28例妊娠合并乳腺癌臨床分析

28例妊娠合并乳腺癌臨床分析【摘要】目的探討妊娠合并乳腺癌的孕期管理和預(yù)后。方法回顧性分析2006年1月1日至2020年12月31日在我院住院的28例妊娠合并乳腺癌患者的臨床資料，分析其臨床特點(diǎn)、妊娠結(jié)局和預(yù)后。結(jié)果28例妊娠合并乳腺癌患者中，平均年齡（33±6）歲，確診孕周（5~40+6）周，其中浸潤(rùn)性導(dǎo)管癌27例，導(dǎo)管內(nèi)癌1例。妊娠期行乳腺癌根治術(shù)3例，妊娠期單純化療13例，化療方案均采用EC（柔比沙星+環(huán)磷酰胺）方案，期待治療7例。引產(chǎn)/分娩后，患者進(jìn)行乳腺癌綜合治療，隨訪至今，22例患者存活，3例失訪，3例患者因全身轉(zhuǎn)移而死亡。28例妊娠合并乳腺癌患者中，5例選擇終止妊娠，23例分娩，分娩孕周（32+2~41）周，早產(chǎn)11例，足月產(chǎn)12例，新生兒隨訪生長(zhǎng)發(fā)育正常，體健。結(jié)論妊娠合并乳腺癌惡性程度高，臨床分期較晚，需要多學(xué)科協(xié)作團(tuán)隊(duì)制定個(gè)體化治療方案，妊娠中晚期手術(shù)或化療相對(duì)安全，新生兒存活率高，患者腫瘤預(yù)后有所改善?！娟P(guān)鍵詞】乳腺癌；妊娠；妊娠結(jié)局；臨床Clinicalcharacteristicsof28pregnanciescomplicatedwithbreastcancer「Abstract」ObjectiveToexplorethemonitoringandprognosisofpregnanciescomplicatedwithbreastcancer.MethodsAretrospectivecohortincluding28pregnanciescomplicatedwithbreastcancerintheFirstAffiliatedHospital,SunYat-senUniversitybetweenJanuary1st2006andDecember31st2020.Theclinicalcharacteristics,obstetricoutcomesandprognosiswereinvestigated.ResultsAmong28pregnanciescomplicatedwithbreastcancer,themeanmaternalagewas33±6years,withdiagnosisatmeangestationalage(5-40+6)wks.Atotal27caseswasinvasiveductalcarcinomaand1caseintraductalcarcinoma.Therewere3pregnanciesunderwentsurgeryand13pregnanciestookEC(Roubifloxacin+cyclophosphamide)chemotherapyregimen.7caseswereexpectedtobetreated.Allcasesreceivedtherapyafterabortionordelivery.Therewere22casessurvive,3casesdiedand3caseslosstofollow-up.Themeangestationalageatbirthwas(32+2~41)weeks,including11pretermdeliveryand12termdelivery.Allthenewbornsshowednobirthdefectandnoabnormalitywasfoundintheirphysicaldevelopment,duringfollow-up.ConclusionDuetothehighriskofpregnancycomplicatedwithbreastcancer,casesusuallyarediagnosedatadvancedstage.Multidisciplinarycollaborativeandindividualizedprecisediagnosisandtreatmentareencouraged.Surgeryorchemotherapyduringpregnancywillincreasethesurvivalrateoffetalandimprovetheprognosisofpatients.【Keywords】Breastcancer；Pregnancy；Pregnancyoutcome；Clinical乳腺癌（breastcancer）是發(fā)達(dá)國(guó)家女性最常見(jiàn)的惡性腫瘤，也是妊娠期常見(jiàn)的惡性腫瘤之一，僅次于宮頸癌。妊娠合并乳腺癌（gestationalbreastcancer,GBC）指妊娠期間確診的乳腺癌，是一種特殊類(lèi)型的乳腺癌ADDINEN.CITE<EndNote><Cite><Author>Macdonald</Author><Year>2020</Year><RecNum>5</RecNum><DisplayText>[1]</DisplayText><record><rec-number>5</rec-number><foreign-keys><keyapp="EN"db-id="xwevaddfqwwrv7ewpey55etyzzesttfp0p9r"timestamp="1635608675">5</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Macdonald,H.R.</author></authors></contributors><auth-address>HoagHospital,NewportBeach,California. KeckSchoolofMedicine,UniversityofSouthernCalifornia,LosAngeles,California.