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Breast Cancer

by Mary Ann Kosir, MD

  • Among women, breast cancer is the second most common cancer and the second most common cause of cancer deaths.

  • Typically, the first symptom is a painless lump, usually noticed by the woman.

  • Monthly self-examination, yearly breast examination by a doctor, and mammography done periodically are usually recommended for women who are over 40 or who are at increased risk.

  • If a solid lump is detected, doctors take a sample by using a hollow needle or by making an incision and removing part or all of the lump, then examine the tissue under a microscope (biopsy).

  • Breast cancer almost always requires surgery, sometimes with radiation therapy, chemotherapy, other drugs, or a combination.

  • Outcome is hard to predict and depends partly on the characteristics and spread of the cancer.

Breast cancer is the second most common cancer among women after skin cancer and, of cancers, is the second most common cause of death among women after lung cancer. Experts estimate that in 2013, breast cancer will be diagnosed in about 232,000 women in the United States, and about 39,000 women will die of it. About 1% of breast cancers occur in men.

Many women fear breast cancer, partly because it is common. However, some of the fear about breast cancer is based on misunderstanding. For example, the statement, “One of every eight women will get breast cancer,” is misleading. That figure is an estimate based on women from birth to age 95. It means that theoretically, one of eight women who live to age 95 or older will develop breast cancer. However, a 40-year-old woman has only a 1 in 1,200 chance of developing breast cancer during the next year and about a 1 in 120 chance of developing it during the next decade. But as she ages, her risk increases.

What Are the Risks of Developing or Dying of Breast Cancer?

Risk (%)

In 10 Years

In 20 Years

In 30 Years

Age (Years)

Develop

Die

Develop

Die

Develop

Die

30

0.4

0.1

2.0

0.6

4.3

1.2

40

1.6

0.5

3.9

1.1

7.1

2.0

50

2.4

0.7

5.7

1.6

9.0

2.6

60

3.6

1.0

7.1

2.0

9.1

2.6

70

4.1

1.2

6.5

1.9

7.1

2.0

Based on information from Feuer EJ et al: The lifetime risk of developing breast cancer. Journal of the National Cancer Institute 85(11):892-897, 1993.

Several factors affect the risk of developing breast cancer. Thus, for some women, the risk is much higher or lower than average. Most factors that increase risk, such as age and certain abnormal genes, cannot be modified. However, regular exercise, particularly during adolescence and young adulthood may reduce the risk of developing breast cancer. Smoking, regularly drinking alcoholic beverages, and using hormone therapy with estrogen and progesterone may increase the risk.

Did You Know...

  • Fewer than 1% of women have the genes for breast cancer.

Far more important than trying to modify risk factors is being vigilant about detecting breast cancer so that it can be diagnosed and treated early, when it is more likely to be cured. Early detection is more likely when women have mammograms (see Breast Disorders:Mammography ). Regular breast self-examinations are also recommended (see How to Do a Breast Self-Examination).

Types

Breast cancer is usually classified by the kind of tissue in which the cancer starts and the extent of the cancer's spread.

Kind of tissue

There are many different kinds of tissue in the breast. Cancer can develop in most of these tissues, including

  • Milk ducts (called ductal carcinoma): About 90% of all breast cancers are this type.

  • Milk-producing glands, or lobules (called lobular carcinoma)

  • Fatty or connection tissue (called sarcoma): This type is rare.

Paget disease of the nipple (see Paget Disease of the Nipple) is a ductal breast cancer that affects the skin over and around the nipple. The first symptom is a crusty or scaly nipple sore or a discharge from the nipple. Slightly more than half of the women who have this cancer also have a lump in the breast that can be felt. Paget disease may be in situ or invasive. Because this disease usually causes little discomfort, women may ignore it for a year or more before seeing a doctor. The prognosis depends on how invasive and how large the cancer is as well as whether it has spread to the lymph nodes.

Phyllodes breast tumors are relatively rare, accounting for less than 1% of breast cancers. About half are cancerous. They originate in breast tissue around milk ducts and milk-producing glands. The tumor spreads to other parts of the body (metastasizes) in about 10 to 20% of women who have it. The prognosis is good unless the tumor has metastasized.

Extent of spread

Breast cancer can remain within the breast or spread anywhere in the body through the lymphatic vessels or bloodstream. Cancer cells tend to move into the lymphatic vessels in the breast. Most lymphatic vessels in the breast drain into lymph nodes in the armpit (axillary lymph nodes). One function of lymph nodes is to filter out and destroy abnormal or foreign cells, such as cancer cells. If cancer cells get past these lymph nodes, the cancer can spread to other parts of the body. Breast cancer tends to spread to bones and the brain but can spread to any area, including the lungs, liver, skin, and scalp. Breast cancer can appear in these areas years or even decades after it is first diagnosed and treated. If the cancer has spread to one area, it probably has spread to other areas, even if it cannot be detected right away.

The spread of breast cancer is usually classified as

  • Carcinoma in situ

  • Invasive cancer

Carcinoma in situ means cancer in place. It is the earliest stage of breast cancer. Carcinoma in situ may be large and may even affect a substantial area of the breast, but it has not invaded the surrounding tissues or spread to other parts of the body. More than 25% of all breast cancers diagnosed in the United States are carcinoma in situ.

Ductal carcinoma in situ is confined to the milk ducts of the breast. It does not invade surrounding breast tissue, but it can spread along the ducts and gradually affect a substantial area of the breast. This type accounts for 20 to 30% of breast cancers. It is detected most often by mammography. This type may become invasive.

Lobular carcinoma in situ develops within the milk-producing glands of the breast. It often occurs in several areas of both breasts. Women with this type have a 1 to 2% chance each year of developing invasive breast cancer in the affected or the other breast. This type accounts for 1 to 2% of breast cancers. Usually, lobular carcinoma in situ cannot be seen on a mammogram and is detected only by biopsy.

Invasive cancer can be classified as follows:

  • Localized: The cancer has invaded surrounding tissues but is confined to the breast.

  • Regional: The cancer has invaded tissues near the breasts, such as the chest wall or lymph nodes.

  • Distant (metastatic): The cancer has spread from the breast to other parts of the body (metastasized).

Invasive ductal carcinoma begins in the milk ducts but breaks through the wall of the ducts, invading the surrounding breast tissue. It can also spread to other parts of the body. It accounts for about 80 to 90% of invasive breast cancers.

