patho dr faeza breast ca 3rd lecture

1. BREAST CANCERBREAST CANCER
March. 22. 2015March. 22. 2015

3. Breast Carcinoma Statistics
• One in eight women will get
breast cancer,
• one third of women with breast
cancer will die of the disease.

4. Risk Factors for Breast Cancer
 Estrogen, Long & Strong exposure. (F/M ratio = 100/1)
• Geography
• Family historty; (1st
degree, early age, bilat)/ 2 folds
• Age (Peak; 60 – 70y)
• Menstrual history & Reproductive history.
- (Early menarch & late Menopause)
- Pregnancy
- (Nilliparous, Late 1st
pregnancy)
- (1st
delivery at 18 y, / 1st
delivery at 30 y)
- Lactation, decrease risk
- Oophorectomy (decrease the risk to 1/3)
• Benign breast disease (Hx of previous breast pathology)
- Fibrocystic disease +/- epith hyperplasia +/- atypia.
- CIS
- 0X, 2X, 5X, 10X

5. Risk Factors for Breast Cancer
• Estrogen (exogenous), increase risk to 2.5 folds
 In 2002 Estrogen declared as carcinogen by National
Toxicology Program.
• Oral contraceptive
• Radiation Exposure
• Carcinoma of the contralateral breast or endometrium
• Obesity
• High fat diet
• Alcohol
• Smoking
• Environmental Toxins
• Breast augmentation.
• ABORTIONS?

6. Causes of Breast Cancer
• Genetic
• Environmental
• Hormonal

7. Breast Cancer Pathology
Ductal Ca. (85 – 93%)
Lobular Ca. (7 – 15%)
In Situ Carcinomas (CIS) (15 )
Invasive Carcinomas (85%)
Special Subtypes (> 5%)

8. Ductal Carcinoma in Situ
• Clinical:
– DCIS usually does not present as a palpable
mass, if it does it is usually high grade and a
large lesion
• Mammogram:
– The most common method of detection is by
identifying calcifications
• MRI
• FNA
• Biopsy

9. Mammography showing a normal breast (left) and a cancerous breast
(right).

10. Stellate lesion
Calcifications
Mammogrm:
-Calcification
- fibrous parenchyma
Mammogrm:
-1% false positive
-20% false negative
-Calcification, positive
-50 - 60% in ca.
-20% in benign

11. DCIS is
confined to
within the
ductal
system

13. Linear and
branching
calcifications

14. Architectural Patterns of
DCIS
• Comedo (high grade)
– Grade 3 nuclei and necrosis
– Often has associated microcalcifications
• Solid (Low grade)
– Carcinoma fills and distends the ducts
• Micropapillary (Low grade)
– Papillary structures that extend into the lumen
of the duct
• Cribriform (Low grade)
– Forms a rigid “cartwheel” pattern

15. The adult, resting Breast
connective tissue
adipose
well developed ducts
connective
tissue
scanty
secretory
units

17. Cribriforming
DCIS
Secondary
lumina

18. Micropapillary DCIS
Papillae

19. DCIS, “Comedoca”, microcalcifications

20. Pathobiologic Events Associated with DCIS

21. DCIS: actin Stain of Myoepithelium

22. Natural History
• 5 Year survival = 100%
< 50 or > 50 year
• If untreated ;
– 28% developed invasive cancer
– 10 fold increase in RR to controls

23. Axillary lymph nodes
• Axillary LN involvement is <1%
• Axillary LN dissection is not recommended
• Sentinel lymph node biopsy?
– Not recommended.
– Consider: extensive high grade DCIS or
palpable mass (increased chance of invasive
disease being found)

24. • Mammography is the standard for
detection of DCIS.
• MRI could help especially in high-grade
DCIS

25. Burstein H et al. N Engl J Med 2004;350:1430-1441
The Risk of Ipsilateral or Contralateral Breast Tumor for Patients with DCIS Treated
with Excision Alone; Excision and Radiotherapy; Excision, Radiotherapy, and
Tamoxifen; or Excision, Radiotherapy, and Placebo

26. Lobular Carcinoma in Situ (LCIS)
• Multicentric , Bilateral
• Proliferation of neoplastic population of
cells within the TDLU
• may extend into adjacent ducts.

