Investigation of the Influence of Anti-Hormone Therapy, Menstrual Cycle, Risk Profile, and Growth Rate on Treatment Decisions for Hormone Receptor-Positive, HER2-Negative Breast Cancer

Breast cancer (mammary carcinoma) is a malignant disease of the mammary gland tissue in which certain cells of the mammary gland multiply uncontrollably. Treatment of the disease depends on numerous factors, such as the patient’s overall health, the tumor’s growth rate (Ki-67 index), the presence of detectable hormone receptors on the surface of the cancer cells (estrogen receptor-positive, progesterone receptor-positive), and the increased expression of the HER2 protein on the cells (HER2-positive). If hormone receptors are detected, anti-hormone therapy is a core element of treatment and can be used prior to surgical removal of the tumor (neoadjuvant). One class of drugs used in standard anti-hormone therapy is aromatase inhibitors such as anastrozole, letrozole, and exemestane, with or without GnRH agonists/antagonists (e.g., goserelin). Another group consists of “selective estrogen receptor modulators” (SERMs), which include tamoxifen. After surgery, further treatment (e.g., anti-hormonal therapy or chemotherapy) may be initiated (adjuvant). However, even with treatment, the disease may recur or become uncontrollable (refractory). An important factor in calculating the risk of disease recurrence is the so-called PAM50. This is a molecular diagnostic test that analyzes the activity of 50 genes in tumor tissue. Studies to date suggest that tumor growth in estrogen receptor-positive breast cancer may be influenced by the menstrual cycle. There is evidence that the increased levels of the hormone estradiol following ovulation are associated with an elevated Ki-67 index.

The aim of this observational study is to investigate the influence of the menstrual cycle phase on the tumor’s growth rate (Ki-67 index). Another objective is to examine the extent to which neoadjuvant anti-hormone therapy, the Ki-67 index, and the individual genetic risk profile (PAM50) may influence the recommendation for adjuvant therapy. To this end, patients are divided into three groups based on their current treatment. Patients receiving tamoxifen are included in Group A, and patients currently taking an aromatase inhibitor (possibly in combination with a GnRH agonist if they are premenopausal) are assigned to Group B. Group C includes patients who are not receiving neoadjuvant antihormonal therapy. As part of the study, blood tests are performed, questionnaires regarding the menstrual cycle are administered, and a tissue sample from the tumor is examined before surgery (via biopsy) and after surgical removal. After completion of treatment, patients will be followed up for up to 10 years.

Women aged 18 and older with hormone receptor-positive, HER2-negative, non-metastatic breast cancer are eligible to participate in this study. Both premenopausal and postmenopausal women are included in this study. The disease must be unilateral; in other words, only one breast may be affected. Patients must not be eligible for neoadjuvant chemotherapy, and the breast cancer must have been pretreated only with tamoxifen, aromatase inhibitors, or goserelin. Surgical removal of the tumor must be scheduled to take place in Tübingen or Freiburg. No other cancer may have been diagnosed in the past 10 years, and no hormonal birth control methods may have been used within the past 6 months.