What is the role of the Progesterone (Pr) receptor in the female reproductive system and breast cancer?

From the Guidelines

The progesterone receptor (PR) plays a crucial role in the female reproductive system and breast cancer development, and its presence is a key factor in determining the effectiveness of hormonal therapies in breast cancer treatment. In the reproductive system, PR mediates progesterone's effects on the uterus, preparing the endometrium for embryo implantation, maintaining pregnancy, and regulating menstrual cycling. PR exists in two isoforms (PR-A and PR-B) that work together to control gene expression in target tissues. In breast tissue, PR cooperates with estrogen receptor to regulate normal breast development during puberty and pregnancy. In breast cancer, PR status serves as an important biomarker and prognostic indicator. PR-positive breast cancers generally have better outcomes and respond well to hormonal therapies like tamoxifen or aromatase inhibitors, as shown in a study by the American Society of Clinical Oncology 1. These treatments work by blocking hormone signaling that would otherwise promote cancer growth. The presence of PR often indicates a functional estrogen receptor pathway, as PR expression is typically induced by estrogen. Clinically, breast cancers are classified by their hormone receptor status (PR and ER) along with HER2 status to guide treatment decisions, and the American Society of Clinical Oncology has provided guidelines for the use of endocrine therapy in hormone receptor-positive breast cancer 1. Understanding PR's dual role in normal physiology and cancer helps explain why targeting hormone pathways remains a cornerstone of breast cancer treatment.

Some key points to consider in the treatment of breast cancer include:

• The use of adjuvant endocrine therapy in hormone receptor-positive breast cancer, as recommended by the American Society of Clinical Oncology 1
• The classification of breast cancers by their hormone receptor status (PR and ER) and HER2 status to guide treatment decisions 1
• The importance of PR status as a biomarker and prognostic indicator in breast cancer, with PR-positive breast cancers generally having better outcomes and responding well to hormonal therapies 1
• The role of PR in the female reproductive system, including its effects on the uterus and regulation of menstrual cycling, as well as its cooperation with estrogen receptor in breast tissue 1

Overall, the progesterone receptor plays a critical role in both the female reproductive system and breast cancer development, and its presence is a key factor in determining the effectiveness of hormonal therapies in breast cancer treatment. The most recent and highest quality study, published in 2016 by the American Society of Clinical Oncology, provides guidance on the use of endocrine therapy in hormone receptor-positive breast cancer, and recommends that PR status be used to guide treatment decisions 1.

From the FDA Drug Label

The physical examination should include special reference to blood pressure, breasts, abdomen and pelvic organs, including cervical cytology and relevant laboratory tests. Women with a strong family history of breast cancer or who have breast nodules should be monitored with particular care. Long-term intramuscular administration of Medroxyprogesterone acetate (MPA) has been shown to produce mammary tumors in beagle dogs.

The role of the Progesterone (Pr) receptor in the female reproductive system and breast cancer is not directly addressed in the provided drug label. However, it can be inferred that progesterone plays a role in the female reproductive system, as progestin therapy is mentioned to affect various aspects of female health, including menstruation and breast health.

• The label mentions the importance of monitoring women with a strong family history of breast cancer.
• It also notes that long-term administration of Medroxyprogesterone acetate (MPA) has been shown to produce mammary tumors in beagle dogs 2. However, the label does not provide direct information on the role of the Pr receptor in breast cancer.

From the Research

Role of Progesterone Receptor in Female Reproductive System

• The progesterone receptor (PR) is a master regulator in female reproductive tissues, controlling developmental processes and proliferation and differentiation during the reproductive cycle and pregnancy 3, 4.
• PR plays a crucial role in the regulation of target gene expression in response to binding its cognate steroid hormone, progesterone 3, 4.
• The progesterone receptor is a member of the nuclear receptor family of ligand-dependent transcription factors 3, 4.

Role of Progesterone Receptor in Breast Cancer

• PR also plays a role in the progression of endocrine-dependent breast cancer 3, 4.
• The expression of PR in breast cancer cells can influence the growth and progression of the disease 5, 6.
• Studies have shown that the loss of PR status in breast cancer cells can occur after neoadjuvant chemotherapy, which may have significant clinical implications 6.

Interaction between Progesterone Receptor and Estrogen Receptor

• The progesterone receptor can interact with the estrogen receptor (ER) to regulate the expression of target genes 7.
• The interaction between PR and ER can influence the growth and progression of breast cancer cells, particularly in ER-positive breast cancer 7.
• Different progestins can differentially regulate the interaction between PR and ER, which may have implications for the treatment of breast cancer 7.