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Breast cancer

Definition

Breast cancer is a malignant (cancerous) growth that begins in the tissues of the breast. Over the course of a lifetime, one in eight women will be diagnosed with breast cancer.

Causes, incidence, and risk factors

There are several different types of breast cancer.

Ductal carcinoma begins in the cells lining the ducts that bring milk to the nipple and accounts for more than 75% of breast cancers.
Lobular carcinoma begins in the milk-secreting glands of the breast but is otherwise fairly similar in its behavior to ductal carcinoma. Other varieties of breast cancer can arise from the skin, fat, connective tissues, and other cells present in the breast.

Some women have what is known as HER2-positive breast cancer. HER2, short for human epidermal growth factor receptor-2, is a gene that helps control cell growth, division, and repair. When cells have too many copies of this gene, cell growth speeds up. It’s believed that HER2 plays a key role in turning healthy cells into cancerous ones. Some women with breast cancer have too much HER2, and are therefore considered HER2-positive. Research suggests that women with HER2-positive breast cancer have a more aggressive disease and a higher risk of recurrence than those who have HER2 negative breast cancer.

Risk factors for breast cancer include:

Age and Gender -- As with most cancers, age is a significant factor. In fact, 77% of new cases and 84% of breast cancer deaths occur in women aged 50 and older. More than 80% of breast cancer cases occur in women over 50. Less than 1% of breast cancers occur in men. The risk of breast cancer is clearly related to hormonal influences, but how these affect the disease and particularly types of the disease is not yet clear.
Genetic Factors and Family History of Breast Cancer -- Some families appear to have a genetic tendency for breast cancer. Two variant genes have been found that appear to account for this: BRCA1 and BRCA2. The genes p53 and BARD1 also appear to be important. Researchers have identified several other defective genes that may cause breast cancer, including BRCA3 and Noey2 (which is a disease inherited only from the father's side of the family). These discoveries suggest that breast cancer occurs when the body’s anti-cancer surveillance and control systems, which normally get rid of abnormal cells, fail to work. The body's reduced ability to get rid of abnormal cells leads to damage that gradually accumulates. Women carrying mutated BRCA1 and/or BRCA2 genes start with pre-existing dysfunction of this system and have a "head start" in this damaging process. Hormones are important because they encourage cell growth. High levels of hormones during a woman's reproductive years, especially when they are not interrupted by the hormonal changes of pregnancy, appear to increase the chances that genetically damaged cells will grow and cause cancer.
Early Menstruation and Late Menopause -- Women who get their periods early (before age 12) or went through menopause late (after age 55) are at higher risk. Also, women who have never had children or who had them only after the age of 30 have an increased risk.
Oral Contraceptives (birth control pills) -- Birth control pills may slightly increase the risk for breast cancer, depending on age, length of use, and other factors. No one knows how long the effects of the pill last after stopping it.
Hormone Replacement Therapy(HRT) -- Use of HRT has been shown to increase the risk of breast cancer.
Obesity -- Obesity is controversial as a risk factor. Some studies report obesity as a risk of breast cancer, possibly associated with higher levels of estrogen production in obese women.
Alcohol Consumption -- Significant alcohol use (more than 1-2 drinks a day) has been associated with an increased risk of breast cancer.
Chemicals -- Some studies have pointed to exposure to estrogen-like chemicals that are found in pesticides and other industrial products as a possible increased risk of breast cancer.
DES -- Women who took diethylstilbestrol (DES) to prevent miscarriage may have an increased risk of breast cancer after age 40.
Radiation -- People exposed to radiation, particularly during childhood, may face an increased risk for breast cancer in adulthood. Especially at risk are those that received chest irradiation for prior cancers.
Additional Risk Factors -- Some studies show previous breast, uterine, ovarian, or colon cancer, and a strong history of cancer in the family may increase the risk for breast cancer. Such history may indicate genetic factors described above.

The Gail Model is a simple breast cancer risk assessment tool that is available online and takes into account the most important risk factors. A number of other models are also used.

Symptoms

Breast lump or breast mass noted upon breast exam -- usually painless, firm to hard and usually with irregular borders
Lump or mass in the armpit
A change in the size or shape of the breast
Abnormal nipple discharge
- Usually bloody or clear-to-yellow or green fluid
- May look like pus (purulent)
Change in the color or feel of the skin of the breast, nipple, or areola
- Dimpled, puckered, or scaly
- Retraction, "orange peel" appearance
- Redness
- Accentuated veins on breast surface
Change in appearance or sensation of the nipple
- Pulled in (retraction), enlargement, or itching
Breast pain, enlargement, or discomfort on one side only
Any breast lump, pain, tenderness, or other change in a man
Symptoms of advanced disease are bone pain, weight loss, swelling of one arm, and skin ulceration