</auth-address><titles><title>Pregnancyassociatedbreastcancer</title><secondary-title>BreastJ</secondary-title></titles><periodical><full-title>BreastJ</full-title></periodical><pages>81-85</pages><volume>26</volume><number>1</number><edition>2020/01/17</edition><keywords><keyword>AntineoplasticAgents/adverseeffects</keyword><keyword>BreastNeoplasms/diagnosticimaging/*therapy</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Mammography/adverseeffects</keyword><keyword>MedicalOncology/methods</keyword><keyword>Obstetrics/methods</keyword><keyword>Pregnancy</keyword><keyword>PregnancyComplications,Neoplastic/diagnosticimaging/*therapy</keyword><keyword>PrenatalCare/methods</keyword><keyword>*breastmassinpregnancy</keyword><keyword>*cancerinpregnancy</keyword><keyword>*chemotherapyinpregnancy</keyword><keyword>*radiationinpregnancy</keyword></keywords><dates><year>2020</year><pub-dates><date>Jan</date></pub-dates></dates><isbn>1075-122x</isbn><accession-num>31943583</accession-num><urls></urls><electronic-resource-num>10.1111/tbj.13714</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[1]。妊娠合并乳腺癌的發(fā)病率約為15-35/100000ADDINEN.CITE<EndNote><Cite><Author>Knabben</Author><Year>2017</Year><RecNum>4</RecNum><DisplayText>[2]</DisplayText><record><rec-number>4</rec-number><foreign-keys><keyapp="EN"db-id="xwevaddfqwwrv7ewpey55etyzzesttfp0p9r"timestamp="1635608629">4</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Knabben,L.</author><author>Mueller,M.D.</author></authors></contributors><auth-address>DepartmentofObstetricsandGynaecology,UniversityHospitalofBerne,Effingerstrasse102,3010Berne,Switzerland,Phone:+41316321010,Fax:+41316321205. DepartmentofObstetricsandGynaecology,UniversityHospitalofBerneandUniversityofBerne,Berne,Switzerland.</auth-address><titles><title>Breastcancerandpregnancy</title><secondary-title>HormMolBiolClinInvestig</secondary-title></titles><periodical><full-title>HormMolBiolClinInvestig</full-title></periodical><volume>32</volume><number>1</number><edition>2017/08/30</edition><keywords><keyword>Adult</keyword><keyword>BreastNeoplasms/*diagnosis/epidemiology/*therapy</keyword><keyword>DiseaseManagement</keyword><keyword>ExpertTestimony</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Incidence</keyword><keyword>PatientOutcomeAssessment</keyword><keyword>Pregnancy</keyword><keyword>*PregnancyComplications,Neoplastic</keyword><keyword>PregnancyOutcome</keyword><keyword>Prognosis</keyword><keyword>breastcancer</keyword><keyword>fertility</keyword><keyword>obstetricaloutcome</keyword><keyword>pregnancy-associatedbreastcancer</keyword></keywords><dates><year>2017</year><pub-dates><date>Aug29</date></pub-dates></dates><isbn>1868-1883</isbn><accession-num>28850544</accession-num><urls></urls><electronic-resource-num>10.1515/hmbci-2017-0026</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[2]，隨著妊娠年齡的推遲，妊娠合并乳腺癌的發(fā)生率逐年增加。目前對(duì)于妊娠合并乳腺癌的診斷和治療管理主要基于單一機(jī)構(gòu)回顧性隊(duì)列或小病例對(duì)照研究，缺乏大樣本的病例研究。