title: Ovarian ablation for premenopausal breast cancer: A review of treatment considerations and the impact of premature menopause.
abstract: Historically, ovarian ablation (OA) was used as therapy for women with recurrent hormone-receptor-positive (HRP) premenopausal breast cancer. With the publication of the SOFT (Suppression of Ovarian Function Trial) and TEXT (Tamoxifen and Exemestane Trial) randomized trials, there is considerable interest in OA as an adjuvant treatment, either in combination with tamoxifen or an aromatase inhibitor (AI). Thus, we have reviewed current guidelines and key studies on this important topic and have highlighted the relevant biological and pharmacological aspects of the various endocrine therapies. The results of two key randomized trials addressing the use and controversies of OA in premenopausal breast cancer are discussed and recent research emphasizing the detrimental consequences of premature menopause and the cost-effectiveness of OA is presented. In low-risk patients with HRP premenopausal breast cancer, OA is not beneficial and tamoxifen remains the anti-hormone treatment of choice. In high-risk women (previous chemotherapy or women younger than 35), OA in combination with AI is more effective but is arguably not cost-effective, particularly when OA is achieved medically using a GnRH agonist/antagonist. Compared to tamoxifen alone, the SOFT trial showed a 4.5-7.7% reduction in breast cancer relapse using OA (in combination with either tamoxifen or AI) in high-risk women, though the 5-year overall survival benefit was limited (1.4-3.6%). Premature menopause is associated with long-term mortality risks and women often experience significant menopausal symptoms that impact on quality of life. These considerations should play a role in the treatment selection of those patients who may benefit from adjuvant OA.
authors.affiliation: Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Melica
authors.initials: M
authors.lastname: Nourmoussavi
authors.affiliation: Department of Medical Oncology, British Columbia Cancer Agency, Fraser Valley Centre, Surrey, British Columbia, Canada.
authors.forename: Gary
authors.initials: G
authors.lastname: Pansegrau
authors.affiliation: Department of Cellular and Physiological Sciences, University of British Columbia, British Columbia, Canada.
authors.forename: Jason
authors.initials: J
authors.lastname: Popesku
authors.affiliation: Department of Cellular and Physiological Sciences, University of British Columbia, British Columbia, Canada.
authors.forename: Geoffrey L
authors.initials: GL
authors.lastname: Hammond
authors.affiliation: Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Janice S
authors.initials: JS
authors.lastname: Kwon
authors.affiliation: Departments of Obstetrics and Gynecology and Surgical Oncology, British Columbia Cancer Agency and University of British Columbia, Vancouver, British Columbia, Canada. Electronic address: mark.carey@vch.ca.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Carey
mesh_terms: D055011:Ablation Techniques; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000737:chemistry / Q000628:therapy*; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D012739:Gonadal Steroid Hormones / Q000097:blood; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists / Q000037:antagonists & inhibitors; D006801:Humans; D008594:Menopause, Premature; D010052:Ovariectomy; D010053:Ovary / Q000187:drug effects / Q000528:radiation effects / Q000601:surgery; D017697:Premenopause; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D013629:Tamoxifen / Q000627:therapeutic use*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D004967:Estrogens; D012739:Gonadal Steroid Hormones; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013629:Tamoxifen; D007987:Gonadotropin-Releasing Hormone
keywords: Breast cancer; Ovarian ablation; Premature menopause