Invasive lobular carcinoma begins in the milk-producing glands of the breast but invades surrounding breast tissue and spreads to other parts of the body. It is more likely than other types of breast cancer to occur in both breasts. It accounts for 10 to 15% of breast cancers.

Rare types of invasive ductal breast cancers include medullary carcinoma, tubular carcinoma, and mucinous (colloid) carcinoma. Mucinous carcinoma tends to develop in older women and to be slow growing. Women with these types of breast cancer have a much better prognosis than women with other types of invasive breast cancer.

Tumor receptors

All cells, including breast cancer cells, have molecules on their surfaces called receptors. A receptor has a specific structure that allows only particular substances to fit into it and thus affect the cell’s activity. Whether breast cancer cells have certain receptors affects how quickly the cancer spreads and how it should be treated.

  • Estrogen and progesterone receptors: Some breast cancer cells have receptors for estrogen . The resulting cancer, described as estrogen receptor–positive, grows or spreads when stimulated by estrogen . This type of cancer is more common among postmenopausal women than among younger women. About two thirds of postmenopausal women with cancer have estrogen -positive cancer. Some breast cancer cells have receptors for progesterone . The resulting cancer, described as progesterone receptor–positive, is stimulated by progesterone . Breast cancers with estrogen receptors and possibly those with progesterone receptors grow more slowly than those that do not have these receptors, and the prognosis is better.

  • HER2 (HER2/neu) receptors: Normal breast cells have HER2 receptors, which help them grow. (HER stands for human epithelial growth factor receptor, which is involved in multiplication, survival, and differentiation of cells.) In about 20 to 30% of breast cancers, cancer cells have too many HER2 receptors. Such cancers tend to be very fast growing.

Other characteristics

Sometimes cancer is also classified based on other characteristics.

Inflammatory breast cancer is an example. The name refers to the symptoms of the cancer rather than the affected tissue. This type is fast growing and often fatal. Cancer cells block the lymphatic vessels in the skin of the breast, causing the breast to appear inflamed: swollen, red, and warm. Usually, inflammatory breast cancer spreads to the lymph nodes in the armpit. The lymph nodes can be felt as hard lumps. However, often no lump may be felt in the breast itself because this cancer is dispersed throughout the breast. Inflammatory breast cancer accounts for about 1% of breast cancers.

Symptoms

At first, breast cancer causes no symptoms. Most commonly, the first symptom is a lump, which usually feels distinctly different from the surrounding breast tissue. In many breast cancer cases, women discover the lump themselves. Such a lump may be cancer if it is a firm, distinctive thickening that appears in one breast but not the other. Usually, scattered lumpy changes in the breast, especially the upper outer region, are not cancerous and indicate fibrocystic changes. Pain is not usually the first symptom of breast cancer.

In the early stages, the lump may move freely beneath the skin when it is pushed with the fingers.

In more advanced stages, the lump usually adheres to the chest wall or the skin over it. In these cases, the lump cannot be moved at all or it cannot be moved separately from the skin over it. Sometimes women can determine whether they have a cancer that even slightly adheres to the chest wall or skin by lifting their arms over their head while standing in front of a mirror. If a breast contains cancer that adheres to the chest wall or skin, this maneuver may make the skin pucker or dimple or make one breast appear different from the other.

In very advanced cancer, swollen bumps or festering sores may develop on the skin. Sometimes the skin over the lump is dimpled and leathery and looks like the skin of an orange (peau d’orange) except in color.

The lump may be painful, but pain is an unreliable sign. Pain without a lump is rarely due to breast cancer.

Lymph nodes, particularly those in the armpit on the affected side, may feel like hard small lumps. The lymph nodes may be stuck together or adhere to the skin or chest wall. They are usually painless but may be slightly tender.

Occasionally, the first symptom occurs only when the cancer spreads to another organ. For example, if it spreads to a bone, the bone may ache or become weak, resulting in a fracture. If the cancer spreads to a lung, women may cough or have difficulty breathing.

In inflammatory breast cancer, the breast is warm, red, and swollen, as if infected (but it is not). The skin of the breast may become dimpled and leathery, like the skin of an orange, or may have ridges. The nipple may turn inward (invert). A discharge from the nipple is common. Often, no lump can be felt in the breast, but the entire breast is enlarged.

Screening

Because breast cancer rarely causes symptoms in its early stages and because early treatment is more likely to be successful, screening is important. Screening is the hunt for a disorder before any symptoms occur. Screening may include monthly breast self-examination, yearly breast examination by a health care practitioner, mammography, and, if women have an increased risk of breast cancer, magnetic resonance imaging (MRI).

Breast examination

Women can examine their breasts themselves, or a health care practitioner may examine the breasts.

Routine self-examination enables women to detect lumps at an early stage. However, self-examination alone does not reduce the death rate from breast cancer, and it does not detect as many early cancers as routine screening with mammography. Because self-examination may not detect all lumps, women who do not detect any lumps should continue to see their doctor for breast examinations and to have mammograms as recommended.

A breast examination is a routine part of a physical examination. A doctor inspects the breasts for irregularities, dimpling, tightened skin, lumps, and a discharge. The doctor feels (palpates) each breast with a flat hand and checks for enlarged lymph nodes in the armpit—the area most breast cancers invade first—and above the collarbone. Normal lymph nodes cannot be felt through the skin, so those that can be felt are considered enlarged. However, noncancerous conditions can also cause lymph nodes to enlarge. Lymph nodes that can be felt are checked to see if they adhere to the skin or chest wall and if they are matted together. This examination can detect 7 to 10% of cancers that are not seen on mammograms.

How to Do a Breast Self-Examination

1. While standing in front of a mirror, look at the breasts. The breasts normally differ slightly in size. Look for changes in the size difference between the breasts and changes in the nipple, such as turning inward (an inverted nipple) or a discharge. Look for puckering or dimpling.

2. Watching closely in the mirror, clasp the hands behind the head and press them against the head. This position helps make subtle changes caused by cancer more noticeable. Look for changes in the shape and contour of the breasts, especially in the lower part of the breasts.

3. Place the hands firmly on the hips and bend slightly toward the mirror, pressing the shoulders and elbows forward. Again, look for changes in shape and contour.

Many women do the next part of the examination in the shower because the hand moves easily over wet, slippery skin.

