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Breast Cancer

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What Causes Breast Cancer?
Although many risk factors may increase your chance of developing breast cancer, it is not yet known exactly how some of these risk factors cause cells to become cancerous. A woman's hormones somehow stimulate breast cancer growth. Just how this comes about has not yet been figured out.

Researchers are beginning to understand how certain changes in DNA can cause normal breast cells to become cancerous. DNA is the chemical that carries the instructions for nearly everything our cells do. We usually resemble our parents because they are the source of our DNA. However, DNA affects more than our outward appearance.

Some genes (parts of DNA) contain instructions for controlling when our cells grow, divide, and die. Certain genes that promote cell division are called oncogenes. Others that slow down cell division, or cause cells to die at the right time, are called tumor suppressor genes. It is known that cancers can be caused by DNA mutations (changes) that "turn on" oncogenes or "turn off" tumor suppressor genes.

The BRCA genes (BRCA1 and BRCA2) are tumor suppressor genes. When they are mutated, they no longer function to suppress abnormal growth and cancer is more likely to develop. Certain inherited DNA changes (you are born with these) can cause an increased risk for developing cancer in people who carry these changes and are responsible for the cancers that run in some families.
Most DNA mutations related to breast cancer, however, occur in single breast cells during a woman's life rather than having been inherited. These acquired mutations of oncogenes and/or tumor suppressor genes may result from radiation or cancer-causing chemicals. So far, studies have not been able to identify any chemical in the environment or in our diets that is likely to cause these mutations, or a subsequent breast cancer. The cause of most acquired mutations remains unknown.

Women have already begun to benefit in several ways from recent advances in understanding the genetic basis of breast cancer. The section, "What Are the Risk Factors for Breast Cancer?" explains how genetic testing can identify some women who have inherited abnormal BRCA1, BRCA2, CHEK-2, or p53 tumor suppressor genes. These women can then take steps to reduce their risk of developing breast cancers and to monitor changes in their breasts carefully to find cancer at an earlier, more treatable stage. (For more information see the American Cancer Society documents, "Medicines to Reduce Breast Cancer Risk" and "Breast Cancer Early Detection.")

Most breast cancers have several gene mutations that are acquired. That means that these mutations are not inherited. They develop as part of the cancer. Tests to identify other acquired changes in oncogenes or tumor suppressor genes (such as p53) may help doctors more accurately predict the survival outcome of some women with breast cancer. But with the exception of the HER2 oncogene, these tests have not yet been shown to be useful in making decisions about treatment and are used only for research purposes

What Are the Risk Factors for Breast Cancer?
A risk factor is anything that increases your chance of getting a disease, such as cancer. Different cancers have different risk factors. For example, exposing skin to strong sunlight is a risk factor for skin cancer. Smoking is a risk factor for cancers of the lung, mouth, larynx, bladder, kidney, and several other organs.

But having a risk factor, or even several, does not mean that you will get the disease. Most women who have one or more breast cancer risk factors never develop the disease, while many women with breast cancer have no apparent risk factors (other than being a woman and growing older). Even when a woman with breast cancer has a risk factor, there is no way to prove that it actually caused her cancer.

There are different kinds of risk factors. Some factors, like a person's age or race, can't be changed. Others are linked to cancer-causing factors in the environment. Still others are related to personal choices such as smoking, drinking, and diet. Some factors influence risk more than others, and your risk for breast cancer can change over time, due to factors such as aging or lifestyle.

Risk Factors You Cannot Change
Gender: Simply being a woman is the main risk factor for developing breast cancer. Although women have many more breast cells than men, the main reason they develop more breast cancer is because their breast cells are constantly exposed to the growth-promoting effects of the female hormones estrogen and progesterone, thus making breast cancer much more common in women than men. Men can develop breast cancer, but this disease is about 100 times more common among women than men.

Aging: Your risk of developing breast cancer increases as you get older. About 17% of invasive breast cancer diagnoses are among women in their 40s, while about 78% of women with invasive breast cancer are age 50 or older when they are diagnosed.

Genetic risk factors: Recent studies have shown that about 5% to 10% of breast cancer cases are hereditary as a result of gene changes (called mutations). The most common mutations are those of the BRCA1 and BRCA2 genes. Normally, these genes help to prevent cancer by making proteins that keep cells from growing abnormally. However, if you have inherited either mutated gene from a parent, you are at increased risk for breast cancer.

Women with an inherited BRCA1 or BRCA2 mutation have up to an 80% chance of developing breast cancer during their lifetime and at a younger age than those women who are not born with one of these gene mutations in their cells. Women with these inherited mutations also have an increased risk for developing ovarian cancer. Although BRCA mutations are found most often in Jewish women of Ashkenazi (Eastern Europe) origin, they are also seen in African-American women and Hispanic women, many of whom have the kind of mutation seen in Ashkenazi Jewish women.

Other genes have been discovered that might also lead to inherited breast cancers. One of these is the ATM gene. ATM stands for ataxia-telangiectasia mutation. The gene is responsible for repairing damaged DNA. Certain families with a high rate of breast cancer have been found to have mutations of this gene. Another gene, the CHEK-2 gene, also increases breast cancer risk about twofold when it is mutated. Neither one of these genes, however, is a frequent cause of familial breast cancer. But in women who carry the CHEK-2 mutation and have a strong family history of breast cancer, the risk is greatly increased.

Inherited mutations of the p53 tumor suppressor gene can also increase your risk of developing breast cancer, as well as leukemia, brain tumors, and/or sarcomas (cancer of bones or connective tissue). The Li-Fraumeni syndrome, named after the 2 researchers who described this inherited cancer syndrome, is a rare cause of breast cancer.

If you are considering genetic testing, it is strongly recommended that first you talk to a genetic counselor, nurse, or doctor qualified to interpret and explain these tests. It is very important to understand and carefully weigh the benefits and risks of genetic testing before these tests are done. Testing is expensive and is not covered by some health insurance plans. There is concern that people with abnormal genetic test results will not be able to get life insurance or that coverage may only be available at a much higher cost, but many states have passed laws that prevent insurance companies from denying insurance on the basis of genetic testing.

