Exploring the gut microbiome in breast cancer patients treated with CDK4/6 inhibitors

\* 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).