27. Lobular
carcinoma in
situ

28. Invasive (Infiltrating) Breast Carcinoma
 Main histological types;
• Invasive ductal ca.(85%)
• Invasive lobular ca. (7 – 15%)
• Medullary ca. (2%)
• Mucoid ca. (2%)
• Tubular ca. (2%)

29. Invasive (Infiltrating) ductal carcinoma
• The most common (> 85%).
– Mass
– +/- skin dimpling, nipple retraction
• Mammogram;
• MRI
• FNA.
• Biopsy
Correlate with
breast parenchyma
at each quadrant

30. Invas
ive
Duct
Ca

31. Stellate lesion
Calcifications
Mammogrm:
-Calcification
- fibrous parenchyma
Mammogrm:
-1% false positive
-20% false negative
-Calcification, positive
-50 - 60% in ca.
-20% in benign

32. Infiltrating Ductal Ca.
• Gross:
– Firm, gritty, stellate
• Micro:
– Grading depends on:
1) degree of tubule formation
2) nuclear grade
3) mitotic rate
– Fibrosis (desmoplasia)
– +/- calcifications

33. Infiltrating Lobular Carcinoma
• 2nd most common invasive breast cancer.
• +/- mass
• L/M;
- linear profiles of malignant cells “INDIAN” FILE
- low nuclear grade,
- minimal mitosis.
- Dense fibrosis
• multifocal & bilateral
• Same prognosis
as IDC,
if matched for stage
• ER+/ PR +
• HER2 Neg.

35. Uncommon types of
Invasive Carcinoma of the Breast
• Mucinous (Colloid) Ca.
– Older women
– Malignant cells floating in pools of mucin
– Better prognosis than invasive ductal or lobular
• Tubular Carcinoma
– Younger women
– Excellent prognosis
• Medullary carcinoma.
– lots of lymphocytes)
– Is better in behavior

36. Inflammatory Carcinoma
• Invasive carcinoma involving superficial dermal
lymphatic spaces
• Poor prognosis
• so called “inflammatory changes”
- Erythema and induration of the skin,
– Peau d’orange- of involved skin caused by
lymphatic involvement and obstruction

37. Inflammatory carcinoma:
dermal lymphatic spaces
containing tumor cells

38. Paget’s Disease
• Invasion of the SKIN of the nipple or
areola by malignant cells.
• Associated with an underlying cancer:
either IN SITU OR INVASIVE carcinoma
• Clinically-erythema, scaling, ulceration

39. Paget’s Disease of the Nipple
Intra-epidermal
adenocarcinoma cells

40. Extramammary Paget disease

41. Tumor grade
 HISTOLOGY
• WHO grading
Well diff.
Mod. diff.
Poor diff.
• B-R grading
Glands
Nuclei
Mitosis
 CYTOLOGY
– Nuclei
• Size
• Chromatin
• Nucleoli
Nuclear grade 1-3
Good correlation with histologic
grade

42. BREAST CANCER
TNM stage groupingTNM stage grouping
Stage 0Stage 0 Tis N0 M0
Stage IStage I T1* N0 M0
Stage IIAStage IIA T0 N1 M0
T1* N1** M0
T2 N0 M0
Stage IIBStage IIB T2 N1 M0
T3 N0 M0
Stage IIIAStage IIIA T0, T1,* T2 N2 M0
T3 N1, N2 M0
Stage IIIBStage IIIB T4 Any N M0
Any T N3 M0
Stage IVStage IV Any T Any N M1
* Note: T1 includes T1 mic.
** Note: The prognosis of patients with N1a is similar to that of patients with pN0.
AJCC®
Cancer Staging Manual, 5th
edition (1997)
published by Lippincott-Raven Publishers,
Philadelphia, Pennsylvania.