Family history of breast cancer: Breast cancer risk is higher among women whose close blood relatives have this disease. Your risk of developing breast cancer is increased if:

You have 2 or more relatives with breast or ovarian cancer.

Breast cancer occurs before age 50 in a relative (mother, sister, grandmother or aunt) on either side of the family. The risk is higher if your mother or sister has a history of breast cancer. You have relatives with both breast and ovarian cancer.

You have 1 or more relatives with two cancers (breast and ovarian, or 2 different breast cancers).You have a male relative (or relatives) with breast cancer.

You have a family history of breast or ovarian cancer and Ashkenazi Jewish heritage. Your family history includes a history of diseases associated with hereditary breast cancer such as Li-Fraumeni or Cowden Syndrome.

Having 1 first-degree relative (mother, sister, or daughter) with breast cancer approximately doubles a woman's risk. Having 2, first-degree relatives increases her risk 5-fold. Although the exact risk is not known, women with a family history of breast cancer in a father or brother also have an increased risk of breast cancer. Altogether, about 20% to 30% of women with breast cancer have a family member with this disease.

Personal history of breast cancer: A woman with cancer in one breast has a 3- to 4-fold increased risk of developing a new cancer in the other breast or in another part of the same breast. This is different from a recurrence (return) of the first cancer.

Race: White women are slightly more likely to develop breast cancer than are African-American women. African-American women are more likely to die of this cancer. Many experts now feel that the main reason for this is because African-American women have more aggressive tumors (see basal-like breast cancer, below). The reasons for this are not known. Asian, Hispanic, and Native-American women have a lower risk of developing and dying from breast cancer.

Abnormal breast biopsy: Some types of benign breast conditions are more closely linked to breast cancer risk than others. Doctors often divide benign breast conditions into 3 general groups, depending on how they affect this risk: non-proliferative lesions, proliferative lesions without atypia, and proliferative lesions with atypia.

Previous chest radiation: Women who as children or young adults had radiation therapy to the chest area as treatment for another cancer (such as Hodgkin disease or non-Hodgkin lymphoma) are at significantly increased risk for breast cancer. Some reports found the risk to be 12 times normal risk. This varies with the age of the patient at the time of radiation. Younger patients have a higher risk. If chemotherapy was also given, the risk may be lowered if the chemotherapy stopped ovarian hormone production. The risk of developing breast cancer appears to be highest if the breast was still in development (during adolescence) when the radiation was given.

Menstrual periods: Women who started menstruating at an early age (before age 12) or who went through menopause at a late age (after age 55) have a slightly higher risk of breast cancer.

Diethylstilbestrol (DES): In the 1940s through the 1960s some pregnant women were given diethylstilbestrol because it was thought to lower their chances of losing the baby (miscarriage). Recent studies have shown that these women have a slightly increased risk of developing breast cancer. Recent findings have also suggested that women whose mothers took DES during pregnancy may have a higher risk for breast cancer than women not exposed to the drug in utero. For more information on DES see the American Cancer Society document, "DES Exposure: Questions and Answers."

Lifestyle-Related Factors and Breast Cancer Risk
Not having children: Women who have had no children or who had their first child after age 30 have a slightly higher breast cancer risk. Having multiple pregnancies and becoming pregnant at an early age reduces breast cancer risk.

Oral contraceptive use: It is still not certain what part oral contraceptives (birth control pills) might play in breast cancer risk. Studies have suggested that women now using oral contraceptives have a slightly greater risk of breast cancer than women who have never used them. Women who stopped using oral contraceptives more than 10 years ago do not appear to have any increased breast cancer risk. When considering using oral contraceptives, women should discuss their other risk factors for breast cancer with their health care team.

Postmenopausal hormone therapy (also known as hormone replacement therapy, or HRT): It has become clear that long-term use (several years or more) of postmenopausal hormone therapy (PHT), particularly estrogen and progesterone combined, increases your risk of breast cancer. Long-term PHT use may also increase your chances of dying of breast cancer.

If you still have your uterus (womb), doctors generally prescribe estrogen and progesterone (known as combined PHT). Estrogen relieves menopausal symptoms and delays osteoporosis (thinning of the bones that can lead to fractures). But estrogen can increase the risk of developing cancer of the uterus. Progesterone is added to help prevent this.

If you no longer have your uterus, estrogen alone can be prescribed. This is commonly known as estrogen replacement therapy (ERT). This probably does not increase the risk of breast cancer very much, if at all, especially if used for a relatively short period of time.

Several large studies, including the Women's Health Initiative (WHI), have found that there is an increased risk of breast cancer related to the use of combined PHT. The most recent results from the WHI found that not only did combined PHT increase breast cancer risk, but it also increased the likelihood that the cancer would be found at a more advanced stage. This is because it appeared to reduce the effectiveness of mammograms, as more abnormal findings on mammograms were noted. A large study from the United Kingdom has now found that women who took the combined therapy were also more likely to die of breast cancer than women who didn't.

The risk of PHT appears to apply only to current and recent users, and a woman's breast cancer risk seems to return to that of the general population within 5 years of stopping PHT.

Estrogen alone (ERT) does not appear to increase the risk of developing breast cancer. But when used long term (for more than 10 years), ERT has been found to increase the risk of ovarian and breast cancer in some studies.

At this time there appear to be few strong reasons to use postmenopausal hormone therapy (combined PHT or ERT), other than possibly for the temporary relief of menopausal symptoms. In addition to the increased risk of breast cancer, the WHI found that combined PHT also increased the risk of heart disease, blood clots, and strokes, and did not have a beneficial effect on mental function or preventing Alzheimer's disease. It did lower the risk of colorectal cancer and osteoporosis, but this must be weighed against the possible harms, and it should be considered that there are other effective ways to prevent osteoporosis. And, as noted above, while ERT did not seem to have much effect on the risk of breast cancer, it did increase the risk of stroke.

The decision to use PHT should be made by the woman and her doctor after weighing the possible risks (including increased risk of heart disease, breast cancer, strokes, and blood clots) and benefits (relief of menopausal symptoms, reduced risk of osteoporosis), and considering each woman's other risk factors for heart disease, breast cancer, osteoporosis, and the severity of her menopausal symptoms.