與非妊娠女性一樣，妊娠合并乳腺癌的病理類(lèi)型對(duì)患者的綜合治療方案選擇至關(guān)重要，因此，妊娠合并乳腺癌患者建議進(jìn)行細(xì)針活檢以明確病理類(lèi)型，利于后續(xù)治療選擇。研究認(rèn)為，妊娠不影響乳腺癌的治療效果，但妊娠合并乳腺癌的治療時(shí)機(jī)和方案選擇需要考慮胎兒的安全性ADDINEN.CITE<EndNote><Cite><Author>Cordeiro</Author><Year>2017</Year><RecNum>10</RecNum><DisplayText>[3]</DisplayText><record><rec-number>10</rec-number><foreign-keys><keyapp="EN"db-id="xwevaddfqwwrv7ewpey55etyzzesttfp0p9r"timestamp="1635608945">10</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Cordeiro,C.N.</author><author>Gemignani,M.L.</author></authors></contributors><auth-address>DepartmentofGynecologyandObstetrics,JohnsHopkinsSchoolofMedicine,Baltimore,Maryland. BreastService,DepartmentofSurgery,MemorialSloanKetteringCancerCenter,NewYork,NewYork.</auth-address><titles><title>BreastCancerinPregnancy:AvoidingFetalHarmWhenMaternalTreatmentIsNecessary</title><secondary-title>BreastJ</secondary-title></titles><periodical><full-title>BreastJ</full-title></periodical><pages>200-205</pages><volume>23</volume><number>2</number><edition>2017/02/14</edition><keywords><keyword>AntineoplasticAgents/therapeuticuse</keyword><keyword>BreastNeoplasms/*diagnosis/*therapy</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Mammaplasty</keyword><keyword>Mastectomy</keyword><keyword>Mastectomy,Segmental</keyword><keyword>Pregnancy</keyword><keyword>PregnancyComplications,Neoplastic/*diagnosis/*therapy</keyword><keyword>SentinelLymphNodeBiopsy</keyword><keyword>Ultrasonography,Mammary</keyword><keyword>breastcancer</keyword><keyword>chemotherapy</keyword></keywords><dates><year>2017</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>1075-122X(Print) 1075-122x</isbn><accession-num>28191695</accession-num><urls></urls><custom2>PMC5408732</custom2><custom6>NIHMS841805</custom6><electronic-resource-num>10.1111/tbj.12780</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[3]。本研究，我們對(duì)28例妊娠合并乳腺癌的患者進(jìn)行回顧性分析，總結(jié)妊娠合并乳腺癌的臨床特點(diǎn)、診療和妊娠結(jié)局。資料與方法臨床資料回顧性分析2006年1月1日2020年12月31日在中山大學(xué)附屬第一醫(yī)院住院治療的28例妊娠合并乳腺癌患者的臨床資料。納入標(biāo)準(zhǔn)：①妊娠期新發(fā)確診乳腺癌患者；②乳腺癌治療后妊娠期復(fù)發(fā)。排除標(biāo)準(zhǔn)：①妊娠前確診乳腺癌；②妊娠結(jié)束一年后診斷乳腺癌。診斷依據(jù)超聲提示乳腺癌，針吸細(xì)胞學(xué)檢查，病理診斷乳腺癌。評(píng)價(jià)指標(biāo)隨訪記錄納入標(biāo)準(zhǔn)的患者的基本臨床特點(diǎn)、妊娠期并發(fā)癥、確診乳腺癌的孕周、妊娠結(jié)局，包括分娩孕周、胎兒丟失情況、新生兒出生體重和患者乳腺癌治療情況，其中包括治療方法和患者預(yù)后。統(tǒng)計(jì)學(xué)數(shù)據(jù)采用SPSS24.0軟件進(jìn)行分析，符合正態(tài)分布的計(jì)量數(shù)據(jù)以均數(shù)±標(biāo)準(zhǔn)差（x±s）表示，計(jì)數(shù)資料以頻數(shù)表示。結(jié)果（表一及表二）臨床特點(diǎn)28例妊娠合并乳腺癌患者平均年齡33±6歲（23-41歲），其中初產(chǎn)婦9人，經(jīng)產(chǎn)婦19人；自然受孕25人，輔助生殖3人。主要臨床表現(xiàn)為可捫及乳房腫塊，伴或不伴疼痛，超聲提示乳腺癌可能。免疫組化病理診斷及HER基因檢查28例妊娠合并乳腺癌患者均進(jìn)行細(xì)針穿刺細(xì)胞學(xué)活檢和病理檢查，其中乳腺導(dǎo)管內(nèi)癌1例，其余27例均為浸潤(rùn)型導(dǎo)管癌；病理檢查中PR陰性15例，ER陰性14例，PR及ER雙陰性11例，6名患者行HER基因檢查，3例陽(yáng)性。妊娠結(jié)局妊娠合并乳腺癌患者確診時(shí)孕周5-40+6周，其中早孕期確診患者4例，中孕期確診9例，晚孕期確診15例。28例妊娠合并乳腺癌的患者中5例選擇人工流產(chǎn)；12例足月分娩，11例未足月分娩。