4. Raise the left arm. Using three or four fingers of the right hand, probe the left breast thoroughly with the flat part of the fingers. Moving the fingers in small circles around the breast, begin at the nipple and gradually move outward. Press gently but firmly, feeling for any unusual lump or mass under the skin. Be sure to check the whole breast. Also, carefully probe the armpit and the area between the breast and armpit for lumps.

5. Squeeze the left nipple gently and look for a discharge. (See a doctor if a discharge appears at any time of the month, regardless of whether it happens during breast self-examination.)

Repeat steps 4 and 5 for the right breast, raising the right arm and using the left hand.

6. Lie flat on the back with a pillow or folded towel under the left shoulder and with the left arm overhead. This position flattens the breast and makes it easier to examine. Examine the breast as in steps 4 and 5. Repeat for the right breast.

A woman should repeat this procedure at the same time each month. For menstruating women, 2 or 3 days after their period ends is a good time because the breasts are less likely to be tender and swollen. Postmenopausal women may choose any day of the month that is easy to remember, such as the first.

Adapted from a publication of the National Cancer Institute.

Mammography

For this test, x-rays are used to check for abnormal areas in the breast. A technician positions the woman’s breast on top of an x-ray plate. An adjustable plastic cover is lowered on top of the breast, firmly compressing the breast. Thus, the breast is flattened so that the maximum amount of tissue can be imaged and examined. X-rays are aimed downward through the breast, producing an image on the x-ray plate. Two x-rays are taken of each breast in this position. Then plates may be placed vertically on either side of the breast, and x-rays are aimed from the side. This position produces a side view of the breast.

Mammography: Screening for Breast Cancer

Mammography is one of the best ways to detect breast cancer early. Mammography is designed to be sensitive enough to detect the possibility of cancer at an early stage, sometimes years before it can be felt. Because mammography is so sensitive, it may indicate cancer when none is present—a false-positive result. About 85 to 90% of abnormalities detected during screening (that is, in women with no symptoms or lumps) are not cancer. Typically, when the result is positive, more specific follow-up procedures, usually a breast biopsy, are scheduled to confirm the result. Mammography may miss up to 15% of breast cancers.

Having a mammogram every year can reduce the rate of death due to breast cancer by 25 to 35% among women aged 50 and older. As yet, no study has shown that regularly having mammograms can reduce the death rate among women younger than 50. However, evidence may be harder to obtain because breast cancer is not common among younger women. Mammography is usually recommended every year for all women aged 50 and over and every 1 or 2 years for all women aged 40 and over. Mammography is more accurate in older women, partly because as women age, the amount of fatty tissue in breasts increases, and abnormal tissue is easier to distinguish from fatty tissue than other types of breast tissue.

Did You Know...

  • Only about 10 to 15% of the abnormalities detected during routine screening with mammography turn out to be cancer.

The dose of radiation used is very low and is considered safe. Mammography may cause some discomfort, but the discomfort lasts only a few seconds. Mammography should be scheduled at a time during the menstrual period when the breasts are less likely to be tender. Deodorants and powders should not be used on the day of the procedure because they can interfere with the image obtained. The entire procedure takes about 15 minutes.

MRI

MRI is usually used to screen women with a high risk of breast cancer, such as those with a BRCA mutation. For these women, screening should also include mammography and breast examination by a health care practitioner.

Diagnosis

When a lump or another abnormality is detected in the breast during a physical examination or by a screening procedure, other procedures are necessary.

Mammography is usually done first if it was not the way the abnormality was detected. Mammography provides a reference for future comparison. It can also help identify tissue that should be removed and examined under a microscope (biopsied).

If doctors suspect advanced cancer based on symptoms, a biopsy is done first.

Ultrasonography is sometimes used to help distinguish between a fluid-filled sac (cyst) and a solid lump. This distinction is important because cysts are usually not cancerous. Cysts may be monitored (with no treatment) or drained (aspirated) with a small needle and syringe. The fluid from the cyst is examined to check for cancer cells only if the fluid is bloody or cloudy, if little fluid is obtained, or if the lump remains after it is drained. Otherwise, the woman is checked again in 4 to 8 weeks. If the cyst can no longer be felt at this time, it is considered noncancerous. If it has reappeared, it is drained again, and the fluid is examined under a microscope. If the cyst reappears a third time or if it is still present after it was drained, a biopsy is done. Rarely, when cancer is suspected, cysts are removed.

If the abnormality is a solid lump, which is more likely to be cancerous, a sample of tissue is biopsied to check for cancer cells. Doctors may do one of several types of biopsy:

  • Fine-needle aspiration biopsy: Some cells are removed from the lump through a thin needle attached to a syringe.

  • Core needle biopsy: A larger needle with a special tip is used to remove a larger sample of breast tissue.

  • Open (surgical) biopsy: Doctors make a small cut in the skin and breast tissue and remove part or all of a lump. This type of biopsy is done when a needle biopsy is not possible (for example, because no lump is felt). It may also be done after a needle biopsy that does not detect cancer to be sure that the needle biopsy did not miss a cancer.

Often, particularly when no lump is felt, a stereotactic biopsy is done. It helps doctors accurately locate and remove a sample of the abnormal tissue. For this biopsy, doctors take mammograms from two angles and send the two-dimensional images to a computer, which compares them and calculates the precise location of the abnormality in three dimensions. A thin wire or clip may be used to mark the site. Or ultrasonography or MRI may be done to help doctors locate the abnormal tissue. Most women do not need to be hospitalized for these procedures. Usually, only a local anesthetic is needed.

If Paget disease of the nipple is suspected, a biopsy of nipple tissue is usually done. Sometimes this cancer can be diagnosed by examining a sample of the nipple discharge under a microscope.

A pathologist examines the biopsy samples under the microscope to determine whether cancer cells are present. Generally, a biopsy confirms cancer in only a few women with an abnormality detected during mammography. If cancer cells are detected, the sample is analyzed to determine the characteristics of the cancer cells, such as

  • Whether the cancer cells have estrogen or progesterone receptors

  • How many HER2 receptors are present

  • How quickly the cancer cells are dividing

This information helps doctors estimate how rapidly the cancer may spread and which treatments are more likely to be effective.

