From the Guidelines
Goserelin should be given to men with hormone receptor-positive metastatic breast cancer (HR+ MBC) to achieve medical castration by suppressing testosterone production, which is crucial for reducing estrogen-driven tumor growth. When treating male patients with HR+ MBC, goserelin is typically administered as a 3.6 mg subcutaneous implant every 28 days or as a 10.8 mg implant every 12 weeks, usually in combination with aromatase inhibitors like anastrozole or letrozole 1. This combination therapy is necessary because aromatase inhibitors alone in men can lead to increased testosterone levels through feedback mechanisms, potentially stimulating tumor growth. Goserelin works by initially stimulating the pituitary gland to release luteinizing hormone (LH), but with continued administration, it causes downregulation of GnRH receptors, ultimately suppressing LH release and testosterone production.
The use of goserelin in men with HR+ MBC is supported by the American Society of Clinical Oncology (ASCO) guideline, which recommends that men with hormone receptor-positive breast cancer who are candidates for adjuvant endocrine therapy but have a contraindication to tamoxifen may be offered a gonadotropin-releasing hormone (GnRH) agonist/antagonist and an aromatase inhibitor (AI) 1. Additionally, the guideline suggests that men with advanced or metastatic disease should be offered endocrine therapy as first-line therapy, except in cases of visceral crisis or rapidly progressive disease 1.
Some key points to consider when using goserelin in men with HR+ MBC include:
- Monitoring testosterone levels during treatment to ensure adequate suppression, with a target of achieving castrate levels (typically <50 ng/dL) 1
- Managing side effects, such as hot flashes, sexual dysfunction, bone density loss, and metabolic changes, throughout treatment 1
- Considering the use of goserelin in combination with aromatase inhibitors, as this combination has been shown to be effective in reducing estrogen-driven tumor growth 1
Overall, the use of goserelin in men with HR+ MBC is a crucial component of treatment, and its use should be guided by the most recent and highest-quality evidence available 1.
From the Research
Rationale for Goserelin in HR+ MBC for Men
- Goserelin, a GnRH agonist, is used to treat hormone receptor-positive metastatic breast cancer (HR+ MBC) by reducing testosterone levels, which can fuel the growth of HR+ breast cancer cells 2.
- The use of goserelin in men with HR+ MBC is based on its ability to suppress testosterone production, thereby reducing the stimulus for tumor growth 3.
- In premenopausal women, goserelin has been shown to improve distant recurrence-free interval when used in combination with tamoxifen or as a single agent 2.
Mechanism of Action
- Goserelin works by binding to gonadotropin-releasing hormone (GnRH) receptors in the pituitary gland, leading to a decrease in luteinizing hormone (LH) and follicle-stimulating hormone (FSH) production, which in turn reduces testosterone levels 3.
- The reduction in testosterone levels decreases the growth stimulus for HR+ breast cancer cells, leading to a decrease in tumor growth and progression 2.
Clinical Evidence
- A study published in 2022 demonstrated a 20-year benefit from adjuvant goserelin and tamoxifen in premenopausal patients with breast cancer, with significant improvements in distant recurrence-free interval 2.
- Another study published in 2016 discussed the use of immunotherapy and hormone-therapy in metastatic breast cancer, including the use of goserelin as a hormone-therapy option 3.
Treatment Considerations
- The use of goserelin in men with HR+ MBC should be considered in the context of the patient's overall treatment plan, including other hormone-therapy options and potential side effects 2, 3.
- The selection of goserelin as a treatment option should be based on individual patient characteristics, including tumor biology and medical history 4, 5, 6.