Signs and tests

Any worrisome breast changes should be confirmed and investigated by a medical professional. After getting as much information as possible about the symptom and any risk factors, the physician performs a physical examination including both breasts, armpits, and the area of the neck and chest. Additional tests and treatment may then be recommended:

X-ray mammography may help identify the breast mass.
Ultrasound (sonogram) can show whether the lump is solid or fluid-filled.
Needle aspiration or needle biopsy of breast lumps can demonstrate if they are fluid-filled and provide material to send to the laboratory for analysis. In the case of very small abnormalities visible only on mammography, special techniques are necessary.
A surgical biopsy or breast lump removal provides a portion or all of a breast lump for laboratory study.

If breast cancer is diagnosed, additional testing is performed, including chest X-ray and blood tests. Surgery, radiation, chemotherapy, or a combination of these may then be recommended, not only for treatment, but also to help determine the stage of disease. Staging is important to help guide future treatment and follow-up, and to give some idea of what to expect in the future.

Stages of Breast Cancer (from the American Joint Committee on Cancer):

STAGE 0. In Situ ("in place") disease in which the cancerous cells are in their original location within normal breast tissue. Known as either DCIS (ductoral carcinoma in situ) or LCIS (lobular carcinoma in situ) depending on the type of cells involved and the location, this is a pre-cancerous condition, and only a small percentage of DCIS tumors progress to become invasive cancers. There is some controversy within the medical community on how to best treat DCIS.
STAGE I. Tumor less than 2 cm in diameter with no spread beyond the breast
STAGE IIA. Tumor 2 to 5 cm in size without spread to axillary (armpit) lymph nodes or tumor less than 2 cm in size with spread to axillary lymph nodes
STAGE IIB. Tumor greater than 5 cm in size without spread to axillary lymph nodes or tumor 2 to 5 cm in size with spread to axillary lymph nodes
STAGE IIIA. Tumor smaller than 5 cm in size with spread to axillary lymph nodes which are attached to each other or to other structures, or tumor larger than 5 cm in size with spread to axillary lymph nodes
STAGE IIIB. The tumor has penetrated outside the breast to the skin of the breast or of the chest wall or has spread to lymph nodes inside the chest wall along the sternum
STAGE IV. A tumor of any size with spread beyond the region of the breast and chest wall, such as to liver, bone, or lungs

Many additional factors besides staging can influence the recommended treatment and the likely outcome. These can include the precise cell type and appearance of the cancer, whether the cancer cells respond to hormones, and the presence or absence of genes known to cause breast cancer.

Treatment

The choice of initial treatment is based on many factors. For stage I, II, or III cancers, the main considerations are to adequately treat the cancer and prevent a recurrence either at the place of the original tumor (local) or elsewhere in the body (metastatic). For stage IV cancer, the goal is to improve symptoms and prolong survival. However, in most cases, stage IV breast cancer cannot be cured.

Surgery may consist only of breast lump removal (lumpectomy ), or partial, total, or radical mastectomy, usually with the removal of one or more lymph nodes from the armpit (axilla). Special procedures to find the most likely lymph nodes to which cancer may have spread (sentinel nodes) are often used.
Radiation therapy can be directed at the tumor, the breast, the chest wall, or other tissues known or suspected to have remaining cancer cells.
Chemotherapy is often used to kill cancer cells that may still remain in the breast or that may have already spread to other parts of the body.
Biologicals are an entirely new type of anti-cancer drug. Biologicals can be used alone or with chemotherapy. Trastuzumab (Herceptin) is an example of this class of drugs. It affects how cancer cells function and grow. Some 20 - 25% of breast cancers respond to trastuzumab. Trastuzumab is not chemotherapy, but it may be combined with chemotherapy. Recent studies show that adding trastuzumab to chemotherapy or treating with trastuzumab after chemotherapy helps prevent the cancer from coming back and can make people who had HER2-positive breast cancer live longer.
Hormonal therapy with tamoxifen is used to block the effects of estrogen that may otherwise help breast cancer cells to survive and grow. Most women with breast cancers which express estrogen or progesterone on their surface benefit from treatment with tamoxifen. A new class of medicines called aromatase inhibitors, such as Aromasin, have been shown to be as good or possibly even better than tamoxifen in women with stage IV breast cancer.

Most women receive a combination of these treatments. For stage 0 breast cancer, mastectomy or lumpectomy plus radiation is the standard treatment. However, there is some controversy on how best to treat DCIS. For stage 1 and 2 disease, lumpectomy (plus radiation) or mastectomy with at least "sentinel node" lymph node removal is standard treatment.

Chemotherapy with or without trastuzumab, hormone therapy, or both may be recommended following surgery. The presence of breast cancer in the axillary lymph nodes is very useful for staging and the appropriate follow-up treatment.

