1. Breast cancer (BC) epidemiology and pathology Gábor Cserni, MD, PhD, DSc Bács-Kiskun County Teaching Hospital Kecskemét, Hungary

4. ACS Facts and Figures 2010 n=207090 n=1970 Estimated deaths: 39840 Estimated deaths: 390

5. ACS 2010

8. Progression of BC (IDC) at the level of histological lesions UDH ADH LG DCIS IG DCIS HG DCIS IDC GI IDC GII IDC GIII Outdated model Usual type ductal hyperplasia does not proges s into atypical ductal hyperplasia.

9. Progression of BC (IDC) at the level of histological lesions UDH ADH LG DCIS IG DCIS HG DCIS IDC GI IDC GII IDC GIII Outdated model Usual type ductal hyperplasia does not proges s into atypical ductal hyperplasia.

10. Progression of BC (IDC) at the level of histological lesions FEA ADH LG DCIS IG DCIS HG DCIS IDC GI IDC GII IDC GIII Low-grade pathway High-grade pathway

13. Low grade vs high grade DCIS

16. Invasive lobular carcinoma Discohesive cells arranged in „ indian files ”, or in „g ee se lines”, often in a targetoid pattern around normal ducts http:// ioway.nativeweb.org / images / indianfile.jpg

19. Invasive lobular carcinoma E-cadherin (control upper left corner)

32. Sentinel LN (SLN) biopsy i s a functional selection from all of the regional LNs, by the identification of the most likely site (s) of regional metastases (sn) : modifier for cases staged by SLN biopsy only – e.g. pT1c pN1mi(sn) only if less than 6 SNs .

39. Nottingham TENOVUS study Dalton LW et al. Mod Pathol 2000;13:730-5. cit Elston CW, Ellis IO. Histopathology 1991

40. Grade in T1N0M0 BC Frkovic Grazio S et al. J Clin Pathol 2002;55:88-92. 270 patients 12.5 years median FU BC specific survival is grade dependent . MI (based on tertile cut offs) – strongest predictive component Low: 0-2/10HPF Intermediate: 3-8/10HPF High: 9- /10HPF (HPF diameter: 0.5 mm) 64% with mitotic score 1

42. BC Specific Survival (A) and Distant Metastasis Free Survival (B) in G1, G2 G3 carcinomas (below) and in G2 carcinomas with 10% MIB index cut-off (right). G2a vs G2b Aleskandarany MA, et al. Breast Cancer Res Treat 2010 EPub AOP (Median MIB1 LI was 15%)

43. Examples of Ki-67 staining in breast cancers with mitotic score 1-3 SCORE 2 SCORE 3 SCORE 1 Cserni G. 22nd European Congress of Pathology, 2009, Florence

46. (About) 150 cells, 27-37 Ki-67 positive: 18-25% Ki-67 index Y Y Y Y Y Y Y Y ? ? ? ? Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y ? ? ? ? ? N N ? N? N?

50. ER status of response to endocrine therapy

52. IHC for HER2 Extracellular Intracellular Transmembrane Trastuzumab HERCEPTIN ™ - 4D5 H-MoAb Reacting with cystein-rich EC domain II TAB 250 Mouse MoAb SP3 Rabbit MoAb 4B5 Rabbit MoAb CB11 Mouse MoAb A0485 Polyclonal Herceptest ™ Polyclonal Lapatinib - TYVERB ™ Tyr-kinase inhibitor

54. HER2-testing – consideration of trastuzumab therapy Modified from Bilous M, et al. Mod Pathol 2003;16:173–82 FIS H T umo r sample trastuzumab t herapy + – 2+ 3+ 1+ 0 + – FISH IHC trastuzumab t herapy trastuzumab t herapy +/- +/- Repeat/?

57. HER2-testing – consideration of trastuzumab therapy Modified from Bilous M, et al. Mod Pathol 2003;16:173–82 ( F ) IS H T umo r sample trastuzumab t herapy + – 2+ 3+ 1+ 0 + – ( F ) ISH IHC trastuzumab t herapy trastuzumab t herapy +/- +/- Repeat/?

58. 3+ 2+ (F-C-S)ISH for IHC 2+ cases FISH CISH SISH

62. THE END