breast cancer

Breast Cancer Screening and treatments every woman - and man - should know.

More about Breast Cancer: Demographics Causes and symptoms Diagnosis Treatment Prognosis Prevention Special Concerns Resources

Definition

Breast cancer is caused by the development of malignant cells in the breast. The malignant cells originate in the lining of the milk glands or ducts of the breast (ductal epithelium), defining this malignancy as a cancer. Cancer cells are characterized by uncontrolled division leading to abnormal growth and the ability of these cells to invade normal tissue locally or to spread throughout the body, in a process called metastasis.

Description

Breast cancer arises in the milk-producing glands of the breast tissue. Groups of glands in normal breast tissue are called lobules. The products of these glands are secreted into a ductal system that leads to the nipple. Depending on where in the glandular or ductal unit of the breast the cancer arises, it will develop certain characteristics that are used to sub-classify breast cancer into types. The pathologist will denote the subtype at the time of evaluation with the microscope. Ductal carcinoma begins in the ducts, lobular carcinoma has a pattern involving the lobules or glands. The more important classification is related to the evaluated tumor's capability to invade, as this characteristic defines the disease as a true cancer. The stage before invasive cancer is called in situ, meaning that the early malignancy has not yet become capable of invasion. Thus, ductal carcinoma in situ is considered a minimal breast cancer.

The primary tumor begins in the breast itself but once it becomes invasive, it may progress beyond the breast to the regional lymph nodes or travel (metastasize) to other organ systems in the body and become systemic in nature. Lymph is the clear, protein-rich fluid that bathes the cells throughout the body. Lymph will work its way back to the bloodstream via small channels known as lymphatics. Along the way, the lymph is filtered through cellular stations known as nodes, thus they are called lymph nodes. Nearly all organs in the body have a primary lymph node group filtering the tissue fluid, or lymph, that comes from that organ. In the breast, the primary lymph nodes are under the armpit, or axilla. Classically, the primary tumor begins in the breast and the first place to which it is likely to spread is the regional lymph nodes. Cancer, as it invades in its place of origin, may also work its way into blood vessels. If cancer gets into the blood vessels, the blood vessels provide yet another route for the cancer to spread to other organs of the body.

Breast cancer follows this classic progression though it often becomes systemic or widespread early in the course of the disease. By the time one can feel a lump in the breast it is often 0.4 inches, or one centimeter, in size and contains roughly a million cells. It is estimated that a tumor of this size may take one to five years to develop. During that time, the cancer may metastasize, or spread by lymphatics or blood to areas elsewhere in the body.

When primary breast cancer spreads, it may first go to the regional lymph nodes under the armpit, the axillary nodes. If this occurs, regional metastasis exists. If it proceeds elsewhere either by lymphatic or blood-borne spread, the patient develops systemic metastasis that may involve a number of other organs in the body. Favorite sites of systemic involvement for breast cancer are the lung, bones, liver, and the skin and soft tissue. As it turns out, the presence of, and the actual number of, regional lymph nodes containing cancer remains the single best indicator of whether or not the cancer has become widely metastatic. Because tests to discover metastasis in other organs may not be sensitive enough to reveal minute deposits, the evaluation of the axilla for regional metastasis becomes very important in making treatment decisions for this disease.

If breast cancer spreads to other major organs of the body, its presence will compromise the function of those organs. Death is the result of extreme compromise of vital organ function.

— Richard A. McCartney, M.D.

Key Terms: Adjuvant therapy, Aneuploid, Aspiration biopsy, Benign, Biopsy, Estrogen-receptor assay, Hormones, Hormone therapy, Lumpectomy, Lymph nodes, Malignant, Mammography.

Definition

Breast cancer is caused by the development of malignant cells in the breast. The malignant cells often originate in the lining of the milk glands or ducts of the breast (ductal epithelium). Cancer cells are characterized by uncontrolled division leading to abnormal growth and the ability of these cells to invade normal tissue locally or to spread throughout the body, in a process called metastasis.

Description

Breast cancer often arises in the milk-producing glands of the breast tissue. Groups of glands in normal breast tissue are called lobules. The products of these glands are secreted into a ductal system that leads to the nipple. Depending on where in the glandular or ductal unit of the breast the cancer arises, it will develop certain characteristics that are used to sub-classify breast cancer into types. The pathologist will denote the subtype at the time of evaluation with the microscope. Ductal carcinoma begins in the ducts, and lobular carcinoma has a pattern involving the lobules or glands. The more important classification is related to the evaluated tumor's capability to invade, as this characteristic defines the disease as a true cancer. The stage before invasive cancer is called in situ, meaning that the early malignancy has not yet become capable of invasion. Thus, ductal carcinoma in situ is considered a minimal breast cancer.

