Breast cancer is the most common cancer diagnosed among American women and is the second most common cause of cancer deaths (lung cancer is number one). Based on data from 1988 to 1990, 12% of women (or one in eight women) are expected to develop breast cancer in their lifetime. It is important to understand, however, that these numbers are based on the assumption that all women will live to 70 years of age. The risk of having breast cancer at younger ages is lower. For example at age 50, only two in 100 women have the diagnosis of breast cancer. Although these numbers are alarmingly high, they are tempered by the fact that only 3.6% of women (1 in 28) actually die from breast cancer.
The incidence of breast cancer appears to be rising. Most people know at least one affected person. Although reports suggest an increase in the number of new cases of breast cancer, it remains unclear whether this is truly an increase in the occurrence of breast cancer or simply earlier detection as a result of improved and widespread screening with mammography and physical examination. Despite the fact that the incidence may be increasing, it is reassuring to know that the death rate from breast cancer is not.
Now that we are aware of these facts, what can we do with them? Clearly they are important statistics to be aware of, but they reflect studies of populations of women. As an individual woman, if diagnosed with breast cancer, the risk feels like (and actually is) 100%. Is there anything that a woman can do to modify her risk and try to prevent the development of this disease? Currently there are no known ways to prevent breast cancer. Thus the current aim is to effectively and efficiently screen all women with the intent to detect breast cancer at its earliest stage, when it is small and still confined to the breast. Early-stage breast cancer can be cured in up to 90% of cases, and these women can continue to live a long and healthy life.
Guidelines for screening have been established by different societies such as the American Cancer Society (ACS) and the American College of Obstetricians and Gynecologists (ACOG). Depending on an individual woman’s risk factors, they may be modified to suit her needs. Unfortunately, assessing a woman’s risk of developing breast cancer remains an imprecise practice. Although models have been developed, they are not accurate enough to precisely predict an individual woman’s risk of breast cancer. The purpose of this article is to review the important risk factors in order to educate and enable you to have a perspective of your true risk. The second goal of this article is to discuss the currently available screening methods to detect breast cancer. Once armed with this information, a woman can make a rational decision regarding her commitment to a screening program, as well as to answer other questions such as: Can I use birth control pills? Should I take hormone replacement therapy in the menopause? When should I start having mammograms? How will genetic testing for the BRCA1 and BRCA2 genes affect my care and that of my family? Should I have a prophylactic mastectomy?
Although knowledge is a powerful tool, risk analysis for a disease as severe as breast cancer should not be left to the patient alone. Seek out the advice of a gynecologist or internist. There are also specialists, such as genetic counsellors, who have a special interest and training in the field.Back to beginning of Risk Factors section
Internationally, the incidence and death rates from breast cancer can vary up to five fold from country to country. Nations that have the highest occurrence of breast cancer are the United States, Canada, and Northern European countries. Regions of the world with intermediate disease rates include South America, Central America, and the Caribbean countries. The lowest rates are among the Asian countries, especially Japan, China, and India. Even within a country, breast cancer incidence can vary from region to region; however, these differences are not nearly as striking as the international differences. Another interesting observation is that when a woman migrates from her country of origin to another, her risk and the risk of her offspring change and approach that of the natives of her new country. This supports the fact that geographic or environmental factors, in addition to genetic predispositions, play a role in the development of breast cancer.
Incidents of breast cancer vary among different ethnic groups. In the United States, Caucasian women have the highest incidence, women of African-American, Asian, or Hispanic heritage are at intermediate risk, and American Indians have the lowest risk. Whether this is entirely inheritable, or whether environmental, dietary, and lifestyle variables contribute to the differences, remains to be determined.Back to beginning of Risk Factors section
Certain risk factors cannot be changed. For example, breast cancer is 20 times more common in women than men. Aging is another unavoidable risk. Breast cancer is practically unheard of in women who are less than 20 years of age. One Canadian study found the incidence of breast cancer to be 1 per 10,000 women aged 20 - 34 years, increasing to 7 per 10,000 among women between 35 - 44 years. Although the seven fold increase that occurs in the childbearing years is the steepest rate of rise, the likelihood of developing breast cancer continues to escalate with advancing age, at 18 per 10,000 women ages 45 - 59 years and 30 per 10,000 women who are older than 60. Thus, advancing age is an indisputable risk factor.