Breast-feeding and pregnancy: Some studies suggest that breast-feeding may slightly lower breast cancer risk, especially if breast-feeding is continued for 1.5 to 2 years. Other studies found no impact on breast cancer risk.

The explanation of this may be that both pregnancy and breast-feeding reduce a woman's total number of lifetime menstrual cycles. This may be similar to the reduction of risk due to late menarche (start of menstrual periods) or early menopause, which also decrease the total number of menstrual cycles. One study concluded that having more children and breast-feeding longer could reduce the risk of breast cancer by half.

Alcohol: Use of alcohol is clearly linked to an increased risk of developing breast cancer. The risk increases with the amount of alcohol consumed. Compared with nondrinkers, women who consume 1 alcoholic drink a day have a very small increase in risk. Those who have 2 to 5 drinks daily have about 1½ times the risk of women who drink no alcohol. Alcohol is also known to increase the risk of developing cancers of the mouth, throat, and esophagus. The American Cancer Society recommends limiting your consumption of alcohol.

Obesity and high-fat diets: Obesity (being overweight) has been found to be a breast cancer risk in all studies, especially for women after menopause. Although your ovaries produce most of your estrogen, fat tissue produces a small amount of estrogen. Having more fat tissue after menopause can increase your estrogen levels and, thereby, increase your likelihood of developing breast cancer.

The connection between weight and breast cancer risk is complex, however. For example, risk appears to be increased for women who gained weight as an adult but is not increased among those who have been overweight since childhood. Also, excess fat in the waist area may affect risk more than the same amount of fat in the hips and thighs. Researchers believe that fat cells in various parts of the body have subtle differences in their metabolism that may explain this observation.

Studies of fat in the diet have not clearly shown that this is a breast cancer risk factor. Most studies found that breast cancer is less common in countries where the typical diet is low in total fat, low in polyunsaturated fat, and low in saturated fat.

On the other hand, many studies of women in the United States have not found breast cancer risk to be related to dietary fat intake. Researchers are still not sure how to explain this apparent disagreement. Many scientists note that studies comparing diet and breast cancer risk in different countries are complicated by other differences (such as activity level, intake of other nutrients, and genetic factors) that might also alter breast cancer risk.

More research is needed to better understand the effect of the types of fat eaten and body weight on breast cancer risk. But it is clear that calories do count and fat is a major source of these. A diet high in fat has also been shown to influence the risk of developing several other types of cancer, and intake of certain types of fat is clearly related to heart disease risk. The American Cancer Society recommends you maintain a healthy weight throughout your life and limit your intake of processed and red meats.

Physical activity: Evidence is growing that physical activity in the form of exercise reduces breast cancer risk. The only question is how much exercise is needed. In one study from the Women's Health Initiative (WHI) as little as 1.25 to 2.5 hours per week of brisk walking reduced a woman's risk by 18%. Walking 10 hours a week reduced the risk a little more. The American Cancer Society Guidelines on Nutrition and Physical Activity for Cancer Prevention recommend that you engage in 45 to 60 minutes of intentional physical activity 5 or more days a week.

Factors with Uncertain, Controversial, or Unproven Effect on Breast Cancer Risk
Antiperspirants: Internet e-mail rumors have suggested that chemicals in underarm antiperspirants are absorbed through the skin, interfere with lymph circulation, cause toxins to build up in the breast, and eventually lead to breast cancer. There is very little experimental or epidemiological evidence to support this rumor. Chemicals in products such as antiperspirants are tested thoroughly to ensure their safety. One small study recently found trace levels of parabens (used as preservatives in antiperspirants), which have weak estrogen-like properties, in a small sample of breast cancer tumors. However, the study did not look at whether parabens caused the tumors. This was a preliminary finding, and more research is needed to determine what effect, if any, parabens may have on breast cancer risk. On the other hand, a recent large study of breast cancer causes found no increase in breast cancer in women who used underarm antiperspirants or shaved their underarms.

Underwire bras: Internet e-mail rumors and at least one book have suggested that bras cause breast cancer by obstructing lymph flow. There is no scientific or clinical basis for this claim.

Induced abortion: Several studies have provided very strong data that induced abortions have no overall effect on the risk of breast cancer. Also, there is no evidence of a direct relationship between breast cancer and spontaneous abortion (miscarriage) in most of the studies that have been published. Scientists invited to participate in a conference on abortion and breast cancer by the National Cancer Institute (February 2003) concluded that there was no relationship. A recent report of 83,000 women with breast cancer found no link to a previous abortion, either spontaneous (stillbirth) or induced.

Breast implants: Several studies have found that breast implants do not increase breast cancer risk although silicone breast implants can cause scar tissue to form in the breast. Implants make it harder to see breast tissue on standard mammograms, but additional x-ray pictures called implant displacement views can be used to more completely examine the breast tissue.

Environmental pollution: A great deal of research has been reported and more is being done to understand environmental influences on breast cancer risk. The goal is to determine their possible relationships to breast cancer. Currently, research does not show a clear link between breast cancer risk and exposure to environmental pollutants, such as the pesticide DDE (chemically related to DDT), and PCBs (polychlorinated biphenyls).

Tobacco smoke: Most studies have found no link between active cigarette smoking and breast cancer. Though active smoking has been suggested to increase the risk of breast cancer in some studies, the issue remains controversial.

An issue that continues to be an active focus of scientific research is whether secondhand smoke may increase the risk of breast cancer. Both mainstream and secondhand smoke contain about 20 chemicals that, in high concentrations, cause breast cancer in rodents. Chemicals in tobacco smoke reach breast tissue and are found in breast milk.

The evidence regarding secondhand smoke and breast cancer risk in human studies is controversial, at least in part because the risk has not been shown to be increased in active smokers. One possible explanation for this is that tobacco smoke may have different effects on breast cancer risk in smokers and in those who are just exposed to smoke.

A report from the California Environmental Protection Agency in 2005 concluded that the evidence regarding secondhand smoke and breast cancer is "consistent with a causal association" in younger, mainly premenopausal women. The 2006 US Surgeon General's report, The Health Consequences of Involuntary Exposure to Tobacco Smoke, concluded that there is "suggestive but not sufficient" evidence of a link at this point. In any case, women should be told that this possible link to breast cancer is yet another reason to avoid contact with secondhand smoke.

