For Undergraduate Medical students (MBBS)

1. Breast Pathology
Breast Carcinoma
Dr.CSBR.Prasad, M.D.

2. RISK FACTORS
“Common denominator for most of these
factors is strong and or prolonged estrogen
stimulation operating on a genetically
susceptible background”.

3. 1. Age
2. Age at menarche
3. First live birth
4. First degree relatives with breast cancer
5. Breast biopsies
6. Race
RISK FACTORS

4. Age
• Rare < 20years
• 70% of breast cancers occur in women
>50yrs
RISK FACTORS

5. Age at menarche
Attaining menarche before 11yrs increases the
risk of breast cancer by 20%.
(comparing women who reached menarche >14yrs)
RISK FACTORS

6. Age at first child birth:
Full term pregnancy before 20yrs of age
reduces the risk by 50%.
(in comparison to nulliparous women or women over
the age of 35yrs at their first child birth)
RISK FACTORS

7. Age at first child birth:
“Pregnancy results in terminal differentiation of
epithelial cells, removing them from the potential
pool of cancer precursors”
RISK FACTORS

8. First degree relatives with breast cancer:
Majority of breast cancers occur in women
without any such family history.
Only 13% have family history of affected 1°
relative.
RISK FACTORS

9. Breast biopsies:
There is increased risk of developing breast
cancer in those with previous biopsies
showing atypical hyperplasia.
RISK FACTORS

10. Race: risk of developing breast cancer after
50yrs of age in different races…..
CAUCASIANS 1:15
AFRICAN AMERICAN 1:20
ASIAN 1:26
HISPANIC 1:27
(Figures show the risk of developing an invasive
carcinoma within the next 20yrs at age of 50.)
RISK FACTORS

11. • Estrogen exposure
• Radiation exposure
• Ca of endometrium / Ca of contralateral breast
• Geographic influence
• Diet
• Obesity
• Exercise
• Breast feeding
• Environmental toxins
Additional RISK FACTORS

12. Estrogen exposure:
• HRT may increase the risk slightly
• ER+PR increases the risk more than ER alone
• OCs are unlikely to increase the risk
• Oophorectomy decreases the risk of developing
breast carcinoma by 75%.
Additional RISK FACTORS

13. Radiation exposure:
• Therapeutic radiation
• Exposure to atomic energy radiation
The following factors increases the risk
1-younger age
2-higher radiation dose
Additional RISK FACTORS

14. Carcinoma of contralateral breast / EM:
Increases the risk due to shared estrogen effect.
Additional RISK FACTORS

15. Geographical influence:
Incidence of breast cancer in US & Europe is 4-7x
higher than other countries.
Risk of breast cancer increases in immigrants over
several generations.
No specific factor have been identified, but diet,
physical activity have been implicated.
Additional RISK FACTORS

16. Diet:
High fat
Low ß-carotene
High alcohol
Additional RISK FACTORS

17. Breast feeding: decreases the risk of breast Ca.
Environmental toxins: organochloride pesticides
(they may have estrogen effect)
Tobacco: no relation to breast carcinoma
but, associated with periductal mastitis.
Additional RISK FACTORS

18. Risk factors for Breast Cancer
Major Minor
Gender (Female > Male) Early menarche
Age Late menopause
Family history (1° relative
with premenopausal or
bilateral breast cancers)
Obesity
Personal h/o contralateral breast
cancer
Low dose radiation
Noninvasive carcinoma (Ductal
or Lobular carcinoma in situ)
Benign proliferative changes
with atypia
Source: Sabiston – Text book of Surgery, 15th
Ed, Vol-1

19. Etiology and Pathogenesis
“The major risk factors for the development
of breast cancer are hormonal and genetic
(family history)”
Etiology can be better understood by dividing them
into:
Hereditary breast cancers &
Sporadic breast cancers.

20. Hereditary breast carcinoma
• 13% of women with familial br.ca. have
one affected relative.
• 1% have multiple affected relatives.
• ~3-5% of all breast carcinomas are
familialy occuring.

