Risk factors for breast cancer

here are several well-recognized factors associated with increased risk of breast cancer. Role of some other factors are not so well established. Well-established risk factors for breast cancer include increasing age, family history of breast cancer, and exposure to female reproductive hormones. Factors that are not well established include, dietary factors, and environmental factors. Almost half of all women who develop breast cancer have no recognizable risk factors except advancing age.

Another approach is to divide risk factors for breast cancer in to two groups. The first group consists of risk factors over which the individual has no control, otherwise known as non-modifiable risk factors. This would include risk factors like increasing age, female gender, genetic factors, family history of breast cancer, personal history of breast cancer, and race. The other group consists of factors that can be modified by the person, so that the risk of development of breast cancer can be decreased. Modifiable risk factors for breast cancer include smoking, alcohol consumption, use of hormonal replacement therapy, decreased physical activity, obesity, increased intake of animal fat.

Age:
Age is an important risk factor for the development of breast cancer. Breast cancer is extremely uncommon among women younger than 30 years. The incidence of breast cancer among women aged 30 to 34 is 24 per 100,000 while the incidence among women aged 55 to 59 is about 296 per 100,000 women.

Familial factors:
Presence of a family member with breast cancer would increase the risk of development of breast cancer. Some of these women may have distinct genetic mutations like BRCA1 or BRCA2 mutations and this will be discussed under a separate heading below. Unlike patients who are carriers of well-recognized genetic mutations like BRCA1 and BRCA2, most woman with familial factors do not have any evidence of genetic alterations that would increase the risk of breast cancer. The increased breast cancer risk in this group of women may be caused by a group of breast cancer promoting genes. Environmental factors may be playing some role in these patients with family history of breast cancer, and it is difficult to separate environmental factors form familial and genetic factors.

If a woman, has a first degree relative (mother, daughter, or sister) with diagnosis of breast cancer, the risk of that woman developing breast cancer is 1.7 times higher (called relative risk) compared to the general population. If that first-degree relative of that woman had developed breast cancer prior to the menopause, the relative risk for her would be 3 fold. On the other hand if that relative had breast cancer after menopause, the relative risk for that woman would be 1.5 fold. If that relative had developed bilateral breast cancer then the relative risk for her would be 5 fold higher. Again if that relative who developed bilateral breast cancer had developed the breast cancer prior to menopause, the relative risk for her would be 9 fold higher.

Hormonal factors:
The duration of exposure to female hormone correlates with the risk of development of breast cancer. Early onset of initiation of menstrual cycles, late onset of menopause, and state of not having any children are associated with increased length of exposure to estrogen hormones and is also associated with increased risk of breast cancer. Obesity is associated with increased levels of estrogen hormone; and both obesity and postmenopausal hormone therapy are associated with increased risk of breast cancer in post-menopausal women. The risk of breast cancer in woman who had natural menopause at the age of 45 is only half compared to woman who had natural menopause at the age 55. Women who undergo removal of both ovaries have markedly reduced incidence of breast cancer if they do not receive hormone replacement therapy. For each year or delayed onset of menstruation in a woman there is about 20 percent reduction in the risk of breast cancer.

Risk of development of breast cancer is related to the age at which a woman attains first full term pregnancy. If the woman attains first pregnancy after age 30 they have about 2 to 5 fold increase in the risk of breast cancer compared to women who had their first full term pregnancy prior to age 18. Women who never had any children have about 1.4 fold higher risk of development of breast cancer compared to women who had one or more full term pregnancies. Studies also have shown that longer duration of breast-feeding is associated with decreased risk of breast cancer. The interactive role of abortion and breast cancer risk is not very clear. Studies have shown that abortion nullifies any beneficial effect produced by the pregnancy. Studies have shown that hormone replacement therapy is associated with increased risk of breast cancer, but at this time there is no convincing evidence to suggest that use of oral contraceptives increase the risk of breast cancer.

Geographic location:
Incidence of breast cancer varies among women in different geographic locations. There is much as five fold difference in the incidence of breast cancer between the countries that have highest incidence and lowest incidence of breast cancer. The incidence of breast cancer is significantly lower in Japan, Thailand, Nigeria, and India compared to Denmark, New Zealand, U.K. and the United States. These differences in the incidence of breast cancer are most likely related to the difference in dietary habits, cultural differences, environmental factors and the average number of pregnancies. The fact that the first generation Japanese women who have migrated to the United States in early ages and the second generation Japanese women who are born in the United States have almost identical risk of breast cancer development gives strength to the environmental and cultural theory.