How Breast Cancer Spreads

The primary tumor begins in the breast itself but once it becomes invasive, it may progress beyond the breast to the regional lymph nodes or travel (metastasize) to other organ systems in the body and become systemic in nature. Lymph is the clear, protein-rich fluid that bathes the cells throughout the body. Lymph will work its way back to the bloodstream via small channels known as lymphatics. Along the way, the lymph is filtered through cellular stations known as nodes, thus they are called lymph nodes. Nearly all organs in the body have a primary lymph node group filtering the tissue fluid, or lymph, that comes from that organ. In the breast, the primary lymph nodes are under the armpit, or axilla. Classically, the primary tumor begins in the breast and the first place to which it is likely to spread is the regional lymph nodes. Cancer, as it invades in its place of origin, may also work its way into blood vessels. If cancer gets into the blood vessels, the blood vessels provide yet another route for the cancer to spread to other organs of the body.

Breast cancer follows this classic progression though it often becomes systemic or widespread early in the course of the disease. By the time one can feel a lump in the breast it is often 0.4 inches, or one centimeter, in size and contains roughly a million cells. It is estimated that a tumor of this size may take one to five years to develop. During that time, the cancer may metastasize.

When primary breast cancer spreads, it may first go to the regional lymph nodes under the armpit, the axillary nodes. If this occurs, regional metastasis exists. If it proceeds elsewhere either by lymphatic or blood-borne spread, the patient develops systemic metastasis that may involve a number of other organs in the body. Common sites of systemic involvement for breast cancer are the lung, bones, liver, and the skin and soft tissue. As it turns out, the presence of, and the actual number of, regional lymph nodes containing cancer remains the single best indicator of whether or not the cancer has become widely metastatic. Because tests to discover metastasis in other organs may not be sensitive enough to reveal minute deposits, the evaluation of the axilla for regional metastasis becomes very important in making treatment decisions for this disease.

If breast cancer spreads to other major organs of the body, its presence will compromise the function of those organs. Death can result from compromise of these vital organs' functions.

Demographics

Every woman is at risk for breast cancer. If she lives to be 85, there is a one out of nine chance that she will develop the condition sometime during her life. As a woman ages, her risk of developing breast cancer rises dramatically regardless of her family history. The breast cancer risk of a 25-year-old woman is only one out of 19,608; by age 45, it is one in 93. In fact, less than 5% of cases are discovered before age 35 and the majority of all breast cancers are found in women over age 50.

In 2002, 200,000 new cases of breast cancer were diagnosed. About 45,000 women die of breast cancer each year, accounting for 16% of deaths caused by cancer in women. However, deaths from breast cancer are declining in recent years, a reflection of earlier diagnosis from screening mammograms and improving therapies.

Causes and Symptoms

There are a number of risk factors for the development of breast cancer, including:

• family history of breast cancer in mother or sister
• early onset of menstruation and late menopause
• reproductive history: women who had no children or have children after age 30 and women who have never breastfed have increased risk
• history of abnormal breast biopsies

Though these are recognized risk factors, it is important to note that more than 70% of women who get breast cancer have no known risk factors. Having several risk factors may boost a woman's chances of developing breast cancer, but the interplay of predisposing factors is complex. In addition to those accepted factors listed above, some studies suggest that high-fat diets, obesity, or the use of alcohol may contribute to the risk profile. Another factor that may contribute to a woman's risk profile is hormone replacement therapy (HRT).

HRT provides significant relief of menopausal symptoms, prevention of osteoporosis, and possibly protection from cardiovascular disease and stroke. While physicians have long known a small increased risk for breast cancer was linked to use of HRT, a landmark study released in 2003 proved the risk was greater than thought. The Women's Health Initiative found that even relatively short-term use of estrogen plus progestin is associated with increased risk of breast cancer, diagnosis at a more advanced stage of the disease, and a higher number of abnormal mammograms. The longer a woman used HRT, the more her risk increased.

Of all the risk factors listed above, family history is the most important. In The Biological Basis of Cancer, the authors estimate that probably about half of all familial breast cancer cases (families in which there is a high breast cancer frequency) have mutations affecting the genes BRCA-1 and BRCA-2. In 2003, scientists discovered a third gene called EMSY. However, breast cancer due to heredity is only a small proportion of breast cancer cases; only 5%–10% of all breast cancer cases will be women who inherited a susceptibility through their genes. Nevertheless, when the family history is strong for development of breast cancer, a woman's risk is increased.