After cancer is diagnosed, doctors usually consult a cancer specialist (oncologist) to determine which tests should be done. Tests may include

  • A chest x-ray to determine whether the cancer has spread

  • Blood tests, including a complete blood count (CBC), liver function tests, and measurement of calcium, also to determine whether the cancer has spread

  • Bone scanning (imaging of bones throughout the body—see Tests for Musculoskeletal Disorders : Bone Scanning) if the tumor is large, if the lymph nodes are enlarged, if women have bone pain, or if the calcium level is high to determine whether cancer has spread to the bones

  • Computed tomography (CT) of the abdomen if liver function is abnormal, if the liver is enlarged, or if the cancer has spread within the breast

  • MRI to accurately determine how large the tumor is, whether the chest wall is involved, and how many tumors are present so that surgery can be planned accordingly

Staging

When cancer is diagnosed, a stage is assigned to it, based on how advanced it is. The stage helps doctors determine the most appropriate treatment and the prognosis. Stages of breast cancer may be described generally as in situ (not invasive) or invasive. Stages may be described in detail and designated by a number (0 through IV) and a letter (A through C).

Stages of Breast Cancer

Stage

Description

5-Year Survival Rate*

In situ carcinoma

0

The tumor is confined, usually to a milk duct or milk-producing gland, and has not invaded surrounding breast tissue, or Paget disease of the nipple with no lump is present.

93%

Localized and regional invasive cancer

IA

The tumor is 2 centimeters (about 3/4 inch) or less in diameter and cancer cells have not spread beyond the breast.

88%

IB

The tumor is 2 centimeters or less in diameter, or there is no tumor in the breast and lymph nodes near the breast contain microscopic amounts of cancer cells.

88%

IIA

The tumor is 2 centimeters or less in diameter or there is no tumor in the breast, and cancer cells have spread to one to three lymph nodes in the armpit.

or

The tumor is larger than 2 centimeters but no larger than 5 centimeters (about 2 inches) in diameter, but cancer cells have not spread beyond the breast.

81%

IIB

The tumor is larger than 2 centimeters but no larger than 5 centimeters in diameter, and cancer cells have spread to one to three lymph nodes in the armpit.

or

The tumor is larger than 5 centimeters in diameter but has not spread beyond the breast.

74%

IIIA

The tumor can be any size or there is no tumor, and cancer cells have spread to lymph nodes in the armpit that are matted together or stuck to the skin or chest wall or to lymph nodes near the breastbone on the same side as the tumor but not to those in the armpit.

or

The tumor is larger than 5 centimeters in diameter and cancer cells have spread to one to three lymph nodes in the armpit.

67%

IIIB

The tumor can be any size and cancer cells have spread to the chest wall and/or skin, the breast is swollen, or sores have formed on the breast.

or

Inflammatory breast cancer is present.

Cancer cells may have spread to the lymph nodes in the armpit or near the breastbone.

41%

IIIC

The tumor can be any size plus at least one of the following:

  • It has spread to lymph nodes in the armpit and near the breastbone.

  • It has spread to lymph nodes under or above the collar bone.

Cancer cells may have spread to the chest wall and/or skin or caused swelling or sores, or inflammatory breast cancer may be present.

49%

Metastatic cancer

IV

The tumor, regardless of size, has spread to distant organs or tissues, such as the lungs or bones, or to lymph nodes distant from the breast.

15%

*The percentage of people who are still alive 5 years after treatment.

Microscopic amounts of cancer cells in lymph nodes are called microinvasion.

Prognosis

Generally, a woman's prognosis depends on how invasive and how large the cancer is, what type of cancer it is, and whether it has spread to the lymph nodes.

Women with breast cancer tend to have a worse prognosis if they have any of the following:

  • Diagnosis of breast cancer during their 20s and 30s

  • Larger tumors

  • Cancer that has rapidly dividing cells, including tumors that do not have well-defined borders or cancer that is dispersed throughout the breast

  • Tumors that do not have estrogen or progesterone receptors

  • Tumors that have too many HER2 receptors

  • The BRCA1 gene

Having the BRCA2 gene probably does not make the current cancer result in a worse outcome. However, having either BRCA gene increases the risk of developing a second breast cancer.

Prevention

Taking drugs that decrease the risk of breast cancer (chemoprevention) is recommended for the following women:

  • Those over age 60

  • Those who are over age 35 and have had a previous lobular carcinoma in situ

  • Those who have BRCA1 or BRCA2 gene mutations

  • Those who have a high risk of developing breast cancer based on their current age, age at menarche, age at first live childbirth, number of first-degree relatives with breast cancer, and results of prior breast biopsies

These drugs include tamoxifen and raloxifene. Women should ask their doctor about possible side effects before beginning chemoprevention. Risks of tamoxifen include cancer of the uterus (endometrial cancer), blood clots in the legs or lungs, cataracts, and possibly stroke. These risks are higher for older women. Raloxifene appears to be about as effective as tamoxifen in postmenopausal women and to have a lower risk of blood clots and cataracts. Both drugs may also increase bone density and thus benefit women who have osteoporosis. For postmenopausal women, raloxifene is an alternative to tamoxifen.

Treatment

Usually, treatment begins after the woman’s condition has been thoroughly evaluated, about a week or more after the biopsy. Treatment options depend on the stage and type of breast cancer and the receptors that the cancer has. However, treatment is complex because the different types of breast cancer differ greatly in characteristics such as growth rate, tendency to spread (metastasize), and response to various treatments. Also, much is still unknown about breast cancer. Consequently, doctors may have different opinions about the most appropriate treatment for a particular woman.

The preferences of a woman and her doctor affect treatment decisions. Women with breast cancer should ask for a clear explanation of what is known about the cancer and what is still unknown, as well as a complete description of treatment options. Then, they can consider the advantages and disadvantages of the different treatments and accept or reject the options offered. Losing some or all of a breast can be emotionally traumatic. Women must consider how they feel about this treatment, which can deeply affect their sense of wholeness and sexuality.

Doctors may ask women with breast cancer to participate in research studies investigating a new treatment. New treatments aim to improve the chances of survival or quality of life. All women who participate in a research study are treated because a new treatment is compared with other effective treatments. Women should ask their doctor to explain the risks and possible benefits of participation, so that they can make a well-informed decision.

Treatment usually involves surgery and often includes radiation therapy, chemotherapy, and hormone-blocking drugs.

Surgery

The cancerous tumor and varying amounts of the surrounding tissue are removed. There are two main options for removing the tumor: breast-conserving surgery and removal of the breast (mastectomy). For women with invasive cancer (stage I or higher), mastectomy is no more effective than breast-conserving surgery plus radiation therapy as long as the entire tumor can be removed during breast-conserving surgery. However, it is more important for doctors to be sure they remove the whole cancer than to risk leaving tissue that may contain cancer. Before surgery, chemotherapy may be used to shrink the tumor before removing it. This approach sometimes enables some women to have breast-conserving surgery rather than mastectomy.

