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Breast Cancer

What Causes Breast Cancer?

Last updated on:
20/03/2012

Contributing Author: Guy Slowik FRCS

The exact cause or causes of breast cancer remain unknown. Yet scientists have identified a number of risk factors that increase a person's chance of getting this disease. Certain risk factors, such as age, are beyond our control; whereas others, like drinking habits, can be modified.

Age

The risk of breast cancer increases with age. For example, annual breast cancer rates are 8-fold higher in women who are 50 years old, in comparison with women who are 30. Most breast cancers (about 80%) develop in women over the age of 50. In one age group (40 to 45 years), breast cancer is ranked first among all causes of death in women. Breast cancer is uncommon in women younger than 35, with the exception of those who have a family history of the disease.

Previous Breast Cancer

If a woman has already had breast cancer, she has a greater chance of developing a new cancer in the other breast. Such a new, or 'second,' cancer arises from a completely different location and should not be confused with a cancer that has recurred (come back) or metastasized (spread) from another site. The likelihood of a new cancer increases by 0.5% to 0.7% each year after the original diagnosis. After 20 years, a woman has a 10% to 15% chance of developing a new breast cancer.

A previous diagnosis of lobular carcinoma in situ (a localized tumor) is associated with a 10% to 30% greater breast cancer risk, and a previous diagnosis of ductal carcinoma in situ is associated with a 30% to 50% greater risk.

Family History Of Breast Cancer

Approximately 85% of women with breast cancer do NOT report a history of breast cancer within their families. Of the remaining 15%, about one-third appear to have a genetic abnormality. The risk of breast cancer is about two times higher among women who have a first-degree relative (mother, sister, or daughter) with this disease. The risk is increased 4- to 5-fold if the relative's cancer was found before menopause (the end of menstruation) and involved both breasts. The risk also is increased if breast cancer occurs in several family generations.

In addition, an increased risk of breast cancer has been found in families with other inherited disorders, such as ataxia telangiectasia (a progressive disease of the motor system) and Li-Fraumeni syndrome.

Genetic Mutations

About 5% to 10% of all breast cancers are hereditary. Scientists have identified certain genetic mutations (permanent changes in genetic material) that place people at increased risk of breast cancer. To date, the genes that have been most studied include BRCA1 and BRCA2. Some American women - many of whom are descendants of Ashkenazi Jews from Eastern and Central Europe - have an inherited BRCA1 mutation. Each will have up to a 90% lifetime risk of developing breast cancer. More than half will be diagnosed with breast cancer by age 50. In some BRCA1 families, there is a likelihood of developing both breast and ovarian cancers. The BRCA2 genetic mutation also is prevalent among families with Ashkenazi backgrounds.

In addition, many other genes may be associated with breast cancer, including the genes named p53, AT, the GADD repair group, the RB suppressor gene, and the HER-2/neu oncogene (a gene that contributes to cancer). Some of these genes directly influence breast cancer risk, whereas others are involved in the general processes of cancer growth and metastasis.

Hormones

Breast cancer risk is increased in women with the longest known exposures to sex hormones, particularly estrogen (female sex hormone). Therefore, breast cancer risk is increased in women who have a history of

  • early first menstrual period (before age 12),
  • late menopause (end of menstruation),
  • no pregnancies,
  • late pregnancy (after age 30), or use of
  • birth control pills (the 'Pill;' oral contraceptives - 'OCs').

It should be mentioned that the Pill's exact hazards are difficult to assess, since risk apparently disappears in women who have not used oral contraceptives for more than 10 years.

Estrogen replacement therapy (ERT), also known as hormone replacement therapy (HRT), is used by many older women to relieve the symptoms of menopause. Certain studies indicate that ERT may increase the risk of breast cancer after long-term use (10+ years). Yet there is no official consensus on ERT, because scientists also have found that the increase in breast cancer risk is eliminated within 5 years of stopping ERT. In addition, some researchers have reported an increased risk of breast cancer in women taking estrogen or estrogen plus progestin, whereas others have not. Because of these uncertainties - and the fact that ERT has a number of positive benefits (e.g., lowered risks of bone fractures and heart attack) - a physician should be consulted about risks and benefits before a person uses ERT.

Nice To Know:

Estrogen

Scientists are finding more evidence that a woman's lifetime exposure to her sex hormones - especially estrogen - is directly related to her chance of getting breast cancer. Two key factors also appear to be involved in this association: exercise and body fat.

Exercise

A woman's exposure to estrogen is lowered by exercise, which affects the menstrual cycle and can inhibit ovulation (release of an egg from the ovaries). Research suggests that the less a woman ovulates (that is, the fewer ovulation cycles she has), the lower her risk of breast cancer. This may explain why women who have had many pregnancies, or who experienced late menstruation and early menopause, are at lower risk for breast cancer than never-pregnant women and those women who menstruated early and had a late menopause. So exercise - with its apparent ability to affect estrogen and, likewise, ovulation - may indirectly lower the risk of breast cancer.

Body fat

Although a woman's ovaries stop making sex hormones after menopause, her body still produces estrogen. This is possible because aromatase, an enzyme manufactured by body fat, can make estrogen from androstenedione, a steroid released by the adrenal glands. Postmenopausal women with more body fat have more aromatase. Therefore, they can convert more androstenedione into estrogen. So the high levels of circulating estrogen caused by excess body fat may be linked with an increased risk of breast cancer in postmenopausal women.

