Basement membrane in lobule.

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2 Bahram Memar, MD

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4 Basement membrane in lobule.

5 Normal lobule-luteal phase Normal lobule-follicular phase

6 Lactating breast

7 Greater than 95% are adenocarcinomas in situ carcinomas and invasive carcinomas. all breast carcinomas arise from cells in the terminal duct lobular unit

8 not resemblance of the involved spaces to normal ducts or lobules cell biology E-cadherin

9 Ductal Carcinoma in Situ from fewer than 5% of all carcinomas to 15% to 30% of carcinomas in well-screened populations Among cancers detected mammographically, almost half are DCIS

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11 five architectural subtypes: Comedocarcinoma Solid cribriform Papillary Micropapillary Paget disease

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18 natural history of DCIS low-grade DCIS develop invasive cancer at a rate of about 1% per year high-grade or extensive DCIS progress to invasive carcinoma at higher rates Mastectomy for DCIS is curative for over 95%

19 Breast conservation is appropriate for most women with DCIS but results in a slightly higher risk of recurrence major risk factors for recurrence are: (1) grade (2) size (3) margins

20 DCIS is typically monofocal and skip lesions with a gap of more Than 10 mm are uncommon Some centers desire a 20 mm margin of uninvolved tissue, others only a 1 or 2 mm margin narrower margins and radiotherapy

21 REDUCING THE RISK: wide margins (i.e., at least 1 cm) radiation therapy tamoxifen

22 Paget disease

23 Lobular Carcinoma in Situ (LCIS) LCIS is always an incidental biopsy finding bilateral in 20% to 40% 80% to 90% before menopause loss of expression of E-cadherin

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25 E-cadherin

26 In the absence of mammographic screening, palpable Rarely, breast cancer presents as an axillary nodal metastasis or distant metastasis

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28 Distribution of Histologic Types of Breast Cancer Total Cancers Percentage CARCINOMA IN SITU [*] Ductal carcinoma in situ 80 Lobular carcinoma in situ 20 INVASIVE CARCINOMA No-special-type carcinoma ( ductal ) 79 Lobular carcinoma 10 Tubular/cribriform carcinoma 6 Mucinous (colloid) carcinoma 2 Medullary carcinoma 2 Papillary carcinoma 1 Metaplastic carcinoma <1

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30 Gene expression profiling, which can measure the relative quantities of mrna for essentially every gene, has identified five major patterns of gene expression in the NST group: luminal A luminal B Normal basal-like HER2 positive correlate with prognosis and response to therapy, and thus have taken on clinical importance

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32 Luminal A (40% to 55% of NST cancers the largest group ER positive and HER2/neu negative gene signature is dominated by the dozens of genes under the control of ER increased transcription of genes thought to be characteristic of normal luminal cells. well- or moderately differentiated, and most occur in postmenopausal women. generally slow growing and respond well to hormonal treatments. clinical trials are attempting to identify different types or combinations of chemotherapeutic agents that may be efficacious for ER-positive cancers.

33 Luminal B 15% to 20% of NST cancers also expresses ER generally of higher grade, has a higher proliferative rate, and often overexpresses HER2/neu sometimes referred to as triple-positive cancers. a major group of ER-positive cancers that are more likely to have lymph node metastases

34 Normal breast like 6% to 10% of NST cancers a small group of usually well-differentiated ERpositive, HER2/neu-negative cancers similarity of their gene expression pattern to normal tissue not yet clear whether or not this is a specific tumor expression pattern

35 Basal-like 13% to 25% of NST cancers absence of ER, PR, and HER2/neu expression of markers typical of myoepithelial cells (e.g., basal keratins, P-cadherin, p63, or laminin), progenitor cells, or putative stem cells (e.g., cytokeratins 5 and 6) Basal was chosen as a general term that covers all of these cell types. Basal-like cancers are a subgroup of ER-PR-HER2/neu triple-negative carcinomas Members of this group include: medullary carcinomas metaplastic carcinomas (e.g., spindle cell carcinomas or matrix-producing carcinomas), carcinomas with a central fibrotic focus.

36 distinct genetic and epidemiologic features Many carcinomas arising in women with BRCA1 mutations an increased incidence in certain ethnic populations and in young women. generally high grade and have a high proliferation rate. aggressive course, frequent metastasis to viscera and the brain, and a poor prognosis approximately 15% to 20% will have a pathologic complete response to chemotherapy; cure may be possible in this chemosensitive subgroup.

37 HER2 positive 7% to 12% of NST cancers ER-negative carcinomas that overexpress HER2/neu protein In over 90% of HER2/neu positive cancers, amplification of 17q21 FISH,mRNA gene arrays, immunohistochemistry Rarely mechanisms other than gene amplification usually : poorly differentiated high proliferation rate high frequency of brain metastasis.

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40 The histologic hallmark, dyscohesive infiltrating tumor cells, often arranged in single file or in loose clusters or sheets Tubule formation is absent. The cytologic appearance is identical to the cells of atypical lobular hyperplasia and LCIS. Signet-ring cells,are common. Desmoplasia may be minimal or absent.

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45 pattern of metastasis mistaken for signet ring carcinoma biallelic loss of expression of CDH1

46 Medullary Carcinoma sixth decade and presents as a well-circumscribed benign lesion clinically and radiologically soft, fleshy

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48 Tubular carcinoma

49 Invasive cribriform carcinoma

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51 Medullary carcinoma

52 Invasive papillary carcinoma

53 Invasive micropapillary carcinoma

54 A grade 3 invasive carcinoma of breast exhibiting metaplastic matrix producing characteristics

55 cytokeratins 5,6

56 Metaplastic carcinoma

57 cytoplasm

58 excellent prognosis group comprises: the special types (tubular, cribriform, mucinous) tubulolobularcarcinoma good group: tubular mixed mixed ductal NST and special type and classical lobular carcinoma; the average group : mixed lobular medullary and atypical medullary carcinoma the poor group : ductal NST, mixed ductal and lobular solid lobular carcinoma grade 3 basal type carcinoma

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61 Score for proportion Score for intensity 0 = no staining 0 = no staining 1 = <1 percent nuclei staining 1 = weak staining 2 = 1 10 percent nuclei staining 2 = moderate staining 3 = percent nuclei staining 3 = strong staining 4 = percent nuclei staining 5 = percent nuclei staining

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66 The pathology laboratory has a major role to play in both the diagnosis and the prediction of prognosis of breast cancer

67 the most valuable prognostic factors appear to be those which can be assessed on routinely fixed, processed and stained material: histologic grade lymph node stage tumor size vascular invasion tumor type

68 Nottingham Prognostic Index (NPI)= (Size (cm) 0.2) + lymph node stage (1 3) + grade (1 3)

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