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Previous breast disease
Breast cancer is one form of breast disease, but by and large, most breast problems, such as breast infections and benign tumors, are not malignant (cancerous). Breast infections, most commonly occurring during breastfeeding, do not increase a woman’s risk of breast cancer. Benign growths or tumors are a heterogeneous group of lesions and have different long-term consequences. Fibrocystic breast disease (an ill-defined condition where the breast can feel lumpy and there may be some mild discomfort) and fibroadenomas (the most common benign breast tumor found in young women, ages 20-40 years) are not felt to increase a woman’s risk of developing breast cancer. However, breast masses that display hyperplasia (an excessive or abnormal growth pattern, determined by examination by a pathologist of tissue samples obtained by a biopsy) are associated with a 6 - 8-fold greater risk of developing breast cancer compared to women who have never had a breast lesion. Thus, it is exceedingly important for women who have had this diagnosis to maintain a regular schedule of examinations by knowledgeable breast specialist who can accurately interpret the results of a breast exam and mammogram and treat the findings appropriately.
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Women who survived the atomic bombing of Hiroshima and Nagasaki were subsequently found to have high rates of breast cancer. It has also been observed that women who received radiation therapy to the chest as treatment for medical ailments are also at greater risk of breast cancer. Today, high doses of radiation are reserved for treatment of cancers, such as Hodgken’s disease. Now that young women are surviving these once deadly tumors, we are finding that the treatment predisposes them to second cancers. The risk of developing breast cancer seems to be increased only among those women who receive radiation before 40 years of age and is greater for teenage women as opposed to women in their 30’s at the time of treatment.
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A family history of breast cancer has long been identified as one of the strongest risk factors. A thorough family history of breast cancer is the first and most important testing of a genetic risk. One’s likelihood of developing breast cancer is doubled if a first-degree relative (mother, sister, daughter) has breast cancer. If multiple family members have been afflicted, then the risk may be 4 - 6 fold greater than the general population. Early onset of disease (less than 50 years old) and bilateral breast cancer (cancer involving both breasts) are also associated with a greater likelihood of a genetic predisposition.
Until recently, there was nothing other than a family history that could provide information regarding an individual woman’s risk of breast cancer. However, over the past 3 - 4 years, advances in science and medicine have allowed us to perform genetic testing on individuals and their family members. The two most important genes that have been identified are BRCA1 and BRCA2. Specific mutations (changes in the normal sequence of DNA) of these genes can be passed down from generation to generation and may place the person at risk of breast, ovarian, and other cancers. Mutations in these two genes account for 70 - 80% of inherited breast cancer, but other “cancer susceptibility genes” have also been identified.
Mutations in the BRCA1 and BRCA2 genes have been receiving a lot of attention by both the medical and non-medical population. Specific mutations have been found in high frequency in different ethnic groups. One such mutation occurs quite commonly among the Ashkenazi Jewish population, at a frequency of 1 in 100 persons, as opposed to a rate of 1 in 300 - 800 non-Ashkenazi individuals. However, it appears that only those women who both carry the mutation, and have a significant family history of breast cancer, are truly at an increased risk of breast cancer. Many people who carry this mutation will never develop cancer. The yet-to-be-understood, unpredictable nature of this may be due to other factors that may modify breast cancer risks, such as diet, reproductive factors, and environment. It is precisely for this reason that screening all women for a genetic susceptibility is unwarranted at this time and would only result in heightened anxiety for women and their families who may not be at risk at all. In addition, it would certainly result in the performance of additional and possibly unnecessary testing and treatment.
The other pitfall of genetic testing for the BRCA1 and BRCA2 mutations is that up to 50% of women with breast and/or ovarian cancer along with a significant family history will have normal results. This only emphasizes our incomplete knowledge of the genetic factors. Thus, a negative result is not a guarantee that one will never develop cancer.
Nonetheless, if a woman and her family members who are affected with breast and/or ovarian cancer are found to harbor the mutation, it is estimated that she has a 70 - 80% risk of breast cancer and a 20 - 40% risk of developing ovarian cancer in her lifetime (based on an expected lifetime of 70 years).
The decision to be tested must be considered thoroughly. First and foremost, genetic counseling must be obtained from a center that has a special interest and expertise in the topic. The biologic uncertainties of the results must be confronted and understood before testing. The results may have major ramifications on both the personal and medical aspects of the lives of all family members. Issues of confidentiality must be addressed because of the real concerns of discrimination in employment and when obtaining life and medical insurance.
