教育演講8:乳癌篩檢及治療之爭論
Controversy of Breast Cancer Screen and Management

程 序 表

E8-1
乳癌篩檢及治療之爭論
Controversy of Breast Cancer Screen and Management
黃俊升
臺大醫院乳房醫學中心 臺大醫學院外科

  相較於歐美,台灣仍是乳癌發生率低的地區。然而台灣的乳癌發生率迅速地增加,是台灣婦女最常見的癌症,非侵襲性的零期乳癌僅佔 10%不到,乳癌死亡率也高居婦女常見死亡原因之一。因此衛生署國民健康局提供45歲以上婦女每兩年一次乳房X光攝影篩檢,目前約有 20%的婦女接受檢查。
在歐美,乳房X光攝影被證明可以有效降低乳癌死亡率,因此歐美國家通常建 議 50歲以上應做乳房X光攝影篩檢,至於篩檢的頻率則不一致。40-50歲之間的婦女乳房X光攝影篩檢的效益,則仍未有定論。2009年美國USPSTF研究認為40歲開始乳房攝影篩檢較50歲才開始篩檢所增加的效益有限,且每年篩檢較每兩年篩檢無甚大差別。然而美國癌症協會及美國放射醫學會則認為40歲起每年一次乳房X光攝影仍符合最大的成本效益。而英國目前則提供50歲以上婦女每三年一次乳房X光攝影篩檢。
不同的年齡層乳癌篩檢的效益不同,或許與腫瘤生物特性有關。50歲以下婦女若罹患乳癌,腫瘤成長速度快。因此,50歲以上的婦女每兩年,甚至三年篩檢一次或許已足夠,而40-49歲的婦女說不定每年篩檢仍嫌不足。另外,乳房X光攝影篩檢受限於乳房組織的緻密程度,由於更年期以前的婦女通常較更年期以後的婦女乳房緻密,許多人認為40-50歲婦女乳房較為緻密的關係,即便每年作乳房X光攝影篩檢未必有效。
台灣的乳癌發生率雖然近年來急遽上升,但相較於歐美發生率仍低,因此為利用有限的?源,衛生署的政策最早是倡導婦女乳房自我檢查。然而上海研究發現:乳房自我檢查並不是早期發現乳癌的有效方法。台灣在1992-1997年間也曾針對家族有乳癌患者之一等親做乳癌篩檢,雖然高危險群的乳癌篩檢在成本效益上是符合的,然而有乳癌家族史的乳癌患者畢竟只佔所有乳癌的5%左右,因此針對乳癌高危險群做篩檢仍然不能偵測到大部分的乳癌案例。
相較於歐美國家,台灣乳癌發生的年齡層較早,一半的乳癌在更年期之前發生。由於早發性乳癌的預後通常較差,因此40-49歲的婦女乳癌篩檢在台灣似乎更為重要。由於更年期前的婦女乳房緻密,因此加上另一個乳房篩檢工具,例如乳房超音波或磁振造影,可能可以在緻密的乳房偵測到乳房X光攝影未能看見的腫塊。我們的研究初步證實乳房超音波在篩檢的輔助效益。
一個前瞻性的研究發現,用乳房超音波篩檢3626位乳房組織緻密但乳房觸診和乳房攝影結果都是正常的婦女,結果有0.3%的人發現乳癌。
乳房超音波作為大量婦女乳癌篩檢的問題之一,是因為常常偵測不出伴隨零期乳癌出現的顯微鈣化。乳房X光攝影是偵測顯微鈣化最靈敏的工具,但顯微鈣化所伴隨的零期乳癌有些並不一定會轉換成一期以上的乳癌。因此,也許可以將乳房X光攝影篩檢的間隔拉長,其間加上乳房超音波的檢查,來幫助發現乳房X光攝影所偵測不到未有顯微鈣化的乳癌。
根據加拿大最近發表的研究報告顯示,40-50歲的婦女每年定期做乳房X光攝影篩檢再加上自我檢查及醫師觸診,相較於一般的社區醫療行為,也就是婦女摸到腫塊不定期去醫院做乳癌篩檢(包括乳房X光攝影),兩者死亡率沒有差別。因此40-50歲之間的婦女,即便每年作一次乳房X光攝影篩檢仍然未能顯著降低死亡率。
而這些乳癌不管是腫瘤的大小與臨床的分期,與乳房X光攝影偵測到觸摸不到的乳癌並無差別 ,但相較於摸得到的乳癌則通常較小,且分期較早。在緻密乳房的婦女,超音波篩檢可使乳癌偵測率提高17%,而且使得影像檢查才可以偵測到的乳癌增加37%。這些結果顯示,乳房超音波在偵測摸不到的腫瘤上非常有效,尤其是這些腫瘤可能是乳房X光攝影在停經前婦女緻密的乳房上所未能偵測到的。日本的一個研究亦顯示,在只做觸診的15935個婦女,只有5個乳癌被發現,可是在另一組加上乳房超音波檢查的18539名婦女中,則有22個乳癌被發現,而且60%的乳癌是摸不到的早期乳癌,而50%的婦女則是小於50歲。
然而許多研究顯示,零期乳癌雖然可能慢慢發展成為浸潤性乳癌,也就是一期以上的乳癌(大約有30-50%的零期乳癌會轉變成一期以上的乳癌),可是其他的零期乳癌則會萎縮消失,或者是持續不變,仍然是零期乳癌。另外,是不是所有一期以上的乳癌都是從零期乳癌發展過來,目前仍未完全確定。
一個西方的研究報告顯示,每1000名40-49歲的婦女做乳癌篩檢,將會有1.5個病例為零期乳癌,而另外1.5個病例為一期以上的乳癌;如果是50歲以上的婦女篩檢,則零期乳癌的部分仍然只有2個案例,但是一期以上的乳癌卻增加為7個案例。由此可見,(零期乳癌的發現與年齡無關)年紀較大的婦女,乳癌發生率高,而乳腺較不緻密, 因此比年紀較輕的婦女容易發現一期以上的乳癌。在美國的研究報告中,摸不到的乳癌中以顯微鈣化來表現的約佔42%,可是在台大醫院的經驗裡,幾乎所有用乳房X光攝影偵測到的觸摸不到的乳癌,都是因為偵測到顯微鈣化而被發現。因此,在乳房較為緻密的情況,即年紀較輕的婦女,乳房超音波應該有機會發現許多乳房X光攝影所未能偵測到的觸摸不到的乳癌。
