Bahram Memar, MD

Basement membrane in lobule.

Normal lobule-follicular phase

Normal lobule-luteal phase

Lactating breast

Greater than 95% are adenocarcinomas

in situ carcinomas and invasive carcinomas.

all breast carcinomas arise from cells in the terminal duct lobular unit

not resemblance of the involved spaces to normal ducts or lobules

cell biology E-cadherin

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 DCIShalf are DCIS

five architectural subtypes: Comedocarcinoma Solid cribriform Papillary Micropapillary

Paget disease

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 ratescarcinoma at higher rates

Mastectomy for DCIS is curative for over 95%

Breast conservation is appropriate for most women with DCIS but results in a slightly higher risk of recurrence

major risk factors for recurrence are: major risk factors for recurrence are: (1) grade(2) size(3) margins

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 margintissue, others only a 1 or 2 mm margin

narrower margins and radiotherapy

REDUCING THE RISK:

wide margins (i.e., at least 1 cm) radiation therapy tamoxifen

Paget disease

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

E-cadherin

In the absence of mammographic screening, palpable

Rarely, breast cancer presents as an axillary nodal Rarely, breast cancer presents as an axillary nodal metastasis or distant metastasis

Total Cancers PercentageCARCINOMA IN SITU[*] 15–30

Ductal carcinoma in situ 80

Lobular carcinoma in situ 20

INVASIVE CARCINOMA 70–85

No-special-type carcinoma (“ductal”) 79

Distribution of HistologicTypes of Breast Cancer

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

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 Aluminal Bluminal BNormalbasal-likeHER2 positive

correlate with prognosis and response to therapy, and thus have taken on clinical importance

“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.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.

Luminal B” 15% to 20% of NST cancers also expresses ER generally of higher grade, has a higher proliferative

rate, and often overexpresses HER2/neusometimes referred to as triple-positive cancers. sometimes referred to as triple-positive cancers.

a major group of ER-positive cancers that are more likely to have lymph node metastases

“Normal breast–like” 6% to 10% of NST cancers a small group of usually well-differentiated ER-

positive, HER2/neu-negative cancers similarity of their gene expression pattern to normal

tissuetissue not yet clear whether or not this is a specific tumor

expression pattern

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.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.

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. 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.

“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 17q21amplification of 17q21 FISH,mRNA gene arrays, immunohistochemistry Rarely mechanisms other than gene amplification

usually : poorly differentiated high proliferation rate high frequency of brain metastasis.

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 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.

pattern of metastasis

mistaken for signet ring carcinoma

biallelic loss of expression of CDH1

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

Tubular carcinoma

Invasive cribriform carcinoma

Medullary carcinoma

Invasive papillary carcinoma

Invasive micropapillary carcinoma

A grade 3 invasive carcinoma of breast exhibiting metaplasticmatrix producing characteristics

cytokeratins 5,6

Metaplastic carcinoma

cytoplasm

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 mixed lobular

medullary and atypical medullary carcinoma the poor group :

ductal NST, mixed ductal and lobular solid lobular carcinoma grade 3 basal type carcinoma

Score for proportion Score for intensity0 = no staining 0 = no staining1 = <1 percent nuclei staining 1 = weak staining2 = 1–10 percent nuclei staining 2 = moderate 2 = 1–10 percent nuclei staining 2 = moderate

staining3 = 11–33 percent nuclei staining 3 = strong

staining4 = 34–66 percent nuclei staining5 = 67–100 percent nuclei staining

The pathology laboratory has a major role to play in both the

diagnosis and the prediction of prognosis of breast diagnosis and the prediction of prognosis of breast cancer

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 lymph node stage tumor size vascular invasion tumor type

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