This document provides an overview of malignant breast tumors, including their increasing incidence, risk factors, prevention, and etiology. It discusses how breast cancer is more common in Western nations and increases with age. Genetic factors like mutations in BRCA1, BRCA2, p53 and ATM genes account for hereditary cases. Hormonal influences like early menarche, late menopause, and hormone replacement therapy can also increase risk. Environmental factors such as diet, smoking, alcohol, and radiation exposure play a role in breast cancer development and incidence.

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: