年轻女性乳腺癌治疗相关闭经因素

　　对于年轻女性乳腺癌患者，围绕治疗相关闭经存在独有的治疗问题和生存问题，包括生育力保护和卵巢功能管理等内分泌治疗。

　　2021年7月27日，英国《自然》旗下《乳腺癌》在线发表美国哈佛大学达纳法伯癌症研究所、麻省总医院、贝斯以色列和新英格兰女执事医疗中心、梅奥医学中心、康奈尔大学威尔医学院、斯坦福大学、科罗拉多大学癌症中心、加拿大多伦多大学森尼布鲁克健康科学中心、意大利热那亚大学圣马蒂诺综合医院的年轻女性乳腺癌研究报告，对年轻女性乳腺癌治疗相关闭经影响因素进行了大样本前瞻定量分析。

HOHO (Helping Ourselves, Helping Others): The Young Women's Breast Cancer Study (NCT01468246)

　　该多中心前瞻队列研究对2006～2016年被诊断为乳腺癌的年龄≤40岁女性自我报告月经结局进行连续调查，通过逻辑回归模型对治疗相关闭经影响因素进行分析。

　　结果发现，被诊断为乳腺癌后，第1年789例患者其中286例（36.2%）发生治疗相关闭经，但是大多数恢复月经，第2年699例患者其中120例（17.2%）发生治疗相关闭经。

　　第1年治疗相关闭经率较高的显著影响因素包括：

  • 年龄较大（36～40岁与≤30岁、31～35岁相比，治疗相关闭经率高71%、33%，P=0.02）

  • 体重指数正常（正常与超重相比，治疗相关闭经率高41%，P<0.01）

  • 化疗（化疗与不化疗相比，治疗相关闭经率高555%，P<0.01）

  • 他莫昔芬（用与不用相比，治疗相关闭经率高155%，P=0.01）

　　大多数标准治疗方案的治疗相关闭经率相似，除了多柔比星＋环磷酰胺、紫杉醇＋曲妥珠单抗：

  • 多西他赛＋卡铂＋曲妥珠单抗±帕妥珠单抗：55.6%

  • 多西他赛＋环磷酰胺±曲妥珠单抗和帕妥珠单抗：41.8%

  • 多柔比星＋环磷酰胺＋紫杉醇±曲妥珠单抗和帕妥珠单抗：44.1%

  • 多柔比星＋环磷酰胺：25%

  • 紫杉醇＋曲妥珠单抗：11.1%

　　因此，该研究结果表明，对于年轻女性乳腺癌患者，体重指数较低似乎是治疗相关闭经的独立预测因素，该结果对于日益肥胖人群研究解读和患者医疗具有重要意义。此外，这些数据还表明，越来越多被用于取代蒽环类方案的紫杉类＋铂类或环磷酰胺方案治疗相关闭经率较高。总体而言，这些数据将有助于为需要接受治疗的女性提供生育力保护策略，以及对雌激素受体阳性乳腺癌年轻女性现代化疗后可能需要进行卵巢抑制。

NPJ Breast Cancer. 2021 Jul 27. Online ahead of print.

Treatment-related amenorrhea in a modern, prospective cohort study of young women with breast cancer.

Philip D. Poorvu, Jiani Hu, Yue Zheng, Shari I. Gelber, Kathryn J. Ruddy, Rulla M. Tamimi, Jeffrey M. Peppercorn, Lidia Schapira, Virginia F. Borges, Steven E. Come, Ellen Warner, Matteo Lambertini, Shoshana M. Rosenberg, Ann H. Partridge.

Dana-Farber Cancer Institute, Boston, MA, USA; Massachusetts General Hospital, Boston, MA, USA; Beth Israel Deaconess Medical Center, Boston, MA, USA; Mayo Clinic, Rochester, MN, USA; Weill Cornell Medicine, New York, NY, USA; Stanford University, Palo Alto, CA, USA; University of Colorado Cancer Center, Aurora, CO, USA; Sunnybrook Health Sciences Centre, Toronto, ON, Canada; University of Genova, Genova, Italy; IRCCS Ospedale Policlinico San Martino, Genova, Italy.

Young women with breast cancer experience unique treatment and survivorship issues centering on treatment-related amenorrhea, including fertility preservation and management of ovarian function as endocrine therapy. The Young Women's Breast Cancer Study is a multi-center, prospective cohort study of women diagnosed at age ≤40, enrolled from 2006 to 2016. Menstrual outcomes were self-reported on serial surveys. We evaluated factors associated with treatment-related amenorrhea using logistic regression. One year post-diagnosis, 286/789 (36.2%) experienced treatment-related amenorrhea, yet most resumed menses (2-year treatment-related amenorrhea: 120/699; 17.2%). Features associated with 1-year treatment-related amenorrhea included older age (odds ratio: ≤30 versus 36-40=0.29 (0.17-0.48), odds ratio: 31-35 versus 36-40=0.67 (0.46-0.94), P=0.02); normal body mass index (odds ratio: ≥25 versus 18.5-24 =0.59 (0.41-0.83), P<0.01); chemotherapy (odds ratio: chemo versus no chemo=5.55 (3.60-8.82), P<0.01); and tamoxifen (odds ratio: =1.55 (1.11-2.16), P=0.01). Treatment-related amenorrhea rates were similar across most standard regimens (docetaxe l/ carboplatin / trastuzumab ± pertuzumab: 55.6%; docetaxel / cyclophosphamide ± trastuzumab / pertuzumab: 41.8%; doxorubicin / cyclophosphamide / paclitaxel ± trastuzumab / pertuzumab: 44.1%; but numerically lower with AC alone (25%) or paclitaxel / trastuzumab (11.1%). Among young women with breast cancer, lower body mass index appears to be an independent predictor of treatment-related amenorrhea. This finding has important implications for interpretation of prior studies, future research, and patient care in our increasingly obese population. Additionally, these data describe treatment-related amenorrhea associated with use of docetaxel/cyclophosphamide, which is increasingly being used in lieu of anthracycline-containing regimens. Collectively, these data can be used to inform use of fertility preservation strategies for women who need to undergo treatment as well as the potential need for ovarian suppression following modern chemotherapy for young women with estrogen-receptor-positive breast cancer.

CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov, NCT01468246

DOI: 10.1038/s41523-021-00307-8

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