Ovarian Function Suppression (OFS) is a treatment approach for premenopausal women with hormone receptor-positive breast cancer. This therapy reduces the body’s estrogen production, a hormone that can promote the growth of certain breast cancer cells. The goal of OFS is to diminish the hormonal environment that supports cancer progression.
Understanding Ovarian Function Suppression
Ovarian function suppression targets hormone receptor-positive (HR+) breast cancer, which accounts for approximately 70% to 80% of all breast cancer tumors. These cancer cells possess specific proteins called hormone receptors that bind to estrogen or progesterone, signaling the cells to grow and multiply. Estrogen is considered the primary hormone that fuels the growth of these cancer cells.
In premenopausal women, the ovaries are the main source of estrogen production. By suppressing the function of the ovaries, OFS aims to lower overall estrogen levels, thereby inhibiting the growth of HR+ breast cancer cells. This treatment is a component of adjuvant endocrine therapy for premenopausal patients, often combined with other hormonal treatments.
Methods of Achieving Ovarian Function Suppression
Several methods can be employed to achieve ovarian function suppression, each with distinct characteristics regarding permanence and reversibility. Surgical oophorectomy involves the permanent removal of both ovaries, leading to an immediate and irreversible cessation of ovarian estrogen production. This method can be considered for women with an increased risk of ovarian cancer or those who desire permanent OFS.
Radiation therapy can also induce ovarian failure, permanently impairing the ovaries’ ability to produce hormones. Both surgical removal and radiation-induced ablation result in a permanent interruption of ovarian estrogen synthesis.
Medical suppression, primarily through the use of gonadotropin-releasing hormone (GnRH) agonists, offers a temporary and potentially reversible way to achieve OFS. Drugs like goserelin (Zoladex) and leuprolide (Lupron) work by initially stimulating and then desensitizing the pituitary gland’s GnRH receptors. This action suppresses the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), which are hormones that signal the ovaries to produce estrogen. The temporary nature of GnRH agonists means that ovarian function may return after the medication is stopped, though this is not guaranteed for all patients.
OFS as Part of a Comprehensive Treatment Plan
Ovarian function suppression is often integrated into a broader treatment strategy for premenopausal women with hormone receptor-positive breast cancer to enhance outcomes. It is frequently combined with other endocrine therapies, such as tamoxifen or aromatase inhibitors. Tamoxifen works by blocking estrogen receptors on cancer cells, preventing estrogen from binding and stimulating growth. The addition of OFS to tamoxifen has shown improvements in disease-free survival and overall survival in studies.
Aromatase inhibitors (AIs), such as anastrozole, letrozole, and exemestane, primarily block the production of estrogen in non-ovarian tissues, like fat cells. In premenopausal women with functioning ovaries, AIs alone are generally not effective because the ovaries continue to produce significant amounts of estrogen. Therefore, for AIs to be effective in this patient population, OFS is necessary to shut down ovarian estrogen production, creating a low-estrogen environment where AIs can work efficiently.
Pivotal clinical trials, including the Suppression of Ovarian Function Trial (SOFT) and the Tamoxifen and Exemestane Trial (TEXT), have provided substantial evidence supporting the benefits of these combination strategies. These trials demonstrated that combining OFS with tamoxifen or exemestane improved disease-free survival and, in some cases, overall survival, particularly for younger women with a higher risk of recurrence. The SOFT trial, for instance, showed that tamoxifen plus OFS resulted in better disease-free survival and overall survival compared to tamoxifen alone. These studies underscore that intensifying adjuvant endocrine therapy, especially with OFS, can be beneficial for patients at a higher risk of recurrence.
Navigating the Effects of Ovarian Function Suppression
Undergoing ovarian function suppression can lead to various side effects, as the treatment induces a menopausal state. Common symptoms include hot flashes, night sweats, vaginal dryness, changes in mood, and a decrease in libido.
A significant long-term health consideration with OFS is its impact on bone health. The reduction in estrogen levels can lead to an increased risk of bone mineral density loss, potentially resulting in osteoporosis and a higher chance of fractures. Regular monitoring of bone density, often through bone scans, is recommended. Strategies to mitigate bone loss include calcium and vitamin D supplementation, and in some cases, bisphosphonate medications may be prescribed.
For premenopausal women, the implications of OFS for future fertility are a serious concern. Since OFS aims to halt ovarian function, it can compromise the ability to conceive naturally. Discussions about fertility preservation options, such as egg or embryo freezing, are important and should ideally occur before initiating OFS.
Given that OFS therapy is often administered for an extended period, typically 5 to 10 years, consistent adherence is important for maximizing treatment effectiveness. Managing side effects and open communication with the healthcare team about any side effects or concerns can help in developing strategies to manage them effectively and support long-term compliance.