The relationship between body fat and breast cancer is much more complex in younger, menstruating women; however, exercise appears to be beneficial, no matter what a woman's body size.

Breast Disease (Benign)

Most benign breast diseases such as nonproliferative (not rapidly dividing) fibrocystic "disease" (temporary changes in the breasts that coincide with the menstrual cycle) - do NOT increase the risk of breast cancer. Yet risk is increased when the breast tissue shows specific characteristics, such as

  • complex fibroadenoma (fibrous, benign tumor of glandular tissue),
  • hyperplasia (abnormal increase in cell number), or
  • atypia (abnormal cellular structure).

Moderate or severe hyperplasia alone may increase breast cancer risk by 1.5- to 4-fold; however, when associated with atypia, the risk may be increased as much as 5-fold. If a woman also has a family history of breast cancer in first-degree relatives, her risk may be increased 11-fold.

Alcohol Use

The risk of breast cancer is increased among women who drink. Women who consume one alcoholic beverage a day have a slightly increased risk of breast cancer. By contrast, breast cancer risk is nearly doubled in women who have more than three drinks daily. Although the basis for this association is unknown, there is a recognized relationship between the consumption of more than two drinks a day and an increased level of estrogen in the blood.

Radiation Exposure

A significantly increased risk of breast cancer has been found in women who received radiation therapy in the chest area during childhood or young adulthood. Because of former medical practices (for example, the repeated use of fluoroscopic x-rays to check the lungs for tuberculosis), women over 45 generally have more exposure to radiation than younger women. In addition, an increased risk of breast cancer has been seen in women who were exposed to atomic bomb radiation at Hiroshima and Nagasaki, Japan.

Other Potential Risk Factors

A number of variables are potential, but unproven, risk factors for breast cancer. They include:

  • dietary fat

    There are conflicting results concerning the relationship between dietary fat and breast cancer. Many U.S. studies have found no association between the two; however, international findings suggest that breast cancer rates are minimal in countries where the standard diet is low in fat (particularly animal fat). It is known that fat cells play a role in estrogen production, especially in postmenopausal women. Therefore, being overweight may contribute to risky estrogen exposure in such individuals.

  • environmental pollutants

    Pollutants - such as pesticides made from organochlorides (organic compounds in which chlorine is bound to carbon) - may add to a person's risk of breast cancer, although research has not definitely established an association with such exposure.

  • cigarette smoking

    Smoking has not been shown to increase the risk of breast cancer. Yet because smoking increases the risk of so many other cancers - as well as heart disease and lung emphysema - most physicians advise women to quit. In addition, smoking can limit the treatment options of breast cancer patients, since certain types ofreconstructive surgery cannot be used for women who smoke.

  • abortion/miscarriage history

    Some studies have reported an increased risk of breast cancer among women who have had induced abortions. Yet a large, more recent survey disputes these findings. When the pregnancy histories of over 16,000 American women were analyzed, there was only a slight risk of breast cancer among those who had experienced either spontaneous miscarriages or induced abortions.

  • above-average body height/weight

    Some researchers have suggested that above-average body height/body weight relationships may be associated with an increased risk of breast cancer. For example, the heaviest 10% of women age 50 and older may have up to a 20% higher risk of breast cancer, and the tallest 10% of women age 30 to 49 years may have a 30% higher risk. Such associations are probably the result of hormonal factors - particularly estrogen levels- in the respective subgroups.

Unproven Protective Factors

In contrast to the potentially harmful effects of a person's lifestyle or family history, some factors actually may reduce the risk of breast cancer. Such factors are believed to have protective or preventive benefits. They include

  • regular exercise
  • early pregnancy, and
  • breast-feeding.

Researchers at the University of Southern California School of Medicine have reported that the risk of early breast cancer is reduced by more than 50% in women (aged 40 years and younger) who exercise for four hours a week. Similarly, a recent study from the Netherlands Cancer Institute suggests that women who exercise on a regular basis may substantially reduce their risk of breast cancer. The researchers found that benefits were greatest in women who kept their weight in proportion to their height. The protective effect of exercise may result from its estrogen-lowering effects. In addition, exercise changes body fat composition, influences ovulation (egg release), and has a favorable effect upon natural immunity.

If a woman experiences a full-term early pregnancy (pregnancy before age 30), research suggests that she may reduce her risk of breast cancer; however, until menopause, a woman's overall risk of getting breast cancer remains very low, whether or not she gives birth.

There continues to be a debate about whether or not breast-feeding prevents the development of breast cancer. Some studies suggest that young women (age 20 or less) who have breast-fed for 6 or more months protect themselves against early breast cancer (breast cancer that occurs before age 50); others claim reductions in breast cancer risk after breast-feeding for 1 ½ to 2 years. Still other studies have found no association between breast- feeding and breast cancer. Yet there seems to be some agreement that breast-feeding does not influence the development of late (postmenopausal) breast cancer.

 
 

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From Andrew Maynard - Chair of the University of Michigan Department of Environmental Health Sciences, with help from David Faulkner - 2013 Master of Public Health graduate.