乳腺癌患者妊娠安全性大数据分析

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极少女性完成乳腺癌治疗后妊娠，许多患者和医生仍然担心乳腺癌患者妊娠对生育结局和母体安全可能带来不利影响。

2021年7月1日，美国临床肿瘤学会《临床肿瘤学杂志》在线发表意大利热那亚大学圣马蒂诺综合医院、米兰大学欧洲肿瘤研究院、英国爱丁堡大学、比利时布鲁塞尔自由大学、天主教鲁汶大学、美国哈佛大学达纳法伯癌症研究所、梅奥医学中心、韩国蔚山大学首尔峨山医院、墨西哥国家癌症研究所、蒙特雷理工学院、法国古斯塔夫鲁西研究所、西班牙巴塞罗那大学医院肿瘤研究所、荷兰癌症研究所、阿姆斯特丹大学、瑞士日内瓦大学医院、欧洲肿瘤学院的研究报告，对乳腺癌患者妊娠安全性的最新研究证据进行了系统回顾与荟萃分析。

作者首先通过美国国家医学图书馆、美国科学信息研究所、英国考科蓝数据库对2020年1月31日前发表的全部乳腺癌患者妊娠研究进行系统文献检索，随后对乳腺癌后妊娠比例、生育结局和母体安全进行评定，最后采用随机效应模型计算合并相对风险、比值比、风险比及其95%置信区间。

结果，从6462篇文献筛选出39篇文献，包括来自普通人群的809万3401例对照女性和11万2840例乳腺癌患者，其中7505例乳腺癌确诊后妊娠。

乳腺癌患者与普通人群对照女性相比：

妊娠比例：低60%（相对风险：0.40，95%置信区间：0.32～0.49，P

剖宫产比例：高14%（比值比：1.14，95%置信区间：1.04～1.25，P=0.007）

低出生体重比例：高50%（比值比：1.50，95%置信区间：1.31～1.73，P

早产比例：高45%（比值比：1.45，95%置信区间：1.11～1.88，P=0.006）

小于胎龄比例：高16%（比值比：1.16，95%置信区间：1.01～1.33，P=0.039）

完成妊娠比例：相似（比值比：1.21，95%置信区间：0.48～3.03，P=0.689）

自发流产比例：相似（比值比：1.04，95%置信区间：0.86～1.26，P=0.696）

人工流产比例：相似（比值比：1.40，95%置信区间：0.71～2.76，P=0.329）

先兆子痫比例：相似（比值比：1.03，95%置信区间：0.27～3.98，P=0.963）

产后出血比例：相似（比值比：0.88，95%置信区间：0.57～1.37，P=0.567）

先天异常比例：相似（比值比：1.63，95%置信区间：0.89～2.98，P=0.112）

妊娠与未妊娠的乳腺癌患者相比：

发病死亡风险：低34%（风险比：0.66，95%置信区间：0.49～0.89）

总体死亡风险：低44%（风险比：0.56，95%置信区间：0.45～0.68）

对潜在混杂因素进行校正后，无论患者特征、肿瘤特征、治疗特征、妊娠结局、妊娠时间如何，上述结果相似。

因此，该研究结果表明，乳腺癌患者与普通人群对照女性相比，虽然妊娠较少，剖宫产、低出生体重、早产、小于胎龄比例较高，但是完成妊娠、自发流产、人工流产、先兆子痫、产后出血、先天异常比例相似；妊娠与未妊娠的乳腺癌患者相比，发病或死亡风险反而较低。这些结果为乳腺癌患者妊娠安全性提供了令人安心的证据，强烈支持进一步考虑乳腺癌患者的妊娠意愿，并将此作为其生存期医疗计划和期望恢复正常生活的重要组成部分。

J Clin Oncol. 2021 Jul 1. Online ahead of print.

Pregnancy After Breast Cancer: A Systematic Review and Meta-Analysis.