Night work: Several studies have suggested that women who work at night, for example, nurses on a night shift, may have an increased risk of developing breast cancer. However, this increased risk has not yet been proven and more studies are in progress. According to some researchers, the effect may be due to disruption in melatonin, a hormone that is affected by light, but other hormones are also being studied.

Can Breast Cancer Be Prevented?
A woman at average risk for breast cancer might reduce her risk somewhat by changing those risk factors that can be changed. If you give birth to several children and breast-feed them for several months, avoid alcohol, exercise regularly, and maintain a slim body, you are decreasing your risk of getting breast cancer. Likewise, avoiding PHT will avoid increasing your risk. (See the section, "What Are the Risk Factors for Breast Cancer?".)

Other than these lifestyle changes, the most important action a woman can take is to follow early detection guidelines. Following the American Cancer Society's guidelines for early detection (outlined in the section, "Can Breast Cancer Be Found Early?") will not prevent breast cancer but can help find cancers when the likelihood of successful treatment is greatest.

If you are a woman with a strong family history of breast cancer or with a known genetic mutation of a BRCA gene, there are things you can do to reduce your chances of developing breast cancer. We strongly recommend genetic counseling before any of these steps. It is important to know if your mutation is BRCA1 or BRCA2. BRCA1 cancers may not be prevented by tamoxifen or raloxifene.

Also, if you have had DCIS, LCIS, or biopsies that have shown premalignant or pre-cancerous changes, you might also consider treatment to reduce your breast cancer risk.

Genetic testing for BRCA gene: Recently the US Preventive Services Task Force made recommendations for genetic testing. They recommended that only people with a strong family history should be evaluated. Women who are NOT of Ashkenazi (Eastern European) Jewish heritage should be referred for genetic evaluation if they have:
1. Two first-degree relatives with breast cancer, one of whom was diagnosed when they were younger than 50, or
2. Three or more first or second degree relatives diagnosed with breast cancer at any age, or
3. A first degree relative diagnosed with cancer in both breasts, or
4. Two or more first or second degree relatives diagnosed at any age, or
5. A male relative with breast cancer

Women of Ashkenazi (Eastern European) Jewish heritage should be referred for genetic evaluation if they have:
1. A first degree relative with breast or ovarian cancer at any age or
2. Two second degree relatives on the same side of the family with breast or ovarian cancer at any age.

Early Detection, Diagnosis and Staging
Based on scientific research and expert opinion, the ACS has established recommendations to detect cancer early in asymptomatic people (without symptoms of cancer). The ACS believes that early detection examinations and tests can help save lives and reduce suffering from cancers of the breast, colon, rectum, cervix, prostate, testis (testicles), oral cavity (mouth), and skin. Some of these cancers can be found early by self examinations (such as breast self-examination), physical examinations by a health professional (such examinations of the breast, thyroid gland, skin, colon and rectum, testicles, and prostate), and by x-ray or laboratory tests (such as mammography, the Pap test, and the prostate-specific antigen or PSA blood test). In many cases, a combination of two or more early detection approaches (such as mammography, clinical breast examination by a health professional, and breast self-examination) is the most effective strategy.

The 5-year relative survival rate for people with cancers for which the ACS has specific early detection recommendations (breast, colon, rectum, cervix, prostate, testis, oral cavity, and skin) is about 82%. The 5-year survival rate is defined as the percentage of people alive at least five years after diagnosis of cancer. The 5-year relative survival rate calculation excludes people who die of other causes. Both rates include people regardless of the type of treatment, if any, they receive. The outlook for survival for people with these cancers is greatly improved by early detection.

How Is Breast Cancer Diagnosed?
If screening tests or your signs and symptoms suggest breast cancer, your doctor will use one or more methods to determine if the disease is present and to evaluate the stage of the cancer.

Signs and Symptoms
Although widespread use of screening mammograms has increased the number of breast cancers found before they cause any symptoms, some breast cancers are not found by mammogram, either because the test was not done or because, even under ideal conditions, mammograms cannot find every breast cancer.

The most common sign of breast cancer is a new lump or mass. A painless, hard mass that has irregular edges is more likely to be cancerous, but some cancers are tender, soft, and rounded. For this reason, it is important that a health care professional experienced in diagnosing breast diseases check any new breast mass or lump.

Other signs of breast cancer include a generalized swelling of part of a breast (even if no distinct lump is felt), skin irritation or dimpling, nipple pain or retraction (turning inward), redness or scaliness of the nipple or breast skin, or a discharge other than breast milk. Sometimes a breast cancer can spread to underarm lymph nodes and cause swelling there even before the original tumor in the breast tissue is large enough to be felt.

Medical History and Physical Exam
The first step in evaluation of a woman with suspected breast cancer is a complete medical history and physical exam. Your doctor will ask questions about your symptoms, any other health problems, and risk factors for benign breast conditions and breast cancer (such as whether any of your relatives had benign breast conditions, breast cancer, ovarian cancer, or other cancers).

Your breast will be thoroughly examined to locate any lump or suspicious area and to feel its texture, size, and relationship to the skin and chest muscles. Any changes in the nipples or the skin of your breast will be noted. The lymph nodes under the armpit and above the collarbones may be palpated (felt), because enlargement or firmness of these lymph nodes might indicate spread of breast cancer. Your doctor will also perform a complete physical exam to judge your general health and whether there is any evidence the cancer has spread.

In addition to the medical history and physical exam, imaging tests and biopsies may be done.

Imaging Tests to Diagnose Breast Disease
Mammograms: Although mammograms are mostly used for screening, they can also be used to examine the breast of a woman who has a breast problem. This can be a breast mass, nipple discharge, or an abnormality that was found on a screening mammogram. In some cases, special images known as cone views with magnification are used to make a small area of altered breast tissue easier to evaluate.

A diagnostic mammogram may show that a lesion (area of abnormal tissue) has a high likelihood of being benign (not cancer). In these cases, it is common to ask the woman to come back sooner than usual for a recheck, usually in 4 to 6 months. On the other hand, a diagnostic mammogram may show that the abnormality is not worrisome at all, and the woman can then return to having routine yearly mammograms. Finally, the diagnostic work-up may suggest that a biopsy is needed to tell if the lesion is cancer. Even if the mammograms show no tumor, if you or your doctor can feel a lump, then usually a biopsy will be needed to make sure it isn't cancer. One exception would be if an ultrasound exam finds that the lump is a cyst.

