By Dr. L. Sarrel

It’s important to learn about the types of breast cancer, different diagnostic tests, and the treatment options that are available today.

Luckily, in the vast majority of cases, there is no need to make instant decisions when you are diagnosed with breast cancer. You are likely to be told that you can safely take a few weeks or even longer to have further tests, gather information (usually to get additional medical opinions), mull over your options, and then choose a course of treatment. Sometimes your doctor will strongly urge particular treatments; in other cases, she or he will leave more of the decision making to you. This is reasonable because the results of different treatment approaches are often the same. Therefore, the most important factor is how you feel.

During this time, you can expect your own recall and understanding to be less than optimal because of the stress you are under. It can be helpful to have someone accompany you on your doctor visits — your husband, a grown child or a close friend. They can even take notes or tape record the discussions.

You will learn from your doctor that not all breast cancers are the same. Information about your particular condition will usually be gathered by way of a biopsy (a bit of the tumor is removed by a surgeon and studied by a pathologist). Other tests such as blood tests, X-rays, nuclear medicine scans, ultrasounds, CT scan, or MRI (magnetic resonance imaging) can supplement this information. Since you may have several tests done by different specialists, possibly even in different localities, it is important that you have one doctor who coordinates all the information for you. This might be your family doctor, internist, general surgeon who specializes in breast cancer, or a medical oncologist (a doctor who specializes in the medical rather than surgical treatment of cancer).

Doctors often refer to the process of assessing cancer as a “staging study.” With breast cancer, this means learning:

1. The site of the cancer
2. The size of the tumor
3. Whether signs of cancer have spread to underarm lymph nodes
4. Whether the cancer has spread to other parts of the body (metastasized) - most commonly to bone, liver, or lungs
5. Which treatments would be most appropriate
6. Your “prognosis” - what you can expect in terms of possible cure or disease-free span of life

A reminder: The majority of women with breast cancer will be completely cured.

Lymph node studies
When breast cancer cells have spread to nearby underarm lymph nodes, the chance that cells have spread into other parts of the body is greater. Knowing how extensively the cancer has invaded the lymph nodes, if it has at all, is important information when deciding on the best course of treatment. Until about ten years ago, doctors usually removed most of the adjacent lymph nodes at the time of mastectomy (removal of the breast) or lumpectomy (removal of the cancerous area only). Sometimes they removed a sample of the closest nodes (we have about 10-15 under each arm). Removing underarm lymph nodes can have unwanted consequences such as painful arm swelling that may be permanent. In addition, studies also suggest that lymph node removal in and of itself does not affect the cure rate.

A new way of gathering information about lymph node status has recently become available. Using a blue dye and/or a radioactive tracer, doctors can identify the first node in your underarm that receives lymph node drainage. This is called the “sentinel” node. When this node is free of cancer there is little chance cancer is in any of the other nodes. If there is cancer in this node, the doctor will do further lymph node removal to evaluate the extent that the disease has spread.

Hormonal studies
Finding out if either of the female hormones, estrogen or progesterone, has stimulated the cancer growth is a test that can be performed primarily for breast cancer patients. The tissue removed in surgery is tested for ‘hormone receptors.” In some ways it can be considered good news if your tumor is found to be “hormone receptor positive.” That’s because you may benefit from a “hormone antagonist,” a substance that can be used to treat the cancer by blocking hormone stimulating effects. The most commonly used hormone antagonist is “Tamoxifen” (Nolvadex). Women who have “receptor positive” breast cancers show the highest long-term cure rates.

Treatment choices  — local control
Once you have been diagnosed with breast cancer, the next thing to consider is treatment. “Local control” is treatment of the cancer in the breast and the regional lymph system. Surgery or a combination of surgery and radiation usually accomplishes this.

Until about 1960, breast cancer was treated by removal of the entire breast and varying amounts of surrounding tissue, an operation called a “radical mastectomy.” Now lumpectomy, an equally effective and less radical approach is often used. It involves removal of the lump or mass, along with a small area of surrounding normal tissue. This is followed by radiation treatment aimed at the cancer site and, less intensively, to the rest of the breast. In most cases, this produces only minor to moderate cosmetic alteration to the breast. Mastectomy may still be necessary for a woman when there is a large breast mass, when biopsy findings show particular cell types, or when there is extreme involvement of the lymph system adjacent to the breasts.

There is another type of breast cancer, ductal cancer in situ (DCIS), in which mastectomy is often recommended. It is recommended, not because of the severity of the cancer (it is rarely life-threatening), but because it is diffused through the breast and is resistant to radiation. It is not unusual for doctors to recommend double mastectomy when DCIS is diagnosed. It is sadly ironic that the least threatening form of breast cancer should require such radical treatment. Hopefully, new ways of treating DCIS will be found.

We should also mention that some women who are not very concerned about breast preservation might decide to choose mastectomy over lumpectomy and radiation. Of course, once a woman understands the implications of her choices, the ultimate decision rests with her.

