of unique antibiotic administration as prophylaxis for an invasive procedure is allowed.
* Active disease requiring treatment with an immunomodulatory agent. Low dose oral corticosteroids (equivalent to 8 mg or less of prednisone) or topical corticosteroids are allowed.
* Serological positivity for human immunodeficiency virus (HIV) or hepatitis C (HCV).
* Known active hepatitis.
* Active inflammatory bowel disease or documented malabsorption.
* Alcohol consumption (\>3 glasses/day).

Conditions2

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