(Hanahan and Weinberg, 2000) (Kelsey and Bernstein, 1996) (mammary ductal epithelium) (mammary lobular) (Kelsey and Horn-Ross, 1993) (World Health Organization) 1981 3-1 (non-invasive) (invasive) Paget (International Union Against Cancer) TNM (3-2) (3-3 ) (differentiation) Scarff-Bloom-Richardson (SBR) (1) (differentiation or tubular formation)(2) (pleomorphism)(3) (hyperchromatic and 34
mitotic nuclei) 3-5 6-7 8-9 35
3-1 (noninvasive) (intraductal carcinoma) (lobular carcinoma in situ) (invasive) (invasive ductal carcinoma) (invasive ductal carcinoma with predominately intraductal carcinoma) (invasive lobular carcinoma) (mucinous carcinoma) (medullary carcinoma) (papillary carcinoma) (tubular carcinoma) (adenocystic carcinoma) (secretory carcinoma) (apocrine carcinoma) (carcinoma with metaplasia) Paget (Paget s disease) Azzopardi et al. : Histological typing of breast tumors. Geneva: World Health Organization, 1981. 36
3 3-2 TNM (Tumor) Tis (Nodes) (Metastasis) N0 T1 1 N0 A T0 T1 1 T2 N1 N1 2 N0 B T2 T3 N1 N0 A T0 T1 1 T2 T3 N2 N2 N2 N1, N2 B T4 T N N3 T N M1 1, T1 T1mic 2, pn1a pn0 3, Tis T0 T1 (T1mic, 0.1 ; T1a, 0.1 0.5 ; T1b, 0.5 1 ; T1c, 1 2 )T2 T3 T4 ( ; T4a, ; T4b, ; T4c, T4a T4b; T4d, )N0 N1 [pn1a, 0.2 ; pn1b, (i) 1-3 / 0.2 2 ; (ii) 4 / 0.2 2 ; (iii) / 2 ; (iv) / 2 ]N2 N3 M1 ( ) 2 Hermanek P. and Sobin LH. (editors) : TNM classification of malignant tumours. 5 th ed. International Union Against Cancer. Wiley-Liss Company, New York 1997. 37
3-3 (differentiation or tubular formation) 1. 75% 2. 10~75% 3. 10% 1 2 3 (pleomorphism) 1 1. 2 2. 3 3. (mitotic counts) Leitz Ortholux Nikon Labophot Leitz Diaplan x25 x40 x40 0.59mm 0.44mm 0.63mm Grade I3-5, Grade II6-7, Grade III8-9, 0-9 0-5 0-11 1 10-19 6-10 12-22 2 >20 >11 >23 3 Fletcher C, Diagnostic histopahology of tumors. 2 th ed. Churchill Livingstone Company, 2000. 38
3712 7.11% 31.48 995 3.40% 8.58, 2001 15-21 (Kelsey and Horn-Ross, 1993) 2001 (Kelsey and Horn-Ross, 1993) (Kelsey and Horn-Ross, 1993) (Kelsey and Horn-Ross, 1993) 39
(Kelsey et al., 1993; Kelsey and Horn-Ross, 1993Kelsey and Bernstein, 1996) (Kelsey and Horn-Ross, 1993Ziegler et al., 1993) (Chie et al., 1995) 3-4 (Kelsey and Bernstein, 1996) 40
(breast cancer susceptibility gene) (1) (carcinogen) (2) (3) (Newman et al., 1997; Rock et al. 2000) 17 (17q21) BRCA1 BRCA1 (Miki et al., 1994) 13 (13q12) BRCA2 (Wooster et al., 1994) Li-Fraumeni syndrome 17 (17p13) TP53 (Li et al., 1988Malkin et al., 1990) (autosomal dominant inheritance) BRCA 41
11q22-23 ATM (ataxia telangiectasis mutated gene) (Gatti et al., 1988Swift et al., 1991Savitsky, 199511p15.5 HRAS1 VNTR (Krontiris et al., 1993)11p15.2-15.1 TSG101 (Li et al., 1997) 10q23 PTEN (Li et al., 1997; Lynch et al., 1997) (3-5 ) (duct) -- (alveolus) - (lobules) - - - (King et al., 1993Pike et al., 1993) (Kelsey and Horn-Ross, 1993Kelsey and Bernstein, 1996) 42
(Kelsey and Horn-Ross, 1993) (prolactin) (sex-hormone-binding globulin) (non-protein-bounded estradiol) androgen (androstenedione) estrone (Kelsey and Bernstein, 1996; King et al., 1993Pike et al., 1993) 43
3-4 4.0 ( ) BRCA1 / BRCA2 2.1-4.0 ( 1.2-2.0 45 40 (40 (40 ) (50 ) 4 30 11 55 20 15 45 Kelsey et al. : Epidemiology and Prevention of Breast Cancer. Annu. Rev. Public Health, 15:47-67, 1996. 44
3-5 (gene frequency) % (gene penetrance) 70 (attributable risk) % BRCA1 17q21 0.06 85% 5 BRCA2 13q12.3 63% 3 TP53 17p13.1 0.005 <1 ATM 11q22-23 0.5 17% 7 HRAS1 VNTR 11p15.5 5.8 8% 9 PTEN 10q23 0.02 TSG101 11p15.1-15.2 Ford et al. : The genetics of breast and ovarian cancer. Br. J. Cancer. 71: 806, 1995Greene et al. : Genetics of breast cancer. Mayo. Clin. Proc. 72:56, 1997 ; Chen et al., Mutation analysis of the putative tumor suppression gene PTEN/MMAC1 in sporadic breast cancer. Breast Cancer Res Treat. 55:85, 1999 ; Greenblatt et al. Mutation in the p53 tumor suppressor gene: clues to cancer etiology and molecular pathogenesis. Cancer Res. 58:859, 1994. 45