Breast-conserving surgery

This surgery leaves as much of the breast intact as possible. There are several types:

  • Lumpectomy is removal of the tumor with a small amount of surrounding normal tissue.

  • Wide excision or partial mastectomy is removal of the tumor and a somewhat larger amount of surrounding normal tissue.

  • Quadrantectomy is removal of one fourth of the breast.

Breast-conserving surgery is usually combined with radiation therapy (see Radiation Therapy).

The major advantage of breast-conserving surgery is cosmetic: This surgery may help preserve body image. Thus, when the tumor is large in relation to the breast, this type of surgery is less likely to be useful. In such cases, removing the tumor plus some surrounding normal tissue means removing most of the breast. Breast-conserving surgery is usually more appropriate when tumors are small. In about 15% of women who have breast-conserving surgery, the amount of tissue removed is so small that little difference can be seen between the treated and untreated breasts. However, in most women, the treated breast shrinks somewhat and may change in contour.

Mastectomy

Mastectomy is the other main surgical option. There are several types. In all types, all breast tissue is removed, but which other tissues and how much of them are left in place or removed vary by type:

  • Skin-sparing mastectomy leaves the muscle under the breast and enough skin to cover the wound. Reconstruction of the breast is much easier if these tissues are left. The lymph nodes in the armpit are not removed.

  • Simple mastectomy leaves the muscle under the breast and the lymph nodes in the armpit.

  • Modified radical mastectomy consists of removing some lymph nodes in the armpit but leaves the muscle under the breast.

  • Radical mastectomy consists of removing the lymph nodes in the armpit and the muscle under the breast. This procedure is rarely done now unless the cancer has invaded the muscle under the breast.

Surgery for Breast Cancer

Surgery for breast cancer consists of two main options.

In breast-conserving surgery, only the tumor and an area of normal tissue surrounding it are removed. Breast-conserving surgery includes the following:

  • Lumpectomy: A small amount of surrounding normal tissue is removed.

  • Wide excision (partial mastectomy): A somewhat larger amount of the surrounding normal tissue is removed.

  • Quadrantectomy: One fourth of the breast is removed.

In mastectomy, all breast tissue is removed. But there several types. Which other tissues (skin, lymph nodes, muscle) and how much of them are removed vary by type.

Lymph node assessment

Doctors assess lymph nodes to determine whether cancer has spread to the lymph nodes in the armpit. If cancer is detected in the lymph nodes, it is more likely to have spread to other parts of the body. In such cases, different treatment may be needed.

Doctors first feel the armpit to check for enlarged lymph nodes. Depending on what doctors find, they may do one or more of the following:

  • Ultrasonography to check for lymph nodes that may be enlarged

  • A biopsy (by removing a lymph node or taking a sample of tissue with a needle using ultrasonography to guide placement of the needle)

  • Axillary lymph node dissection: Removal of many (typically 10 to 20) lymph nodes in the armpit

  • Sentinel lymph node dissection: Removal of only the lymph node or nodes that cancer cells are most likely to spread to

If doctors feel an enlarged lymph node in the armpit or are uncertain whether lymph nodes are enlarged, ultrasonography is done. If an enlarged lymph node is detected, a needle is inserted into it to remove a sample of tissue to be examined (fine-needle aspiration or core biopsy). Ultrasonography is used to guide placement of the needle. If cancer is detected, axillary lymph node dissection is usually done. Removing many lymph nodes in the armpit, even if they contain cancer, does not help cure the cancer. However, it does help remove cancer from the armpit and helps doctors decide what treatment to use.

If the biopsy after ultrasonography does not detect cancer, a sentinel lymph node biopsy is done because even if there are no cancer cells in a biopsy sample, cancer cells may be present in other parts of a lymph node.

If doctors cannot feel any enlarged lymph nodes in the armpit, they do a sentinel lymph node biopsy as part of the operation to remove the cancer.

A sentinel lymph node biopsy is usually done instead of axillary lymph node dissection to assess the lymph nodes that otherwise appear normal. For a sentinel lymph node biopsy, doctors inject a blue dye and a radioactive substance into the breast near the tumor. These substances map the pathway from the breast to the first lymph node (or nodes) in the armpit. Doctors then make a small incision in the armpit, enabling them to see the area around the tumor. Doctors look for lymph nodes that look blue and give off a radioactive signal (detected by a handheld device). These lymph nodes are the ones that cancer cells are most likely to have spread to. These nodes are called sentinel lymph nodes because they are the first to warn that cancer has spread. Doctors remove these nodes and send them to a laboratory to be checked for cancer. If the sentinel lymph nodes do not contain cancer cells, no other lymph nodes are removed.

If the sentinel nodes contain cancer, axillary lymph node dissection may be done, depending on various factors, such as

  • Whether a mastectomy is planned

  • How many sentinel nodes are present and whether the cancer has spread outside the node.

Axillary lymph node dissection may also be done based on what is found during surgery. Before the initial surgery is done, women may be asked whether they are willing to let the surgeon do more extensive surgery if cancer has spread to the lymph nodes. Otherwise, a second surgical procedure, if needed, is done later.

Removal of lymph nodes often causes problems because it affects the drainage of fluids in tissues. As a result, fluids may accumulate, causing persistent swelling (lymphedema) of the arm or hand. Arm and shoulder movement may be limited. If lymphedema develops, it is treated by specially trained therapists. They teach women how to massage the area, which may help the accumulated fluid drain, and how to apply a bandage, which helps keep fluid from reaccumulating. The affected arm should be used as normally as possible, except that the unaffected arm should be used for heavy lifting. Women should exercise the affected arm daily as instructed and bandage it overnight indefinitely.

Other problems that may occur after lymph nodes are removed include temporary or persistent numbness, a persistent burning sensation, and infection. If lymph nodes have been removed, women may be advised to ask health care practitioners not to insert catheters or needles in veins in the affected arm and not to measure blood pressure in that arm. These procedures makes lymphedema more likely to develop or worsen. Women are also advised to wear gloves whenever they are doing work that may scratch or injure the skin of the hand and arm on the side of the surgery. Avoiding injuries and infections can help reduce the risk of developing lymphedema.