Dietary factors:
Several studies tried to establish a relationship between dietary intake of fat and breast cancer, but at this time there is no apparent relationship between consumption of standard quantity of dietary fat and breast cancer.

Weight and physical activity:
Weight gain after age of 18 years is associated with significantly increased risk of development of breast cancer in the post-menopausal age. The increase fat content in the overweight woman causes increased production of estrogen hormone, which is thought to be responsible for the increased risk of breast cancer. The same explanation can be given to the finding of decreased risk of breast cancer found in women who have increased level of physical activity. Level of physical activity is related to the estrogen hormone level in a pre-menopausal woman. Ovarian cycle may also be affected by physical activity.

Alcohol consumption:
Findings from many studies suggest that there is a positive correlation between alcohol consumption and breast cancer risk. The relative risk of breast cancer in a woman who takes one drink per day is 1.1 and in a woman who takes two drinks per day is 1.2. Increased risk of breast cancer associated with alcohol is again related to increased levels of estrogen hormone production. There is some evidence to suggest that intake of folic acid counters the effect of alcohol intake to some extent.

Consumption of fruits and vegetables:
There is some evidence to suggest that increase consumption of fruits and vegetables are associated with decreased risk of breast cancer.

Race:
Caucasian women have increased risk of development of breast cancer compared to African American women. This difference is not very apparent until the menopausal age. Incidence of breast cancer is twice in Caucasian women compared to American Asian, or Hispanic women. Among different ethnic groups in the United States, breast cancer risk is lowest in Native Americans. Even though the incidence of breast cancer is lower in African American women compared to the Caucasian population, the African America population has a higher breast cancer death rate (31.0 per 100,000) compared to Caucasian women or in fact, compared to any other racial or ethnic population in the United States. Difference biologic and genetic differences in tumors including mutations specific to African American women, the presence of risk factors, access to health system, health behaviors and relatively later stage at the time of diagnosis of disease may contributed to decreased survival of African American women with breast cancer.

Socio-economic factors:
Breast cancer is more common among women of higher socio-economic background. It is unlikely that the socio-economic factors have a direct role in increasing the risk of breast cancer, but this is most likely related to the life style differences like age at first childbirth, and number of pregnancies between women of lower socio-economic status and higher socioeconomic status.

Previous history of breast diseases:
Diagnosis of previous breast disease, regardless of benign or malignant may increase the risk of breast cancer. Benign breast diseases are divided in to proliferative and non-proliferative diseases. Non-proliferative diseases are not associated increased risk of breast cancer, where as, development of a proliferative breast cancer in a women would increase the risk of occurrence of breast cancer. Among proliferative diseases of the breast, the increased breast cancer risk is closely associated with the degree of proliferation.

The following are some of the prolifertive breast diseases and the relative risk of breast cancer associated with these diseases.

• Ductal hyperplasia 1.5 to 2 fold increase
• Sclerosing Adenosis 1.5 to 2 fold increase
• Atypical Ductal Hyperplasia 4 to 5 fold increase
• Atypical lobular Hyperplasia 4 to 5 fold increase

The 15-year risk of breast cancer development in a woman who has developed atypical hyperplasia is 20 percent, if she has positive family history of breast cancer in close relatives. This compares with 8 percent 15-year risk if she has no close family member who have been diagnosed with breast cancer. Also it appears that proliferative breast disease is more common in women who have family history of breast cancer compared to those women who have no such family history. It is also to be noted here that majority of breast biopsies performed in women would result in the diagnosis of non-proliferative breast diseases, and the proliferative breast diseases are the clear minority. Of all biopsies only 31 percent will show proliferative changes and only 3.9 percent of all biopsies would show atypical hyperplasia.

Exposure to radiation
Exposure to radiation is associated with increased risk of breast cancer. This is true with regard to radiation exposure associated with medical imaging or therapeutic procedures and radiation exposure associated with nuclear explosion as occurred in Hiroshima. Development of breast cancer follows a long latent period after exposure to radiation has occurred. The risk of development of breast cancer depends at the age of the woman at the time of the exposure to radiation, younger the woman, greater is the risk of development of breast cancer. This is because the developing breast is more sensitive to the damaging effects or the radiation. Exposure to radiation after age 40 causes only minimal increase in the risk of breast cancer, where as exposure early in life is associated with significantly increased risk. Women who had radiation therapy near to the breast area early in life, for example, as a treatment for lymphoma have very high risk of developing breast cancer later in life. Studies have confirmed increased incidence of breast cancer among survivors of nuclear explosion in Hiroshima.

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