21. • Two genes are well characterized:
• BRCA-1 located on Chr# 17q
• BRCA-2 located on Chr# 13q
These two genes are highly penetrant autosomal
dominant genes.
Hereditary breast carcinoma

22. • Action of BRCA-1 & 2:
1-they act as tumor suppressor genes
2-they are involved in DNA repair mechanisms
They are identical in size (81 & 84kb)
They are functionally identical
Hundreds of mutations have been reported involving
these two genes.
Hereditary breast carcinoma

23. Hereditary breast carcinoma
• BRCA-1 mechanism -1
DNA damage
Phosphorylation of BRCA-1
Activation of check point kinases and effector proteins
Initiation of DNA repair mechanisms

24. Hereditary breast carcinoma
• BRCA-1 mechanism -2
DNA damage
Binding of BRCA-1, 2 & RAD51 to nuclear –dot-complex
Initiation of DNA repair

25. • BRCA-2 mechanism of action:
Product from BRCA-2 can bind directly to
DNA and initiate the repair of double
stranded DNA.
Hereditary breast carcinoma

26. • Why the loss of these functions of BRCA-1
and or 2 specifically affects the breast?
---it’s not exactly clear.
---probably other cell types have additional
mechanisms for DNA repair, that the breast
tissue lacks.
Hereditary breast carcinoma

27. • Other genes involved in familial breast carcinoma:
this accounts for <10% of familial breast
carcinomas.
1-CHEK-2 (cell cycle check point kinase gene) - 5%
2-p53 mutations in Li-Fraumeni syndrome - 18x
3-PTEN mutation in Cowden’s syndrome – 25-50%
4-LKB-1 gene mutation in Peutz-Jegher syndrome
5-ATM gene mutaion in ataxia-telangiectasia – 7%
After all these genes 2/3rds of familial breast
carcinomas remain unexplained.
Hereditary breast carcinoma

28. Sporadic breast carcinomas
• Major risk factor is exposure to hormones
(Gender, age at menarche and menopause, reproductive
history, breast feeding, and exogenous estrogens).
They occur more commonly in post menopausal women
They over express ER.

29. • Action of estrogens:
-Metabolites of estrogens can generate DNA
damaging free radicals.
-ER drive the premalignant cells to
malignancy.
Sporadic breast carcinomas

30. Nature of BRCA-1 induced tumors
• Poorly differentiated
• Syncytial growth pattern
• They have pushing margins
• They show lymphocytic infiltration
• Do not express hormone receptors
• They do not over express HER2/neu

31. They don not have distinct morphological
appearances.
Nature of BRCA-2 induced tumors

33. Source: Sabiston – Text book of Surgery, 15th
Ed, Vol-1

34. Mechanism of
estrogen action
on cancer cells
having estrogen
receptor.
Source: Sabiston – Text
book of Surgery, 15th
Ed,
Vol-1

35. Source: Sabiston – Text book of Surgery, 15th
Ed, Vol-
1
Significance of negative surgical
margins in Invasive (A)
compared with intraductal (B)
carcinoma.

36. Source: Sabiston – Text book of Surgery, 15th
Ed, Vol-
1

37. Source: Sabiston – Text book of Surgery, 15th
Ed, Vol-
1

38. Source: Sabiston – Text book of Surgery, 15th
Ed, Vol-
1

39. Gynecomastia in
Chief Chengwayo

40. Source: Sabiston –
Text book of
Surgery, 15th
Ed,
Vol-1

41. -Phyllode’s
tumor in a
women of
18years.
-Weight 18kgs.
-Ulceration
(arrow) due
to pressure.

43. Paget’s disease of
the nipple.

44. Mandor’s disease

45. Bilateral ductectasia with fistula formation and nipple retraction.

46. Polythelia with
congenital
inversion of
the nipple.

47. Schirrhous
carcinoma of
the breast.
Note the
shrinkning
and elevation
of the breast
with nipple
retraction.

48. Peau d’ orange of
the breast

49. Large fungating carcinoma of the right breast with
enlarged axillary lymphnodes.

50. Lymphangiosarcoma developed after 3years after radical
mastectomy.

51. Carcinma of the male
breast.

52. Carcinoma of the male breast – advanced.