一個研究顯示50歲以下的婦女與50歲以上的婦女相較,在第一次乳癌篩檢發現有問題的機會是一樣的,然而經過切片證實有問題的比率卻相當懸殊,50歲以前的婦女大概只有4%被證實有問題,但是50歲以後的婦女卻高達18%。因此單以乳房X光攝影做篩檢,50歲以下的婦女可能會接受較多不必要的切片檢查。
重要參考文獻:依一般科學論文之參考文獻撰寫體例,列出所引用之參考文獻,並於計畫內容引用處標註之。
1. Department of Health, Executive Yuan, Taipei, Taiwan, Cancer Registry Annual Report (1997).
2. Lai MS. Yen MF. Kuo HS. Koong SL. Chen TH. Duffy SW. Efficacy of breast-cancer screening for female relatives of breast-cancer-index cases: Taiwan multicentre cancer screening (TAMCAS). Intl J Cancer 1998; 78:21-26.
3. Chie WC, Chang KJ. Factors related to tumor size of breast cancer at treatment in Taiwan. Prev. Med 1994; 23:91-97.
4. Thomas DB. Gao DL. Self SG. Allison CJ. Tao Y. Mahloch J. Ray R. Qin Q. Presley R. Porter P. Randomized trial of breast self-examination in Shanghai: methodology and preliminary results. J Natl Cancer Inst 1997; 89:355-365.
5. Ng EH. Ng FC. Tan PH. Low SC. Chiang G. Tan KP. Seow A. Emmanuel S. Tan CH. Ho GH. Ng LT. Wilde CC. Results of intermediate measures from a population-based, randomized trial of mammographic screening prevalence and detection of breast carcinoma among Asian women: the Singapore Breast Screening Project [published erratum appears in Cancer 1998 Jul 1;83(1):191]. Cancer 1998; 82:1521-1528.
6. Chan LK. Lam HS. Chan ES. Lau Y. Chan M. Gwi E. Leung TY. Mammogram screening of Chinese women in Kwong Wah Hospital, Hong Kong. Australasian Radiology 1998; 42:6-9.
7. Baines CJ. Miller AB. Mammography versus clinical examination of the breasts. [Review] [26 refs] J Natl Cancer Inst. Monographs 1997; 22:125-129.
8. Hendrick RE, Smith RA, Rutledge JH III, Smart CR. Benefit of screening mammography for women aged 40-49: a new meta-analysis of randomized controlled trials. Monogr Natl Cancer Inst 1997; 22:87-92.
9. Smart CR, Hendrick RE, Rutledge JH III, Smith RA. Benefit of mammography screening in women ages 40-49 years: current evidence from randomized controlled trials. Cancer 1995; 75:1619-1626 [Erratum: Cancer 1995; 75:2788.]
10. Falun Meeting Organizing Committee and Collaborators. Breast-cancer screening with mammography in women aged 40-49 years: Swedish Cancer Society and th Swedish National Board of Health and Welfare – report of the organizing committee and collaborators, Falun Meeing, Falun, Sweden (21 and 22 March 1996). Int J Cancer 1996; 68:693-699.
11. Andersson I, Janzon L. Reduced breast cancer mortality in women under age 50: updated results from Malmo Mammographic Screening Program. Monogr Natl Cancer Inst 1997; 22:63-67.
12. Eastman P. NCI adopts new mammography screening guidelines for women. J Natl Cancer Inst 1997; 89:538-540.
13. Feig SA, D’Oris CJ, Hendrick RE, et al. American College of Radiology guidelines for breast cancer screening. AJR Am J Roentgenol 1998; 171:29-33.
14. Leitch AM, Dodd GD, Costanza M, et al. American Cancer Society guidelines for the early detection of breast cancer: updated 1997. CA Cancer J Clin 1997; 47:150-153.
15. Stapleton S. House: annual mammograms at 40. American Medical News 1999; 42(no. 27):27, 29.
16. Kerlikowske K, Grady D, Barclay J, Sickles EA, Eaton A, Ernster V. Positive predictive value of screening mammography by age and family history of breast cancer. JAMA 1993; 270:2444-2450.
17. Peer PGM, van Dijck JAAM, Hendriks JHCL, et al: Age dependent growth rate of primary breast cancer. Cancer 1993; 71:3547-3551.
18. Tabar L. Fagerberg G, Chen H-H, et al: Efficacy of breast cancer screening by age: New results from the Swedish Two-County trial. Cancer 1995; 75:2507-2517.
19. Duffy, S.W., Chen, H.H., Tabar, L., Fagerberg, G. and Paci, E., Sojourn time, sensitivity and positive predictive value of mammography screening for breast cancer in women age 40-49. Int J Epidemiol 1996; 25:1139-1145.
20. Mandelson MT. Oestreicher N. Porter PL. White D. Finder CA. Taplin SH. White E. Breast density as a predictor of mammographic detection: comparison of interval- and screen-detected cancers. J Natl Cancer Inst 2000; 92:1081-1087.
21. Kolb TM. Lichy J. Newhouse JH. Occult cancer in women with dense breasts: detection with screening US—diagnostic yield and tumor characteristics. Radiology 1998; 207:191-199.
22. Kerlikowske K, Grady D, Barclay J, et al: Positive predictive value of screening mammography by age and family history of breast cancer. JAMA 1993; 270:2444-2450.
23. Cheng SH, Tsou MH, Liu MC, Jian JJ, Cheng JCH, Leu SY, Hsieh CY, and Huang AT. Unique features of breast cancer in Taiwan. Breast Cancer Research and Treatment 2000; 63:213-233.
24. Lo YL, Yu JC, Huang CS, Tseng SL, Chang TM, chang KJ, Wu CW, Shen CY. Allelic loss of the BRCA1 and BRCA2 genes and other regions on 17q and 13q in breast cancer among women from Taiwan- the area of low incidence but earlier onset. Int J Cancer 1998; 79:580-587.
25. Gordon PB, Goldenberg SL. Malignant masses detected only by US. A retrospective review. Cancer 1995; 76:626-630.
26. Teh W. Wilson AR. The role of ultrasound in breast cancer screening. A consensus statement by the European Group for Breast Cancer Screening. [Review] [24 refs] European Journal of Cancer 1998; 34:449-450.
27. Huang CS, Wu CY, Chu JS, Lin JH, Hsu SM, Chang KJ. Microcalcifications of non-palpable breast lesions detected by ultrasonography: correlation with mammography and histopathology. Ultrasound Obstet Gynecol 1999; 13:431-436.
28. Leucht WJ, Leucht D, Kiesel L. Sonographic demonstration and evaluation of microcalcifications in the breast. Breast Disease 1992; 5:105-123.
29. Okamoto H. Ogawara T. Arihara F. Kobayashi K. Inoue S. Nagahori K. Yamamoto M. Sekikawa T. Matsumoto Y. Usefulness of ultrasonography combined with conventional physical examination in mass screening for breast cancer: a retrospective study of Yamanashi Health Care Center results from 1989 to 1994. Japanese Journal of Cancer Research 1996; 87:317-323.
30. Smith RA. Screening fundamentals [Review] JNCI Monographs 1997; 22:15-9.
31. Age-related accuracy of screening mammography: how should it be measured? [Review] [50 refs] Radiology 2000; 214:633-640.
32. Ernster VL. Barclay J. Increases in ductal carcinoma in situ (DCIS) of the breast in relation to mammography: a dilemma. [Review] [34 refs] J Natl Cancer Inst. Monographs 1997; 22:151-156.
33. Page DL, Dupont WD, Rogers LW, et al: intraductal carcinoma of the breast: Follow-up after biopsy only. Cancer 1982; 49:751-758.
34. Rosen PP, Braun DW, Kinne DE: The clinical significance of pre-invasive breast cancer. Cancer 1980; 46:919-925.
35. Sickles EA. Mammographic features of 300 consecutive non-palpable breast cancers. Am J Roentgenol 1986; 146:661-663.