What Is a Sentinel Lymph Node?

A network of lymphatic vessels and lymph nodes drain fluid from the tissue in the breast. The lymph nodes are designed to trap foreign or abnormal cells (such as bacteria or cancer cells) that may be contained in this fluid. Sometimes cancer cells pass through the nodes into the lymphatic vessels and spread to other parts of the body. Although fluid from breast tissue eventually drains to many lymph nodes, the fluid usually drains first through one or only a few nearby lymph nodes. Such lymph nodes are called sentinel lymph nodes because they are the first to warn that cancer has spread.

Breast reconstruction surgery

Breast reconstruction surgery may be done at the same time as a mastectomy or later. Most often, the surgery is done by inserting an implant (made of silicone or saline) or by reconstructing the breast using tissue taken from other parts of the woman’s body.

Before inserting an implant, doctors use a tissue expander, which resembles a balloon, to stretch the remaining chest skin and muscle to make room for the breast implant. The tissue expander is placed under the chest muscle during mastectomy. The expander has a small valve that health care practitioners can access by inserting a needle through the skin. Over the next several weeks, a salt solution (saline) is periodically injected through the valve to expand the expander a little at a time. After expansion is complete, the expander is surgically removed, and the implant is inserted.

Alternatively, tissues taken from the woman's body (such as muscle and tissues under the skin) can be used for reconstruction. These tissues are taken from the abdomen, back, or buttock and moved to the chest area to create the shape of a breast.

The nipple and surrounding skin are usually reconstructed in a separate operation done later. Various techniques can be used. They include using tissue from the woman's body and tattooing.

Surgery may also be done to modify (augment or reduce) the other breast to make both breasts match.

Rebuilding a Breast

After a general surgeon removes a breast tumor and the surrounding breast tissue (mastectomy), a plastic surgeon may reconstruct the breast. A silicone or saline implant may be used. Or in a more complex operation, tissue may be taken from other parts of the woman’s body, such as the abdomen, buttock, or back. Reconstruction may be done at the same time as the mastectomy—a choice that involves being under anesthesia for a longer time—or later—a choice that involves being under anesthesia a second time. Reconstruction of the nipple and surrounding skin is done later, often in a doctor's office. A general anesthetic is not required.

In many women, a reconstructed breast looks more natural than one that has been treated with radiation therapy, especially if the tumor was large.

If a silicone or saline implant is used and enough skin was left to cover it, the sensation in the skin over the implant is relatively normal. However, neither type of implant feels like breast tissue to the touch. If skin from other parts of the body is used to cover the breast, much of the sensation is lost. However, tissue from other parts of the body feels more like breast tissue than does a silicone or saline implant.

Silicone occasionally leaks out of its sack. As a result, an implant can become hard, cause discomfort, and appear less attractive. Also, silicone sometimes enters the bloodstream. Some women are concerned about whether the leaking silicone causes cancer in other parts of the body or rare diseases such as systemic lupus erythematosus (lupus). There is almost no evidence suggesting that silicone leakage has these serious effects, but because it might, the use of silicone implants has decreased, especially among women who have not had breast cancer.

Radiation Therapy

Radiation therapy is used to kill cancer cells at and near the site from which the tumor was removed, including nearby lymph nodes. Radiation therapy after mastectomy reduces the risk of cancer recurring near the site and in nearby lymph nodes. It may improve the chances of survival of women who have large tumors or cancer that has spread to several nearby lymph nodes.

Side effects include swelling in the breast, reddening and blistering of the skin in the treated area, and fatigue. These effects usually disappear within several months, up to about 12 months. Fewer than 5% of women treated with radiation therapy have rib fractures that cause minor discomfort. In about 1% of women, the lungs become mildly inflamed 6 to 18 months after radiation therapy is completed. Inflammation causes a dry cough and shortness of breath during physical activity that last for up to about 6 weeks. Lymphedema may develop after radiation therapy.

To improve radiation therapy, doctors are studying several new procedures. Many of these aim to target radiation to the cancer more precisely and spare the rest of the breast from the effects of radiation. In one procedure, tiny radioactive seeds are inserted through a catheter to the tumor site (called brachytherapy). This type of radiation therapy can be completed in only 5 days. In a procedure called intraoperative radiation therapy, radiation is applied during surgery. It is not yet clear whether these new procedures are as effective as traditional radiation therapy.

Drugs

Chemotherapy and hormone-blocking drugs can suppress the growth of cancer cells throughout the body. Chemotherapy and sometimes hormone-blocking drugs are used in addition to surgery and radiation therapy if cancer cells are detected in the lymph nodes and often if they are not. These drugs are often started soon after breast surgery and are continued for several months. Some, such as tamoxifen, may be continued for 5 to 10 years. These drugs delay the recurrence of cancer and prolong survival in most women. Analyzing the genetic material of the cancer (predictive genomic testing) may help predict which cancers are susceptible to chemotherapy or hormone-blocking drugs.

Chemotherapy

Chemotherapy is used to kill rapidly multiplying cells or slow their multiplication. Chemotherapy alone cannot cure breast cancer. It must be used with surgery or radiation therapy. Chemotherapy drugs are usually given intravenously in cycles. Sometimes they are given by mouth. Typically, a day of treatment is followed by 2 or more weeks of recovery. Using several chemotherapy drugs together is more effective than using a single drug. The choice of drugs depends partly on whether cancer cells are detected in nearby lymph nodes.

Commonly used drugs include cyclophosphamide, doxorubicin, epirubicin, 5-fluorouracil, methotrexate, and paclitaxel (see Table: Some Chemotherapy Drugs). Side effects (such as vomiting, nausea, hair loss, and fatigue) vary depending on which drugs are used. Chemotherapy can cause infertility and early menopause by destroying the eggs in the ovaries. Chemotherapy may also suppress the production of blood cells by the bone marrow and thus cause anemia or bleeding or increase the risk of infections. So drugs, such as filgrastim or pegfilgrastim, may by used to stimulate the bone marrow to produce blood cells.

