Breast cancer is a very important health problem in the United States and other countries around the world. Breast cancer occupies second rank as the leading cause of cancer deaths in American women. Until recently cancer of the breast topped the list of leading causes of cancer deaths in women, but lately lung cancer has claimed the top position. If skin cancer is excluded, cancer of the breast is the commonest cancer among American women. According to the WHO, more than 1.2 million women are diagnosed breast cancer each year across the world. These numbers represent tremendous challenges posed by breast cancer in the United States and across the world.

Breast cancer claims the top position as the leading cause of deaths from cancer among women aged between 40 and 55 years. Breast cancer can occur in males too; with about 1450 new cases of male breast cancer diagnosed every year within the United States of America. It is comforting to note that the deaths from breast cancer among women of all ages have declined in the United States by 2.8% for every year from 1990 to 2000. The declining mortality rates may be attributed to the successful screening programs and advances in the therapy of breast cancer.

Risk of development of cancer of the breast varies among different ethnic groups within the United States of America. Caucasian women living within the United States have about 13.1% lifetime risk of developing breast cancer. African American women have comparatively lower risk of development of breast cancer and the lifetime risk of breast cancer among this subpopulation is approximately 9.6 (Data from SEER). Even though Black women have a lower incidence of breast cancer compared to Caucasian women, the mortality rate is approximately 28 percent higher in African American women compared to White women. There has been an upward trend in the incidence of earlier forms of breast cancer in the United States. The incidence of the earliest type of breast cancer known as DCIS has increased by about 130 percent over the last few years. It is reasonable to assume that the higher occurrence of earlier forms of breast cancer is the direct result of an excellent screening program.

Risk factors for breast cancer.

There are a few well recognized factors, which if present in a person could be associated with an increased risk of breast cancer. Role of some of the other factors are not so well established. Well-established risk attributes for breast cancer include increasing age, family history of breast cancer, and exposure to female reproductive hormones like estrogen. Factors that are not proven yet include, dietary factors, and environmental factors. Having talked about risk factors, it should be mentioning that in almost half of all women, who develop breast cancer, no recognizable risk factors except advancing age may be found.

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

Age
Age is a significant risk factor for the development of of breast cancer. Breast cancer is very unusual among women younger than 30 years. The incidence of breast malignancy 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 family members with breast cancer history would increase the risk of development of breast cancer. Some of these women may have clearly distinct genetic mutations like BRCA1 or BRCA2 mutations and this will be discussed under a separate heading below. Most women with familial risk factors do not carry any identifiable genetic mutations that would increase the risk of breast cancer. The increased risk of developing breast cancer in this group of women may be caused by a group of breast cancer promoting genes. Environmental factors might be having some role in these patients with family history of breast cancer, and it is difficult to separate these environmental factors form familial and genetic factors.

If a woman, has one 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 the women in question had developed breast cancer previous to the menopause, the relative risk for the woman would be 3 fold. Conversely if that relative of the women in question had breast cancer after menopause, the relative risk of breast cancer for the women in question would be 1.5 fold. If that relative had been diagnosed with bilateral breast cancer, then the relative risk for her would be 5 fold higher. Again if that relative who had diagnosis of breast cancer on both sides had this diagnosis previous to menopause, the relative risk of breast cancer for the woman would be 9 fold higher.

Hormonal factors
The duration of exposure correlates well with the risk of development of breast cancer. Early onset of initiation of menstrual cycles, delayed onset of menopause, and state of not having any children are associated with increased length of exposure to estrogen hormone and is also associated with increased risk of breast cancer. Obesity is linked to increased levels of estrogen hormone production. Obesity and post-menopausal hormone replacement treatment are associated with increased risk of breast cancer in post-menopausal women. The risk of development of breast malignancy in women who had natural menopause at the age of 55 is only half when compared to those women who had natural menopause at the age of 45. Women who had surgical removal of both ovaries have markedly reduced incidence of breast cancer if they do not receive hormone replacement treatment. For each year of delay in the 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 also related the age at which a woman attains first full term pregnancy. If a woman attains first pregnancy after age 30, she may have about 2 to 5 fold increase in the risk of breast cancer compared to a woman who had her first full term pregnancy previous to age 18. Women who never had any children have approximately 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 lengthier periods 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 indicated that abortion nullifies any beneficial effects produced by the pregnancy. Studies have shown that postmenopausal hormone replacement 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 widely among women in different geographic locations. There is much as five fold variation in the incidence of breast cancer between the countries that have highest incidence and lowest incidence of breast cancer.

of breast cancer.

