1. Breast Carcinoma Dr. Ashraf A. Fatah Assistant professor
Faculty of medicine
Majma’ah University

2. Breast carcinoma- 0BJECTIVES
The epidemiology & Impact.
The etiology & morphology.
Discuss the laboratory diagnosis.
(Robbins Basic Pathology, 8th ed. P ).

3. What is Breast Carcinoma?
Breast ca. is groups of heterogeneous disease with a wide array of histological appearances, clinical characteristic , and prognosis.
Breast ca. is most prevalent “non-skin” malignancy, primarily affects women but also can affect men(1%) (F>>M).
Breast ca. is the second cause of cancer related death among women .
WHO >1 million diagnosed worldwide yearly
1 out of 9 women who live to age 90- USA.
Underlying Genetic& enviromental predisposing factors.

4. Anatomic origins of common breast lesions

5. Epidemiology- incidence
Incidence of old female become to increase due to:
Awareness ___________
II.Mammography
Small DCIS lesion.
________________
III. Apply national Screening program for early detection

6. Epidemiology- Risks (BCRAT)
Gender (M= 1% risk)
Age (peak75-80,46y)
Age menarche (early menarche & late menopause)
Age at First Live Birth-1st pregnancy20
Late menopause..
Family hx:1st degree
Genetic abn. BRCA1 and BRCA2 mutations
Radiation therapy
Atom bomb exposure
Race/Ethnicity
Atypical Hyperplasia& cancer in other breast.
Breast density
Obesity in young <40–decrease risk
Estrogen exposure -replacement .
Alcohol consumptio
Tobacco,smoking& diet- still not clear

7. Epidemiology- Risks (BCRAT)
Factors associate with decrease risk:
Obesity:<40y female- anovulatory cycles.
Coffee (caffeine)-consumption.
Breast Lactation suppresses ovulation.
Exercise- small protective effects.
Reducing endogenous estrogens by drug or oophorectomy
Major risk factors for the development of breast cancer are hormonal and genetic
Conclusion: what is the major risk factors?

8. The impact of breast cancer
Long-term side effects of treatment
Emotional effects&Your relationships
Changes to your body- esp. young ladies.
Diet and physical activity
Practical issues: work, money or insurance.
Fund-burden for diagnosis, molecular workup and Researches

9. Breast carcinoma-0BJECTIVES
Discuss the epidemiology & Impact of breast cancer.
Define the etiology+morphology.
Discuss the laboratory diagnosis.
(Robbins Basic Pathology, 8th ed. P ).

10. Breast carcinoma- Etiology
Based on risks factors the etiology divided into two categories;
1. Hereditary breast cancer- 12% of cancer, Genetic mutation affect 1st degree relatives in BRCA1, BRCA2, P53, CHEK2 genes.
2. Sporadic breast cancer duet to Hormonal exposure- gender, age at menarche, menopause, reproductive hx, breastfeeding, exogenous estrogens(play a direct role in carcinogenesis)

11. BRCA1/BRCA2,P53 &CHEK2 tumor suppressor GENES
BRCA1 (chr17): single gene hereditary cancer risk 52%= 2% of all breast ca.-poor differentiated with medullary feature, ER negative
BRCA2(chr13) : single gene hereditary cancer risk 32%= 1% of all breast ca. poor differentiated, ER positive.
P53 (chr17): single gene hereditary cancer risk 3%= <1% of all breast ca
CHEK2(chr22)single gene hereditary ca= 5%

12. BRCA1/BRCA2, P53 tumor suppressor GENES
These Genes mutations are associated : increased risk for Male breast ca(BRCA2) Pancreatic, prostate, ovarian ca.
The majority of sporadic cancers occur in postmenopausal ,hormonal exposure and are ER positive.
Metabolites of estrogen can cause mutations or generate DNA-damaging free radicals in cell.

13. BREAST CARCINOMA-MORPHOLOGY

14. The normal breast depend on a complex interplay between luminal cells, myoepithelial cells, stroma.
A. Breast Duct syst.
B. Lobules
C. Nipple
D. Fat + CT
E. Vessels (Lymphatic blood)
F. Attached to Chest Muscle & Ribs
A. Cells lining duct
B. Basement membrane
C. Open central duct

15. Morphologic changes displayed from left to right according to the risk for subsequent invasive ca.

16. CLASSIFICATION OF BREAST CARCINOMA
It is not one disease, but many, heterogeneous group.
Greater>95% are adenocarcinoma from ducts and lobules- classified in to:
In-situ carcinoma (15-30%)- increase with Mammography-(calcification+ periductal fibrosis )
(lobular & Ductal)
Invasive carcinoma (infiltrating)(70-85%) (lobular & Ductal)

17. CLASSIFICATION OF BREAST CARCINOMA
Distribution of Histologic Types of Breast Cancer
Percentages
Types
15- 30%
Carcinoma In-situ
80%
DCIS
20%
LCIS
70- 85%
Invasive carcinoma
79%
IDC- NOS
10%
Lobular carcinoma 6%
Tubular/cribriform carcinoma 2
Mucinous (colloid) carcinoma
Medullary carcinoma
Papillary carcinoma
< 1
Metaplastic carcinoma

18. Ductal carcinoma in-situ(DCIS)
involve Ductal System.
Vague palpable mass
* +micro-calcification
+\-Nipple discharge
+ periductal fibrosis
limited to BM
5 VARIANTS (Comedo, solid, papillary, micropapillary, cribriform).
A. Cells lining duct
C. Intact basement membrane
D. Open central duct