Not all lumps detected in the breast are cancerous. Fibrocystic changes in the breast are extremely common. Also known as fibrocystic condition of the breast, fibrocystic changes are a leading cause of non-cancerous lumps in the breast. Fibrocystic changes also cause symptoms of pain, swelling, or discharge and may become evident to the patient or physician as a lump that is either solid or filled with fluid. Complete diagnostic evaluation of any significant breast abnormality is mandatory because though women commonly develop fibrocystic changes, breast cancer is common also, and the signs and symptoms of fibrocystic changes overlap with those of breast cancer.

Diagnosis

The diagnosis of breast cancer is accomplished through biopsy of a suspicious lump or mammographic abnormality that has been identified. (A biopsy is the removal of tissue for examination by a pathologist. A mammogram is a low-dose, 2-view, x-ray examination of the breast.) The patient may be prompted to visit her doctor upon finding a lump in a breast, or she may have noticed skin dimpling, nipple retraction, or discharge from the nipple. The patient may not have noticed a symptom or abnormality, and a lump was detected by a screening mammogram.

When a Patient Has No Signs or Symptoms

Screening involves the evaluation of women who have no symptoms or signs of a breast problem. Mammography has been helpful in detecting breast cancer that cannot be identified on physical examination. However, 10%–13% of breast cancer does not show up on mammography, and a similar number of patients with breast cancer have an abnormal mammogram and a normal physical examination. These figures emphasize the need for examination as part of the screening process.

Screening

It is recommended that women get into the habit of doing monthly breast self examinations to detect any lump at an early stage. If an uncertainty or a lump is found, evaluation by an experienced physician and a mammogram is recommended. The American Cancer Society (ACS) has made recommendations for the use of mammography on a screening basis. In 2003, the ACS updated its guidelines concerning screening mammograms. The most notable change was that women should begin annual screening at age 40 instead of age 50. (in the past, the ACS, recommended beginning mammograms at age 40, but only ever one or two years instead of annually.) Women at higher risk for breast cancer should benefit from beginning screenings at earlier ages and at more frequent intervals.

Because of the greater awareness of breast cancer in recent years, screening evaluations by examinations and mammography are performed much more frequently than in the past. The result is that the number of breast cancers diagnosed increased, but the disease is being diagnosed at an earlier stage than previously. The earlier the stage of disease at the time it is discovered, the better the long-term outcome (prognosis) becomes.

When a Patient Has Physical Signs or Symptoms

A common finding that leads to diagnosis is the presence of a lump within the breast. Skin dimpling, nipple retraction, or discharge from the nipple are less frequent initial findings prompting biopsy. Though bloody nipple discharge is distressing, it is most often caused by benign disease. Skin dimpling or nipple retraction in the presence of an underlying breast mass on examination is a more advanced finding. Actual skin involvement, with edema or ulceration of the skin, are late findings.

The presence of a breast lump is a common sign of breast cancer. If the lump is suspicious and the patient has not had a mammogram by this point, a study should be done on both breasts prior to anything else so that the original characteristics of the lesion can be studied. The opposite breast should also be evaluated mammographically to determine if other problems exist that were undetected by physical examination.

Whether an abnormal screening mammogram or one of the signs mentioned above followed by a mammogram prompted suspicion, the diagnosis is established by obtaining tissue by biopsy of the area. There are different types of biopsy, each utilized with its own indication depending on the presentation of the patient. If signs of widespread metastasis are already present, biopsy of the metastasis itself may establish diagnosis.

Biopsy

Depending on the situation, different types of biopsy may be performed. The types include incisional and excisional biopsies. In an incisional biopsy, the physician takes a sample of tissue, and in excisional biopsy, the mass is removed. Fine needle aspiration biopsy and core needle biopsy are kinds of incisional biopsies.

Fine Needle Aspiration Biopsy

In a fine needle aspiration biopsy, a fine-gauge needle may be passed into the lesion and cells from the area suctioned into the needle can be quickly prepared for microscopic evaluation (cytology). (The patient experiencing nipple discharge can have a sample taken of the discharge for cytological evaluation, also.) Fine needle aspiration is a simple procedure that can be done under local anesthesia, and will tell if the lesion is a fluid-filled cyst or whether it is solid. The sample obtained will yield much diagnostic information. Fine needle aspiration biopsy is an excellent technique when the lump is palpable and the physician can easily hit the target with the needle. If the lesion is a simple cyst, the fluid will be evacuated and the mass will disappear. If it is solid, the diagnosis may be obtained. Care must be taken, however, because if the mass is solid and the specimen is non-malignant, a complete removal of the lesion may be appropriate to be sure.

