Adjuvant Endocrine Therapy of Perimenopausal and Recently Postmenopausal Women With Hormone Receptor-Positive Breast Cancer

Abstract

Although 5 years of tamoxifen has been the standard adjuvant endocrine therapy for premenopausal women with hormone receptor-positive breast cancer for more than 2 decades, emerging results suggest that either switching to an aromatase inhibitor after 5 years of tamoxifen when postmenopausal or continuing tamoxifen for an additional 5 years can further decrease relapse risk. As a result, more premenopausal breast cancer patients will be continuing adjuvant endocrine therapy through the menopause transition. In this setting, questions arise regarding continued tamoxifen use through 10 years and/or the timing and appropriateness of switching to an aromatase inhibitor. In addition, it is now recognized that estrogen levels substantially decline for approximately 2 years after the last menstrual period and that chemotherapy and/or tamoxifen-induced amenorrhea preclude reliable ovarian function determination. Because aromatase inhibitors are only effective in a low estrogen environment without ovarian estrogen production, determination of the optimal endocrine adjuvant therapy for perimenopausal women and those recently postmenopausal represent a challenge requiring understanding of current clinical study results and the potential for interactions among therapeutic interventions, ovarian function, and clinical outcome. Available options include tamoxifen for 10 years, tamoxifen for 5 years followed by aromatase inhibitors, tamoxifen with a luteinizing hormone-releasing hormone (LHRH) agonist, aromatase inhibitor with an LHRH agonist or aromatase inhibitor with bilateral oophorectomy. Although completed (Austrian Breast Cancer Study Group [ABCSG]-12) and ongoing (SOFT [Suppression of Ovarian Function Trial], TEXT [Tamoxifen and Exemestane Trial]) clinical trials are addressing some issues, many questions will remain requiring individualized clinical judgement. Rationale supporting the available endocrine therapy options in this setting and recommendations for clinical management follow.