乳腺癌妇女在孕期可以接受治疗，不会增加胎儿和孕妇不良结局的风险，该项国际性研究于8月16日在线刊登在《柳叶刀肿瘤》（Lancet Oncology）杂志上。然而，研究者确实发现宫内暴露于化疗的胎儿比未暴露的胎儿出生体重要低，也有更多的并发症，但是两组间没有显著差异。重要的是，没有重大的出生缺陷。
之前有两项研究表明，妊娠对于妇科肿瘤或乳腺癌的预后没有有害影响，如果可能应该保持妊娠，此外，研究还发现预后和治疗的成功取决于病人本身，在维护胎儿的同时为母亲提供标准治疗是可能的。
在本项研究中，Sibylle Loibl博士及其同事对登记库中447例在妊娠期间被诊断为早期(413例)或转移性(34例)乳腺癌的患者的预后进行了评估。诊断时的中位胎龄为24周(5~40周)，患者的中位年龄为33岁(22~51岁)。
197例在妊娠期间接受化疗，171例在分娩后接受化疗。在妊娠期间接受治疗的患者中，共有90%使用蒽环类抗生素；8%合用环磷酰胺、甲氨蝶呤和氟尿嘧啶；7％使用紫杉类。无1例患者在妊娠期间接受曲妥珠单抗、内分泌治疗或放疗。
选择在妊娠期间接受化疗的早期乳腺癌患者往往比选择在分娩后进行化疗的患者具有更晚期的疾病，而且肿瘤分期和淋巴结状况较差。在校正这些方面的差异后，研究者发现两组患者在无病生存率和总生存率方面均无显著差异。
妊娠期间接受化疗和分娩后接受化疗的早期乳腺癌患者，估计3年无病生存率为70.2% vs. 74.3%，估计3年总生存率为84.9% vs. 87.4%，估计5年无病生存率为61.1% vs. 64.4%，估计5年总生存率为77% vs. 82.4%。
共获得373例新生儿的数据，其中203例在子宫内暴露于化疗，170例无此暴露。妊娠期暴露组新生儿的出生体重稍低于未暴露组，但无统计学差异。此外，两组在主要出生缺陷、婴儿身高、Apgar评分、血红蛋白浓度、白细胞计数、血小板计数或脱发方面无显著差异。两组随母亲出院的婴儿比例也无显著差异(34% vs. 41%)。
妊娠期间接受化疗者的不良事件发生率高于分娩后接受化疗者(15% vs. 4%)。然而，这一差异缘于妊娠期间暴露于化疗组的早产和胎膜早破发生率较高。大部分并发症见于早产婴儿，不论化疗暴露的时间点如何。
该研究的数据不足以解释为什么接受化疗的孕产妇的早产率较高。不过，原因可能在于身心上的双重应激，以及接受化疗的孕产妇更易于发生可诱发分娩的感染。此外，细胞毒性药物可能通过一些尚不清楚的机制促进分娩。然而，两组的先兆子痫发生率相似，因此已知由细胞毒性药物诱导产生的氧化应激并非早产的诱发因素。
研究者总结指出，上述结果表明孕中期或孕晚期接受乳腺癌化疗者的妊娠预后与分娩后才接受化疗的孕产妇无显著差异，但这一结果仍有待其他研究的证实。
述评：未能回答的问题还需要更多的数据
Olivier Mir博士和Paul Berveiller博士指出，尽管该研究结果表明蒽环类为基础的化疗对于孕中期和孕晚期是可行的，但是如何最佳使用细胞毒药物仍是不确定的。未来研究不仅应探讨妊娠期间化疗的毒性影响，而且还应探讨细胞毒性药物在孕产妇体内的药代动力学，因为妊娠生理改变可显著影响药物分布。对于这类人群，是否应增加剂量尚不确定，因为这么做可能会导致重度血小板减少、中性粒细胞减少和感染，并对母亲和婴儿产生潜在不良影响。此外，还应探讨通过优化药物选择和给药方案是否可最大程度地降低该研究观察到的胎儿风险轻微增加。 （生物谷Bioon.com）
doi:10.1016/S1470-2045(12)70261-9
PMC:
PMID:
Treatment of breast cancer during pregnancy: an observational study
Prof Sibylle Loibl MD a , Sileny N Han MD b, Prof Gunter von Minckwitz MD a, Marijke Bontenbal MD d, Alistair Ring MD e, Prof Jerzy Giermek MD f, Prof Tanja Fehm MD g, Kristel Van Calsteren PhD h, Sabine C Linn MD j, Bettina Schlehe MD k, Mina Mhallem Gziri MD c, Pieter J Westenend MD l, Prof Volkmar Müller MD m, Liesbeth Heyns MSc c, Brigitte Rack PhD n, Ben Van Calster PhD i, Prof Nadia Harbeck MD o, Miriam Lenhard PhD p, Michael J Halaska PhD q, Prof Manfred Kaufmann MD r, Valentina Nekljudova PhD a, Prof Frederic Amant PhD b
Background
Little is known about the treatment of breast cancer during pregnancy. We aimed to determine whether treatment for breast cancer during pregnancy is safe for both mother and child.
Methods
We recruited patients from seven European countries with a primary diagnosis of breast cancer during pregnancy; data were collected retrospectively if the patient was diagnosed before April, 2003 (when the registry began), or prospectively thereafter, irrespective of the outcome of pregnancy and the type and timing of treatment. The primary endpoint was fetal health for up to 4 weeks after delivery. The registry is ongoing. The study is registered with ClinicalTrials.gov, number NCT00196833.
Findings
From April, 2003, to December, 2011, 447 patients were registered, 413 of whom had early breast cancer. Median age was 33 years (range 22—51). At the time of diagnosis, median gestational age was 24 weeks (range 5—40). 197 (48%) of 413 women received chemotherapy during pregnancy with a median of four cycles (range one to eight). 178 received an anthracycline, 15 received cyclophosphamide, methotrexate, and fluorouracil, and 14 received a taxane. Birthweight was affected by chemotherapy exposure after adjustment for gestational age (p=0·018), but not by number of chemotherapy cycles (p=0·71). No statistical difference between the two groups was observed for premature deliveries before the 37th week of gestation. 40 (10%) of 386 infants had side-effects, malformations, or new-born complications; these events were more common in infants born before the 37th week of gestation than they were in infants born in the 37th week or later (31 [16%] of 191 infants vs nine [5%] of 195 infants; p=0·0002). In infants for whom maternal treatment was known, adverse events were more common in those who received chemotherapy in utero compared with those who were not exposed (31 [15%] of 203 vs seven [4%] of 170 infants; p=0·00045). Two infants died; both were exposed to chemotherapy and delivered prematurely, but both deaths were thought not to be related to treatment. Median disease-free survival for women with early breast cancer was 70·6 months (95% CI 62·1—105·5) in women starting chemotherapy during pregnancy and 94·4 months (lower 95% CI 64·4; upper 95% CI not yet reached) in women starting chemotherapy after delivery (unadjusted hazard ratio 1·13 [95% CI 0·76—1·69]; p=0·539).
Interpretation
Although our data show that infants exposed to chemotherapy in utero had a lower birthweight at gestational age than did those who were unexposed, and had more complications, these differences were not clinically significant and, since none of the infants was exposed to chemotherapy in the first trimester, were most likely related to premature delivery. Delay of cancer treatment did not significantly affect disease-free survival for mothers with early breast cancer. Because preterm birth was strongly associated with adverse events, a full-term delivery seems to be of paramount importance.
