Harbor-UCLA Medical Center, Department of Medicine, Torrance, CA.
Harbor-UCLA Medical Center, Department of Medicine, Torrance, CA; Los Angeles Biomedical Research Institute at the Harbor-UCLA Medical Center, Torrance, CA.
Clin Breast Cancer. 2014 Jun;14(3):147-53. doi: 10.1016/j.clbc.2013.12.010. Epub 2013 Dec 27.
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.
尽管他莫昔芬(tamoxifen)作为激素受体阳性乳腺癌绝经前女性的标准辅助内分泌治疗已超过 20 年,但新出现的结果表明,在接受他莫昔芬治疗 5 年后,无论绝经后患者转为芳香化酶抑制剂,还是继续接受他莫昔芬治疗 5 年,都可以进一步降低复发风险。因此,更多的绝经前乳腺癌患者将在绝经过渡期间继续辅助内分泌治疗。在这种情况下,人们开始关注他莫昔芬是否需要延长至 10 年使用,以及何时以及是否适合转为芳香化酶抑制剂。此外,人们现在认识到,在最后一次月经后,雌激素水平大约会下降 2 年,并且化疗和/或他莫昔芬诱导的闭经会妨碍可靠的卵巢功能测定。由于芳香化酶抑制剂仅在没有卵巢雌激素产生的低雌激素环境中有效,因此,确定围绝经期和近期绝经后女性的最佳内分泌辅助治疗方案是一项挑战,需要了解当前的临床研究结果以及治疗干预、卵巢功能和临床结局之间的潜在相互作用。可选择的方案包括他莫昔芬治疗 10 年、他莫昔芬治疗 5 年后转为芳香化酶抑制剂、他莫昔芬联合促黄体生成激素释放激素(luteinizing hormone-releasing hormone,LHRH)激动剂、芳香化酶抑制剂联合 LHRH 激动剂或芳香化酶抑制剂联合双侧卵巢切除术。虽然已完成(Austrian Breast Cancer Study Group [ABCSG]-12)和正在进行(SOFT [Suppression of Ovarian Function Trial]、TEXT [Tamoxifen and Exemestane Trial])的临床试验正在解决一些问题,但仍有许多问题需要根据个体情况进行判断。以下是支持该治疗选择的依据以及临床管理建议。
Breast Cancer Res Treat. 2003
Clin Breast Cancer. 2007-2
Curr Opin Obstet Gynecol. 2010-2
Cochrane Database Syst Rev. 2009-10-7
Clinics (Sao Paulo). 2020-4-3
Clin Adv Hematol Oncol. 2015-10