Reconstruction
Women having a mastectomy can have breast reconstruction at the time of the mastectomy, or at a later date. The cosmetic result is often superior when done at the time of mastectomy. Usually consultation with a plastic surgeon is recommended before a mastectomy, when reconstruction is being considered.

Reconstruction is not recommended at the time of mastectomy for a woman who will have chemotherapy. This is because any problems with healing or infection could delay chemotherapy and that is not advisable.

Beyond the breast — systemic control
We all know that cancer cells can spread to other parts of the body and grow there, destroying and displacing normal tissue. This is referred to as metastatic disease. When breast cancer is first detected, there is no way to be absolutely sure it hasn’t already spread. But with certain tests, your doctor can tell what the odds are that your cancer will spread.

Treating breast cancer that has metastasized to other parts of the body is a separate, complex topic. One important treatment to note is adjuvant therapy. Adjuvant therapy is the use of hormonal or chemical agents throughout the body in an attempt to reduce the possibility of developing metastases. These agents work by killing off tiny deposits of cancer cells that may be in the body.

Chemotherapy
Chemotherapy involves chemical agents are administered intravenously and kill off fast growing cells. Treatments occur periodically, over a period of months. Unfortunately, these chemicals also affect certain normal cells and thus cause unwanted side affects — mouth sores, loss or thinning of hair, nausea and vomiting, fatigue, and other symptoms. Once the chemotherapy is complete, the side effects go away. There are also many drugs to aid with side effects and many women find that, most of the time, they can carry on a fairly normal routine.

Hormonal treatment
As described above (under “hormonal studies”), your doctor may recommend a hormone antagonist either before or after chemotherapy, or as the only adjuvant treatment. The hormone-like drugs enter a cancer cell and turn it off by interfering with internal messages coming from genes in the cell. These drugs have few side effects, are taken in pill form, and are usually discontinued after five years.

Other forms of cancer
There are some other forms of breast cancer we have not discussed here. If you have one of these more unusual types, the treatment options described do not apply. In fact, each and every woman with breast cancer has her own, unique situation. What we have described are very general guidelines.

What is on the horizon?
As you read this, new and exciting methods for early diagnosis and treatments are under investigation. Cancer antibodies are being tested. There are gene products that may be able to target breast cancer cells without harming normal cells. So in the future, there may be treatments that have virtually no side effects and are more effective than anything in our current arsenal. New drugs, which appear to reduce the risk of developing breast cancer, are also being studied.

Alternative treatments
We have described traditional, well-tested approaches. If you would like information on alternative therapies, consult with your doctor. You can also obtain information directly from the American Cancer Society, whose headquarters are in Atlanta, Georgia, and which has branch offices in many major U.S. cities. You can also contact the Office of Alternative Medicine at the National Cancer Institute
9000 Rockville Pike, Building 31, Room 5B35, MSC2182
Bethesda, Md, 20892

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Getting to know your breasts will help you detect any abnormalities. So make a date each month to perform a self-exam five to seven days after the start of your period. You’ll need to follow these steps for a complete and accurate examination:

1. Walk over to the mirror and take a good look at your breasts. It’s important to notice the shape and contour of each breast.
2. Lift your arms above your head to check the underside of your breasts. See if there is any dimpling.
3. Place your hands by your side and push your breasts together. This will also determine if there is any dimpling.
4. Take a moment while you’re in the shower to check up and down your breast and armpit area. You’ll need to raise one arm in the air while you use the other one for the examination. You can check for lumps or hard areas by either moving your fingers up and down or by gently pressing in a circular motion.
5. Lie down and repeat step 4.

Start taking care of your breasts with these simple, yet important steps.

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Screening for a disease, whether it be a cancer or not, involves the employment of diagnostic studies that will identify the disease in a person who is otherwise without symptoms. Since breast cancer is not a preventable condition, the method to improve survival for women who are diagnosed is to detect the cancer at an earlier stage. Currently, the three major forms of breast cancer screening are mammography, self-breast examinations, and physician breast examinations.

Mammography is a well-accepted method to screen for breast cancer. Abundant evidence demonstrates an up to 30% reduction in breast cancer deaths in women over 50 years old, who undergo regular mammography. It is well-accepted that all women over 50 have an annual mammography.

A tremendous amount of controversy exists regarding the usefulness of mammography in women who are under 50 years old. Adding to the confusion for both physicians and patients were the conflicting recommendations from the National Cancer Institute (NCI)and the American Cancer Society (ACS). Within the space of a year, the NCI announced that mammograms were unnecessary for women in their 40’s and the ACS altered their recommendations stating that women in their 40’s should be tested every one to two years. The ACS based their recommendations on the following facts:

1. Breast cancer is the single leading cause of death for women between the ages of 40 - 49, occurring in 1 out of 66 women.
2. Some studies do report a significant improvement in survival among the screened population of women in this age category.
3. The radiation exposure of mammograms is so low that it does not cause appreciable harm.

Thus, the current ACS guidelines are that all women should have a baseline mammogram between the ages of 35 - 40 years, then every 1-2 years in their 40’s, and annually from age 50. Women who are deemed to be high risk may have their screening protocol modified and should consult their physicians.

