David Cohen, M.D.·Published 18 June 2008·10 min read
Key points
While there are many factors that have been postulated to influence breast cancer risk, only a small number are felt to be significant.
Despite this, it is still important to identify the patient who might be at increased risk due to a family history of breast cancer.
Age Increasing age is associated with an increasing risk of breast cancer.
Table 4.2 summarizes the likelihood that a woman at a particular age will develop breast cancer.
While there are many factors that have been postulated to influence breast cancer risk, only a small number are felt to be significant. Table 4.1 outlines these major risk factors.
Age Increasing age is associated with an increasing risk of breast cancer. Over-whelmingly, age is the most significant risk factor for breast cancer development. Prior to menopause, the likelihood that a woman will develop breast cancer is relatively low. At menopause, there appears to be a plateau in risk, after which there is again a slow rise in incidence. While it is true that one in nine women will develop breast cancer in their lifetime, it is more helpful to define risk by the actual incidence at a given point in time a woman's life.
Table 4.2 summarizes the likelihood that a woman at a particular age will develop breast cancer. While it demonstrates that, even at the age of 80, the risk of breast cancer is not one in nine, it also underscores the fact that breast cancer is much more likely to occur in the postmenopausal years.
Family History By far, the majority of breast cancer cases are sporadic in nature. Familial or hereditary factors are implicated in the development of only 25% of all breast cancers.
Table 4.1. Major risk factors
Age
Family history
Personal history of benign or malignant disease
Reproductive factors
Environmental exposures
Despite this, it is still important to identify the patient who might be at increased risk due to a family history of breast cancer. By documenting the family history of a woman, a physician can determine the magnitude of increased risk that a given patient might experience.
While any family history of breast cancer does increase a woman's risk of future breast cancer development, that increase is often insignificant. If a single first- or second-degree maternal relative of a woman had breast cancer postmenopausally, the absolute increase in breast cancer risk for that woman is negligible. At least one-half of the cases of breast cancer in which family history is documented fall into this category. Table 4.3 illustrates the lifetime risk of breast cancer development when various relatives have a history of breast cancer.
Much more significant in terms of increased risk of breast cancer development is the documented or presumed presence of an inherited susceptibility gene. Approximately 10% of breast cancers develop as a result of a mutation in a gene. Currently, mutations in two genes, BRCA1 and BRCA2, have been identified.
Written and revised by
David Cohen, M.D.
Our doctors write and review articles for accuracy and keep them up to date.
health.am provides general information, not medical advice. Always consult a qualified health professional about your own health.
Mutations in these two genes are likely to account for approximately 80% of inherited breast cancer cases. This type of mutation is more likely to be present in families in which the breast cancer cases are present in multiple females in multiple generations, are premenopausal and are bilateral. Additionally, a large proportion of families that carry the BRCA1 mutation, cases of ovarian cancer have also existed. While the clinical scenario associated with these mutations will be discussed in greater detail in another chapter, it is important to be aware of their contribution to risk of breast cancer.
An individual whose mother carries such a mutation has a 50% probability of inheriting that mutation. If a patient carries a mutation, the lifetime risk of breast cancer has been estimated to be anywhere from 60-90%.
Furthermore, the likelihood of contralateral disease after an index breast cancer is over 50%.{pagebreak}
Personal History The majority of all breast biopsies are benign. In general, the findings are important only because they provide reassurance for the patient and the physician. The finding of either atypical hyperplasia or lobular carcinoma in situ (LCIS) at biopsy has significant implications, however; women whose biopsies demonstrate either pathologic entity are at increased risk for future development of breast cancer. These two findings are present in approximately 1-5% of breast biopsies, depending on the completeness of the pathologic examination.
Atypical hyperplasia refers to proliferative breast disease in which the appearance of the ductal or lobular epithelium is significantly altered from that of the normal breast epithelium. Several large, retrospective studies have served to define the relative risk of breast cancer in the population of women who have this pathologic finding.