23例分娩的患者的分娩孕周（32+2~41）周，15例剖宮產(chǎn)，8例順產(chǎn)，新生兒均存活。1例化療2個(gè)療程行產(chǎn)科彩超發(fā)現(xiàn)胎兒一側(cè)側(cè)腦室增寬11mm，產(chǎn)后復(fù)查頭顱彩超無(wú)異常。乳腺癌治療及預(yù)后28例妊娠合并乳腺癌患者中，5例患者（例2、5、10、17、25）引產(chǎn)后進(jìn)行腫瘤的綜合治療；3例患者（例3、6和21）妊娠期行乳腺癌根治術(shù)，其中例21術(shù)后行化療（妊娠期）；13例（例4、8、9、11、12、15、16、18-22、28）患者妊娠期行化療，化療方案是EC方案（柔比沙星+環(huán)磷酰胺），本研究中化療均于發(fā)現(xiàn)腫瘤后中晚孕期開(kāi)始，化療療程為1~7個(gè)不等，一般化療間隔2~3周。定期行胎兒彩超監(jiān)測(cè)胎兒生長(zhǎng)發(fā)育及羊水等情況，未發(fā)現(xiàn)胎兒生長(zhǎng)受限或羊水過(guò)少。其余患者均期待治療，定期復(fù)查。例1在剖宮產(chǎn)術(shù)中同時(shí)行乳腺癌根治術(shù)，18例患者在引產(chǎn)/分娩后行乳腺癌根治術(shù)或保乳手術(shù)，術(shù)后化療；例24產(chǎn)后行化療和內(nèi)分泌治療。28例患者中3例失訪，余患者均在引產(chǎn)/分娩后進(jìn)行乳腺癌綜合治療，臨床病理分期I期3例，II期14例，III期3例，IV期5例。隨訪至今，隨訪年限1年至13年不等，目前22例患者存活，3例因全身多發(fā)轉(zhuǎn)移死亡，3例失訪。討論妊娠合并乳腺癌的臨床特點(diǎn)乳腺癌是女性妊娠期最常見(jiàn)的惡性腫瘤之一，本研究中報(bào)道28例妊娠合并乳腺癌，臨床FIGOIII和IV期共8例患者（占28.57%）；ER和PR陰性率高于非妊娠期乳腺癌患者。由于妊娠期激素水平的改變，乳房觸診往往不可靠，因此大部分妊娠期乳腺癌確診時(shí)是晚期ADDINEN.CITEADDINEN.CITE.DATA[4]。研究發(fā)現(xiàn)，妊娠期乳腺癌的主要臨床表現(xiàn)為乳房腫塊、乳頭溢液和腋窩淋巴結(jié)腫大ADDINEN.CITEADDINEN.CITE.DATA[5]，而本研究中大部分妊娠合并乳腺癌的患者在妊娠期可觸及乳房腫塊，伴或不伴疼痛，與非妊娠期乳腺癌患者的臨床表現(xiàn)相似。妊娠合并乳腺癌的孕期診斷鉬靶檢查是非妊娠期乳腺癌的首選篩查方法，若選擇鉬靶檢查，建議遮蔽下腹部的同時(shí)控制最小的輻射計(jì)量（0.001-0.01mGy），考慮射線可能致流產(chǎn)和胎兒畸形，因此，孕期建議行超聲檢查，超聲檢查具有高靈敏性和特異性，對(duì)胎兒無(wú)致畸影響，具有無(wú)創(chuàng)和安全特點(diǎn)，是妊娠期女性乳腺癌篩查的首選方法。目前對(duì)于妊娠期行MR檢查進(jìn)一步確診乳腺癌具有爭(zhēng)議。而細(xì)針穿刺細(xì)胞學(xué)檢查是乳腺癌的確診方法，與非妊娠期乳腺癌一樣，乳腺癌的病理類(lèi)型對(duì)系統(tǒng)治療起著至關(guān)重要作用，本研究中28例妊娠合并乳腺癌患者均進(jìn)行細(xì)針穿刺細(xì)胞學(xué)檢查確診乳腺癌。普遍認(rèn)為妊娠合并乳腺癌的生物學(xué)特點(diǎn)不同于非妊娠期女性，通常表現(xiàn)更具有侵襲性的表型，低分化、雌激素受體（ER）陰性、HER陽(yáng)性或三陰性亞型ADDINEN.CITE<EndNote><Cite><Author>Bakhuis</Author><Year>2021</Year><RecNum>2</RecNum><DisplayText>[6]</DisplayText><record><rec-number>2</rec-number><foreign-keys><keyapp="EN"db-id="xwevaddfqwwrv7ewpey55etyzzesttfp0p9r"timestamp="1635608268">2</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Bakhuis,CFJ</author><author>Suelmann,BBM</author><author>vanDooijeweert,C</author><author>Linn,S</author><author>vanderWall,E</author><author>vanDiest,PJ</author></authors></contributors><titles><title>ReceptorStatusofBreastCancerDiagnosedduringPregnancy:ALiteratureReview</title><secondary-title>Criticalreviewsinoncology/hematology</secondary-title></titles><periodical><full-title>Criticalreviewsinoncology/hematology</full-title></periodical><pages>103494</pages><dates><year>2021</year></dates><accession-num>34715316</accession-num><label>5.833</label><urls></urls><electronic-resource-num>10.1016/j.critrevonc.2021.103494</electronic-resource-num></record></Cite></EndNote>[6]。本研究中，25例孕期行乳腺免疫組化病理檢查結(jié)果：孕激素受體及雌激素受體雙陽(yáng)性?xún)H有6例（24%），而兩者雙陰性有11例（44%），雌激素受體（ER）陰性有14例(56%)，有6例進(jìn)行HER基因檢查，3例陽(yáng)性(50%）。指南認(rèn)為，建議所有乳腺癌患者行BRCA基因篩查ADDINEN.CITEADDINEN.CITE.DATA[7]，但目前對(duì)于妊娠期乳腺癌的BRCA基因篩查是否影響治療方案的選擇尚不明確。妊娠合并乳腺癌的治療一旦被確診乳腺癌，治療不宜推遲。治療包括乳腺癌的治療及胎兒方面的監(jiān)護(hù)兩方面。