Hormone-blocking drugs

These drugs interfere with the actions of estrogen or progesterone , which stimulate the growth of cancer cells that have estrogen or progesterone receptors. Hormone-blocking drugs may be used when cancer cells have these receptors, sometimes instead of chemotherapy. These drugs include

  • Tamoxifen: Tamoxifen, given by mouth, is a selective estrogen -receptor modulator. It binds with estrogen receptors and inhibits growth of breast tissue. In women who have estrogen receptor–positive cancer, tamoxifen, taken for 5 years, increases the likelihood of survival by about 25%, and 10 years of treatment may be even more effective. Tamoxifen, which is related to estrogen , has some of the benefits and risks of estrogen therapy taken after menopause (see Menopause:Hormone therapy). For example, it may decrease the risk of osteoporosis and fractures. It increases the risk of blood clots in the legs and lungs. It also substantially increases the risk of developing cancer of the uterus (endometrial cancer). Thus, if women taking tamoxifen have spotting or bleeding from the vagina, they should see their doctor. However, the improvement in survival after breast cancer far outweighs the risk of endometrial cancer. Tamoxifen, unlike estrogen therapy, may worsen the vaginal dryness or hot flashes that occur after menopause.

  • Aromatase inhibitors: These drugs (anastrozole, exemestane, and letrozole) inhibit aromatase (an enzyme that converts some hormones to estrogen ) and thus may reduce the production of estrogen . In postmenopausal women, these drugs may be more effective than tamoxifen. These drugs may be given with tamoxifen or after tamoxifen treatment has been completed. Aromatase inhibitors may increase the risk of osteoporosis.

Raloxifene can be taken to prevent breast cancer, but it is not used to treat it.

Monoclonal antibodies

Monoclonal antibodies are synthetic copies (or slightly modified versions) of natural substances that are part of the body’s immune system. These drugs enhance the immune system’s ability to fight cancer. Trastuzumab, a monoclonal antibody, is used with chemotherapy to treat metastatic breast cancer only when the cancer cells have too many HER2 receptors. This drug binds with HER2 receptors and thus helps prevent cancer cells from multiplying. Trastuzumab is usually taken for a year. It can weaken the heart muscle.

Treatment of Noninvasive Cancer (Stage 0)

For ductal carcinoma in situ, treatment usually consists of a mastectomy or removal of the tumor and a large amount of surrounding normal tissue (wide excision) with or without radiation therapy.

For lobular carcinoma in situ, treatment is less clear-cut. Any part of the tumor not removed during a biopsy is removed surgically, but whether other surgery is necessary or helpful is unknown. For many women, the preferred treatment is close observation with no treatment. Observation consists of a physical examination every 6 to 12 months for 5 years and once a year thereafter plus mammography once a year. No treatment is usually needed. Although invasive breast cancer may develop (the risk is 1.3% per year or 26% for 20 years), the invasive cancers that develop are usually not fast growing and can usually be treated effectively. Furthermore, because invasive cancer is equally likely to develop in either breast, the only way to eliminate the risk of breast cancer for women with lobular carcinoma in situ is removal of both breasts (bilateral mastectomy). Some women, particularly those who are at high risk of developing invasive breast cancer, choose this option.

Women with lobular carcinoma in situ are often given tamoxifen, a hormone-blocking drug, for 5 years. It reduces but does not eliminate the risk of developing invasive cancer. Postmenopausal women may be given raloxifene instead.

Treatment of Localized or Regional Invasive Cancer (Stages I Through III)

For cancers that have not spread beyond nearby lymph nodes, treatment almost always includes surgery to remove as much of the tumor as possible. Lymph node surgery or a sentinel lymph node biopsy is done to help stage the cancer.

A mastectomy or breast-conserving surgery is commonly used to treat invasive cancer that has spread extensively within the milk ducts (invasive ductal carcinoma). Breast-conserving surgery is used only when the tumor is not too large because the entire tumor plus some of the surrounding normal tissue must be removed. If the tumor is large, removing the tumor plus some surrounding normal tissue essentially results in removing most of the breast. Surgery may include standard lymph node surgery and is usually followed by radiation therapy.

Sometimes, when the tumor is too large for breast-conserving surgery, chemotherapy is given before surgery to reduce the size of the tumor. If chemotherapy reduces the size of the tumor enough, breast-conserving surgery may be possible.

Whether radiation therapy, chemotherapy, or both are used after surgery depends on many factors, such as how large the tumor is, whether menopause has occurred, whether the tumor has receptors for hormones, and how many lymph nodes contain cancer cells.

After surgery and radiation therapy, chemotherapy is usually given. If the cancer has estrogen receptors, women who are still menstruating are usually given tamoxifen, and postmenopausal women are given an aromatase inhibitor.

Treatment of Cancer That Has Spread (Stage IV)

Breast cancer that has spread beyond the lymph nodes is rarely cured, but most women who have it live at least 2 years, and a few live 10 to 20 years. Treatment extends life only slightly but may relieve symptoms and improve quality of life. However, some treatments have troublesome side effects. Thus, the decision of whether to be treated and, if so, which treatment to choose can be highly personal.

Most women are treated with chemotherapy or hormone-blocking drugs. However, chemotherapy, especially regimens that have uncomfortable side effects, are often postponed until symptoms (pain or other discomfort) develop or the cancer starts to worsen quickly. Pain is usually treated with analgesics. Other drugs may be given to relieve other symptoms. Chemotherapy or hormone-blocking drugs are given to relieve symptoms and improve quality of life rather than to prolong life. The most effective chemotherapy regimens for breast cancer that has spread include capecitabine, cyclophosphamide, docetaxel, doxorubicin, epirubicin, gemcitabine, paclitaxel, and vinorelbine.

Hormone-blocking drugs are preferred to chemotherapy in certain situations. For example, these drugs may be preferred when the cancer is estrogen receptor–positive, when cancer has not recurred for more than 2 years after diagnosis and initial treatment, or when cancer is not immediately life threatening. Different drugs are used in different situations:

  • Tamoxifen: For women who are still menstruating, tamoxifen is usually the first hormone-blocking drug used.

  • Aromatase inhibitors: For postmenopausal women who have estrogen receptor–positive breast cancer, aromatase inhibitors (such as anastrozole, letrozole, and exemestane) may be more effective as a first treatment than tamoxifen.

  • Progestins: These drugs, such as medroxyprogesterone or megestrol, may be used after aromatase inhibitors and tamoxifen when these drugs are no longer effective.

  • Fulvestrant: This drug may be used when tamoxifen is no longer effective. It destroys the estrogen receptors in cancer cells.

Alternatively, for women who are still menstruating, surgery to remove the ovaries, radiation to destroy them, or drugs to inhibit their activity (such as buserelin, goserelin, or leuprolide) may be used to stop estrogen production.