Stage III patients are usually treated with surgery followed by chemotherapy with or without hormonal therapy. Radiation therapy may also be considered under special circumstances.

Stage IV breast cancer may be treated with surgery, radiation, chemotherapy, hormonal therapy, or a combination of these (depending on the situation).

Support Groups

The stress of breast cancer can often be helped by joining a support group where members share common experiences and problems. See cancer support group.

Expectations (prognosis)

The clinical stage of breast cancer is the best indicator for prognosis (probable outcome), in addition to some other factors. Five-year survival rates for individuals with breast cancer who receive appropriate treatment are approximately:

95% for stage 0
88% for stage I
66% for stage II
36% for stage III
7% for stage IV

The axillary (armpit) lymph nodes are the main passageway that breast cancer cells must use to reach the rest of the body. Their involvement at any time strongly affects the prognosis.

Chemotherapy and hormone therapy can improve prognosis in all patients and increase the likelihood of cure in patients with stage I, II, and III disease.

Complications

Even with aggressive and appropriate treatments, breast cancer often spreads (metastasizes) to other parts of the body such as the lungs, liver and bones. The recurrence rate is about 5% after total mastectomy and removing armpit lymph nodes when the nodes are found not to have cancer. The recurrence rate is 25% in those with similar treatment when the nodes have cancer.

Other complications can be the result of surgery, altered drainage of the lymph from the arm, radiation changes and treatment with chemotherapy and tamoxifen. But the results of delaying or avoiding early detection and treatment of breast cancer are far more distressing and often deadly.

Calling your health care provider

See your health care provider if you are a man or a woman who notices any of the symptoms which could indicate breast cancer or:

If you are a woman, 40 years or older, and have not had a mammogram in the last year.
If you are a woman, 35 years or older, and have a mother or sister with breast cancer, or have already had cancer of the breast, uterus, ovary, or colon.
If you are a woman, 20 years or older, and do not know how or need help to learn how to perform a breast self-examination.

Prevention

Many risk factors cannot be controlled. Some experts in the field of diet and cancer agree that changes in diet and lifestyle may reduce the incidence of cancer generally.

Efforts have focused on early detection since breast cancer is more easily treated and often curable if it is found early. Breast self-examination (BSE), clinical breast examination (CBE) by a medical professional, and screening mammography are the three tools of early detection. Women who carry the BRCA mutations have several effective options for screening and prevention.

Most recommend breast self-examinations (BSE) once a month -- the week following your menstrual period if you are age 20 or older.

Regular clinical breast examinations (CBE) by a health professional are recommended for women between ages 20 and 39, at least every 3 years. After age 40, women should have a CBE by a health professional every year.

Mammography is the most effective way of detecting breast cancer early. The American Cancer Society recommends mammogram screening every year for all women age 40 and older.

The National Cancer Institute (NCI) recommends mammogram screening every 1-2 years for women age 40 and older. For those with risk factors, including a close family member with the disease, annual mammograms should begin 10 years earlier than the age at which the relative was diagnosed.

Questions have been raised about the benefit of screening mammography. Some respected medical organizations such as PDQ, part of the NCI, no longer recommend screening mammography. This is a topic fraught with controversy, and a woman needs to have an informed and balanced discussion with her doctor, along with doing additional reading and researching on her own, to determine if mammography is right for her.

Two drugs are being studied currently that have been shown to reduce the risk of breast cancer: tamoxifen (Nolvadex ®) and raloxifene (Evista ®). Both are anti-estrogens in breast tissue.

Tamoxifen is already widely used to prevent recurrence in women who have been treated for breast cancer. Many other newer hormonal agents, such as aromatase inhibitors and others, are being used after Tamoxifen is stopped, or even in place of Tamoxifen. For some women at very high risk of breast cancer, preventive use of these drugs may be appropriate. This should be discussed with a qualified physician.

Preventive Mastectomy, which is the surgical removal of one or both breasts, is an option to prevent breast cancer for women who are at very high risk for breast cancer.

Possible candidates for this procedure are women who have already had one breast removed due to cancer, women with a strong family history of breast cancer and those who have a mutation in genes p53, BRCA1, or have gene BRCA2.

For additional information on breast cancer, see the website of the American Cancer Society.

References

Piccart-Gebhart MJ, Procter M, Leyland-Jones B, et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med. 2005 Oct 20;353(16):1659-72.

Romond EH, Perez EA, Bryant J, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005 Oct 20;353(16):1673-84.

Menard S, Pupa SM, Campiglio M, Tagliabue E. Biologic and therapeutic role of HER2 in cancer. Oncogene. 2003 Sep 29;22(42):6570-8.