19. Cribriform - Solid DCIS Comedo DCIS

20. Paget’s disease DCIS-Epidermal erythematous&scales

21. Mammogram; calcification Papillary DCIS

22. Lobular carcinoma in situ(LCIS)
Breast Lobular system
1 to 6% of all ca.
Bilateral 20%
No calcification
A. Cells are identical and dyscohesive
B. Cancer cells, but all contained within the lobules
C. BM intact
D.ER+PR positive, her2 is negative
The cells lack the cell adhesion protein E-cadherin

23. Lobular carcinoma in-situ(LCIS)

24. Invasive ductal carcinoma IDC
A. Duct System.
B. irregular border, firm
C. Peau d'orange app
( skin changes-tethering)
D. +\- % LN metas. + desmoplastic stroma
A. Cells lining duct
B. Extra cancer like cells, but acontained within duct
C. Intact basement membrane
D. Open central duct

25. Invasive ductal carcinoma tumor with irregular border + calcifiacation, margins

26. Invasive ductal carcinoma

27. Invasive Lobular carcinoma ILC
Involved lobular System.
B. difficult to be detected.
C. bilterality,multi-centeric, multifocality
D. irregular border, firm.
E. dyscohesive cells. Absent tubules.
F. Cells arranged in single file, loose clusters or sheet, targetoid, occ. Signet-ring cell.G. minimal desmoplasia .
H. ER positive, +\- LCIS& HER2/neu overexpression is very rare.
Graded as: well, moderate, poor differentiation.
Metastasis : occur to the peritoneum and retroperitoneum, the leptomeninges

28. Inavsive Lobular carcinoma

29. Vascular & lymphatic invasion(VLI)
A. Veins in breast
B. Lymph channels
A. Cells lining duct
B. Cancer cells, breaking through BM.
C. Broken BM
D. Cancer entering a lymph channel.
E. Cancer entering vein.

30. Medullary carcinoma
Circumscribed , rapid growing mass + pushing border
solid, syncytium-like cohesive cell.
The cells are highly pleomorphic with frequent mitoses
Poorly differentiated
lymphoplasmacytic infiltrate is prominent

31. Mucinous (colloid) carcinoma.
Soft and Rubbery consistency+ border pushing.
tumor cells are present as small clusters within large pools of mucin.
The borders are typically well circumscribed,
Often good prognosis

32. Tubular carcinoma
completely composed of well-formed tubules lined by a single layer of well-differentiated cells
Myoepithelial absent.
Cribriform+ apocrine snout + calcification.
ER+VE, Her2 -ve

33. Metastatic breast cancer-IDC

34. Breast carcinoma-0BJECTIVES
Discuss the epidemiology & Impact of breast cancer.
Define the etiology + morphology.
Discuss the laboratory diagnosis.
(Robbins Basic Pathology, 8th ed. P ).

35. Signs and Symptoms lump or mass Often painless Discharge or bleeding
Redness or pitting of skin over the breast, like the skin of an orange
Change in size or contours of breast
Change in color or of areola apperance

36. Symptoms In early breast ca Easily self palpated Nipple discharge
May accompanied with axillary LN
Late breast ca
Local usually symptomatic
Depends on metastatic sites

37. Diagnostic tools Breast sonography & guided BIOPSY Mammography
Superior in dense breast, young age
Mammography
Superior in loose(fatty) breast, elder
Cytology
Fine-needle aspiration (FNA)
Biopsy- histopathology
Incision-
Excision- MASTECTOMY\lump
Immunohistochemical studies- receptor

38. CYTOLOGY&CORE ASSESSMENT

39. Macroscopic finding-Mastectomy specimen

40. Receptor status Hormone receptor
Estrogen receptor (%)-diagnostic, therapeutic & prognostic
Progesterone receptor (%)
>10% predict response to hormone tx
Lobular, tubular, mucinous usually positiv
Her2/neu
Associate with invasion, metastasis…
Predict poor prognosis
IHC stain, FISH

41. Breast carcinoma Her2\neu +ve ER postive

42. Ideal Histopathology diagnosis
Size of tumor (TNM-STAGING)
Grade
Tubule Formation (Grading system)
Nuclear Pleomorphism (Grading system)
Mitotic Count (Grading system)
Vascular lymphatic invasion(VLI)
Perineural invasion(PNI)
Nipple involvement- Paget’s disease
Skin involvement
Lymph node metastasis (TNM-STAGING)
Homonal receptors status (ER, PR,Her2)

43. Bloom& Richardson grading system

44. The UICC\TNM classification

45. Molecular diagnosis of breast ca.

46. These tumors tend to be* Prevalence (approximate)
Luminal A
ER+ and/or PR+, HER2-, low Ki67
40%
best prognosis.
Luminal B
ER+ and/or PR+, HER2+ (or HER2- with
high Ki67)
20%
Triple
negative/basal-like
ER-, PR-, HER2-
15-20%
HER2 type
ER-, PR-, HER2+
10-15%
*These are the most common profiles for each subtype. However, not all tumors
within each subtype will have all these features.
ER = estrogen receptor
PR = progestrogne receptor

47. PROGNOSTIC AND PREDICTIVE FACTORS
Invasive carcinoma versus in situ disease.
Distant metastases.
Lymph node metastases.
Tumor size.
Locally advanced disease.
Inflammatory carcinoma

48. Overview What is breast cancer? What are Causes and risks?
How about some Epidemiology?
What’s the deal with BRCA1 and BRCA2?
What’s are the main type of breast carcinoma? How you described different morphological pattern?
How we usually diagnosed breast mass\ tumor specially if it is suspicious?
What’s the ideal histopathology report and how its is significant in our clinical life?