與非妊娠期乳腺癌不同，妊娠合并乳腺癌(PABC)確診時(shí)往往是晚期，而且腫瘤生物學(xué)特點(diǎn)多呈三陰性，這些與較差的無(wú)病生存期和總生存期相關(guān)[8]。是否繼續(xù)妊娠，需對(duì)乳腺腫瘤組織學(xué)類(lèi)型、腫瘤分期、腫瘤生物學(xué)特點(diǎn)以及胎兒孕周進(jìn)行評(píng)估，并結(jié)合患者生育意愿來(lái)決定。治療原則如下：孕周<12周建議終止妊娠后按乳腺癌指南進(jìn)行后續(xù)治療；孕周≥12周可以在妊娠期進(jìn)行安全的乳腺癌治療，包括手術(shù)或化療。本研究中有4例妊娠早期確診乳腺癌，選擇人工流產(chǎn)終止妊娠后進(jìn)行乳腺癌治療。妊娠期合并乳腺癌的最佳治療策略宜由多學(xué)科協(xié)作制定，其中包括乳腺外科、腫瘤學(xué)科、婦科、產(chǎn)科和新生兒組成ADDINEN.CITEADDINEN.CITE.DATA[9]。指南提出，妊娠早、中、晚期均可進(jìn)行乳腺癌手術(shù)，妊娠期行乳房切除術(shù)和保留乳房的乳腺癌切除術(shù)均是安全的，腋窩淋巴結(jié)的手術(shù)處理同非妊娠期乳腺癌，但妊娠期不建議行乳房重建手術(shù)ADDINEN.CITEADDINEN.CITE.DATA[7,10]。對(duì)于腋窩淋巴結(jié)陰性的孕婦，前哨淋巴結(jié)活檢可有效降低淋巴水腫的發(fā)生ADDINEN.CITEADDINEN.CITE.DATA[11]。有研究通過(guò)同位素示蹤淋巴系統(tǒng)閃爍測(cè)定技術(shù)證實(shí)子宮的放射劑量遠(yuǎn)低于致畸劑量，因此，推薦妊娠期乳腺癌手術(shù)中行前哨淋巴結(jié)活檢ADDINEN.CITE<EndNote><Cite><Author>Saha</Author><Year>2016</Year><RecNum>25</RecNum><DisplayText>[11]</DisplayText><record><rec-number>25</rec-number><foreign-keys><keyapp="EN"db-id="xwevaddfqwwrv7ewpey55etyzzesttfp0p9r"timestamp="1635651804">25</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Saha,S.</author><author>Jacklin,R.</author><author>Siddika,A.</author><author>Clayton,G.</author><author>Dua,S.</author><author>Smith,S.</author></authors></contributors><auth-address>DepartmentofBreastSurgery,BroomfieldHospital,Chelmsford,Essex,CM17ET,UnitedKingdom.Electronicaddress:sahasunita@. DepartmentofBreastSurgery,BroomfieldHospital,Chelmsford,Essex,CM17ET,UnitedKingdom.</auth-address><titles><title>Safetyofradioactivesentinelnodebiopsyforbreastcancerandthepregnantsurgeon-Areview</title><secondary-title>IntJSurg</secondary-title></titles><periodical><full-title>IntJSurg</full-title></periodical><pages>298-304</pages><volume>36</volume><number>PtA</number><edition>2016/11/15</edition><keywords><keyword>BreastNeoplasms/*pathology</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>LymphaticMetastasis</keyword><keyword>*OccupationalExposure</keyword><keyword>Pregnancy</keyword><keyword>RadiationProtection</keyword><keyword>SentinelLymphNodeBiopsy/*adverseeffects</keyword><keyword>*Surgeons</keyword><keyword>Breastcancer</keyword><keyword>Occupationalradiationexposure</keyword><keyword>Pregnancyriskradiation</keyword><keyword>Sentinelnodebiopsy</keyword></keywords><dates><year>2016</year><pub-dates><date>Dec</date></pub-dates></dates><isbn>1743-9159</isbn><accession-num>27840311</accession-num><urls></urls><electronic-resource-num>10.1016/j.ijsu.2016.11.019</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[12]。目前關(guān)于乳腺癌手術(shù)在妊娠期安全性的數(shù)據(jù)是有限的，但大多數(shù)數(shù)據(jù)表明，妊娠期行改良的乳腺癌手術(shù)是安全的ADDINEN.CITEADDINEN.CITE.DATA[13]。如孕周較大，術(shù)中應(yīng)注意監(jiān)測(cè)血壓，預(yù)防發(fā)生仰臥性低血壓綜合征，術(shù)中仍應(yīng)密切監(jiān)測(cè)胎兒狀況。另外，由于中晚孕期母體處于血液高凝狀態(tài)，術(shù)后需預(yù)防深靜脈血栓形成。術(shù)后若有宮縮，可予藥物抑制宮縮治療。