Estrogens and breast cancer Original paper

What was studied?

The study investigates the relationship between estrogens and the development of breast cancer, focusing on how estrogen exposure impacts cancer risk and progression. The paper reviews various estrogenic compounds, including endogenous estrogens like estradiol and synthetic ones such as those used in hormone replacement therapy (HRT). It examines the molecular mechanisms by which estrogen acts on estrogen receptors (ER) to influence the proliferation of breast cancer cells. The study also evaluates the role of different estrogen metabolites and their involvement in cancer initiation, particularly highlighting the balance between estrogen’s beneficial effects on bone and cardiovascular health and its potential carcinogenic effects in breast tissue. The relationship between estrogen receptor-positive (ER+) breast cancer and treatment strategies, including selective estrogen receptor modulators (SERMs) and aromatase inhibitors, is also discussed.

Who was studied?

The research mainly focuses on women, particularly those at risk of breast cancer due to hormonal factors such as early menarche, late menopause, and long-term use of HRT. It also includes studies on postmenopausal women and how the use of estrogen-based therapies (e.g., HRT) affects their cancer risk. Additionally, the study looks at breast cancer survivors who are undergoing treatment with SERMs or aromatase inhibitors, and those at higher risk due to genetic factors such as mutations in the BRCA1/BRCA2 genes. The paper also evaluates how estrogen receptor expression, specifically ER-alpha and ER-beta, plays a critical role in the progression of breast cancer and how treatment strategies can influence this.

Most important findings

The study highlights the dual role of estrogens in breast cancer development. On one hand, estrogen promotes the growth of ER-positive breast cancer cells by binding to estrogen receptors, which triggers cell proliferation and resistance to apoptosis. On the other hand, selective estrogen receptor modulators (SERMs) like tamoxifen and aromatase inhibitors (AIs) like letrozole have shown to significantly reduce estrogen-driven breast cancer risk by either blocking estrogen receptors or lowering estrogen levels in postmenopausal women. The paper emphasizes the importance of timing and type of estrogen exposure in cancer risk. For example, long-term exposure to estrogen (whether endogenous or exogenous) is a major risk factor for the development of breast cancer, whereas early use of SERMs or AIs reduces recurrence and metastasis. Additionally, the study examines the influence of estrogen metabolism, particularly the 16α-hydroxyestrone pathway, which is associated with increased cancer risk, while other pathways like the 2-hydroxyestrone pathway are considered protective. The findings indicate that personalized treatment based on estrogen receptor status, genetic factors, and metabolism is crucial for minimizing the carcinogenic effects of estrogen.

Key implications

Clinicians should recognize the critical role of estrogen exposure in both the prevention and progression of breast cancer, particularly in patients with estrogen receptor-positive (ER+) cancers. The study suggests that timing of estrogen exposure, such as starting hormone therapy early versus late in life, can have significant effects on cancer risk. Selective estrogen receptor modulators (SERMs) and aromatase inhibitors should be considered for postmenopausal women at high risk of breast cancer or those undergoing breast cancer treatment. Understanding estrogen metabolism and genetic predisposition can further guide clinicians in making personalized treatment decisions. Moreover, prolonged estrogen exposure, particularly through HRT, should be carefully monitored in women, with consideration of alternative therapies or reduced estrogen use where appropriate. Future research into estrogen metabolites and their relationship with microbiome-related health may provide additional insights into how estrogen influences breast cancer risk and progression.