Despite all of the recent attention that genetic testing has received, it is believed that less than 5 - 10% of all breast cancer is attributable to genetic mutations. In families where breast cancer consistently occurs in younger women, the incidence of these mutations is probably higher. It is also known that certain people who carry this mutation may never develop the disease. Until scientists determine how changes in these important genes allow breast cancer to grow, it will be difficult to counsel women of their individual lifetime risk of cancer and to advise a specific plan to avert cancer. Currently, the options include:
1. An increased surveillance program that includes frequent mammograms initiated at a younger age, diligent self-breast examinations (SBE), and more frequent breast examinations by one’s physician.
2. Participation in a multicenter study that is currently underway evaluating whether treatment with Tamoxifen (a medication that is known to improve the survival and decrease the recurrence rate of breast cancer in women who have already been diagnosed) <link to Breast Cancer & Tamoxifen section> will decrease the incidence of breast cancer in women who are deemed to be “high risk.”
3. Consideration of a prophylactic (preventive) mastectomy and/or removal of both ovaries to avoid cancer.
It is important to stress that none of the above mentioned options have yet been proven to prevent breast cancer, or to improve survival once it has been diagnosed.
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For more than 20 years, there has been a greater appreciation of the relationship between a woman’s reproductive history and her risk of breast cancer. It is a rather well-accepted fact that a first full-term pregnancy at a young age has a protective effect and that first pregnancies after the age of 30 are associated with an increased risk. It is believed that the breast tissue undergoes dramatic changes during a first completed pregnancy that somehow renders it less susceptible to becoming cancerous. In the beginning of a pregnancy, the rising estrogen and progesterone levels stimulate a rapid growth of breast cells, which can actually have a deleterious effect. However, over the course of an entire pregnancy, these cells are converted to differentiated, or specialized breast cells, that are resistant to becoming cancerous. It seems that the earlier this occurs in a woman, the greater the protective effect. It is also well-known that the risk of breast cancer is inversely associated with the number of full-term pregnancies that a woman has experienced. In other words, with increasing numbers of pregnancies, the risk of breast cancer decreases. Three or more full-term pregnancies may decrease a woman’s risk by 50%.
Is it only a full-term pregnancy that confers protection from breast cancer? What are the effects of a miscarriage or an elective termination of pregnancy (abortion)? Are the effects of an elective termination of pregnancy different from an unplanned miscarriage? Are the effects of an abortion different if the woman has had a full-term pregnancy? Does an early pregnancy loss (at 6 - 8 weeks) differ from one at a later stage (5 - 6 months)? Overall it appears that having had a miscarriage is not associated with breast cancer, but an induced termination of pregnancy may slightly increase the risk. Since having an abortion allows women to either postpone childbearing or to choose not to have a child (both independent risk factors for breast cancer) further research needs to be done to clarify whether having an abortion is a true risk factor. Biologically, it is felt that the rising hormone levels at the beginning of a pregnancy stimulate breast cells to proliferate. Cells that are growing rapidly can more easily be converted into a cancer cell. Since the pregnancy is terminated, they do not differentiate into mature breast cells, as occurs in a full-term pregnancy. Since estrogen and progesterone levels are lower in a failing pregnancy, breast cell growth is not as robust. This may explain why miscarriages do not seem to increase the risk of breast cancer.
The fact that many of the studies concerning induced or spontaneous pregnancy losses and breast cancer are controversial, suggests that having had a termination of pregnancy is not a strong risk factor. It is also a relatively arduous topic to study. Obtaining an accurate history of an event that occurred many years ago is often difficult. Many miscarriages are so early that women do not even realize that they were pregnant. In many countries, abortions have only recently become legalized or are still not permissible by law, thus limiting the population of women that can be studied. However, there are other countries, such as the former Soviet Union, where abortions are quite common. It would be interesting to evaluate differences in breast cancer rates among these different countries for any clues that may help answer these questions.
Lactation, or breastfeeding, is also reported to confer protection from breast cancer. When a woman is breastfeeding, ovulation is suppressed and this continues while breast milk remains the main nutrient for the baby. As discussed in the section on hormonal and menstrual factors, one theory is that the risk of breast cancer rises with increasing number of ovulatory cycles in a woman’s life. If this is true, then women who breastfeed for longer periods of time will receive greater protection. Although studies have been controversial, many studies are now demonstrating that breastfeeding for greater than one year may help to diminish one’s risk of breast cancer.
