【原】乳腺癌患者保护生育能力是否安全

SIBCS 2022-08-26 发布于上海

展开全文

　　乳腺癌是年轻女性最常见的癌症，与老年女性相比，通常恶性程度较高、确诊时分期较晚，由于这些因素可能引起预后不佳，年轻女性通常需要接受强化治疗。目前的乳腺癌化疗方案虽然提高了生存率，但是也可能导致不育。此外，对于激素敏感的乳腺癌女性，通常建议推迟妊娠，直至完成5～10年的术后内分泌治疗，这通常可造成年龄相关自然生育率下降。因此，乳腺癌是育龄女性保护生育能力的最常见指征。保护生育能力的方法通常包括激素刺激，但是激素刺激对乳腺癌患者是否安全？会不会刺激乳腺癌复发转移？目前，关于激素刺激保护生育能力是否影响乳腺癌预后的数据样本量都较小。

　　2022年8月25日，《美国医学会杂志》肿瘤学分册在线发表瑞典卡罗林斯卡学院、卡罗林斯卡大学医院、卡罗林斯卡综合癌症中心、斯德哥尔摩南方医院的大样本研究报告，对年轻女性确诊乳腺癌时接受或未接受生育能力保护措施的乳腺癌复发和死亡风险进行了比较。

　　该全国前瞻队列研究对1994年1月1日～2017年6月30日瑞典各个大学医院所辖地区乳腺癌确诊时激素和非激素生育能力保护措施的安全性进行调查。其中，共计425例女性接受了生育能力保护，还从地区乳腺癌登记数据库抽取850例未接受生育能力保护的人群进行比较，并对年龄、确诊日期和地区进行匹配。对随访数据完整亚组241例接受生育能力保护女性和482例未接受生育能力女性的无复发生存进行比较。结局、疾病和治疗相关指标以及社会经济特征的数据来自全国人口统计和医疗保健登记数据库。数据分析于2021年11月～2022年3月进行，并于2022年6月完成。主要结局指标为乳腺癌确诊后的复发和乳腺癌所致死亡。

　　结果，最终研究人群包括乳腺癌确诊时女性1275例，平均年龄32.9±3.8岁。

　　对年龄、日期和地区进行分层，并对出生国家、教育程度、确诊时产次、肿瘤大小、淋巴结转移数量和雌激素受体状态进行校正后，与未接受生育能力保护相比：

激素生育能力保护
乳腺癌所致死亡风险相似（校正后风险比：0.59，95%置信区间：0.32～1.09）
乳腺癌复发死亡风险相似（校正后风险比：0.81，95%置信区间：0.49～1.37）
非激素生育能力保护
乳腺癌所致死亡风险相似（校正后风险比：0.51，95%置信区间：0.20～1.29）
乳腺癌复发死亡风险相似（校正后风险比：0.75，95%置信区间：0.35～1.62）

　　因此，该大样本队列研究结果表明，无论是否采用激素刺激，保护生育能力与乳腺癌女性复发或乳腺癌所致死亡风险增加无关。该研究结果为乳腺癌女性生育能力保护措施安全性提供了亟需的额外证据，并可能影响目前的医疗保健实践，有助于希望保护生育能力的年轻乳腺癌女性获益。

JAMA Oncol. 2022 Aug 25. Online ahead of print.

Relapse Rates and Disease-Specific Mortality Following Procedures for Fertility Preservation at Time of Breast Cancer Diagnosis.

Marklund A, Lekberg T, Hedayati E, Liljegren A, Bergh J, Lundberg FE, Rodriguez-Wallberg KA.

Karolinska Institutet, Sweden; Karolinska University Hospital, Stockholm, Sweden; Karolinska Comprehensive Cancer Centre, Stockholm, Sweden; Southern Hospital, Stockholm, Sweden; BioClinicum, Stockholm, Sweden.

This cohort study investigates the risk of disease-specific mortality and relapse in women who underwent fertility preservation with or without hormonal stimulation compared with women who did not at time of breast cancer diagnosis.

QUESTION: Is fertility preservation at time of breast cancer diagnosis associated with any increased risk of disease-specific relapse or mortality?

FINDINGS: In this population-based Swedish nationwide cohort study that included 1275 women with breast cancer, fertility preservation at time of breast cancer diagnosis was not statistically significantly associated with any increased risk of disease-specific mortality or relapse.

MEANING: Findings of this study support the safety of fertility preservation in women with breast cancer, which is highly relevant for reproductive counseling of women with breast cancer diagnosed at a young age.

IMPORTANCE: Breast cancer (BC) is the most common indication for fertility preservation (FP) in women of reproductive age. Procedures for FP often include hormonal stimulation, but current data are scarce regarding whether using hormonal stimulation for FP is associated with any deterioration in BC prognosis.

OBJECTIVE: To investigate the risk of disease-specific mortality and relapse in women who underwent FP with or without hormonal stimulation compared with women who did not at time of BC diagnosis.

DESIGN, SETTING, AND PARTICIPANTS: This Swedish nationwide prospective cohort study was conducted to assess the safety of hormonal and nonhormonal FP procedures indicated by BC in Sweden from January 1, 1994, through June 30, 2017. Women were identified from any of the regional FP programs located at Swedish university hospitals. A total of 425 women were found to have undergone FP, and 850 population comparators who had not undergone FP were sampled from regional BC registers and matched on age, calendar period of diagnosis, and region. Relapse-free survival was assessed in a subcohort of 241 women who underwent FP and 482 women who had not, with complete data. Nationwide demographic and health care registers provided data on outcome, disease- and treatment-related variables, and socioeconomic characteristics. Data analyses were performed between November 2021 and March 2022 and completed in June 2022.

MAIN OUTCOMES AND MEASURES: Relapse and disease-specific mortality after a diagnosis of BC.

RESULTS: The final study population included 1275 women (mean [SD] age, 32.9 [3.8] years) at the time of BC diagnosis. After stratification by the matching variables age, calendar period, and region, and adjustment for country of birth, education, parity at diagnosis, tumor size, number of lymph node metastases, and estrogen receptor status, disease-specific mortality was similar in women who underwent hormonal FP (adjusted hazard ratio [aHR], 0.59; 95% CI, 0.32-1.09), women who underwent nonhormonal FP (aHR, 0.51; 95% CI, 0.20-1.29), and women who were not exposed to FP (reference). In a subcohort with detailed data on relapse, adjusted rate of disease-specific mortality and relapse were also similar among the groups who underwent hormonal FP (aHR, 0.81; 95% CI, 0.49-1.37), underwent nonhormonal FP (aHR, 0.75; 95% CI, 0.35-1.62), and were not exposed to FP (reference).

CONCLUSIONS AND RELEVANCE: In this cohort study, FP with or without hormonal stimulation was not associated with any increased risk of relapse or disease-specific mortality in women with BC. Results of this study provide much needed additional evidence on the safety of FP procedures in women with BC and may influence current health care practice to the benefit of young women with BC who wish to preserve their fertility.

PMID: 36006625

DOI: 10.1001/jamaoncol.2022.3677