Core Needle Biopsy

Core needle biopsies are also obtained simply under local anesthesia. The larger piece of tissue obtained with its preserved architecture may be helpful in confirming the diagnosis short of open surgical removal. An open surgical incisional biopsy is rarely needed for diagnosis because of the needle techniques. If there remains question as to diagnosis, a complete open surgical biopsy may be required.

Excisional Biopsy

When performed, the excisional, (complete removal) biopsy is a minimal outpatient procedure often done under local anesthesia.

Non-Palpable Lesions

As screening increases, non-palpable lesions demonstrated only by mammography are becoming more common. The use of x rays and computers to guide the needle for biopsy or to place markers for the surgeon performing the excisional biopsy are commonly employed. Some benign lesions can be fully removed by multiple directed core biopsies. These techniques are very appealing because they are minimally invasive; however, the physician needs to be careful to obtain a good sample.

Other Tests

If a lesion is not palpable and has simple cystic characteristics on mammography, ultrasound may be utilized both to determine that it is a cyst and to guide its evacuation. Ultrasound may also be used in some cases to guide fine needle or core biopsies of the breast.

Computed tomography (CT) scans have only rare in the evaluation of breast lesions. Magnetic resonance imaging (MRI) has been used more often in recent years to follow up on suspicious findings from mammograms or for certain patients.

Clinical Staging, Treatments, and Prognosis

Staging

Once diagnosis is established, before treatment is rendered, more tests are done to determine if the cancer has spread beyond the breast. These tests include a chest xray and blood count with liver function tests. Along with the liver function measured by the blood sample, the level of alkaline phosphatase, an enzyme from bone, is also determined. A radionuclear bone scan may be ordered. This test looks at the places in the body to which breast cancer usually metastasizes. A CT scan may also be ordered. The physician will do a careful examination of the axilla to assess likelihood of regional metastasis but unfortunately this exam is not very accurate. Since the axillary node status is the best reflection of possible widespread disease, some or all of these nodes may be removed at the time of surgical treatment. However, recent studies show great success with sentinel lymph node biopsy. This technique removes the sentinel lymph node, or that lymph node that receives fluid drainage first from the area where the cancer is located. If this node is free of cancer, staging can be assigned accordingly. This method saves women the discomfort and side effects associated with removing additional lymph nodes in her armpit.

Using the results of these studies, clinical stage is defined for the patient. This helps define treatment protocol and prognosis. After surgical treatment, the final, or pathologic, stage is defined as the true axillary lymph node status is known. Detailed staging criteria are available from the American Joint Commission on Cancer Manual and are generalized here:

• Stage 1—The cancer is no larger than 2 cm (0.8 in) and no cancer cells are found in the lymph nodes.
• Stage 2—The cancer is between 2 cm and 5 cm, and the cancer has spread to the lymph nodes.
• Stage 3A—Tumor is larger than 5 cm (2 in) or is smaller than 5 cm, but has spread to the lymph nodes, which have grown into each other.
• Stage 3B—Cancer has spread to tissues near the breast, (local invasion), or to lymph nodes inside the chest wall, along the breastbone.
• Stage 4—Cancer has spread to skin and lymph nodes beyond the axilla or to other organs of the body.

Treatment

Surgery, radiation, and chemotherapy are all utilized in the treatment of breast cancer. Depending on the stage, they will be used in different combinations or sequences to effect an appropriate strategy for the type and stage of the disease being treated.

Surgery

Historically, surgical removal of the entire breast and axillary contents along with the muscles down to the chest wall was performed as the lone therapy, (radical mastectomy). In the last 25 years, as it has been appreciated that breast cancer often spreads early, surgery remains a primary option but other therapies have risen in importance.

Today, surgical treatment is best thought of as a combination of removal of the primary tumor and staging of the axillary lymph nodes. A modified radical mastectomy involves removing the whole breast along with the entire axillary contents but not the muscles of the chest wall.

If the tumor is less than 4 cm (1.5 in) in size and located so that it can be removed without destroying the reasonable cosmetic appearance of the residual breast, just the primary tumor and a rim of normal tissue will be removed. The axillary nodes will still be removed for staging purposes, usually through a separate incision. Because of the risk of recurrence in the remaining breast tissue, radiation is used to lessen the chance of local recurrence. This type of primary therapy is known as lumpectomy, (or segmental mastectomy), and axillary dissection.