本研究中，有3例確診乳腺癌后于孕期行乳腺癌根治術(shù)，1例確診為IV期于根治術(shù)后2周行剖宮產(chǎn)術(shù)，另2例為IIb期，行根治術(shù)后分別于38和37周終止妊娠，新生兒預(yù)后均好，2例IIb期患者隨訪至今健康存活。非妊娠期乳腺癌的治療方式包括手術(shù)、化療、放療和內(nèi)分泌治療，考慮對(duì)胎兒的影響，妊娠期乳腺癌的治療方案選擇不同于非妊娠期乳腺癌。關(guān)于妊娠期乳腺癌放療的文獻(xiàn)較少，目前國(guó)際指南均提出禁止妊娠期乳腺癌的放療ADDINEN.CITE<EndNote><Cite><Author>AmouzegarHashemi</Author><Year>2020</Year><RecNum>13</RecNum><DisplayText>[13]</DisplayText><record><rec-number>13</rec-number><foreign-keys><keyapp="EN"db-id="xwevaddfqwwrv7ewpey55etyzzesttfp0p9r"timestamp="1635609272">13</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>AmouzegarHashemi,F.</author></authors></contributors><auth-address>RadiationOncologyResearchCenter,CancerInstitute,TehranUniversityofMedicalSciences,Tehran,Iran.amoozfar@tums.ac.ir.</auth-address><titles><title>RadiotherapyinPregnancy-AssociatedBreastCancer</title><secondary-title>AdvExpMedBiol</secondary-title></titles><periodical><full-title>AdvExpMedBiol</full-title></periodical><pages>125-127</pages><volume>1252</volume><edition>2020/08/21</edition><keywords><keyword>Breast/radiationeffects</keyword><keyword>BreastNeoplasms/*radiotherapy</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Pregnancy</keyword><keyword>PregnancyComplications,Neoplastic/*radiotherapy</keyword><keyword>RiskAssessment</keyword><keyword>Adjuvant</keyword><keyword>Breastcancer</keyword><keyword>Breastradiotherapy</keyword><keyword>Conservativebreastsurgery</keyword></keywords><dates><year>2020</year></dates><isbn>0065-2598(Print) 0065-2598</isbn><accession-num>32816271</accession-num><urls></urls><electronic-resource-num>10.1007/978-3-030-41596-9_16</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[14]，本研究中28例妊娠期乳腺癌患者均未選擇放射治療。Maxwell等ADDINEN.CITE<EndNote><Cite><Author>Maxwell</Author><Year>2019</Year><RecNum>27</RecNum><DisplayText>[14]</DisplayText><record><rec-number>27</rec-number><foreign-keys><keyapp="EN"db-id="xwevaddfqwwrv7ewpey55etyzzesttfp0p9r"timestamp="1636292707">27</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Maxwell,CV</author><author>Al-Sehli,H</author><author>Parrish,J</author><author>D'Souza,R</author></authors></contributors><titles><title>BreastCancerinPregnancy:ARetrospectiveCohortStudy</title><secondary-title>Gynecologicandobstetricinvestigation</secondary-title></titles><periodical><full-title>Gynecologicandobstetricinvestigation</full-title></periodical><pages>79-85</pages><volume>84</volume><number>1</number><dates><year>2019</year></dates><accession-num>30219806</accession-num><label>1.281</label><urls></urls><electronic-resource-num>10.1159/000493128</electronic-resource-num></record></Cite></EndNote>[15]在一項(xiàng)回顧性研究中，22例妊娠合并乳腺癌的患者中16例患者在妊娠期進(jìn)行乳腺癌手術(shù)治療，術(shù)中、術(shù)后未見(jiàn)明顯異常。根據(jù)指南，妊娠期乳腺癌的全身化療原則應(yīng)和非妊娠期乳腺癌一致，但一般建議在妊娠中、晚期進(jìn)行，化療劑量和療程應(yīng)和非妊娠期乳腺癌相同ADDINEN.CITEADDINEN.CITE.DATA[7]。