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Breast and Ovarian Cancer
  Nongenetic Risk Factors

By Kari Danziger, MS, CGC

Reviewed by Beth Crawford, MS, CGC



In recent years, the medical community has learned about both the genetic and nongenetic factors associated with breast and ovarian cancers. Although there is nothing people can do about their genetic legacy, some nongenetic risk factors are in areas that we can actually control.

Some new data from the past year suggests that these nongenetic risk factors may differ in women who have a BRCA1 or BRCA2 mutation than in women who do not have such a mutation. Because these data are new, they are still considered preliminary. However, it is important to keep your BRCA status in mind when considering lifestyle changes to prevent breast and ovarian cancer.

 
 
 

Increasing Age

The majority of breast and ovarian cancers are diagnosed in women over the age of 50, making increased age one of the primary risk factors for both of these types of cancer. The exceptions to this are hereditary breast and ovarian cancer, which are caused by alterations in the BRCA1 and BRCA2 genes. Breast cancer typically occurs in these women at a much younger age, with an average age at diagnosis of about 45.


The average age at which ovarian cancer develops in women who carry BRCA1 or BRCA2 mutations differs depending on which gene their mutation is in. In BRCA1-related cancers, the average age of onset is younger than in the general population (54 years old compared to 62-63 years old in the general population). In BRCA2-related cancers, the average age of onset is the same as in the general population. This may suggest that women with a BRCA1 mutation should consider risk-reduction strategies for ovarian cancer at a younger age than do women with a BRCA2 mutation.

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Estrogen Exposure

In recent years, scientists have discovered that long-term exposure to estrogen may increase a woman's chances of developing breast and ovarian cancer. Estrogen levels are increased by taking estrogen as a medication, but are also high in ovulating women. Thus, anything that decreases the overall time a woman ovulates, such as pregnancy, late onset of menstruation, or early onset of menopause, decreases her lifetime exposure to estrogen and thus her risk for these types of cancer. However, it is not clear that this same pattern exists for women who have BRCA1 and BRCA2 mutations. (For recent news about estrogen exposure affecting breast cancer risk, see Related News below.)

  • Early-onset menstruation/late-onset menopause.
    The younger a woman is when she begins menstruation, and the older she is when menopause begins - the greater her risk of breast cancer.
    Studies indicate that breast tissue is especially susceptible to the effects of estrogen. Thus, the younger a woman is when she begins menstruation, and the older she is when menopause begins — that is, the longer her body is producing estrogen — the greater her risk of breast cancer. Scientists have found that women who begin menstruating at 11 years of age or younger are approximately 20 percent more likely to develop breast cancer than women who did not have their first period until age 14 or older. In contrast, recent data suggest that the risk of breast cancer in women who carry BRCA mutations is not influenced by the age when menstruation begins.
  • Child-bearing history
    Women who have given birth are 30 to 60 percent less likely to develop ovarian cancer
    For most women, pregnancy seems to provide some protection against breast and ovarian cancer. In the case of ovarian cancer, studies have shown that women who have given birth are 30 to 60 percent less likely to develop ovarian cancer than are women who have never been pregnant. In fact, it appears that the more times a woman has experienced childbirth, the less likely she is to develop ovarian cancer. Research also indicates that breast cancer risk is lower in women who have had children, particularly if they gave birth before the age of 30. Part of the reason for this may be that pregnancy causes permanent changes in a woman's breast tissue — alterations that appear to make it less likely that cancer will develop there. Thus, having a baby at a young age provides more protection. (For recent news about how child-bearing history affects your breast cancer risk, see Related News below.)

    It is unclear whether this same relationship between pregnancy and breast cancer risk holds true in women who have BRCA mutations. For the most part, recent studies have found no relationship between age at first pregnancy and breast cancer risk in these women. There is also no consensus as to whether the number of pregnancies changes the risk of breast cancer in women who have BRCA mutations. Although one study found that fewer pregnancies and later age at first childbirth were actually protective against breast cancer in mutation carriers, recent studies have not confirmed this relationship.

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Race

Although breast cancer is among the more common types of cancer in every major racial group, it occurs with varying frequency among different populations. For example, Caucasian women are slightly more likely to develop breast cancer than are women of African descent, and women of Asian and Hispanic descent have a lower risk of breast cancer than those of African descent. Native American women have one of the lowest rates of breast cancer. Ovarian cancer is also more common among Caucasian women, specifically those of North American and Northern European descent. In the United States, Caucasian women and women of Hawaiian descent are at the highest risk for ovarian cancer, followed by women of African, Hispanic, and Asian descent. Once again, the risk is lowest among Native American women.

