Observational study on anti-hormonal therapies for hormone receptor-positive breast cancer in premenopausal and perimenopausal women. The study also evaluates the effect of suppressing hormone production (ovaries) and the benefits of a specific test (MammaPrint® test) for predicting the risk of recurrence.

Breast cancer (mammary carcinoma) is a malignant disease of the breast tissue in which cells multiply uncontrollably. Treatment of the disease depends on numerous factors. An important consideration is whether the affected woman has already reached menopause or not (premenopausal or perimenopausal). In addition, the biological characteristics of the tumor are examined, such as the growth rate (Ki-67 index), the presence of hormone receptors on the surface of the cancer cells (estrogen receptor-positive/progesterone receptor-positive), and the increased expression of the HER2 receptor on the cells (HER2-positive). Women who have not yet reached menopause have higher levels of sex hormones, such as estrogen, in their blood, which can promote the growth of hormone receptor-positive cancer cells. The main source of estrogen in premenopausal women is the ovaries. This is a crucial factor in the treatment and prevention of recurrence.

The standard treatment for this disease consists of anti-hormone therapy, usually administered over several years. If the risk of recurrence is elevated, chemotherapy is also administered. The question of whether ovarian function should also be suppressed has not been conclusively resolved. The higher the risk of recurrence and the younger the patient, the more likely it is that suppressing ovarian hormone production (OHS) will be beneficial. This can be achieved through surgical removal of the ovaries, medication (GnRH analogs), or radiation therapy. While the risk of recurrence has traditionally been assessed “clinically” based on tumor extent, lymph node involvement, and conventional biomarkers (e.g., hormone receptors, Ki-67), the MammaPrint® test analyzes excised tumor tissue for genetic alterations that are intended to predict the risk of recurrence based on the genetic characteristics of the tumor cells. This allows treatment to be tailored more precisely to the patient’s individual risk.

The goal of the PROOFS study is to compare the effectiveness of various standard treatment regimens in hormone-receptor-positive women (premenopausal) with regard to the assessment of relapse risk based on “clinical” criteria (see above) and the results of the MammaPrint® test. The study aims to demonstrate that patients with a low genetic risk according to MammaPrint® have good chances of recovery even without chemotherapy if they are treated with hormone therapy and, if necessary, OFS. The study will also examine how ovarian function suppression is managed in patients following chemotherapy and how reliably patients adhere to anti-hormone therapy. Additionally, the study will assess how well conventional biomarkers predict prognosis compared to the genetic test. Finally, the patients’ quality of life will be monitored over a period of five years.

Women aged 18 to 60, either premenopausal or postmenopausal, whose tumors were examined via a tissue sample (biopsy) prior to the start of treatment are eligible to participate in the study. The tumor must be hormone receptor-positive and HER2-negative and must not have spread (metastasized). The breast cancer must be in an early stage (locally confined, Stage 1–2), although lymph node involvement may be present in some patients. The genetic risk must have been determined using MammaPrint® and must be low, while the “clinical” risk of recurrence—based on traditional criteria such as tumor size—must be classified as moderate to high.