ETIOPATHOGENESIS OF BREAST CANCER

By: Partha Pratim MandalMedical College kolkata

Risk Factors

• Alcohol drinking• Being overweight• Never having children• 1st child >30yrs of age• Hormone Replacement

therapy• Birth control pills• Being exposed to large

amounts of radiation• Smoking

Controllable

• Getting older• First degree relative with

breast cancer• A previous breast biopsy

showing atypical changes• Being young (<12) at the

time of menses• Starting menopause after

age 55• Having an inherited

mutation in the breast cancer genes (BRCA 1 or 2)

Uncontrollable

Age

The risk of getting breast cancer

increases with age

More common at middle age but can

occur at any age group after 20 years

A woman is likely to develop breast

cancer in her 60s than in her 20s

Age as a risk factor

By age 30 1 out of 2,000

By age 40 1 out of 233

By age 50 1 out of 53

By age 60 1 out of 22

By age 70 1 out of 13

By age 80 1 out of 9

Lifetime risk 1 out of 8

Gender

Breast cancer occurs nearly 100 times more often in women

than in men.

In a few African countries, which represent the highest

incidence of male breast cancer, men account for 5–15% of

breast cancer cases

Because awareness among men is less and they are less likely to assume a lump is breast cancer,

which can cause a delay in seeking treatment.

Family History and Genetic Factors

Only 5-10% of breast cancers are inherited.

Families that do have genetic defects in one of two genes, breast cancer gene 1 (BRCA1) or breast cancer gene 2 (BRCA2), have a much greater risk of developing both breast and ovarian cancer.

BRCA1 & BRCA2 MUTATION

Both BRCA1 (located on long arm of chromosome 17) & BRCA2 (located on long arm of chromosome 13) function as a tumor suppressor genes, and for each genes loss of

both alleles is required for the initiation of cancer.

BRCA1 having more risk(35%-45%) than BRCA2 mutation.

Commonest mutation of BRCA1 are 185delAG & 5382insC

HER2 OVEREXPRESSION

HER2. Amplification or overexpression of this oncogene increase development and progression of certain aggressive

types of breast cancer.

It is located at the chromosome 17q12.

Other genes mutation

Occasionally mutation of BRCA3 & p53suppressor also involved.

Non-BRCA1 and non-BRCA2 breast tumors may be associated to rare syndromes, of which breast cancer is only one component. Such syndromes result notably from mutations in TP53 (Li-Fraumeni syndrome), ATM (Ataxia Telangiectasia), PTEN (Cowden syndrome)

RAB11FIP1, and rs4973768 are also associated with increased risk of breast cancer. rs6504950 is associated with lower risk of breast cancer

Early menstruation. Risk increases if

menstruation begin before age 12.

Late menopause. Menopause after age 55, increases

risk.

HORMONESEstrogen. Persistently increased blood levels

of estrogen are associated with an

increased risk of breast cancer.

estrogen does not appear to directly cause

the DNA mutations

Controllable Risk factors

Weight. Being overweight, with excess caloric and fat intake, increases risk, especially after menopause due to conversion of androstenedione to

estrone by adipose tissue.

Age at childbirth. Having first child after age 35 or never having children

increase risk.

Dietary factors

Alcohol. Consumption of alcohol is linked to increased risk of developing breast cancer. Consume 2 to 5 drinks daily have about 1.5 times risk.

Fat . Low fat diet may significantly decrease the risk of breast cancer as well as the recurrence of breast cancer.

Calcium. A high dietary intake of calcium lower the risk of breast cancer.

Dietary factors

Vitamin D. Vitamin D is related to reduced risk of breast cancer and disease prognosis.

Specific dietary fatty acids. Very high consumption of omega-6 fatty acids (PUFAs) increase the risk breast cancer in postmenopausal women.

Hormonal contraception. Hormonal contraceptive with estrogen content may produce a slight increase in the risk of

breast cancer. women who began using hormonal contraceptives before the age of 20 or before their first full-

term pregnancy are at increased risk for breast cancer

Hormone replacement therapy. Taking combined hormone replacement therapy, as prescribed for menopause, can

increase your risk for breast cancer and increases the risk that the cancer will be detected at a more advanced stage.

Selective estrogen receptor modulators (SERMs). they selectively stimulate or inhibit the estrogen receptors of

different target tissues.

Factors in the physical environment

Tobacco. Exposure to tobacco smoke is most problematic between puberty and first

childbirth . The reason is that breast tissue appears most

sensitive to chemical carcinogens breast cells not fully differentiated

until lactation

Passive smoking. it increases breast cancer risk by 70% in

younger, primarily pre-menopausal women.

Radiation. Women who have received high-dose radiation to the chest have a relative risk of breast

cancer between 2.1 to 4.0.Radiation exposure during

adolescence, magnifies deleterious effect.

Factors in the physical environment

Ethylene oxide. A direct correlation between breast cancer rates and exposure to ethylene oxide during medical sterilization processes.

Benzene. High level of benzene exposure can lead to mammary cancer.

DDT. Exposure to DDT before puberty increases the risk of breast cancer later in life.

Factors in the physical environment

Dioxins. Dioxin level exposure in a woman's body correlated with a

more than double chance of developing breast

cancer.

Aromatic amines. More exposure to heterocyclic amines, have also been diagnosed with more

post-menopausal breast cancer.

Polycyclic aromatic hydrocarbon. PAH's

bioaccumulate easily and can copy the estrogen hormone & they have

the ability to harm DNA

Factors in the physical environment

Xenoestrogens . Increasing prevalence of these substances in the environment may explain the increasing incidence of breast cancer

Light at night & disturbance of circadian rhythm. Artificial light during the night can be a factor for breast cancer by disrupting melatonin levels

RACIAL FACTORS

White women are more likely to be diagnosed with the disease.

Black women are more likely to have estrogen receptor negative breast cancers.

Mortality higher among black women.

Factors with minimal impact

Abortion. First-trimester abortion increases the risk of developing breast cancer.

Deodorants. Aluminum-containing underarm antiperspirants underarm increased risk of breast cancer .

Viruses. Human papilloma virus, human cytomegalovirus and the Epstein-Barr virus are suspected to play a role or cause breast cancer

Factors with inconclusive research

Tea. moderate green or black tea consumption (three or

more cups per day) can reduce breast cancer risk.

Mammographic density. High mammographic density is

associated with a higher risk of developing breast cancer.

Red no 3. human breast cell DNA was found positive for

damage when put into contact with Red No. 3

Mammographic density

Thank you……