Neutrophil Extracellular Traps Formation in Breast Cancer Patients Taking Tamoxifen

PRIMARY OBJECTIVE:

I. To examine the effect of long-term tamoxifen (TAM) treatment on excessive NET formation in breast cancer patients.

SECONDARY OBJECTIVES:

I. To understand the molecular mechanisms of tamoxifen-induced NET formation in breast cancer patients by examining the effect of long-term TAM treatment on the NET-induced factors.

II. To correlate the extend of NET formation with clinical data on tamoxifen resistance, drug side-effects, cancer metastasis and comorbidities.

EXPLORATORY OBJECTIVE:

I. To explore the association between the extent of NET formation and clinical data for breast cancer patients treated with TAM in combination with other drugs.

OUTLINE:

Patients undergo collection of blood samples and their medical charts are reviewed.

Inclusion criteria

• Female
• Age criteria for pre-menopausal group: Equal to or greater than 18 years of age and less than or equal to 45 years of age. Patients of age 46-50 will be included if they have not had menstrual cessation for 12 consecutive months.
• Age criteria for menopausal group: At least 51 years of age (median age of menopause). Menopause is defined as cessation of menstrual cycle for 12 consecutive months.
• Diagnosed with ER+ breast cancer
• Being treated with tamoxifen (TAM) for at least 6 months
• CONTROL SUBJECTS: Newly diagnosed ER+ breast cancer patients of the same age group as above on TAM for 0-6 months. This criterion is based on our preliminary results showing that patients taking TAM for 6-7 months exhibit near baseline level of NETs

Exclusion criteria

• Pregnant -The immune modulations geared toward maintenance of pregnancy are known to cause wide-spread alterations in innate and adaptive immune cell functions. In this scenario, divorcing the pregnancy-related changes in myeloid cell function from those relevant to sepsis and cancer will be complicated.
• History of severe congenital neutropenia due to genetic disorders, such as Kostmann Disorder (HAX1 gene mutation), ELA2 gene mutation, Wiskott-Aldrich syndrome (WAS), Growth Factor Independent 1 Protein (GFI1) gene mutation, Colony Stimulating Factor 3 Receptor (CSF3R) gene mutation, Schwachman-Diamond Syndrome, Barth Syndrome, WHIM Syndrome, and Chadiak-Higashi Syndrome (this list notably does not include Myelodysplastic Syndrome, or Acute/Chronic Myeloid Leukemia)
• History of autoimmune disorders, which can affect the body's inflammatory response, such as rheumatoid arthritis, lupus, Crohn's disease, multiple sclerosis, and psoriasis.
• History of chronic viral infections (human immunodeficiency virus [HIV], hepatitis), which can lead to reduced or variable immune cell function.
• A recent positive coronavirus disease (COVID) test