妊娠期乳腺癌治疗的一般信息
发病率
乳腺癌是妊娠期及产后女性最常见的癌症，妊娠期乳腺癌的发病率为1/3000。平均患病年龄在32岁至38岁之间。由于大多数女性选择晚育，因此妊娠期乳腺癌的发病率可能会升高。
解剖
女性乳腺的解剖。乳腺的表面是由乳头、乳晕及皮肤构成。乳腺小叶、淋巴结、腺叶、导管、脂肪和其他组织构成乳腺的内部结构。
诊断性评估
孕妇和哺乳期妇女的乳房自然压痛和充血，可能会妨碍多发肿块的检测和乳腺癌的早期诊断。 延误诊断是很常见的，据报道平均延误时间为5至15个月。
由于这种诊断延迟，乳腺癌检出时，通常比未妊娠、年龄相似人群的肿瘤分期晚。
以下的检查和步骤通常用于确诊妊娠期乳腺癌：
为了检出乳腺癌，建议妊娠期及哺乳期女性经常进行乳房自检，并且产前常规行临床乳腺检查。如果发现异常，需进一步行超声和乳房X线检查等诊断方法。使用适当的屏蔽措施，乳腺X线检查对胎儿的射线暴露风险很低。
然而，乳腺X线检查通常只用于评估主要肿块，或用于定位体格检查有怀疑的隐匿性癌症患者中。
由于在妊娠期乳腺癌患者中，乳腺X线检查至少有25%为假阴性，因此活检对任何可触及的肿块都是必不可少的。局麻下行细针穿刺、空心芯穿刺或切除活检均是安全的诊断检查方法。为了避免妊娠相关变化引起的假阳性结果，病理学医生需要了解患者是否怀孕。
年龄相似的妊娠期女性与非妊娠期女性的乳腺癌病理结果相似。采用竞争性结合测定方法的激素受体试验在妊娠期乳腺癌患者中通常显示为阴性，而这可能是由于妊娠期相关的高血清雌激素水平与受体结合引起的。酶免疫细胞化学受体测定比竞争性结合测定的灵敏度更高。一项关于使用了两种测定方法的研究显示，妊娠期和非妊娠期女性的乳腺癌受体阳性率相似。
该研究的结论是，妊娠期雌激素水平的升高可能导致免疫组织化学检查的受体阳性率高于放射性标记的配体结合测定的受体阳性率，这是因为高水平的内源性雌激素之间有竞争抑制作用。
有关乳腺癌诊断的更多信息，请参阅PDQ乳腺癌治疗摘要中的诊断部分章节。
预后
在所有分期中，妊娠期乳腺癌女性的总生存率均低于非妊娠期乳腺癌女性；
这主要是由诊断延误造起的。
没有研究显示终止妊娠会使乳腺癌的预后获益，终止妊娠也通常不作为治疗方案。
参考文献
General Information About Breast Cancer Treatment During Pregnancy
Incidence
Breast cancer is the most common cancer in pregnant and postpartum women and occurs in about 1 in 3,000 pregnant women. The average patient is between the ages of 32 years and 38 years. Because many women are choosing to delay childbearing, it is likely that the incidence of breast cancer during pregnancy will increase.
Anatomy
Anatomy of the female breast. The nipple and areola are shown on the outside of the breast. The lymph nodes, lobes, lobules, ducts, and other parts of the inside of the breast are also shown.
Diagnostic Evaluation
The natural tenderness and engorgement of the breasts of pregnant and lactating women may hinder detection of discrete masses and early diagnosis of breast cancer. Delays in diagnosis are common, with an average reported delay of 5 to 15 months from the onset of symptoms.
Because of this delay, cancers are typically detected at a later stage than in a nonpregnant, age-matched population.
The following tests and procedures may be used to diagnose breast cancer during pregnancy:
To detect breast cancer, pregnant and lactating women should consider practicing self-examination and undergo a clinical breast examination as part of the routine prenatal examination by a doctor. If an abnormality is found, diagnostic approaches such as ultrasound and mammography may be used. With proper shielding, mammography poses little risk of radiation exposure to the fetus.
Mammograms are only used, however, to evaluate dominant masses and to locate occult carcinomas in the presence of other suspicious physical findings.
