overview of malignant lesions of the breast

1. Malignant tumours of the
breast- overview
Dr. Rupinder Kaur

2. Carcinoma of the breast
► Increasing in incidence.
► Uncommon in <30s, except in some familial cases
► Disease of ‘Western world’
► Incidence higher in N America / Europe vs Asia and Africa
► 2nd most common type of cancer after lung cancer
► 5th most common cause of cancer deaths
► The incidence increases in 4rth to 7th decade

3. Risk Factors:
 Female sex..!, Age, Obesity, high fat diet
 Maternal relative with breast cancer.
 Longer reproductive span.
 Nulliparity, Oral contraceptives
 Later age at first pregnancy.
 Atypical epithelial hyperplasia.
 Previous breast cancer/Endometrial Ca.
 Geographic factors - country
 BRCA1 and BRCA2 genes

4. Prevention: self breast examination

5. Etiology and pathogenesis
► Three set of important influences in breast cancer-
- Genetic factors
- hormonal influences
- environmental factors

6. Carcinoma of the breast- incidence &
epidemiology
Genetic predisposition-
► Family history is a risk for the development of breast
cancer
► The probability of genetic inheritance increases if there are
multiple affected relatives; cancer occurs at young age
► BRCA1 & BRCA2 genes accounts for the majority of the
hereditary breast cancer

7. Etiology and pathogenesis- Genetic
factors
► Germ line mutations in BRCA1, BRCA2, p53 and ATM
gene accounts for majority of rare cases of autosomally
inherited cancer
► These genes probably act as tumour supressor genes
(limiting cell growth) or in DNA repair

8. Genetic factors- BRCA1
► Tumor suppressor gene on chromosome 17
► Autosomal dominant transmission
► Occurs at younger age
► Protein has role in genomic stability
► ~500 different mutations reported
► Possible role in DNA repair
► Risk of breast cancer is >70% by the age of 80 years
► 30-60% increase risk of ovarian, prostate and colon cancer
by the age of 70 years
► Greater incidence of medullary carcinoma and higher
grade tumours

9. Genetic factors- BRCA2
► Tumour suppressor gene on chromosome 13
► Interacts with nuclear protein
► Possible role in DNA repair
► >200 mutations have been identified
► Risk of developing breast cancer is >60%by the age of 70
years
► Occurs at older age (50yrs) later than BRCA1
► Increased risk of other tumours ( male breast, ovary,
bladder, prostate, and pancreas)

10. Genetic factors- P53 gene
► Tumour suppressor gene
► Associated with high proliferative rate, higher histologic &
nuclear grades, aneuploidy and poor survival
► High P53 observed in cancers over expressing HER2 (+)
► Tumours expressing high levels of P53 are usually
ER and PR negative

12. Hormonal influences- estrogen
excess
► Normal breast epithelium contains estrogen and
progesterone receptors which have been identified in
some breast cancers
► Excessive exo- or/endogenous estrogen for longer periods
is associated with increase risk
- early menarche and late menopause- ↑
- unmarried and nulliparous ↑
- lactation ↓
- B/L oopherectomy ↓
- functional ovarian tumour ↑
- oestrogen replacement therapy to post
menopausal ↑

13. Hormonal influences- estrogen
excess
- Decreased risk in obese females in reproductive age
group owing to anovulatory cycles and lower progesterone
levels late in the cycle
- increased risk in postmenopausal obese females because
of mobilization of oestrogen from the fat store

14. Hormonal influences- HER 2/ neu
► Human epidermal growth factor receptor 2
► It is a gene that sends control signals to the cells to grow,
divide and make repairs
► Healthy person has 2 copies of this gene
► Promotes the growth of cancer cells when >2 copies of this
gene is mutated
► In one of every three breast cancers, the cancer cells make
an excess of HER2 due to gene mutation
► Her2 positive cancers tend to be more aggressive, less
responsive to the hormone treatment

15. Environmental & other factors
Environmental and dietary factors
► Consumption of large amount of animal fats ↑
► High calorie food ↑
► Cigarette smoking and alcohol ↑
Proliferative breast disease
► Fibrocystic disease if associated with epithelial hyperplasia
↑
Radiation exposure
► High risk with younger age and high dose

16. Etiology of Breast Carcinoma: