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

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).