Lambertini M, Blondeaux E, Bruzzone M, Perachino M, Anderson RA, de Azambuja E, Poorvu PD, Kim HJ, Villarreal-Garza C, Pistilli B, Vaz-Luis I, Saura C, Ruddy KJ, Franzoi MA, Sertoli C, Ceppi M, Azim HA Jr, Amant F, Demeestere I, Del Mastro L, Partridge AH, Pagani O, Peccatori FA.

University of Genova, Genova, Italy; IRCCS Ospedale Policlinico San Martino, Genova, Italy; European Institute of Oncology IRCCS, Milan, Italy; The University of Edinburgh, Edinburgh, United Kingdom; Université Libre de Bruxelles (ULB), Brussels, Belgium; KU Leuven, Leuven, Belgium; Dana-Farber Cancer Institute, Boston, MA; Mayo Clinic, Rochester, MN; Asan Medical Center, Seoul, Korea; Tecnologico de Monterrey, San Pedro Garza Garcia, Nuevo Leon, Mexico; Instituo Nacional de Cancerologia, Mexico City, Mexico; Institut Gustave Roussy, Villejuif, France; Vall d'Hebron University Hospital (HUVH), Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain; Netherlands Cancer Institute and Amsterdam University Medical Centers, Amsterdam, the Netherlands; Geneva University Hospitals, European School of Oncology, Geneva, Switzerland.

PURPOSE

: Many patients and physicians remain concerned about the potential detrimental effects of pregnancy after breast cancer (BC) in terms of reproductive outcomes and maternal safety. This systematic review and meta-analysis aimed at providing updated evidence on these topics.

METHODS

: A systematic literature review was conducted to identify studies including patients with a pregnancy after BC (PROSPERO number CRD42020158324). Likelihood of pregnancy after BC, their reproductive outcomes, and maternal safety were assessed. Pooled relative risks, odds ratios (ORs), and hazard ratios (HRs) with 95% CIs were calculated using random effects models.

RESULTS

: Of 6,462 identified records, 39 were included involving 8,093,401 women from the general population and 112,840 patients with BC of whom 7,505 had a pregnancy after diagnosis. BC survivors were significantly less likely to have a subsequent pregnancy compared with the general population (relative risk, 0.40; 95% CI, 0.32 to 0.49). Risks of caesarean section (OR, 1.14; 95% CI, 1.04 to 1.25), low birth weight (OR, 1.50; 95% CI, 1.31 to 1.73), preterm birth (OR, 1.45; 95% CI, 1.11 to 1.88), and small for gestational age (OR, 1.16; 95% CI, 1.01 to 1.33) were significantly higher in BC survivors, particularly in those with previous chemotherapy exposure, compared with the general population. No significantly increased risk of congenital abnormalities or other reproductive complications were observed. Compared to patients with BC without subsequent pregnancy, those with a pregnancy had better disease-free survival (HR, 0.66; 95% CI, 0.49 to 0.89) and overall survival (HR, 0.56; 95% CI, 0.45 to 0.68). Similar results were observed after correcting for potential confounders and irrespective of patient, tumor, and treatment characteristics, pregnancy outcome, and timing of pregnancy.

CONCLUSION

: These results provide reassuring evidence on the safety of conceiving in BC survivors. Patients' pregnancy desire should be considered a crucial component of their survivorship care plan.

KEY OBJECTIVE

: Few women conceive following treatment completion for breast cancer (BC). Concerns persist among patients and physicians about the potential detrimental effects of pregnancy after BC in terms of reproductive outcomes and maternal safety. This systematic review and meta-analysis aimed at providing updated evidence on these topics.

KNOWLEDGE GENERATED

: These results provide reassuring evidence on the safety of conceiving in women with previous BC. BC survivors had 60% reduced likelihood of having a subsequent pregnancy compared with the general population. However, no alarming signals in the majority of analyzed reproductive outcomes were observed, including no significantly increased risk of congenital abnormalities. Pregnancy after BC was not associated with any detrimental prognostic effect.

RELEVANCE

: These data strongly support the need for a deeper consideration of patients' pregnancy desire as a crucial component of their survivorship care plan and expectation to return to a normal life.

DOI

: 10.1200/JCO.21.00535