Compared to the general population, the presence of atypical hyperplasia in a woman with no family history of breast cancer indicates a relative risk of breast cancer development of approximately 3-4. If there is a family history of breast cancer in a first-degree relative, the relative risk increases to over 8. Perhaps more helpful in counseling women is the absolute risk of breast cancer development over a 20 year period. If atypical hyperplasia is present, a woman has an approximately 15-20% likelihood of developing breast cancer in either breast over that period of time.
{embed="ref/google-200x90"}
Lobular carcinoma in situ in a biopsy specimen also indicates an increased risk of future breast cancer development. Pathologically, this refers to a finding of cytologically malignant cells distending the lobular units. Despite the malignant appearance of these cells, LCIS does not act in a malignant fashion, neither invading nor metastasizing. While LCIS itself is entirely benign, follow-up studies of patients with this finding demonstrate a risk of between 15-30% for future breast cancer development. As with atypical hyperplasia, the breast in which the LCIS is discovered is not necessarily the breast in which a cancer will develop. One-half of all breast cancers will be identified in the contralateral breast.
A woman's future risk of breast cancer may be altered not only by the findings of a benign breast biopsy but also by a personal history of breast cancer. Once a patient has been treated for a breast cancer, her risk for future breast cancer is significantly increased over that of the general population.
{embed="ref/stat-menu-br-cancer11"}
Due to the increased use of lumpectomy and radiation therapy for the treatment of early breast cancers, many women continue to be at risk for the development of disease in the same breast in which their initial breast cancer was diagnosed. By 10 years, this risk could be 10% or higher. Additionally, all women who are treated for breast cancer, whether with mastectomy or with breast-conservation therapy, are at risk for the development of a contralateral cancer.
Various studies have shown this risk to be between 0.5-1% per year. Thus, by 20 years postdiagnosis of her initial breast cancer, a woman has up to a 20% risk of disease in the opposite breast. Table 4.4 summarizes the risks associated with a woman's biopsy history.
Reproductive Factors Epidemiologic data clearly demonstrate that reproductive factors influence a woman's risk of breast cancer. There is a slight but consistently evident increase in the incidence of breast cancer in women who have early menses and late menopause. Additionally, an early age at first full-term pregnancy appears to be somewhat protective of breast cancer risk.
The mechanism by which these factors influence breast cancer risk appears to be the cyclical hormonal stimulation of the breast. Continuous, uninterrupted stimulation of the breast tissue on a monthly basis promotes proliferation of breast cells. The greater the number of cycles the breast experiences, the more likely there is to be uncontrolled proliferation of cells and eventual breast cancer cell growth. Any decrease in the absolute number of cycles should theoretically decrease the risk of breast cancer. Likewise, an interruption of the normal cycling should also be protective.
Data regarding natural menopause indicate that women who undergo menopause after the age of 55 have twice the risk of breast cancer of women undergoing menopause before the age of 45. Early oophorectomy (before the age of 50) also appears to have a protective effect on breast cancer risk.
Additional studies indicate that a full-term pregnancy by the age of 30 may reduce risk by up to 30 % and that a full-term pregnancy by the age of 20 reduces risk by 50%.
Table 4.4. Relative risks associated with pathologic biopsy findings While data regarding endogenous hormonal factors are fairly consistent, the data regarding the role of exogenous estrogens in the promotion of breast cancer risk are somewhat less well established. Studies of oral contraceptives and of hormone replacement therapy (HRT) have yielded conflicting results. It is likely, however, that long-term use of either agent does increase the risk of breast cancer slightly.
Recent studies of HRT and breast cancer risk indicate that women who are currently using HRT are at increased risk for breast cancer development. A meta-analysis of the largest studies, however, suggests that the increased risk is only about 10% and is of questionable statistical significance.
