• 四川大學華西醫(yī)院甲狀腺乳腺外科（成都，610041）;

　　乳腺癌是女性最常見的惡性腫瘤之一，據(jù)統(tǒng)計，全球每年乳腺癌的發(fā)病人數(shù)約有120萬人，約50萬人死于乳腺癌。在西歐、北美等發(fā)達國家，乳腺癌的發(fā)病率占女性惡性腫瘤的首位，近年來我國許多大城市（如上海、北京、天津等地區(qū)）乳腺癌的發(fā)病率呈不斷上升趨勢[1-3]。乳腺癌已嚴重威脅著女性的健康和生命安全。這要求廣大醫(yī)務工作者努力提高治療效果。

1　乳腺癌的外科治療 
　　對于可手術(shù)的乳腺癌，其治療仍然是以手術(shù)為主的綜合治療，包括化學療法、放射治療、內(nèi)分泌治療、生物治療及靶向治療等。對于晚期乳腺癌，則更強調(diào)綜合治療。手術(shù)是第一種根治乳腺癌的方法，并強調(diào)手術(shù)的徹底性，乳腺癌根治術(shù)成為腫瘤臨床的標準手術(shù)，并在長達近一個世紀的時間里占據(jù)統(tǒng)治地位，而且曾經(jīng)一度流行擴大根治術(shù)。隨著對乳腺癌認識的深入，發(fā)現(xiàn)部分患者即使行擴大根治術(shù)也達不到根治效果，即使在疾病得到治療的同時，患者的生理、心理仍然受到極大的創(chuàng)傷。Fisher提出乳腺癌是全身性疾病而非局部病變，隨即出現(xiàn)了保留胸肌的各種改良根治術(shù)，現(xiàn)代乳腺外科提倡在治療疾病的同時盡可能保留女性乳房的功能和美觀，以保證患者的心理健康。因此，微創(chuàng)技術(shù)在近30多年來得到很大的發(fā)展，開展了多種乳腺微創(chuàng)技術(shù)，如保乳手術(shù)、保腋窩手術(shù)——前哨淋巴結(jié)活檢技術(shù)、乳腔鏡手術(shù)、麥默通（Mammotome，MMT）手術(shù)等，減少了并發(fā)癥，提高了患者的生存質(zhì)量[4-11]。
　　保乳手術(shù)已是一個成熟的乳腺癌治療技術(shù)，在國外已超過50%的患者接受該技術(shù)治療；隨著生活水平的提高，我國乳腺癌患者要求保留乳房的愿望越來越強烈。醫(yī)學的不斷發(fā)展，治療手段的提高，尤其是高效藥物的不斷應用于臨床及放射治療技術(shù)的提高，為保乳治療提供了保障，使得保乳治療取得了與乳腺癌改良根治術(shù)相似的生存率，局部復發(fā)率略高2%[12]。因此，保乳手術(shù)是今后早期乳腺癌外科治療的趨勢。