Because at least 25% of mammograms in pregnancy may be negative in the presence of cancer, a biopsy is essential for the diagnosis of any palpable mass. Diagnosis may be safely accomplished with a fine-needle aspiration, core biopsy, or excisional biopsy under local anesthesia. To avoid a false-positive diagnosis as a result of misinterpretation of pregnancy-related changes, the pathologist should be advised that the patient is pregnant.
Breast cancer pathology is similar in age-matched pregnant and nonpregnant women. Hormone receptor assays using a competitive binding assay are usually negative in pregnant breast cancer patients, but this may be the result of receptor binding by high serum estrogen levels associated with the pregnancy. Enzyme immunocytochemical receptor assays are more sensitive than competitive binding assays. A study that used both assay methods indicated similar receptor positivity between pregnant and nonpregnant women with breast cancer.
The study concluded that increased estrogen levels during pregnancy could result in a higher incidence of receptor positivity detected with immunohistochemistry than is detected by radiolabeled ligand-binding assay because of competitive inhibition by high levels of endogenous estrogen.
Refer to the Diagnosis section in the PDQ summary on Breast Cancer Treatment for more information about the diagnosis of breast cancer.
Prognosis
Overall survival of pregnant women with breast cancer may be worse than survival of nonpregnant women at all stages;
however, this may be primarily the result of delayed diagnosis.
Termination of pregnancy has not been shown to have any beneficial effect on breast cancer outcome and is not usually considered as a therapeutic option.
ReferenceSection
关于乳腺癌治疗和妊娠的分期资料
分期方法
以下检查用于确定癌症的程度：
对妊娠期女性用于确定乳腺癌分期的检查进行了改良，以避免胎儿受到辐射。核扫描会导致胎儿再次暴露辐射。
如果此类扫描对于评估分期至关重要，则可以使用水化和膀胱的Foley导管引流来防止放射性残留。 相对于胎儿的胎龄，辐射暴露时间可能比接受到的放射线的剂量，对胎儿影响更大。
妊娠早期的辐射暴露（>0.1 Gy）可能会增加先天性畸形、精神发育迟滞，和致癌的风险。
带有腹部防护的胸部X线被认为是安全的，但是与所有放射线检查一样，仅在做出治疗决定时才使用它们。
胸部X线检查的辐射量是0.00008 Gy。
对于骨转移的诊断，骨扫描比骨科系列检查更好，因为骨扫描的总辐射量更小，且更加灵敏。骨扫描的辐射量是 0.001 Gy。
肝脏的评估可以使用超声检查进行，而骨转移可以用MRI检查来诊断。妊娠期的核磁共振检查尚不可行，因为钆可穿过胎盘，且与大鼠胎儿畸形相关。
美国癌症联合委员会（AJCC）的分期分组和TNM的定义
更多关于乳腺癌治疗方案的信息，请参阅PDQ乳腺癌分期资料章节。
参考文献
Stage Information for Breast Cancer Treatment and Pregnancy
Staging Evaluation
The following procedures are used to determine the extent of the cancer:
Procedures used for determining the stage of breast cancer are modified for pregnant women to avoid radiation exposure to the fetus. Nuclear scans cause fetal radiation exposure.
If such scans are essential for evaluation, hydration and Foley catheter drainage of the bladder can be used to prevent retention of radioactivity. Timing of the exposure to radiation relative to the gestational age of the fetus may be more critical than the actual dose of radiation delivered.
Radiation exposure during the first trimester (>0.1 Gy) may lead to congenital malformations, mental retardation, and increased relative risk of carcinogenesis.
Chest x-rays with abdominal shielding are considered safe, but as with all radiologic procedures, they are used only when essential for making treatment decisions.
A chest x-ray delivers 0.00008 Gy.
For the diagnosis of bone metastases, a bone scan is preferable to a skeletal series because the bone scan delivers a smaller amount of radiation and is more sensitive. A bone scan delivers 0.001 Gy.
Evaluation of the liver can be performed with ultrasound, and brain metastases can be diagnosed with an MRI scan. Data on MRI during pregnancy are not yet available, but gadolinium crosses the placenta and is associated with fetal abnormalities in rats.