The incidence of breast cancer is much 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 best explained as correlation to the difference in dietary habits, cultural differences, environmental factors and the average number of pregnancies for women. First generation of Japanese women who came to the United States at an early age and the second generation of Japanese women who were born in the United States have almost identical breast cancer risks compared to White women living in the Unites States. This fact provides strength to the argument that those geographic variations in breast cancer risk are correlation to environmental and cultural factors, rather than to genetic factors.

Dietary factors
Several studies tried to illustrate a relationship between dietary intake of fat and breast cancer, but at this time here is no clearly established relationship between consumption of standard quantity of dietary fat and breast cancer.

Weight and physical activity
Weight gain after attaining adult age is associated with significantly increased risk of development of breast cancer in the post-menopausal age. The increase body fat in obese women cause increased production of which is believed to be responsible for the increased risk of breast cancer. The same explanation could also be attributed to the finding of decreased risk of breast cancer found in women who have increased level of physical activity. Level of physical activity is correlation to the level of estrogen in the body in a pre-menopausal woman.

Alcohol consumption
Findings from a number of studies suggest that there is some 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 malignancy associated with alcohol is again correlation to increased levels of estrogen hormone production. There is some evidence to suggest that folic acid supplementation counters the effect of alcohol intake to some extent.

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

Race
Caucasian women have higher risk of development of breast cancer compared to African American women. This difference is not very apparent until women attain menopausal status. Incidence of breast cancer is twice in Caucasian women in comparison to Asians living in America or Hispanic women living in America. Among different ethnic groups in the United States, breast cancer risk can be found to be lowest for Native Americans. Even though the incidence breast cancer is lower in African American women in comparison to the White population, Black women has a higher breast cancer death rate (31.0 per 100,000) when compared to Caucasian women or in fact, compared to any other racial or ethnic population in the United States. There are several factors that contribute to the increased death rates from breast cancer for Black women. These include presence of risk factors, access to health system, behavioral patterns correlation to health, and later stage at which diagnosis was made.

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 causation role of heightening the risk of breast cancer. These observed socio-economic variations are most likely correlation to the life style differences such as age at which first pregnancy occurs, and the total number of pregnancies between women from lower socioeconomic status and higher socioeconomic status.

Prior history of breast diseases
Diagnosis of prior breast disease, regardless of non-malignant or cancerous, may increase the risk of development of breast cancer. Non-cancerous breast diseases are divided into proliferative and non-proliferative subsets. Non-proliferative diseases are not associated with increased risk of development of breast cancer, however, the occurrence of any of the proliferative breast diseases in a woman would elevate the risk of occurrence of breast cancer. Among proliferative diseases of the breast, the degree of increased breast cancer risk is strongly correlation to the degree of proliferation.

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

• 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 had been previously diagnosed with atypical hyperplasia is about 20%, if she has a family history of having breast cancer in her close relatives. This compares with 8 percent 15-year risk if the woman in question has no first-degree family members who had prior diagnosis of breast cancer. Also it appears that proliferative breast diseases are more common in those women who have a history of breast malignancy in the family in comparison to women who have no such family history. It is also to be noted here that majority of breast biopsies performed in women would come back as non-proliferative breast disorders, and subset of proliferative breast diseases are comparatively rare. Of all biopsies about 31 percent would show proliferative disorders and only about 3.9% of all biopsies would show the presence of atypical hyperplasia.

Exposure to radiation
Exposure to radiation is associated with increased risk of breast malignancy. This is true with regard to radiation exposure associated with medical imaging or therapeutic procedures like radiation treatment, and accidental radiation exposure that is associated with nuclear explosion as occurred in Hiroshima and Nagasaki. Development of breast cancer follows a long latent period after exposure to radiation has occurred. The risk of development of breast cancer depends on the age of the woman in question during the period of radiation exposure. In general younger the woman, greater is the risk of development of breast cancer. The difference in age susceptibility to radiation is due to the fact that the developing breast is very sensitive to the damaging effects or the radiation. Exposure to radiation after age 40 causes only slight increase in the risk of development of breast cancer, however exposure early in life could be associated with significantly increased risk. Women who had radiation treatment close to the breast area during early part of life, for example, for Hodgkin's disease have very high risk of breast cancer development during the later part of life. Studies have confirmed the increased incidence of breast cancer among survivors of nuclear explosion in Hiroshima.

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