保留生育功能对乳腺癌女性的长期影响

　　对于乳腺癌女性，保留生育功能的做法正在普及。不过，保留生育功能对乳腺癌女性生育结局的长期影响尚不明确。

　　2020年11月19日，《美国医学会杂志》肿瘤学分册在线发表瑞典卡罗林学院、斯德哥尔摩南方医院、卡罗林大学医院的研究报告，比较了乳腺癌诊断时是否保留生育功能对女性生育结局的长期影响。

　　该全国定群研究对1994年1月1日～2017年6月30日瑞典全国425例保留生育功能的乳腺癌女性长期生育结局进行调查，并从当地乳腺癌登记数据库根据年龄、诊断日期、省份按1∶2抽样匹配850例未保留生育功能的乳腺癌女性。通过人口登记数据库检索活产、辅助生育技术、死亡等数据。数据分析于2020年1月～2020年9月进行。主要结局为保留与未保留生育功能相比，乳腺癌女性的活产、辅助生育技术治疗的风险比，并将死亡作为这些事件累计发生率的竞争风险。

　　结果，保留与未保留生育功能的女性相比：

  • 无生育史较多：71.1%比20.1%

  • 平均年龄较低：32.1±4.0比33.3±3.6岁

  • 雌激素受体阳性率较高：68.0%比60.6%

  • 计划进行化疗比例较高：93.9%比87.7%

  • 平均随访时间：4.6年比4.8年

  • 活产比例较高：22.8%比8.7%（校正风险比：2.3，95%置信区间：1.6～3.3）

  • 五年累计活产比例较高：19.4%比8.6%

  • 十年累计活产比例较高：40.7%比15.8%

  • 辅助生育技术比例较高：11.3%比1.2%（校正风险比：4.8，95%置信区间：2.2～10.7）

  • 全因死亡比例较低：6.4%比12.9%（校正风险比：0.4，95%置信区间：0.3～0.7）

  • 五年累计死亡比例较低：5.3%比11.1%（95%置信区间：3.1%～9.0%、8.7%～14.1%）

　　因此，该瑞典女性乳腺癌诊断后定群研究结果表明，乳腺癌诊断时保留与未保留生育功能的女性相比，虽然乳腺癌诊断后都有可能成功妊娠，但是活产比例显著较高，辅助生育技术治疗比例也较高，对总生存和全因死亡并未产生不良影响。这些信息对于负责育龄期间被诊断为乳腺癌女性肿瘤治疗和生育咨询的临床医师而言非常有价值。

JAMA Oncol. 2020 Nov 19. Online ahead of print.

Reproductive Outcomes After Breast Cancer in Women With vs Without Fertility Preservation.

Marklund A, Lundberg FE, Eloranta S, Hedayati E, Pettersson K, Rodriguez-Wallberg KA.

Karolinska Institutet, Stockholm, Sweden; Sodersjukhuset, Stockholm, Sweden; Karolinska University Hospital, Stockholm, Sweden; Laboratory of Translational Fertility Preservation, Stockholm, Sweden.

This cohort study investigates the long-term reproductive outcomes in women who did or did not undergo fertility preservation at the time of breast cancer diagnosis.

QUESTION: What are the long-term reproductive outcomes after breast cancer in women with vs without a history of fertility preservation?

FINDINGS: In this population-based nationwide cohort study of 425 Swedish women with breast cancer who underwent fertility preservation, fertility preservation at the time of breast cancer diagnosis was associated with a significantly higher rate of postdiagnosis live births and assisted reproduction treatments, without any negative association with all-cause survival following fertility preservation.

MEANING: The findings of this study may be relevant for reproductive counseling of women with breast cancer diagnosed at reproductive age.

IMPORTANCE: The practice of fertility preservation (FP) in women with breast cancer (BC) is spreading, but long-term reproductive outcomes after FP are largely unknown.

OBJECTIVE: To investigate the long-term reproductive outcomes in women who did or did not undergo FP at the time of BC diagnosis.

DESIGN, SETTING, AND PARTICIPANTS: A Swedish nationwide cohort study was conducted to investigate the long-term reproductive outcomes of women with BC receiving FP at 1 of the regional FP programs from 1994 to 2017 (n = 425). Population comparators with BC but without history of FP (n = 850) were sampled from regional BC registers, matched on age, calendar period of diagnosis, and county. Data on live births, assisted reproductive technology (ART) use, and mortality were retrieved from population-based registers. Data analysis was performed from January to September 2020.

EXPOSURES: History of having received FP compared with no history of FP (unexposed).

MAIN OUTCOMES AND MEASURES: The primary outcome was hazard ratios (HRs) of live births and ART treatments following BC in women with vs without FP and the cumulative incidence of these events in the presence of the competing risk of death.

RESULTS: Women who had undergone FP (n = 425) had lower parity (302 [71.1%] were nulliparous compared with 171 [20.1%] in the unexposed group), were younger (mean [SD] age, 32.1 [4.0] vs 33.3 [3.6] years), more often had estrogen receptor-positive tumors (289 [68.0%] vs 515 [60.6%]), and were more often scheduled for chemotherapy (399 [93.9%] vs 745 [87.7%]). Of 425 women exposed to FP, 97 (22.8%) had at least 1 post-BC live birth (mean follow-up, 4.6 years), compared with 74 of 850 women (8.7%) unexposed to FP (mean follow-up, 4.8 years). Overall, live birth rates after BC were significantly higher among women with FP (adjusted hazard ratio [aHR], 2.3; 95% CI, 1.6-3.3). The 5-year and 10-year cumulative incidence of post-BC live births was 19.4% and 40.7% among FP-exposed women vs 8.6% and 15.8% among comparators, respectively. Rates of ART use were also higher in the FP group (aHR, 4.8; 95% CI, 2.2-10.7). The all-cause mortality rate was lower in women exposed to FP (aHR, 0.4; 95% CI, 0.3-0.7), with 5-year cumulative incidence of death of 5.3% (95% CI, 3.1%-9.0%) vs 11.1% (95% CI, 8.7%-14.1%) for women with vs without FP.

CONCLUSIONS AND RELEVANCE: In this cohort study of Swedish women after a BC diagnosis, successful pregnancy after BC was possible both in women with and without FP at the time of diagnosis, but a significantly higher likelihood of post-BC live births and ART treatments was observed in women who underwent FP, without any negative association with all-cause survival. This information is valuable for health care clinicians responsible for oncologic treatment and reproductive counseling of women diagnosed with breast cancer at reproductive age.

PMID: 33211089

DOI: 10.1001/jamaoncol.2020.5957

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