American Joint Committee on Cancer (AJCC) Stage Groupings and Definitions of TNM
Refer to the Stage Information for Breast Cancer section in the PDQ summary on Breast Cancer Treatment for more information.
ReferenceSection
妊娠期女性早期/局部/可手术乳腺癌的治疗方案
一般来说，妊娠期I期或II期乳腺癌与非妊娠期患者治疗方案相同，但同时为了保护胎儿可能需对治疗方案做一些改变。
妊娠期女性早期/局部/可手术乳腺癌的治疗方案包括以下：
妊娠期使用曲妥珠单抗是禁忌症。
手术
手术是妊娠期乳腺癌的首选治疗方案。
关于妊娠期患者前哨淋巴结活检的安全性仅限于几个回顾性病例系列分析。一项研究对8例妊娠早期患者、9例妊娠中期患者、8例妊娠晚期患者的前哨淋巴结进行了活检。16例单独使用锝Tc 99m检查，7例单独使用亚甲基蓝染色检查，2例检测方法不明。所有25例患者的胎儿均存活，其中24例健康，1例患有腭裂（在其他母亲风险因素相同的情况下）。
因为治疗剂量的辐射可能使胎儿暴露在潜在的有害散射辐射中，
如果乳腺癌在妊娠早期被确诊，那么改良性根治术也是一种很好的治疗方案。如果乳腺癌在妊娠晚期被确诊，那么通常会采用联合产后放射治疗的保乳手术治疗方案。
已经进行的一项研究，有助于预测等待接受放疗的风险。
化疗
数据表明，在前三个月后可以安全地使用某些化学治疗药物，大多数孕妇的婴儿安全出生且新生儿发病率较低。
据有限的前瞻性数据表明，在妊娠中期和/或妊娠晚期使用蒽环类化疗（多柔比星联合环磷酰胺或氟尿嘧啶，多柔比星，联合环磷酰胺[FAC]）比较安全。
在妊娠期间使用紫杉烷类药物的安全性数据是有限的。
证据（妊娠中晚期使用化疗）：
激素治疗
通常应在生产前避免使用激素治疗。病例报告和一项关于妊娠期使用他莫昔芬的综述显示，妊娠期使用他莫昔芬与阴道出血、流产、先天性畸形如Goldenhar综合征、和胎儿死亡有相关性。
母乳喂养也不建议与激素治疗同时进行。
靶向治疗
一篇基于17项研究（18例妊娠期，19例新生儿）的系统综述显示，妊娠期禁忌使用曲妥珠单抗。
在所观察到的胎儿并发症中，羊水过少/无羊水是最常见的（61.1%）并发症。在妊娠中期或晚期暴露于曲妥珠单抗的孕妇中，73.3%的孕妇合并羊水过少/无羊水。仅在妊娠早期暴露于曲妥珠单抗的孕妇中，0%（P=0.043）的孕妇合并羊水过少/无羊水。分娩时平均胎龄为33.8周，新生儿出生时平均体重为2261克。52.6%的新生儿为健康新生儿。在长期评估中，所有在出生时没有出现上述问题的儿童都是健康的，中位随访时间为9个月。在9例出生时遇到上述问题的儿童中，其中4例在出生至5.25个月之间死亡。仅在妊娠早期出现曲妥珠单抗暴露的儿童在出生时完全健康。数据表明，对于在曲妥珠单抗治疗期间妊娠并希望继续妊娠的女性，应停止使用曲妥珠单抗。
参考文献
Treatment of Early/Localized/Operable Breast Cancer During Pregnancy
Generally, pregnant women with stage I or stage II breast cancer are treated in the same way as nonpregnant patients, with some modifications to protect the fetus.
Treatment options for early/localized/operable breast cancer in pregnant women include the following:
The use of trastuzumab during pregnancy is contraindicated.
Surgery
Surgery is recommended as the primary treatment of breast cancer in pregnant women.
The data regarding safety of sentinel lymph node biopsy in pregnant patients are limited to several retrospective case series. One study examined sentinel lymph node biopsy in eight patients in the first trimester, nine patients in the second trimester, and eight patients in the third trimester. Technetium Tc 99m alone was used in 16 patients, methylene blue dye alone was used in seven patients, and two patients had unknown mapping methods. All 25 patients had live-born infants, of whom 24 were healthy, and one had a cleft palate (in the setting of other maternal risk factors).