The number of breast tumors discovered that are not invasive, or that are small, or confined to the breast has increased by 100 - 200%. This increase is attributable to the increase in screening activity among women over the last 10 - 20 years. Although this does not prevent breast cancer, the increased early detection will result in prolonged survival among women with breast cancer.

Despite the marked improvement in the technology of mammography, breast examination remains an important component of breast cancer screening. Approximately 15% of breast cancers that can be felt by a woman or her physician are not detected by mammography. This is especially true in younger, premenopausal women who have denser breast tissue, making the mammogram more difficult to interpret. The important lesson to learn from this is that all breast masses need to be evaluated, irrespective of the mammography result. Although breast examinations have never been proven to decrease mortality from breast cancer, it has been shown that a more experienced examiner (whether that be the patient or her healthcare provider) is able to detect smaller masses.

The ACS recommends that all women begin examining their breasts monthly from age 20 and that a doctor perform a breast exam at least every three years from age 20-29 years, and annually thereafter. For details as to how to perform a thorough self -breast exam, please refer to Always ‘Applauds’ and ‘Straight Talk’ sections in ‘Visiting your doctor’, choose the ‘breast self-exam’ option.

Summary
Being a woman, advancing age, genetic tendencies, a previous breast biopsy with hyperplasic features, and exposure to ionizing radiation are the most important risk factors for breast cancer. Menstrual pattern, reproductive history and nutrition also have a modifying effect but are not as strong risk factors. Birth control pills do not appear to cause breast cancer and HRT remains a hotly debated topic. Unfortunately, despite all of the information that is now available, only 25- 50% of breast cancer cases can be explained by our current knowledge. This is testimony to our poor understanding of the biological mechanisms that lead to breast cancer. Future scientific investigation is needed to provide us with a better understanding of the disease so that improved surveillance techniques can be devised. Hopefully, there will be a day when strategies have been outlined to even prevent breast cancer.

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Introduction
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.

International variation
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.

Aging
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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Ionizing radiation
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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Genetic predisposition
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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Reproductive history
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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Menstrual patterns
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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By Dr. Philip Sarrel, M.D.
Breast cancer is the most common form of cancer in women in the United States with one out of nine women developing the disease in her lifetime. In 1998, 178,700 new cases will be diagnosed and 43,500 women will die from the disease. You’ve all probably heard the latest news about the breast cancer drug Tamoxifen, and are wondering if this is something for you, or someone you know. Here is some background that will help you in understanding these stories, and give you a basic background if you would like to discuss this further with your own doctor. The news stories are based on a research report in the September 16, 1998 issue of the Journal of the National Cancer Institute about breast cancer prevention through the use of the drug Tamoxifen. Tamoxifen has been used for many years for women who have had breast cancer and has been proven effective in preventing recurrence of the disease. It is believed that Tamoxifen acts by primarily competing with the female hormone, estrogen, for estrogen receptors in the nuclei of some breast cancer cells. By binding to these receptors and blocking the stimulatory effects of estrogen, Tamoxifen inhibits the growth and metabolism of breast cancer cells. The new study is of the use of Tamoxifen by women who have not had breast cancer but who, for a number of reasons including breast cancer in their family and evidence of pre-cancerous breast disease, are at higher risk of developing breast cancer.

Research Study
• 13,388 women were studied in more than 300 centers throughout the United States. The women received Tamoxifen or an inactive placebo tablet for an average follow-up time of four years.
• Women who received Tamoxifen showed a 49% reduced risk of developing invasive breast cancer.
• All ages of women, from 35 to women in their 70’s and older, showed the protective effect with the benefits, from Tamoxifen, being greatest among the older women and women who had previous medical histories of non-invasive breast cancer.
• Another beneficial effect was a decreased risk of bone fracture of the hip, wrist, and spinal column.

Adverse reactions to Tamoxifen are relatively mild and rarely severe enough to require discontinuation of treatment. The most frequently reported adverse reactions are hot flashes, vaginal discharge, and irregular menses. Deep vein thrombosis and pulmonary embolism, although uncommon, occur more frequently with Tamoxifen than with a placebo. An increased risk of changes in the endometrium (lining of the uterus), including endometrial cancer, has been associated with Tamoxifen treatment. Healthy women in the general population have reported endometrial cancer of 0.7 cases per 1,000 women.

Women with breast cancer, regardless of any treatment they may receive, have an increased risk of endometrial cancer: about 1 case per 1,000 women. Among breast cancer patients treated with Tamoxifen, between 2 and 3 cases per 1,000 women per year may be diagnosed.

The findings in this study are in contrast to two earlier reports — one from Great Britain and the other from Italy. The European studies were done on a smaller number of women and of a different risk group than the American study. The two studies did not find a reduction in breast cancer among the women receiving Tamoxifen compared to those receiving an inactive tablet.

Tamoxifen is not a miracle drug, or a cure-all for everyone. But it provides additional hope for all women in the fight against breast cancer. You should talk to your doctor about the possibilities that Tamoxifen may hold for you.