The American Cancer Society believes the use of mammograms, clinical breast exam, and breast self exam, according to the recommendations previously outlined, offers women the best opportunity for reducing the breast cancer death rate through early detection. This combined approach is clearly better than any one exam. Without question, a breast physical exam without a mammogram would miss the opportunity to detect many breast cancers that are too small for a woman or her doctor to feel but can be seen on mammograms. Although a mammogram is the most sensitive screening method, a small percentage of breast cancers do not show up on mammograms but can be felt by a woman or her doctors.

Breast ultrasound: Ultrasound has become a valuable tool to use with mammography because it is widely available and less expensive than other options, such as MRI. Usually, breast ultrasound is used to target a specific area of concern found on the mammogram. Ultrasound also helps distinguish between cysts and solid masses and between benign and cancerous tumors. Ultrasound may be most helpful in women with high breast density (thickness). The National Cancer Institute (NCI) is sponsoring a clinical trial to evaluate the benefits and risks of adding screening breast ultrasound to screening mammograms in women with dense breasts and a higher risk of breast cancer.

Ultrasound, also known as sonography, uses high-frequency sound waves to outline a part of the body. High-frequency sound waves are transmitted into the area of the body being studied and echoed back. These echoes are picked up by the ultrasound probe. A computer changes the sound waves into an image that is displayed on a screen. You are not exposed to radiation during this test.

Ductogram: This test, also called a galactogram, is sometimes helpful in determining the cause of bloody nipple discharge. In this test a fine plastic tube is placed into the opening of the duct at the nipple. A small amount of contrast medium is injected, which outlines the shape of the duct on an x-ray image, which will show if there is a mass inside the duct.

Full-field digital mammogram (FFDM): A full-field digital mammogram is similar to a standard mammogram in that x-rays are used to produce an image of your breast. The differences are in the way the image is recorded, viewed by the doctor, and stored. Standard mammograms are recorded on large sheets of photographic film. Digital mammograms are recorded and stored on a computer. After the exam, the doctor can view them on a computer screen and adjust the image size, brightness, or contrast to see certain areas more clearly. Digital images can also be sent electronically to another site for a remote consult with breast specialists. While many centers do not offer the digital option at this time, it is expected to become more widely available in the future.

Because digital mammograms cost more than standard mammograms, studies are now under way to determine which form of mammogram will benefit more women in the long run. Some studies have found that women who have a FFDM have to return less often for additional imaging tests because of inconclusive areas on the original mammogram. A recent large study from the National Cancer Institute found that a FFDM was more accurate in finding cancers in women younger than 50 and in women with dense breast tissue, although the rates of inconclusive results were similar between a FFDM and a film mammogram. It is important to remember that a standard film mammogram also is effective for these groups of women, and that they should not miss their regular mammogram if a digital mammogram is not available.

Computer-aided detection and diagnosis (CAD): Over the past 2 decades, computer-aided detection and diagnosis (CAD) has been developed to help radiologists detect suspicious changes on mammograms. This is done most commonly with screen-film mammograms and less often with digital mammograms. Generally, the computer device will scan the mammogram first. It can find tumors that the radiologist can't spot. The radiologist, knowing the results of the CAD, will then review the films to look for lesions the CAD missed. The radiologist will then decide the seriousness of the lesions the CAD found. Early research results suggest that CAD systems help radiologists diagnose more early stage cancers than mammograms alone.

Scintimammography: In scintimammography, a radioactive tracer is injected into a vein to detect breast cancer cells. The tracer attaches to breast cancers and is detected by a special camera. This is a very new technique and is still considered experimental. It may or may not be helpful in evaluating abnormal mammograms.

Tomosynthesis: This technology is an extension of a digital mammogram. Tomosynthesis allows the breast to be viewed as many thin slices and has the possibility of providing a more accurate and earlier diagnosis of breast cancer. This technology is still considered experimental and is not yet commercially available.

Magnetic resonance imaging (MRI): MRI scans use radio waves and strong magnets instead of x-rays. The energy from the radio waves is absorbed and then released in a pattern formed by the type of tissue and by certain diseases. A computer translates the pattern of radio waves given off by the tissues into a very detailed image of parts of the body. A contrast material called gadolinium is often injected to better see details.

Patients have to lie inside a tube, which is confining and can upset people with claustrophobia (a fear of enclosed spaces). The machine also makes a thumping noise that you may find disturbing. Some places provide headphones with music to block this out. MRIs are very expensive, although insurance plans generally pay for them once cancer is diagnosed.

Although MRI machines are quite common, they need to be specially adapted to look at the breast. They can be used to better examine cancers found by mammogram or for screening women who have a high risk of developing breast cancer. A few recent studies have shown that MRI screening for women at increased risk finds more cancers than a standard mammogram. However, it is not yet known if the difference between MRI and mammograms in finding small cancers is great enough to save additional lives. And the MRI studies found many more abnormalities that were not cancers, which led to an increased number of biopsy procedures.

MRI is also used for women who have been diagnosed with breast cancer. It is used to better determine the actual size of the cancer and to look for any other cancers in the breast.

Other Tests
Nipple discharge exam: If you have spontaneous nipple discharge, some of the fluid may be collected and looked at under a microscope to see if any cancer cells are in it. Most nipple discharges or secretions are not cancer. In general, if the secretion appears clear green in color, or milky, cancer is very unlikely. If the discharge is red or red-brown, suggesting that it contains blood, it might possibly be caused by cancer, although an injury, infection, or benign tumor are more likely causes.

Even when no cancer cells are found in a nipple discharge, it is not possible to say for certain that a breast cancer is not present. If a patient has a suspicious mass, a biopsy is necessary, even if the nipple discharge does not contain cancer cells.

Ductal lavage and nipple aspiration: Ductal lavage is an experimental test developed for women who have no symptoms of breast cancer but are at very high risk for the disease. It is not a test to screen for or diagnose breast cancer, but it may help give a more accurate picture of a woman's risk of developing it.