妊娠期化療藥物使用氟尿嘧啶、蒽環(huán)類(lèi)藥物和環(huán)磷酰胺是相對(duì)安全的，研究發(fā)現(xiàn)紫杉醇的應(yīng)用也是相對(duì)安全的；由于曲妥珠單抗可增加羊水過(guò)少的發(fā)生率，因此妊娠期禁用，妊娠期化療的過(guò)程中注意止吐治療，其中昂丹司瓊和胃復(fù)安是安全的ADDINEN.CITEADDINEN.CITE.DATA[16,17]。目前臨床常用的化療方案為蒽環(huán)類(lèi)藥物+環(huán)磷酰胺或序貫紫杉醇類(lèi)，如表柔比星＋環(huán)磷酰胺、表柔比星＋環(huán)磷酰胺序貫多西他賽?；熕幬镉泄撬枰种频母弊饔?，可導(dǎo)致貧血和中性粒細(xì)胞減少癥，建議定期進(jìn)行血細(xì)胞計(jì)數(shù)監(jiān)測(cè)。妊娠不是使用粒細(xì)胞生長(zhǎng)因子的禁忌癥，對(duì)于粒細(xì)胞減少的患者，可以使用粒細(xì)胞生長(zhǎng)因子藥物[18,19]。對(duì)于妊娠期化療的病例，需密切監(jiān)測(cè)胎兒宮內(nèi)狀態(tài)，建議定期行彩超監(jiān)測(cè)胎兒的生長(zhǎng)發(fā)育指標(biāo)、羊水量及多普勒血流情況。本研究中13例患者于妊娠中、晚期行化療，化療方案是表柔比星+環(huán)磷酰胺，化療間隔一般為2~3周，化療后定期監(jiān)測(cè)血紅蛋白及粒細(xì)胞計(jì)數(shù)，大多數(shù)患者有輕度的骨髓抑制，粒細(xì)胞計(jì)數(shù)有輕度下降，僅有一例有嚴(yán)重的粒細(xì)胞計(jì)數(shù)下降，需使用粒細(xì)胞生長(zhǎng)因子治療。孕期定期監(jiān)測(cè)產(chǎn)科彩超，13例患者均未發(fā)現(xiàn)羊水過(guò)少及胎兒生長(zhǎng)受限。分娩后監(jiān)測(cè)新生兒血紅蛋白及粒細(xì)胞計(jì)數(shù)未見(jiàn)異常。研究報(bào)道乳腺癌的內(nèi)分泌治療，尤其他莫昔芬的應(yīng)用會(huì)引起胎兒發(fā)育異常，因此妊娠期禁用內(nèi)分泌治療ADDINEN.CITEADDINEN.CITE.DATA[20]，本研究中無(wú)患者妊娠期應(yīng)用內(nèi)分泌治療或抗HER-2靶向治療。過(guò)去認(rèn)為妊娠合并乳腺癌預(yù)后差，但近年來(lái)，不同的隊(duì)列研究和病例回顧研究發(fā)現(xiàn)調(diào)整患者年齡、腫瘤類(lèi)型和分期后，妊娠期乳腺癌的預(yù)后與非妊娠期乳腺癌預(yù)后無(wú)統(tǒng)計(jì)學(xué)差異ADDINEN.CITEADDINEN.CITE.DATA[21,22]。確診時(shí)已經(jīng)發(fā)生轉(zhuǎn)移的妊娠合并乳腺癌預(yù)后一般較差，5年生存期僅有10%ADDINEN.CITE<EndNote><Cite><Author>Matar</Author><Year>2021</Year><RecNum>3</RecNum><DisplayText>[20]</DisplayText><record><rec-number>3</rec-number><foreign-keys><keyapp="EN"db-id="xwevaddfqwwrv7ewpey55etyzzesttfp0p9r"timestamp="1635608447">3</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Matar,R</author><author>Crown,A</author><author>Sevilimedu,V</author><author>Goldfarb,SB</author><author>Gemignani,ML</author></authors></contributors><titles><title>TimingofPresentationandOutcomesofWomenwithStageIVPregnancy-AssociatedBreastCancer(PABC)</title><secondary-title>Annalsofsurgicaloncology</secondary-title></titles><periodical><full-title>Annalsofsurgicaloncology</full-title></periodical><dates><year>2021</year></dates><accession-num>34709494</accession-num><label>4.061</label><urls></urls><electronic-resource-num>10.1245/s10434-021-10901-6</electronic-resource-num></record></Cite></EndNote>[23]。由于我們的病例回顧研究中的中位隨訪期相對(duì)短，樣本量較小，因此不能評(píng)估妊娠合并乳腺癌的預(yù)后。在我們的研究中，有3例發(fā)生遠(yuǎn)處轉(zhuǎn)移的妊娠期乳腺癌患者死亡。妊娠合并乳腺癌終止妊娠的孕周目前尚無(wú)統(tǒng)一意見(jiàn)。決定終止妊娠的孕周，應(yīng)由乳腺外科、腫瘤學(xué)科、產(chǎn)科及新生兒科等多學(xué)科討論后共同制定。應(yīng)綜合考慮腫瘤組織類(lèi)型、腫瘤分期、腫瘤生物學(xué)特點(diǎn)、孕期腫瘤治療效果以及當(dāng)?shù)匦律鷥褐委熕?，擬35周前終止妊娠的，可提前一周予促胎成熟治療。如乳腺癌病情穩(wěn)定，可考慮37周后再終止妊娠。此外，對(duì)于妊娠期化療的患者，要考慮到化療藥物有骨髓抑制的副作用，包括對(duì)母體及胎兒，而骨髓抑制一般在化療結(jié)束后2~3周恢復(fù)，故建議末次化療時(shí)間和分娩間隔3周，并且至少在孕35周前停止化療[24]。乳腺癌并不是剖宮產(chǎn)指征，對(duì)于無(wú)其他產(chǎn)科剖宮產(chǎn)指征的患者，可以經(jīng)陰道分娩。對(duì)于妊娠期化療的患者，免疫力相對(duì)下降，產(chǎn)后需注意預(yù)防感染。