There has been a greater awareness of the possible association between infertility and the risk of cancer. It is a well-known fact that ovarian and breast cancer are more common among women who have never had a full-term pregnancy. However, being infertile (involuntarily being unable to achieve a pregnancy) does not seem to further increase the risk. Hormonal treatment for infertility and stimulation of ovulation has not been shown to increase the risk of breast cancer; however, long-term monitoring of these treated women will have to be continued.
The reproductive habits of women are not as strong a predictor of breast cancer as is a significant family history, a BRCA1 mutation, or a previous breast biopsy that demonstrated hyperplasia. In general, having a first completed pregnancy after the age of 30 is felt to increase the risk by 20- 100%, as opposed to a possible 300 - 600% increase with a genetic predisposition. However, since the worldwide trend, particularly in developed nations, is for women to delay childbearing and to limit family size, the reproductive choices of women may be an important contributor to the rising incidence of breast cancer.
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Breast tissue is highly responsive to the circulating hormonal environment, especially estrogen and progesterone. The concentrations, duration, and timing of exposure of these hormones during a woman’s life may have a profound impact on the growth and development of the breast, and the likelihood of cancer formation. Recognition of this fact has led investigators to research the effect of the menstrual cycle on breast cancer risks. Numerous studies have found that early onset of menstruation is a risk factor. Women who have their first period before the age of 12 have a 50% greater risk of developing breast cancer than women who begin menstruating after age 15. The age of menopause is also important. Women who are menopausal before 45 years, whether natural or induced, have half the risk of breast cancer compared to a women who cease menstruating after their 55th birthday. Overall, this data is consistent with the notion that the risk of breast cancer is related to the cumulative exposure to estrogen and progesterone and escalates with increasing number of ovulatory cycles in a woman’s life. Other studies have found that women who have irregular menstruation, or inconsistent ovulation, may be at a lesser risk of breast cancer. The fact that women are not ovulating when they are pregnant and lactating also supports the theory of incessant ovulation and breast cancer. On the other hand, it is not simply the amount of hormone that the breast is exposed to, since estrogen and progesterone levels are high throughout a pregnancy. Analyses of circulating hormone levels in the bloodstream have never revealed useful information that may assist in breast cancer risk assessment. Hence, it is the complex relationship between the amount, duration, and timing of exposure, as well as the tissue’s inherent resistance to developing cancer. Finally, environmental and genetic factors will also play a modulating role in the breast’s responsiveness to hormones and likelihood to undergo carcinogenesis.
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Birth control pills and menopausal hormone replacement therapy
Given that an extensive body of literature supports a role for a prolonged reproductive lifespan and cumulative estrogen and progesteroen exposure in the genesis of breast cancer, how does treatment with hormones such as birth control pills (OCP) and menopausal hormone replacement therapy (HRT) affect the risk? There has been a tremendous amount of research on the topic, especially given the fact that many women are exposed to both OCP’s and HRT. Since the increase in use of these hormonal treatments parallels the rise in breast cancer incidence, it is crucial to evaluate whether OCP’s or HRT may be causative. By and large, the use of OCP’s, whether short-term or long-term (greater than 5 - 10 years) does not increase the risk of postmenopausal breast cancer (which is much more common than pre-menopausal breast cancer). The majority of controversy centered around the concern of early onset breast cancer among young woman (less than 25 years) and women who were using OCP’s before a full-term pregnancy. Since premenopausal breast cancer is relatively uncommon, it has been rather difficult to study. Recently a collaborative effort to evaluate 53 different studies encompassing more than 150,000 women failed to show that early use of OCP’s or use prior to a full term pregnancy causes breast cancer. It takes many years for any substance to stimulate a cancer to grow and become clinically recognized. Birth control pills may accelerate the growth of an already existing lesion, resulting in a diagnosis at a younger age. In addition, women who are on OCP’s tend to receive more diligent breast surveillance, which also increases the likelihood of finding an early lesion. Detecting a tumor before it has spread beyond the breast improves a woman’s prognosis and translates into longer survival and a greater chance of a cure.
The question as to whether HRT increases the risk of breast cancer remains hotly debated. Given the theory that breast cancer risks are related to the exposure to estrogen and progesterone, it would seem logical that lengthening one’s exposure to these hormones beyond the reproductive years could stimulate a breast cancer. However, the literature that addresses this topic is by no means unanimous. Several well-designed studies have found no increase in risk among women who have ever taken HRT. It is also well-accepted that short-term treatment (less than 5 - 10 years) is not associated with an increase in breast cancer. However, some studies have shown a 20-30% increase risk over baseline among women with extended treatment (greater than 10 years). Despite this finding, a number of studies have demonstrated better survival among breast cancer patients who were diagnosed while on HRT as opposed to patients who were not taking estrogen at the time of diagnosis. One explanation for the better prognosis among estrogen users is that the diligent breast surveillance allows a diagnosis at an earlier and more curable stage. Alternatively, it has been hypothesized that estrogen stimulates less aggressive breast cancers that are easier to treat and eradicate.