Ductal lavage can be done in a doctor's office or an outpatient facility. An anesthetic cream is applied to numb the nipple area. Gentle suction is then used to help draw tiny amounts of fluid from the milk ducts up to the nipple surface. The fluid droplets that appear help locate the milk ducts' natural openings on the surface of the nipple. A tiny tube (called a catheter) is then inserted into a milk duct opening on the nipple. A small amount of anesthetic is infused into the duct to numb the inside. Saline (salt water) is slowly delivered through the catheter to gently "rinse" the duct and collect cells. The ductal fluid is withdrawn through the catheter and placed into a collection vial. The vial is then sent to a lab, where the cells are viewed under a microscope.

Ductal lavage is not considered appropriate for women who aren't at high risk for breast cancer. It is not clear whether it will ever be a useful tool. The test has not been shown to detect cancer early. It is much more useful as a test of cancer risk rather than as a screening test for cancer. More studies are needed to better define the usefulness of this test.

Nipple aspiration also looks for abnormal cells arising in the ducts, but is much simpler, in that nothing is inserted into the breast. The device for nipple aspiration uses small cups that are placed on the woman's breasts. The device warms the breasts, gently compresses them, and applies light suction to bring nipple fluid to the surface of the breast. The nipple fluid is then collected and sent to a lab for analysis. As with ductal lavage, the procedure may be useful as a test of cancer risk but is not appropriate as a screening test for cancer. The test has not been shown to detect cancer early.

A biopsy is done when mammograms, ultrasound, or the physical exam finds a breast change (or abnormality) that is possibly cancer. A biopsy is the only way to tell if cancer is really present. All biopsy procedures remove a tissue sample for examination under a microscope. There are several types of biopsies, such as fine needle aspiration biopsy, core (large needle) biopsy, and surgical biopsy. Each type of biopsy has its own advantages and disadvantages.

The choice of which to use depends on your specific situation. Some of the factors your doctor will consider include how suspicious the lesion appears, how large it is, where in the breast it is located, how many lesions are present, other medical problems you may have, and your personal preferences. You might want to discuss the advantages and disadvantages of different biopsy types with your doctor.

Fine needle aspiration biopsy (FNAB): A thinner needle is used for FNAB than the ones used for blood tests. The needle can be guided into the area of the breast change while the doctor is feeling (palpating) the lump. The doctor can be a pathologist, radiologist, or surgeon. If the lump can't be felt easily, the doctor might use ultrasound or a method called stereotactic needle biopsy to guide the needle, although most of the time if a stereotactic device is used, a large needle (core) biopsy is done.

Ultrasound lets the doctor watch the needle on a screen as it moves toward and into the mass. For stereotactic needle biopsy, computers map the exact location of the mass using mammograms taken from 2 angles. Then a computer guides the needle to the right spot.

A local anesthetic (numbing medicine) may or may not be used. Because such a thin needle is used for the biopsy, the process of getting the anesthetic may actually be more uncomfortable than the biopsy itself.

Once the needle is in place, fluid is drawn out. If the fluid is clear, the lump is probably a benign cyst. Bloody or cloudy fluid can mean either a benign cyst or, very rarely, a cancer. If the lump is solid, small tissue fragments are drawn out. A pathologist (a doctor specializing in diagnosing disease from tissue samples) will examine the biopsy tissue or fluid to determine if it is cancerous.

Fine needle aspiration biopsies can sometimes miss a cancer and take benign cells from nearby the cancer. If it does not provide a clear diagnosis, or your doctor is still suspicious, a second biopsy or a different type of biopsy should be performed. Stereotactic core needle biopsy: A core biopsy can sample breast changes felt by the doctor, as well as smaller ones pinpointed by ultrasound or mammogram. Depending on whether the abnormal area can be felt, about 3 to 5 cores are usually removed.
The needle used in core biopsies is larger than that used in FNAB. It removes a small cylinder of tissue (about 1/16- to 1/8-inch in diameter and ½-inch long) from a breast abnormality. The biopsy is done with local anesthesia in an outpatient setting.

Two new stereotactic biopsy methods can remove more tissue than a core biopsy. The Mammotome® is also known as vacuum-assisted biopsy. For this procedure the skin is numbed and a small incision (about ¼ inch) is made. A probe is inserted through the incision into the abnormal area of breast tissue. A cylinder of tissue is suctioned into the probe then a rotating knife within the probe cuts the tissue sample from the rest of the breast. The Mammotome procedure is done as an outpatient. No stitches are needed and there is minimal scarring. This method usually removes about twice as much tissue as core biopsies. The ABBI method (short for Advanced Breast Biopsy Instrument) uses a probe with a rotating circular knife and thin heated electrical wire to remove a large cylinder of abnormal tissue.
In some centers, the biopsy is guided by an MRI, which locates the tumors, plots its coordinates, and aims the stereotactic biopsy device into the tumor.

Surgical biopsy: Sometimes, a surgeon is needed to remove all or part of the lump for microscopic examination. An excisional biopsy removes an entire lesion (breast abnormality such as a mass or area containing calcifications), as well as a surrounding margin of normal-appearing breast tissue. In rare circumstances, this type of biopsy can be done in the doctor's office, but it is more commonly done in the hospital's outpatient department under a local anesthesia (you are awake during the procedure, but your breast is numb). Intravenous sedation is often given to make you less aware of the procedure.

During an excisional breast biopsy the surgeon may use a procedure called wire localization if there is a small lump that is hard to locate by touch or if an area looks suspicious on the x-ray but cannot be felt. After the area is numbed with local anesthetic, a thin hollow needle is placed into the breast and x-ray views are used to guide the needle to the suspicious area. A thin wire is inserted through the center of the needle. A small hook at the end of the wire keeps it in place. The hollow needle is then removed, and the surgeon uses the wire to guide him to the abnormal area to be removed.

If a benign condition is diagnosed, no further treatment is needed. If the diagnosis is cancer, there is time for you to learn about the disease and to discuss all treatment options with your cancer care team, friends, and family. There is no need to rush into treatment. You may wish to obtain a second opinion before deciding on what treatment is best for you.