Those women who have taken HRT in the past but are not currently using it are not at increased risk. Interestingly, multiple studies have now shown that the risk of death from breast cancer is lower in women diagnosed while taking hormonal therapy. It is unclear what biologic event is responsible for this finding.
In the past, almost every study investigating oral contraceptive use and breast cancer risk concluded that there was a significant increase in risk associated with their use. The majority of recent studies regarding oral contraceptive use and breast cancer risk, however, have shown that their use has little impact upon breast cancer incidence rates. Even in women who have used oral contraceptives for extended periods of time (greater than 10 years), there is only a minimal, nonsignificant increase in breast cancer cases.
This increase is seen most commonly in the group of women who begin using oral contraceptives at a young age (<20 years). Mortality from breast cancer is not affected by the use of oral contraceptives, either at the time of diagnosis or prior to diagnosis. Furthermore, in studies evaluating risk of breast cancer and either oral contraceptive or HRT use, the presence of a family history of breast cancer does not appear to increase the risk of breast cancer further.{pagebreak}
Radiation Exposure Significant radiation exposure at certain times in a woman's life has been shown to increase the risk of subsequent breast cancer. The initial studies relating to this risk were performed after the atomic bomb was used in Hiroshima and Nagasaki, Japan. Subsequent to the bombings, survivors who were in adolescence or early adulthood at the time of the bombing were noted to have an increased risk of breast cancer.
In contrast, women over the age of 40 at exposure had a decrease in the incidence of subsequent breast cancer. These findings suggest that breast tissue exposed to radiation during particularly active periods of growth is most sensitive to radiation exposure.
The decreased incidence in women nearing menopause most likely occurred because of an induction of premature menopause in this population.
More recent studies of radiation exposure and subsequent breast cancer risk have corroborated the early findings. In a study of patients undergoing fluoroscopic examinations for tuberculosis treatment during adolescence, the risk of breast cancer was double that of the general population. The statistics for increased risk in women having undergone mantle radiation therapy for the treatment of lymphoma during adolescence and early adulthood are even more staggering.
{embed="ref/google-200x90"}
In one review performed at Stanford University, the relative risk of breast cancer development was 136 for women irradiated prior to the age of 15. Even women who underwent radiation between the ages of 20 and 30 had relative risks of breast cancer ranging from 7-19. Thus, all women who receive radiation therapy during adolescence and early adulthood should be considered to carry an increase risk for breast cancer.
{embed="ref/stat-menu-br-cancer11"}
Diet Breast cancer occurs with a greater frequency in countries in which the intake of dietary fat is higher. Additionally, women who move from environments in which there is a low dietary fat consumption to areas with higher dietary fat consumption eventually increase their risk for breast cancer development. These findings have led to the assumption that dietary fat intake must be a significant risk factor for the development of breast cancer.
Despite these findings, case-control studies in which dietary habits of women with breast cancer are compared to those of women without a history of breast cancer have not been able to show a direct relationship between dietary fat consumption and the subsequent risk of breast cancer. Further studies evaluating this relationship are ongoing. It appears that, if dietary fat contributes in any way to breast cancer risk, it is likely to be through its role in altering hormonal regulation.
The relationship of alcohol intake to subsequent risk of breast cancer is less controversial. Almost every study that has investigated this relationship has demonstrated a dose-related increase in breast cancer risk. Even in women drinking approximately one drink per day, the risk of breast cancer is slightly elevated when compared to that of nondrinkers. With increasing alcohol intake (two to five drinks per day), the risk of breast cancer may double.
The effect of antioxidants and vitamins on breast cancer risk is currently of considerable interest. While it is believed that cruciferous vegetables and fruits may play a role in protection from breast cancer risk, studies investigating high-dose vitamin and antioxidant intake have not demonstrated significant reductions in breast cancer risk with their use. Thus, the appropriate role for these agents continues to be controversial.
Alexandra S. Heerdt Breast cancer detection demonstration project: five-year summary report. CA 2003
News
News
News