A number of studies have questioned whether taking HRT further increases the risk of breast cancer in a woman who has a significant family history. Unfortunately, the results are inconclusive, thereby making it difficult to offer specific recommendations to individual women. The effect of OCP’s and HRT among women who carry mutations in the BRCA1 and BRCA2 gene also remains unknown.
More and more women are choosing to add HRT to their armamentarium of preventive care in the menopausal years. Estrogen has well-documented protective effects against osteoporosis and coronary heart disease, and there is increasing information that it may also protect against Alzheimer’s disease and colon cancer. Given the fact that 10 times more women will die of heart disease than breast cancer, it seems clear that the benefits outweigh the risks for most women. Studies have documented longer and healthier lives for women using estrogen. Nonetheless, a woman must be comfortable with her decision to take HRT, and this requires thorough and honest counseling from her physician.
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Environmental and dietary factors
Studying how the environment influences the risk of disease is a laborious task. It is difficult to identify the many different substances to distinguish which substance confers the greatest deleterious effect, and to determine the biological mechanism that eventually produces the disease. There is good evidence that a low-fat and high-fiber diet is associated with a lower risk of colon cancer. Since our eating habits are modifiable, unlike most other breast cancer risk factors, investigators have tried to determine whether various diet changes can effect the likelihood of developing breast cancer. Over a half a century ago it was noticed that high-fat diets increased the risk of breast tumor formation in certain strains of rats. Since that time, fat consumption in humans and its relationship to breast cancer has been studied in many ways. For example, it was noted that the incidence of breast cancer is lower in countries that consume a low-fat diet (such as Japan) compared to countries with high-fat diets. When Japanese women would migrate to different countries, such as the United States, the breast cancer rates would approach that of the natives of their new country, further supporting an environmental or dietary factor. Despite these observational studies, investigations that have compared fat consumption among women with and without breast cancer have been contradictory. Some of the controversy arises from the fact that it is difficult to accurately ascertain the type and amount of food a person consumes. The source of fat may also be significant since it is felt that animal fat may be more deleterious than plant-derived fat. It has also been hypothesized that dietary habits in childhood and adolescence may have a greater influence on breast cancer risks in adulthood. Another confounding factor is that diets that are low in fat tend to be high in fiber. High fiber in the gastrointestinal tract can inhibit estrogen absorption, again linking breast cancer risks to exposure to hormonal exposures. Recently, there has been more attention paid to phytoestrogens (plant estrogens), but our knowledge of these chemicals is still in its infancy. Phytoestrogens may block the cancer promoting effects of estrogen despite the fact that they bind to breast tissue at the same target site. They may also promote chemical reactions to occur that can convert hormones and toxic substances to a less harmful form.
Finally, it is well-known that high-fat diets often result in obesity, which is also recognized as a risk factor for breast cancer. Fat cells contain the machinery to produce estrogen. Male hormones that are made in the ovaries and adrenal glands are used as precursor molecules by the fat cells and converted to estrogens. This again echoes the connection of estrogen and breast cancer.
Certain vitamins have antioxidant properties that can provide a defense mechanism for a cell against a carcinogenic substance. Vitamins A, E, and C have been the most extensively studied. Slight decreases in breast cancer have been found with an increased intake of Vitamin A. There is little supporting evidence that supplemental Vitamin E or C will further decrease the breast cancer risk.
Substantial evidence has now accumulated connecting alcohol consumption and breast cancer. An average of two drinks per day may increase the risk by 40 - 70% over baseline. Moderate alcoholic intake alters the metabolism of estrogen, thereby again linking estrogen to breast cancer.
Given the controversy surrounding diet and breast cancer, it is difficult to recommend a specific diet that can significantly decrease the likelihood of developing breast cancer. Certainly for both cancer prevention and cardiovascular fitness, it appears prudent to maintain a low animal fat diet that is rich in fiber. The role of Vitamin A-rich foods deserves further investigation. Given the opposing dual effects of moderate alcoholic consumption (increasing the risk of breast cancer but decreasing the risk of heart disease), advice needs to be cautious and individualized.
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