Imaging Tests to Detect Breast Cancer Spread
Chest x-ray: This test may be done to see whether the breast cancer has spread to your lungs.

Bone scan: This procedure helps show if a cancer has metastasized (spread) to your bones. The patient receives an injection of radioactive material called technetium diphosphonate. The amount of radioactivity used is very low and causes no long-term effects. The radioactive substance is attracted to diseased bone cells throughout the entire skeleton. Areas of diseased bone will be seen on the bone scan image as dense, gray to black areas, called "hot spots."

These areas may suggest metastatic cancer is present, but arthritis, infection, or other bone diseases can also cause a similar pattern. To distinguish among these conditions, the cancer care team may use other imaging tests or take bone biopsies. Bone scans can find metastases earlier than regular x-rays but sometimes, even when the cancer has spread to the bones, the bone scan won't show it. Other imaging studies such as CT or MRI will be needed.

Computed tomography (CT): The CT scan is an x-ray procedure that produces detailed cross-sectional images of your body. Instead of taking one picture, like a regular x-ray, a CT scanner takes many pictures as it rotates around you. A computer then combines these pictures into an image of a slice of your body. The machine creates several pictures of the part of your body that is being studied. This test can help tell if your cancer has spread into your liver or other organs. Often after the first set of pictures is taken you will receive an intravenous injection of a contrast agent, or "dye," that helps better outline structures in your body. A second set of pictures is then taken.

CT scans can also be used to precisely guide a biopsy needle into a suspected metastasis. For this procedure, called a CT-guided needle biopsy, you remain on the CT scanning table while a radiologist advances a biopsy needle toward the location of the mass. CT scans are repeated until the doctors are sure that the needle is within the mass. A fine needle biopsy sample (tiny fragment of tissue) or a core needle biopsy sample (a thin cylinder of tissue about ½-inch long and less than 1/8-inch in diameter) is removed and sent to be examined under a microscope.

CT scans take longer than regular x-rays. You need to lie still on a table, and the part of your body being examined is placed within the scanner, a doughnut-shaped machine that completely surrounds the table. The test is painless, but you may find it uncomfortable to hold still in certain positions for minutes at a time.

You will need an IV (intravenous) line through which the contrast dye is injected. The injection can also cause some flushing (redness and warm feeling). Some people are allergic and get hives or, rarely, more serious reactions like trouble breathing and low blood pressure can occur. Be sure to tell the doctor if you have ever had a reaction to any contrast material used for x-rays. You may be asked to drink 1 to 2 pints of a solution of contrast material. This helps outline the intestine so that it is not mistaken for tumors.

Magnetic resonance imaging (MRI): This is described above as a way of looking for breast cancer as a supplement to mammograms. Traditionally, MRI scans have been used to look for cancer spread, just like CT scans. MRI scans are particularly helpful in examining the brain and spinal cord. MRI scans are a little more uncomfortable than CT scans. First, they take longer -- often up to an hour. Second, you have to lie inside a narrow tube, which is confining and can upset people with claustrophobia (a fear of enclosed spaces). The machine also makes a thumping noise that you may find disturbing. Some centers provide headphones with music to block this out.

Positron emission tomography (PET): PET uses glucose (a form of sugar) that contains a radioactive atom, which is injected into a vein and travels throughout the body. A special camera can detect the radioactivity. Cancer cells of the body absorb large amounts of the radioactive sugar, because of the high amount of energy that they use. PET is useful when your doctor thinks the cancer has spread but doesn't know where. A PET scan can be used instead of several different x-rays because it scans your whole body. Some of the newer machines are able to perform both a PET and CT scan at the same time (PET/CT scan). This allows the radiologist to compare areas of higher radioactivity on the PET with the appearance of that area on the CT.

It is important to follow the eating, drinking, and activity directions you are given before the PET scan.

This test can be used as a diagnostic aid to a mammogram, especially in looking for cancer in axillary lymph nodes. So far, most studies show it isn't very sensitive in finding small deposits of cancer in lymph nodes, although it can find big ones.

Laboratory Examination of Breast Cancer Tissue
Types of breast cancer: The tissue removed during the biopsy is examined in the lab to see whether the cancer is in situ (not invasive) or invasive. The biopsy is also used to determine the cancer's type. The different types of breast cancer are defined in the section, ""What Is Breast Cancer?".

The most common types, invasive ductal and invasive lobular cancer, are treated in the same way. In some cases, breast cancer types that tend to have a more favorable prognosis (medullary, tubular, and mucinous cancers) are treated differently. For example, hormone therapy or chemotherapy may be recommended for small stage I cancers with unfavorable microscopic features, but not for small cancers of the types associated with a more favorable prognosis.

Grades of breast cancer: A pathologist looks at the tissue sample under a microscope and then assigns a grade to it. The grade helps predict the patient's prognosis because cancers that closely resemble normal breast tissue tend to grow and spread more slowly. In general, a lower grade number indicates a slower-growing cancer that is less likely to spread, while a higher number indicates a faster-growing cancer that is more likely to spread.

Histologic tumor grade (sometimes called its Bloom-Richardson grade, Scarff- Bloom-Richardson grade, or Elston-Ellis grade) is based on the arrangement of the cells in relation to each other: whether they form tubules; how closely they resemble normal breast cells (nuclear grade); and how many of the cancer cells are in the process of dividing (mitotic count). This system of grading is used for invasive cancers but not for in situ cancers.

Grade 1 (well-differentiated) cancers have relatively normal-looking cells that do not appear to be growing rapidly and are arranged in small tubules.

Grade 2 (moderately differentiated) cancers have features between grades 1 and 3.

Grade 3 (poorly differentiated) cancers, the highest grade, lack normal features and tend to grow and spread more aggressively.

The tumor grade is most important in patients with small tumors without lymph node involvement. Patients with small, well-differentiated tumors may require no further treatment after the tumor is removed, while patients with moderately or poorly differentiated tumors usually receive additional hormonal or chemotherapy.

What's New in Breast Cancer Research and Treatment?
Studies continue to uncover lifestyle factors and habits that alter breast cancer risk. Ongoing studies are looking at the effect of exercise, weight gain or loss, and diet on breast cancer risk. Studies on the best use of genetic testing for BRCA1 and BRCA2 mutations continue at a rapid pace. Other genes are being identified. This will occur more rapidly now that the human genome has been sequenced.