本研究中，23例分娩的患者，4例在35周前分娩，8例在35~37周分娩，11例在37周后分娩，經(jīng)陰道分娩有8例，剖宮產(chǎn)有15例，新生兒結(jié)局均良好，圍產(chǎn)期均無(wú)發(fā)生感染。妊娠期確診的乳腺癌的治療是具有挑戰(zhàn)性的，需要多學(xué)科協(xié)作團(tuán)隊(duì)個(gè)體化處理。妊娠期乳腺癌的發(fā)病率低，妊娠期治療需要考慮患者腫瘤病情、孕周和對(duì)胎兒的影響，治療方案選擇主要參考國(guó)際指南，目前普遍認(rèn)為妊娠中晚期進(jìn)行乳腺癌的化療相對(duì)安全，可有效改善患者的預(yù)后?！緟⒖嘉墨I(xiàn)】ADDINEN.REFLIST1. MacdonaldHR.Pregnancyassociatedbreastcancer.BreastJ2020;26:81-5.2. KnabbenL,MuellerMD.Breastcancerandpregnancy.HormMolBiolClinInvestig2017;32.3. CordeiroCN,GemignaniML.BreastCancerinPregnancy:AvoidingFetalHarmWhenMaternalTreatmentIsNecessary.BreastJ2017;23:200-5.4. GanmaaD,EnkhmaaD,BaatarT,UyangaB,GantsetsegG,HeldeTT,Jr.,etal.MaternalPregnancyHormoneConcentrationsinCountrieswithVeryLowandHighBreastCancerRisk.IntJEnvironResPublicHealth2020;17.5. JohanssonALV,AnderssonTM,HsiehCC,Jirstr?mK,CnattingiusS,FredrikssonI,etal.Tumorcharacteristicsandprognosisinwomenwithpregnancy-associatedbreastcancer.IntJCancer2018;142:1343-54.6. BakhuisC,SuelmannB,vanDooijeweertC,LinnS,vanderWallE,vanDiestP.ReceptorStatusofBreastCancerDiagnosedduringPregnancy:ALiteratureReview.Criticalreviewsinoncology/hematology2021:103494.7. GradisharWJ,AndersonBO,AbrahamJ,AftR,AgneseD,AllisonKH,etal.BreastCancer,Version3.2020,NCCNClinicalPracticeGuidelinesinOncology.JNatlComprCancNetw2020;18:452-78.8.KausarSuleman,AsifHusainOsmani,HashemAlHashem.BehaviorandOutcomesofPregnancyAssociatedBreastCancer.AsianPacificJournalofCancerPrevention,AsianPacJCancerPrev.

2019;20(1):135–138.9. ShacharSS,GallagherK,McGuireK,ZagarTM,FasoA,MussHB,etal.MultidisciplinaryManagementofBreastCancerDuringPregnancy.Oncologist2017;22:324-34.10. CommitteeOpinionNo.696:NonobstetricSurgeryDuringPregnancy.ObstetGynecol2017;129:777-8.11. HanSN,AmantF,CardonickEH,LoiblS,PeccatoriFA,GheysensO,etal.Axillarystagingforbreastcancerduringpregnancy:feasibilityandsafetyofsentinellymphnodebiopsy.BreastCancerResTreat2018;168:551-7.12. SahaS,JacklinR,SiddikaA,ClaytonG,DuaS,SmithS.Safetyofradioactivesentinelnodebiopsyforbreastcancerandthepregnantsurgeon-Areview.IntJSurg2016;36:298-304.13. ShahNM,ScottDM,KandagatlaP,MoravekMB,CobainEF,BurnessML,etal.YoungWomenwithBreastCancer:FertilityPreservationOptionsandManagementofPregnancy-AssociatedBreastCancer.AnnSurgOncol2019;26:1214-24.14. AmouzegarHashemiF.RadiotherapyinPregnancy-AssociatedBreastCancer.AdvExpMedBiol2020;1252:125-7.15. MaxwellC,Al-SehliH,ParrishJ,D'SouzaR.BreastCancerinPregnancy:ARetrospectiveCohortStudy.Gynecologicandobstetricinvestigation2019;84:79-85.16. TehraniOS.SystemicTreatmentsinPregnancy-AssociatedBreastCancer.AdvExpMedBiol2020;1252:115-24.17. KuchiraR,MomoK,IsozakiH,KoshizukaH,KidaM,WatanabeA,etal.Doxorubicin-andCyclophosphamide-BasedChemotherapyforPregnantWomenWithStageIIIaBreastCancer.AmJTher2021.18.LoiblS,SchmidtA,GentiliniO,etal.Breastcancerdiagnosedduringpregnancy:adaptingrecentadvancesinbreastcan