　　對于因種種原因未保留乳腺的患者，術(shù)后乳房重建越來越來引起患者及醫(yī)生的重視。乳房重建有自體組織重建和假體重建兩種方式。自體組織重建具有能夠造就更加柔軟、外觀自然且下垂的乳房的優(yōu)點，是目前在歐美發(fā)達國家應用非常廣泛的重建方式。然而自體組織重建需要足夠的供區(qū)組織，需要較長的恢復時間，有受區(qū)皮瓣壞死、供區(qū)手術(shù)瘢痕、腹壁或背部肌肉薄弱甚至腹壁疝等風險[13,14]。與自體組織重建相比，假體重建具有手術(shù)時間較短、術(shù)后恢復快、技術(shù)難度相對較小、不產(chǎn)生供區(qū)多余手術(shù)瘢痕等優(yōu)點。因此假體重建是符合我國現(xiàn)狀、更容易被患者接受、更容易被醫(yī)生實施的一種重建方式。從時間上可分為一期重建和二期重建。
　　乳腺癌前哨淋巴結(jié)活檢術(shù)的開展有望替代腋窩淋巴結(jié)清掃術(shù)，從而減少甚至避免腋窩淋巴結(jié)清掃帶來的疼痛、麻木、水腫、運動障礙等并發(fā)癥。對前哨淋巴結(jié)微轉(zhuǎn)移的檢測可以提高分期的準確性，改變一部分患者的治療決策。
　　早期診斷、早期治療仍然是提高乳腺癌治療療效的最好措施。近年來，隨著B型超聲儀器和診斷能力的不斷提高，B型超聲檢查逐漸成為乳腺疾病中的常規(guī)檢查方法。臨床上，越來越多的無癥狀和體征的微小病灶被超聲檢查發(fā)現(xiàn)，卻難以對病灶的性質(zhì)作出正確的診斷，必須依靠準確切除病灶并進行病理檢查。B型超聲引導下對無體征病灶置入導絲標記定位切除活檢技術(shù)，在乳腺癌的早期診斷中具有重要價值。與鉬靶X線引導下的標記定位切除活檢技術(shù)相比，超聲引導下的導絲定位具有操作簡便、定位準確、無放射性損傷、不受致密型乳腺的影響等優(yōu)勢，但對于簇狀細小鈣化灶，鉬靶X線引導下的標記定位切除活檢仍然是首選。
　　外科手術(shù)技術(shù)的進步與各種先進的手術(shù)器械的應用密不可分。電刀在手術(shù)中的應用，使外科手術(shù)技術(shù)得到了根本上的改進，尤其是乳腺癌這種大創(chuàng)面的手術(shù)，在減少術(shù)中出血、縮短手術(shù)時間等方面較傳統(tǒng)的銳性解剖體現(xiàn)出明顯的優(yōu)勢。近年來，超聲刀在止血方面較傳統(tǒng)電刀有較明顯的優(yōu)勢，在腋窩清掃時避免了電刺激引起的肌肉收縮，減少了對腋窩神經(jīng)血管損傷的風險。MMT術(shù)和乳腔鏡的應用使乳腺外科的微創(chuàng)技術(shù)得到了進一步發(fā)展[8-11]。