Because radiation in therapeutic doses may expose the fetus to potentially harmful scatter radiation,
modified radical mastectomy is the treatment of choice if the breast cancer was diagnosed early in pregnancy. If diagnosed late in pregnancy, breast-conserving surgery with postpartum radiation therapy has been used for breast preservation.
An analysis has been performed that helps to predict the risk of waiting to have radiation.
Chemotherapy
Data suggest that it is safe to administer certain chemotherapeutic drugs after the first trimester, with most pregnancies resulting in live births with low rates of morbidity in the newborns.
Anthracycline-based chemotherapy (doxorubicin plus cyclophosphamide or fluorouracil, doxorubicin, and cyclophosphamide [FAC]) appears to be safe to administer during the second and/or third trimester on the basis of limited prospective data.
Safety data on the use of taxanes during pregnancy are limited.
Evidence (use of chemotherapy during the second and/or third trimester of pregnancy):
Endocrine Therapy
Endocrine therapy is generally avoided until after delivery. Case reports and a literature review of tamoxifen during pregnancy show that tamoxifen administration during pregnancy is associated with vaginal bleeding, miscarriage, congenital abnormalities such as Goldenhar syndrome, and fetal death.
Breastfeeding is also not recommended concurrently with endocrine therapy.
Targeted Therapy
The use of trastuzumab during pregnancy is contraindicated based on results of a systematic review of 17 studies (18 pregnancies, 19 newborns).
Of the fetal complications noted, occurrence of oligohydramnios/anhydramnios was the most common (61.1%) adverse event. Of the pregnancies exposed to trastuzumab during the second or third trimester, 73.3% of the pregnancies were complicated with oligohydramnios/anhydramnios. Of the pregnancies exposed to trastuzumab exclusively during the first trimester, 0% (P = .043) of the pregnancies were complicated with oligohydramnios/anhydramnios. The mean gestational age at delivery was 33.8 weeks, and the mean weight of newborns at delivery was 2,261 grams or 4.984 pounds. In 52.6% of cases, a healthy neonate was born. At the long-term evaluation, all children who were without problems at birth were healthy, with a median follow-up of 9 months, and four of nine children who faced troubles at birth had died within an interval ranging from birth to 5.25 months. All children exposed to trastuzumab in utero exclusively in the first trimester were completely healthy at birth. The data suggest that for women who become pregnant during trastuzumab administration and wish to continue pregnancy, trastuzumab should be stopped and pregnancy would be allowed to continue.
ReferenceSection
妊娠期晚期乳腺癌的治疗方案
对妊娠期晚期（III期或IV期）乳腺癌患者，没有标准的治疗方案。大多数研究显示，患有III期或IV期乳腺癌的妊娠患者5年生存率为10%。
应避免妊娠早期放射治疗。在妊娠期早期/局部/可手术的乳腺癌一章中讨论过，妊娠早期之后可给与化疗。
因为母亲的寿命可能是有限的，在妊娠早期接受治疗会有造成胎儿受伤的风险，
有关是否继续妊娠的问题，应与患者及其家人讨论。治疗性流产不能改善预后。
参考文献
Treatment of Advanced Breast Cancer During Pregnancy
There is no standard treatment for patients with advanced (stage III or stage IV) breast cancer during pregnancy. Most studies show a 5-year survival rate of 10% in pregnant patients with stage III or IV disease.
First-trimester radiation therapy should be avoided. Chemotherapy may be given after the first trimester as discussed in the section on Early/Localized/Operable Breast Cancer During Pregnancy.
Because the mother's life span may be limited, and there is a risk of fetal damage with treatment during the first trimester,
issues regarding continuation of the pregnancy should be discussed with the patient and her family. Therapeutic abortion does not improve prognosis.