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Breast Biopsies

Researchers have found that women who have had breast biopsies are at increased risk of developing breast cancer — even if those past biopsies did not reveal the presence of cancer. Scientists do not believe, however, that the biopsies themselves are responsible for the increased breast cancer risk. Rather, they suspect that the women having biopsies are already at increased risk — either because their breasts are lumpy and thus difficult to examine, or because they are being followed for a condition that increases their chances of developing breast cancer (such as the precancerous condition atypical hyperplasia or the nonmalignant lumps called fibroadenomas).

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Previous Breast Cancer or Precancerous Condition

Women who have already been diagnosed with breast cancer appear to be at elevated risk for developing a subsequent primary breast cancer (not a recurrence of the original cancer). The risk for women with breast cancer is about 1 to 2 percent per year, or approximately 10 percent lifetime risk of developing a second breast cancer. For women with a BRCA mutations, the risk is about 5 percent per year risk for a second breast cancer or a 40 to 60 percent lifetime risk of a second primary breast cancer.

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Exposure to Radiation

Woman who were treated with chest radiation treatment as children or young adults have a significantly increased risk of breast cancer. One study showed that as many as 35 percent of women who had received radiation to treat Hodgkin's disease prior to the age of 16 would develop breast cancer by age 40. In addition, 85 to 100 percent of the women in this group who did develop breast cancer had tumors that were located within the area where radiation was applied (or the margins of that area).

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Hormone Replacement Therapy

Breast Cancer Risk

Women who receive hormone replacement therapy (HRT) to counter some of the effects of menopause may be increasing their risk for breast cancer. It appears that women who use therapies that include both estrogen and progestin are at greater risk for breast cancer than are women who use estrogen alone. According to most studies, the risk of breast cancer increases by approximately two percent per year of HRT use, so that a woman who uses HRT for five years will have about a ten percent increase in her risk of breast cancer compared with if she had not used HRT. It is important to note, however, that breast cancer risk with HRT applies to current users and recent users, but a woman's breast cancer risk returns to the general population risk level within five years of stopping HRT.

HRT also seems to increase breast cancer risk in women with BRCA mutations who reach menopause before developing breast cancer. (For more information about how HRT affects breast cancer risk, see Related News below.)

Ovarian Cancer Risk

It is unclear whether HRT has an impact on a woman's risk of developing ovarian cancer, however, most studies suggest that there is not an association between HRT and ovarian cancer. If you are considering taking HRT in order to reduce your risk of ovarian cancer, it is important to discuss the pros and cons of HRT with your doctor. Include all personal risk factors in the decision, including heart disease, breast and ovarian cancer, and osteoperosis.

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Birth Control Pills

Birth control pills substantially reduce the risk of developing ovarian cancer

It is very clear that oral contraceptives or birth control pills substantially reduce the risk of developing ovarian cancer. However, there is also evidence that they increase the risk for breast cancer. Thus, any woman considering the use of birth control pills must weigh the protection they offer against ovarian cancer against the possibility that they increase the risk for breast cancer. For women with BRCA mutations — who are at considerably increased risk for both types of cancer — this can be a very difficult choice.

Breast Cancer

For women in the general population, oral contraceptives (OCs) appear to cause a small increase in the risk of breast cancer during the time the OCs are used and for about ten years thereafter. However, because breast cancer risk is low in very young women, the increase in risk does not translate into a high risk of breast cancer. For instance, only one additional case of breast cancer would be expected among 20,000 women who used OCs between ages 20 and 25.

Unfortunately, a recent study has raised concern that in women with inherited risk for breast cancer, oral contraceptives may have a greater impact on the risk of developing breast cancer. Although this study did not determine whether the women had BRCA mutations, it showed that in women who took OCs, the more family members she had with breast cancer, the more her risk of breast cancer increased. In women who had a sister or mother with breast cancer, the risk of developing breast cancer among OC users compared with non-users was 3.3 times as great. The risk increased with increasing number of family members, up to an 11-fold increase in risk in women who had five or more family members with breast cancer and used oral contraceptives, compared with those who did not.

For recent news about whether birth control pills increase breast cancer risk, see Related News below.

Ovarian Cancer

Multiple studies have shown a 40 to 50 percent decrease in ovarian cancer risk in women who take oral contraceptives — an effect that seems to increase with the amount of time women use them. For example, studies have found that the risk for ovarian cancer drops 10 to 12 percent in women who have used oral contraceptives for a year but that it drops by approximately 50 percent in those who have taken birth control pills for five or more years. In addition, it appears that the ovarian cancer protection continues for at least 10 to 15 years after a woman has stopped taking oral contraceptives.