For cancers that have too many HER2 receptors and that have spread throughout the body, trastuzumab can be used alone or with chemotherapy such as paclitaxel or with hormone-blocking drugs. Trastuzumab can also be used with hormone-blocking drugs to treat women who have estrogen receptor–positive breast cancer.

In some situations, radiation therapy may be used instead of or before drugs. For example, if only one area of cancer is detected and that area is in a bone, radiation to that bone might be the only treatment used. Radiation therapy is usually the most effective treatment for cancer that has spread to bone, sometimes keeping it in check for years. It is also often the most effective treatment for cancer that has spread to the brain.

Surgery may be done to remove single tumors in other parts of the body (such as the brain) because such surgery can relieve symptoms. It is unclear whether removing the breast helps prolong life when cancer has spread to other parts of the body and has been treated and controlled.

Bisphosphonates (used to treat osteoporosis), such as pamidronate or zoledronate, reduce bone pain and bone loss and may prevent or delay bone problems that can result when cancer spreads to bone.

Treating Cancer Based on Type

Type

Possible Treatments

Ductal carcinoma in situ (cancer confined to the milk ducts of the breast)

Mastectomy

Removal of the tumor and a large amount of surrounding normal tissue (wide excision) with or without radiation therapy

Lobular carcinoma in situ (cancer confined to the milk-producing glands of the breast)

Surgery to remove the tumor

Observation plus regular examinations and mammograms

Tamoxifen or, for some postmenopausal women, raloxifene to reduce the risk of invasive cancer

Rarely, bilateral mastectomy (removal of both breasts) to prevent invasive cancers

Stages I and II (early-stage) cancer

Chemotherapy before surgery if the tumor is larger than 5 centimeters (about 2 inches) or is stuck to the chest wall

Breast-conserving surgery to remove the tumor and some surrounding tissue, usually followed by radiation therapy

Sometimes mastectomy with breast reconstruction

After surgery, chemotherapy, hormonal therapy, trastuzumab, or a combination, except in some postmenopausal women with tumors smaller than 1 centimeter (about 0.4 inches)

Stage III (locally advanced) cancer (including inflammatory breast cancer)

Chemotherapy or sometimes hormonal therapy before surgery to reduce the tumor’s size

Breast-conserving surgery or mastectomy if the tumor is small enough to be completely removed

Mastectomy for inflammatory breast cancer

Usually, radiation therapy after surgery

Sometimes chemotherapy, hormonal therapy, or both after surgery

Stage IV (metastatic) cancer

If cancer causes symptoms and occurs in several sites, hormone therapy, ovarian ablation therapy,* or chemotherapy

If the cancer cells have too many HER2 receptors, trastuzumab

Radiation therapy for the following:

  • Metastases to the brain

  • Metastases that recur in the skin

  • Metastases that occur in one area of bone and that cause symptoms

For metastases to bone, IV bisphosphonates (such as zoledronate or pamidronate) to reduce bone pain and bone loss

Paget disease of the nipple

Usually, the same as for other types of breast cancer

Occasionally, surgical removal of only the nipple with some surrounding normal tissue (local excision)

Breast cancer that recurs in the breast or nearby structures

Radical or modified radical mastectomy sometimes preceded by chemotherapy or hormone therapy

Phyllodes tumors

Wide excision

Radiation therapy if the tumor is cancerous

Mastectomy if the tumor is large

*Ovarian ablation therapy involves removing the ovaries or using drugs to suppress estrogen production by the ovaries.

Treatment of Specific Types of Breast Cancer

For inflammatory breast cancer, treatment usually consists of both chemotherapy and radiation therapy. Mastectomy is usually done.

For Paget disease of the nipple, treatment is usually similar to that of other types of breast cancer. It often involves simple mastectomy or breast-conserving surgery plus removal of the lymph nodes. Breast-conserving surgery is usually followed by radiation therapy. Less commonly, only the nipple with some surrounding normal tissue is removed.

For phyllodes tumors (whether cancerous or not), treatment usually consists of removing the tumor and a large amount of surrounding normal tissue (wide excision). If the tumor is large in relation to the breast, a simple mastectomy may be done. After surgical removal, about 20 to 35% of tumors recur near the same site. If the tumor is cancerous, radiation therapy is used.

Follow-up Care

After treatment is completed, follow-up physical examinations, including examination of the breasts, chest, neck, and armpits, are done every 3 months for 2 years, then every 6 months for 5 years from the date the cancer was diagnosed. Regular mammograms and breast self-examinations are also important. Women should promptly report certain symptoms to their doctor:

  • Any changes in their breasts

  • Pain

  • Loss of appetite or weight

  • Changes in menstruation

  • Bleeding from the vagina (if not associated with menstrual periods)

  • Blurred vision

  • Any symptoms that seem unusual or that persist

Diagnostic procedures, such as chest x-rays, blood tests, bone scans, and computed tomography (CT), are not needed unless symptoms suggest the cancer has recurred.

The effects of treatment for breast cancer cause many changes in a woman’s life. Support from family members and friends can help, as can support groups. Counseling may be helpful.

End-of-Life Issues

For women with metastatic breast cancer, quality of life may deteriorate, and the chances that further treatment will prolong life may be small. Staying comfortable may eventually become more important than trying to prolong life. Cancer pain can be adequately controlled with appropriate drugs (see Symptoms During a Fatal Illness : Pain). So if women are having pain, they should ask their doctor for treatment to relieve it. Treatments can also relieve other troublesome symptoms, such as constipation, difficulty breathing, and nausea. Psychologic and spiritual counseling may also help.

Women with metastatic breast cancer should prepare advance directives indicating the type of care they desire in case they are no longer able to make such decisions (see Advance Directives). Also, making or updating a will is important.

Resources In This Article

Drugs Mentioned In This Article

  • Generic Name
    Select Brand Names
  • EVISTA
  • NOLVADEX
  • CRINONE
  • NEULASTA
  • CARAC
  • ELLENCE
  • CYTOXAN (LYOPHILIZED)
  • NEUPOGEN
  • OTREXUP
  • TAXOL
  • AROMASIN
  • ARIMIDEX
  • FEMARA
  • HERCEPTIN
  • PROVERA
  • MEGACE
  • No US brand name
  • XELODA
  • NAVELBINE
  • AREDIA
  • ZOLADEX
  • GEMZAR
  • FASLODEX
  • LUPRON
  • TAXOTERE