2　乳腺癌的內(nèi)科治療 
　　乳腺癌的內(nèi)科治療主要包括化學療法、內(nèi)分泌治療和靶向治療。
　　大量臨床資料顯示，乳腺癌術(shù)后輔助化學療法可以改善乳腺癌患者的生存率，50歲以下可降低復發(fā)率和病死率分別為37%和27%，50歲以上為22%和14%，對乳腺癌的治療作用得到肯定，占有重要地位[15,16]。對局部晚期可手術(shù)乳腺癌患者提倡新輔助化學療法。新輔助化學療法可以使腫瘤縮小以利于手術(shù)，消滅微小轉(zhuǎn)移灶，并且有藥敏試驗的效果，是術(shù)后輔助治療方案選擇的依據(jù)。研究顯示新輔助化學療法能夠提高患者的生存率[17,18]。蒽環(huán)類（多柔比星和表柔比星為代表）和紫杉類（紫杉醇、多烯紫杉醇）化學療法藥物的先后問世，均是乳腺癌化學療法的一次突破，療效得到進一步提高[16,19,20]。
　　乳腺癌是雌激素依賴性腫瘤，內(nèi)分泌治療有效，對雌激素受體（estrogen receptor，ER）和（或）孕激素受體（progestogerone receptor，PR）陽性的患者，其療效與化學療法相當。但對ER、PR陰性患者療效差，內(nèi)分泌治療2~8周內(nèi)起效，療效維持時間長于化學療法，不良反應小，患者生活質(zhì)量高，在門診即可進行治療，與化學療法無交叉耐藥，可以單獨使用，內(nèi)分泌治療無效時，患者仍有機會改用化學療法。一項50歲以上ER陽性患者應用他莫昔芬（tamoxifen，TAM）治療5年的Meta分析顯示:TAM可以減少復發(fā)風險42%，減少死亡風險32%[21]。阿那曲唑與TAM單獨和聯(lián)合應用試驗（anastrozole tamoxifen alone and combination， ATAC）、BIG198（interpreting breast international group1-98， BIG198）和TAM或依西美坦輔助治療多中心試驗（TAM exemestane adjuvant multinational， TEAM）均顯示，對于絕經(jīng)后患者，芳香化酶抑制劑（aromatase inhibitor，AI），包括阿那曲唑、來曲唑和依西美坦，療效優(yōu)于TAM。因此，絕經(jīng)后患者的內(nèi)分泌治療應首選AI[22-25]。
　　靶向治療是目前乳腺癌治療的研究熱點。曲妥珠單抗是人源化的人類表皮細胞生長因子受體-2（human epidermalgrowth factor receptor-2，Her-2）單克隆抗體，與Her-2有高度親合力，與Her-2特異性結(jié)合后能阻止癌細胞內(nèi)信號傳遞從而抑制腫瘤細胞生長?？梢詥为毷褂?，也可以聯(lián)合化學療法或內(nèi)分泌治療。多個臨床研究表明，曲妥珠單抗可以使Her-2過表達的乳腺癌患者獲益[26-29]。
　　腫瘤新生血管形成是腫瘤研究最為活躍的領(lǐng)域之一。其中研究最多的是血管內(nèi)皮生長因子（vascular endothelial growth factor，VEGF）。貝伐珠單抗是一種重組人源化抗VEGF單克隆抗體，能與VEGF受體（VEGFR1和VEGFR2）特異性結(jié)合，阻礙VEGF生物活性形式產(chǎn)生，從而抑制腫瘤血管的生成，達到治療腫瘤的目的[30-32]。
　　破骨細胞及其前體細胞表面的核因子κB受體活化因子配體（receptor activator of neuclear factor-kappa B ligand，RANKL）特異性靶向抑制劑狄諾塞麥，是一種完全人源化的免疫球蛋白G2單克隆抗體，能高親合力地和RANKL特異結(jié)合，阻斷配體和受體的相互作用，抑制破骨細胞形成并抑制其功能及存活，從而降低溶骨，增加骨密度和強度。多項試驗證明，對于乳腺癌患者來說狄諾塞麥無論是對于其相關(guān)性骨質(zhì)疏松或者骨轉(zhuǎn)移都能起到很好的治療作用[33-38]。
　　另外，環(huán)氧化酶-2抑制劑塞來昔布、酪氨酸激酶抑制劑吉非替尼和拉帕替尼，無論是在動物實驗還是在臨床實驗中，都顯示出對乳腺癌的治療效果[39,40]?？傊?，分子靶向藥物有望成為繼化學藥物、激素類藥物之后的又一類新型藥物，并有可能成為今后乳腺癌藥物研究的主要方向。

3　乳腺癌的放射治療進展 
　　乳腺癌綜合治療中的放射治療是其重要組成部分，隨著放射治療設備的改進和技術(shù)的提高以及放射生物學研究的進展，尤其是適形調(diào)強放射治療的不斷發(fā)展，提高了乳腺靶區(qū)內(nèi)照射劑量的均勻性，減少對周圍正常組織尤其是對肺和心臟的損傷幾率，放射治療效果明顯提高[41,42]。
　　乳腺癌治療是綜合性治療，相信隨著醫(yī)藥科學及邊緣學科的進一步發(fā)展進步，會有更多更先進的診斷治療手段和藥物進入臨床，從而使廣大乳腺癌患者受益。

引用本文： 李宏江. 乳腺癌的治療現(xiàn)狀. 華西醫(yī)學, 2011, 26(7): 961-964. doi: 復制

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