Perhaps the most important finding, though, has been that combined estrogen and progestin (not estrogen alone) when used as postmenopausal hormone therapy increases a woman's risk of developing breast cancer.

A large, long-term study funded by the National Institute of Environmental Health Sciences (NIEHS) is now underway to help find the causes of breast cancer.

Recent results of studies that are still in progress suggest that selective estrogen-receptor modulators (SERMs) lower breast cancer risk in women with certain breast cancer risk factors. Further research with SERMs, such as tamoxifen (also used in breast cancer treatment) and raloxifene and drugs such as aromatase inhibitors, is expected to lead to ways to prevent many breast cancers. So far, most women are reluctant to take these medications because of concern about side effects.

MRI-assisted Breast Biopsy
A new biopsy technique now makes it possible to obtain tissue samples during a vacuum-assisted breast biopsy procedure with magnetic resonance imaging (MRI)-assisted guidance. This method allows many samples to be taken through a single small incision in the skin, using only local anesthesia (numbing of the area). This biopsy technique is being studied in women with a personal or family history of breast cancer, those who have undergone previous breast surgery, and women with dense breast tissue who cannot get accurate screenings with tests such as ultrasound or mammograms.

Breast Reconstruction Surgery
Although the number of women with breast cancer choosing breast conservation therapy has been steadily increasing, there are some women who, for medical or personal reasons, choose mastectomy. Some of them also choose to have reconstructive surgery to restore the breast's appearance.

Technical advances in microvascular surgery (reattaching blood vessels) have made free flap procedures an option for breast reconstruction. Recent studies suggest that a new procedure known as skin-sparing mastectomy is as effective as the usual type of modified radical mastectomy for many women. This new procedure offers the advantage of less scar tissue and a reconstructed breast that seems more natural.

For several years, concern over a possible link between breast implants and immune system diseases has discouraged some women from choosing implants as a method of breast reconstruction. Recent studies have thoroughly reviewed this complex issue. Although women should be aware that implants can cause some side effects (such as firm or hard scar tissue formation), they can be assured that women with implants do not have any greater risk for immune system diseases than women who have not had this surgery.

Similarly, the concern that breast implants increase the risk of breast cancer recurrence or formation of new cancers is not supported by current evidence.

Dose Dense Chemotherapy
Recent research has suggested that giving chemotherapy more often (every 2 weeks) at the usual doses may work better in preventing recurrence than the usual schedule (every 3 weeks). Clinical trials are in progress to define the role of dose density in adjuvant therapy. Because of this aggressive schedule, growth factors must be given to prevent low blood counts, a common and serious side effect of chemotherapy.

Monoclonal Antibodies
Antibodies are proteins produced by immune system cells that attach to certain chemicals that the body recognizes as not being part of its own normal tissues. Antibodies help your body resist infections, and even cancer.

Monoclonal antibodies are a special type of antibody that can be mass-produced in laboratories. Trastuzumab is the first monoclonal antibody drug used to treat women with breast cancer. It works by preventing the HER2/neu protein from promoting excessive growth of breast cancer cells and may also help the immune system fight the cancer.

Other monoclonal antibodies that recognize the HER2/neu protein are being tested in clinical trials, as are monoclonal antibodies that block other growth-promoting molecules of breast cancer cells. Monoclonal antibodies that have been designed to guide immune system cells, chemotherapy drugs, or radiation therapy directly to the tumor are also being tested.

In order for cancers to grow, blood vessels must develop to nourish the cancer cells. This process is called angiogenesis. Looking at angiogenesis in breast cancer specimens can help predict prognosis. Some studies have found that breast cancers surrounded by many new, small blood vessels are likely to be more aggressive. Bevacizumab is an anti-angiogenesis drug that doctors have recently begun using in combination with the chemotherapy drug paclitaxel in patients with metastatic breast cancer.

New drugs are being developed that may be useful in stopping breast cancer growth by preventing new blood vessels from forming. Several of these drugs are being tested in clinical trials, and studies of new, more potent anti-angiogenesis drugs are expected to begin soon.

Gene-expression Studies and New Breast Cancer Classifications
One of the mysteries of breast cancer is that doctors cannot always accurately predict which women have a higher risk that their cancer will come back. That is why almost every woman, except for those with small tumors, receives some sort of treatment after surgery. To better pick out who will need adjuvant therapy, researchers have looked at many aspects of breast cancers. The best test seems to be one that looks at the genes in breast cancer cells. Scientists have been able to link certain patterns of genes with more aggressive cancers -- those that tend to come back and spread to distant sites. Preliminary studies suggest that some women with favorable patterns might be able to avoid adjuvant therapy after surgery, but most experts feel that more research is needed before this new technology should be used routinely.

Research using sophisticated technology for detecting patterns of gene expression has suggested some new ways of classifying breast cancers. The current types of breast cancer are based on appearance of tumors under a microscope. It appears that a new classification, based on molecular features, may be better able than the current classification to predict prognosis and response to several types of breast cancer treatment. The new research suggests four types of breast cancers:

Luminal A and Luminal B types: The luminal types are estrogen receptor positive, usually low grade, and tend to grow slowly. The gene expression patterns of these cancers are similar to normal cells that line the breast ducts and glands (the lining of a duct or glad is called its lumen). Luminal A cancers have the best prognosis. Luminal B cancers generally grow somewhat faster than the luminal A cancers and their prognosis is not quite as good.

HER2 type: These cancers have extra amounts of HER2 DNA, RNA, and protein. They usually have a high grade appearance under the microscope. These cancers tend to grow rapidly and have a poor prognosis, although they often can be treated successfully with trastuzumab.

Basal type: These cancers lack estrogen receptors and have normal amounts of HER2. These are high-grade cancers that grow rapidly and have a poor prognosis. This type is common among women with BRCA gene mutations. For reasons that are not well understood, this cancer is particularly common among young African-American women.

Research continues in this area as scientists look for ways to apply new technology to better understand and improve the treatment of breast cancer.

Courtesy: www.cancer.org, Please visit the website for further information

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