ReferenceSection
关于妊娠期和乳腺癌的特殊注意事项
哺乳
停止哺乳不能改善预后。但是，如果计划进行手术，则需要停止哺乳，以减少乳房的大小和血液供应。如果要进行化疗，也需停止哺乳，因为许多抗肿瘤药物（如环磷酰胺和甲氨蝶呤）在全身给药时，可能在母乳中出现高水平聚集，并会影响哺乳中的婴儿。接受化疗的女性不应进行母乳喂养。
母亲乳腺癌的胎儿结局
没有研究结果显示母亲患乳腺癌会对胎儿产生不利影响，
并且没有病例报导乳腺癌的癌细胞会发生母婴传播。
乳腺癌病史患者的妊娠
基于有限的回顾性研究数据，妊娠并不会危害有乳腺癌病史患者的生存率，且没有结果显示会对婴儿产生有害影响。
有些医生建议患者在确诊后等待2年再尝试怀孕。这是由于早期复发的出现，可能影响患者决定是否怀孕。
目前对骨髓移植术后妊娠和全身或局部使用大剂量化疗药物后妊娠的情况了解非常少。一份研究报告显示，因血液系统疾病行骨髓移植的术后妊娠，观察到25%患者出现早产儿和低出生体重儿。
参考文献
Special Considerations for Pregnancy and Breast Cancer
Lactation
Suppression of lactation does not improve prognosis. If surgery is planned, however, lactation is suppressed to decrease the size and vascularity of the breasts. If chemotherapy is to be given, lactation is also suppressed because many antineoplastic agents (i.e., cyclophosphamide and methotrexate), when given systemically, may occur in high levels in breast milk and would affect the nursing baby. Women receiving chemotherapy should not breastfeed.
Fetal Consequences of Maternal Breast Cancer
No damaging effects on the fetus from maternal breast cancer have been demonstrated,
and there are no reported cases of maternal-fetal transfer of breast cancer cells.
Pregnancy in Patients With a History of Breast Cancer
Based on limited retrospective data, pregnancy does not appear to compromise the survival of women with a previous history of breast cancer, and no deleterious effects have been demonstrated in the fetus.
Some physicians recommend that patients wait 2 years after diagnosis before attempting to conceive. This allows early recurrence to become manifest, which may influence the decision to become a parent.
Little is known about pregnancy after bone marrow transplantation and high-dose chemotherapy with or without total-body irradiation. In one report of pregnancies after bone marrow transplantation for hematologic disorders, a 25% incidence of preterm labor and low birth weight for gestational-age infants was noted.
ReferenceSection
变更总结（03/29/2019）
定期审查 PDQ 癌症信息总结，并在获得新信息后进行更新。本节描述了截至上述日期对本总结所做的最新变更。
对本节作了编辑上的修改。
本总结由 PDQ 成人治疗编辑委员会撰写和维护，其在编辑上独立于 NCI。总结反映了文献的独立审查，不代表 NCI 或 NIH 的政策声明。关于总结政策和 PDQ 编辑委员会在维护 PDQ 总结中的作用的更多信息，请参见关于本 PDQ 总结和 PDQ®-NCI 综合癌症数据库页面。
Changes to This Summary (03/29/2019)
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
Editorial changes were made to this section.
This summary is written and maintained by the PDQ Adult Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® - NCI's Comprehensive Cancer Database pages.
About This PDQ Summary
Purpose of This Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of breast cancer during pregnancy. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.
Reviewers and Updates
This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).
Board members review recently published articles each month to determine whether an article should:
Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.
The lead reviewers for Breast Cancer Treatment During Pregnancy are:
Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's Email Us. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.
Levels of Evidence
Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.
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The preferred citation for this PDQ summary is:
PDQ® Adult Treatment Editorial Board. PDQ Breast Cancer Treatment During Pregnancy. Bethesda, MD: National Cancer Institute. Updated
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About This PDQ Summary
Purpose of This Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of breast cancer during pregnancy. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.
Reviewers and Updates
This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).
Board members review recently published articles each month to determine whether an article should:
Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.
The lead reviewers for Breast Cancer Treatment During Pregnancy are:
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Levels of Evidence
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PDQ® Adult Treatment Editorial Board. PDQ Breast Cancer Treatment During Pregnancy. Bethesda, MD: National Cancer Institute. Updated
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Disclaimer
Based on the strength of the available evidence, treatment options may be described as either “standard” or “under clinical evaluation.” These classifications should not be used as a basis for insurance reimbursement determinations. More information on insurance coverage is available on Cancer.gov on the Managing Cancer Care page.
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