German Breast Group, Neu-Isenburg, Germany.
Lancet Oncol. 2012 Sep;13(9):887-96. doi: 10.1016/S1470-2045(12)70261-9. Epub 2012 Aug 16.
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.
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.
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).
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.
BANSS Foundation, Biedenkopf, Germany and the Belgian Cancer Plan, Ministry of Health, Belgium.
对于妊娠期乳腺癌的治疗，人们知之甚少。我们旨在确定在妊娠期进行乳腺癌治疗是否对母婴均安全。
我们从 7 个欧洲国家招募了患有原发性妊娠期乳腺癌的患者；如果患者在 2003 年 4 月（登记开始时）之前被诊断为乳腺癌，则回顾性收集数据，或者在之后无论妊娠结局以及治疗类型和时间如何均前瞻性收集数据。主要终点是产后 4 周内胎儿健康状况。该登记正在进行中。该研究在 ClinicalTrials.gov 注册，编号为 NCT00196833。
从 2003 年 4 月至 2011 年 12 月，登记了 447 名患者，其中 413 名患有早期乳腺癌。中位年龄为 33 岁（范围 22-51 岁）。诊断时，中位妊娠周数为 24 周（范围 5-40 周）。413 名女性中有 197 名（48%）在妊娠期接受了化疗，中位数为 4 个周期（范围 1-8 个周期）。178 名接受了蒽环类药物治疗，15 名接受了环磷酰胺、甲氨蝶呤和氟尿嘧啶治疗，14 名接受了紫杉烷类药物治疗。在调整了妊娠年龄后，化疗暴露对出生体重有影响（p=0·018），但对化疗周期数没有影响（p=0·71）。在 37 周妊娠前早产方面，两组之间没有观察到统计学差异。386 名婴儿中有 40 名（10%）出现了副作用、畸形或新生儿并发症；这些事件在 37 周妊娠前出生的婴儿中比在 37 周或以后出生的婴儿中更常见（191 名婴儿中有 31 名[16%]，195 名婴儿中有 9 名[5%]；p=0·0002）。对于已知母亲治疗情况的婴儿，与未暴露于化疗的婴儿相比，接受宫内化疗的婴儿更常发生不良事件（203 名婴儿中有 31 名[15%]，170 名婴儿中有 7 名[4%]；p=0·00045）。两名婴儿死亡；两名均接受了化疗并早产，但均被认为与治疗无关。早期乳腺癌女性开始化疗时的无病生存中位时间为 70·6 个月（95%CI 62·1-105·5），而在分娩后开始化疗的女性为 94·4 个月（下 95%CI 64·4；上 95%CI 尚未达到）（未调整的危险比 1·13 [95%CI 0·76-1·69]；p=0·539）。
尽管我们的数据表明，与未暴露于化疗的婴儿相比，接受宫内化疗的婴儿在妊娠周数时的出生体重较低，并且并发症更多，但这些差异没有临床意义，而且由于没有婴儿在妊娠早期接受化疗，这些差异很可能与早产有关。延迟癌症治疗并未显著影响早期乳腺癌母亲的无病生存率。由于早产与不良事件密切相关，因此足月分娩似乎至关重要。
BANSS 基金会，德国比登科普夫和比利时癌症计划，比利时卫生部。