These findings of decreased risk for ovarian cancer apply to women with BRCA1 and BRCA2 mutations as well: One study found a 20 percent reduction in ovarian cancer risk for BRCA1 and BRCA2 mutation carriers who had taken oral contraceptives for as long as three years and a 60 percent reduction in risk for those who had taken them for six years or longer. Because the risk of ovarian cancer is high and this cancer is difficult to detect with screening, OC's strong impact on ovarian cancer risk in mutation carriers makes them an attractive offer to consider. However, this must be weighed against the recent data suggesting that they may substantially increase the risk of breast cancer in mutation-carriers.

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Fertility Treatment

Although there is some evidence to suggest that ovarian stimulation as infertility treatment increases the risk of ovarian cancer, too few women have been studied for too short a duration to establish a clear link. While early studies suggested a large increase in risk, later studies have not been able to confirm those findings.

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Breast-Feeding

Some scientists believe that breast feeding may reduce ovarian cancer risk in premenopausal women, perhaps because ovulation is suppressed during breast-feeding. They also suspect that breast feeding may slightly decrease a woman's risk of breast cancer, especially if breast feeding is continued for 1.5 to 2 years. However, these results are inconclusive, and other studies have found lactation history to have no impact on breast cancer risk.

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Lifestyle Factors

Although there are many risk factors for both breast and ovarian cancer that women can do nothing to change, there are certain lifestyle-related risk factors that are within their control, including:

  • Eating a low fat diet
  • Avoiding obesity
  • Leading an active lifestyle
  • Quitting smoking
  • Reducing alcohol intake

For more news about how lifestyle factors can affect breast and ovarian cancer risk, see Related News below.

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Related News
In order to view these articles you will need to have a MyGeneticHealth account. If you are not already a member, selecting the article will automatically take you to a page where you can sign up.
Estrogen Exposure
Gene variant linked to earlier puberty in girls
Having children before age 30 cuts breast cancer risk
Hormone Replacement Therapy
Estrogen therapy may increase breast cancer risk
Hormones do not further increase breast cancer risk
HRT use increases cumulative risk of breast cancer at age 70
Birth Control Pills
Older birth control pills linked to breast cancer
Breast Feeding
Lifestyle
Body size plays role in breast cancer risk
Exercise may cut ovarian cancer risk
Smoking ups risk for less favorable breast cancer

 

References

Jernstrom, H., C. Lerman, et al. (1999). "Pregnancy and risk of early breast cancer in carriers of BRCA1 and BRCA2." Lancet 354: 1846-50.

Boyd, J., Y. Sonoda, et al. (2000). "Clinicopathologic features of BRCA-linked and sporadic ovarian cancer." JAMA 283: 2260-65.

Wang, Y., T. TenHave, et al. (2000). "Effect of hierarchical clustered sampling in multicenter, family-based studies: example of reproductive history and breast cancer risk in BRCA1 mutation carriers." ASHG Abtracts 2000: #223.

King, M. and N. C. Group (2000). "Breast and ovarian cancer risks among women with BRCA1 and BRCA2 mutations in the New York Breast Cancer Study (NYBCS) (abstract)." Am J Human Genetics 67(suppl 2): 53.

Collaborative Group on Hormonal Factors in Breast Cancer. (1997). "Breast cancer and hormone replacement therapy: collaborative reanalysis of data from 51 epidemiological studies of 52,705 women with breast cancer and 108,411 women without breast cancer." Lancet 350: 1047-59.

Coughlin, S., A. Giusozzi, et al. (2000). "A meta-analysis of estrogen replacement therapy and risk of epithelial ovarian cancer." J Clin Epidemiology 53: 367-75.

Purdie, D., C. Bain, et al. (1999). "Hormone replacement therapy and risk of epithelial ovarian cancer." Br J Cancer 81: 559-63.

Burke, W. (2000). "Oral contraceptives and breast cancer." JAMA 284: 1837-8.

Collaborative Group on Hormonal Factors in Breast Cancer. (1996). "Breast cancer and hormonal contraceptives: collaborative reanalysis of individual data on 53,297 women with breast cancer and 100,239 women without breast cancer from 54 epidemiological studies." Lancet 347: 1713-27.

Grabrick, D., L. Hartmann, et al. (2000). "Risk of breast cancer with oral contraceptive use in women with a family history of breast cancer." JAMA 284: 1791-98.

 

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