43. BREAST CANCER
Tumor definitionsTumor definitions
• TX Primary tumor cannot be assessed
• T0 No evidence of primary tumor
• Tis Carcinoma in situ: Intraductal carcinoma, lobular carcinoma in situ,
or Paget’s disease of the nipple with no tumor
• T1 Tumor 2 cm or less in its greatest diameter
T1mic Microinvasion more than 0.1 cm or less in its greatest diameter
T1a Tumor more than 0.1 cm but not more than 0.5 cm in its greatest diameter
T1b Tumor more than 0.5 cm but not more than 1 cm in its greatest diameter
T1c Tumor more than 1 cm but not more than 2 cm in its greatest diameter
• T2 Tumor more than 2 cm but not more than 5 cm in its greatest diameter
• T3 Tumor more than 5 cm in its greatest diameter
• T4 Tumor of any size with direct extension to (a) chest wall or (b) skin, only as
described below
T4a Extension to chest wall
T4b Edema (including peau d’orange) or ulceration of the skin of the breast
or satellite skin nodules confined to the same breast
T4c Both (T4a and T4b)
T4d Inflammatory carcinoma
AJCC®
Cancer Staging Manual, 5th
edition (1997)
published by Lippincott-Raven Publishers, Philadelphia,
Pennsylvania.

44. BREAST CANCER
Commonly assessed prognosticCommonly assessed prognostic
factorsfactors
Slamon DJ. Chemotherapy Foundation. 1999;46.
Winer E, et al. Cancer: Principles & Practice of Oncology. 6th ed.
2001;1651-1717.
Nuclear grade
Estrogen/progesterone
receptors
HER2/neu overexpression
Number of positive axillary nodes
Tumor size
Lymphatic and vascular invasion
Histologic tumor type
Histologic grade

45. BREAST CANCER
5-year survival as function of the number5-year survival as function of the number
of positive axillary lymph nodesof positive axillary lymph nodes
0%
20%
40%
60%
80%
5-YearSurvival5-YearSurvival
0 1 2 3 4 5 6-10 11-15 16-20 >20
Number of Positive NodesNumber of Positive Nodes
Harris J, et al. Cancer: Principles & Practice of
Oncology. 5th ed. 1997;1557-1616.

46. Histopathologic Grade
If B-R score is 3, 4, 5 = low grade
If B-R score is 6, 7 = Intermediate grade
If B-R score is 8, 9 = High grade

47. Total Cancers Per Cent
In Situ Carcinoma 15–30
Ductal carcinoma in situ, DCIS 80
Lobular carcinoma in situ, LCIS 20
Invasive Carcinoma 70–85
No special type ductal carcinoma (“NOS") 79
Lobular carcinoma 10
Tubular/cribriform carcinoma (Better prognosis than
average)
< 5
Mucinous (colloid) carcinoma (Better prognosis than
average)
2
Medullary carcinoma (Better prognosis than average) 2
Papillary carcinoma (Better prognosis than average) 1
Metaplastic carcinoma, (Squamous)

48. The “Triple Test”: (Screening)
– Clinical picture
– Mammographic findings
– Cytologic findings
 Biopsy. (diagnosis)

49. MALE BREAST
• GYNECOMASTIA (related to
hyperestrogenism)
• CARCINOMA (1% of ♀ )

50. Gynecomastia
• Reversible enlargement of the male breast
• Unilateral or bilateral subareolar mass +/-pain
• Ductal and stromal proliferation
• Etiology- Systemic disease-hyperthyroidism,
cirrhosis, chronic renal failure
– Drugs-cimetidine, digitalis, tricyclic
antidepressants, marijuana
– Neoplasms-pulmonary, testicular germ cell tumors
– Hypogonadism: testicular atrophy, exogenous
estrogen, Klinefelter’s syndrome

52. GYNECOMASTIA (NO lobules)

53. Periductal
edema
Epithelial hyperplasia

54. Adenocarcinoma

55. Carcinoma of the Male Breast
• < 1% of breast cancer
• Very rare occurrence; F/M = 100:1
• Infiltrating ductal carcinoma.
• Tends to present at a more advanced stage
– Less fat and breast tissue, therefore involvement
of chest wall occurs earlier
• Similar prognosis when matched, stage for stage,
with female breast cancer
• Associated with inherited BRCA2 mutation

57. Multistage Model of
Carcinogenesis
Normal
Atypical
Hyperplasia
Carcinoma
In Situ
Invasive
Carcinoma
Metastasis

58. QUIZ
1. List the benign breast diseases that increase a
patient’s risk of developing breast cancer and
classify these conditions by the degree of risk.