Sentinel lymph node biopsy, a technique for identifying which nodes in the axilla drain the tumor, has been developed to provide selective sampling and further lessen the degree of surgical trauma the patient experiences.

When patients are selected appropriately based on the preoperative clinical stage, all of these surgical approaches have been shown to produce similar results. In planning primary surgical therapy, it is imperative that the operation be tailored to fit the clinical circumstance of the patient.

The pathologic stage is determined after surgical treatment absolutely defines the local parameters. In addition to stage, there are other tests that are very necessary to aid in decisions regarding treatment. Handling of the surgical specimen is thus very important. The tissue needs to be analyzed for the presence or absence of hormone receptors and a receptor called HER-2. The presence of these receptors will influence additional therapies. Microscopic evaluation may also include the assessment of lymphatic or blood vessel invasion as these predict a worse outcome. The DNA of the tumor cells is quantitatively analyzed to help decide the biologic aggressiveness of the tumor. These parameters will be utilized collectively along with the axillary lymph node status to define the anticipated aggressiveness of the cancer. This assessment, along with the age and general condition of the patient, will be considered when planning the adjuvant therapies. Adjuvant therapies are treatments utilized after the primary treatment to help ensure that no microscopic disease exists and to help prolong patients' survival time.

Radiation

Like surgical therapy, radiation therapy is a local modality—it only treats the exposed tissue. Radiation is usually given post-operatively after surgical wounds have healed. The pathologic stage of the primary tumor is now known and this aids in treatment planning. The extent of the local surgery also influences the planning. Radiation may not be needed at all after modified radical mastectomy for stage I disease, but is almost always utilized when breast-preserving surgery is performed. If the tumor was extensive or if multiple nodes were involved, the field of tissue exposed will vary accordingly. Radiation is utilized as an adjunct to surgical therapy and is considered an important modality in gaining local control of the tumor. The use of radiation therapy does not affect decisions for adjuvant treatment. In the past, radiation was used as an alternative to surgery on occasion. However, now that breast-preserving surgical protocols have been developed, primary radiation treatment of the tumor is no longer performed. Radiation also has an important role in the treatment of the patient with disseminated disease, particularly if it involves the skeleton. Radiation therapy can affect pain control and prevention of fracture in this circumstance.

Drug Therapy

Many breast cancers, particularly those originating in post-menopausal women, are responsive to hormones. These cancers have receptors on their cells for estrogen and progesterone. Part of primary tumor assessment after removal of the tumor is the evaluation for the presence of these estrogen and progesterone receptors. If they are present on the cancer cells, altering the hormone status of the patient will inhibit tumor growth and have a positive impact on survival. The drug tamoxifen binds up these receptors on the cancer cells so that the hormones can't have an effect and, in so doing, inhibits tumor growth. If the patient has these receptors present, tamoxifen is commonly prescribed for five years as an adjunct to primary treatment. Adjuvant hormonal therapy with tamoxifen has few side effects but they have to be kept in mind, particularly the need for yearly evaluation of the uterus.

In late 2003, cancer experts were beginning to recommend a new group of drugs called aromatase inhibitors (Arimidex, common name anastrozole, or more recently Femara and Novartis, common name letrozole) as an alternative to tamoxifen. New guidelines also recommend letrozole following five years of tamoxifen therapy. These drugs fight breast cancer differently, but early research shows they fight it as effectively and with fewer side effects.

Shortly after the modified radical mastectomy replaced the radical mastectomy as primary surgical treatment, it was appreciated that survival after local treatment in stage II breast cancer was improved by the addition of chemotherapy. Adjuvant chemotherapy for an interval of four to six months is now standard treatment for patients with stage II disease. The addition of systemic therapy to local treatment in patients who have no evidence of disease is performed on the basis that some patients have metastases that are not currently demonstrable because they are microscopic. By treating the whole patient early, before widespread disease is diagnosed, the adjuvant treatment improves survival rates from roughly 60% for stage II to about 75% at five years after treatment. The standard regimen of CMF, or cytoxan, methotrexate, and fluorouracil, is given for six months and is well tolerated. The regimen of cytoxan, adriamycin (doxorubicin), and fluorouracil, (CAF), is a bit more toxic but only requires four months. (Adriamycin and cytoxin may also be used alone, without the fluorouracil.) The two methods are about equivalent in results. Adjuvant hormonal therapy may be added to the adjuvant chemotherapy as they work through different routes.

As one would expect, the encouraging results from adjuvant therapy in stage II disease have led to the study of similar therapy in stage I disease. The results are not as dramatic, but they are real. Currently, stage I disease is divided into categories a, b, and c on the basis of tumor size. Stage Ia is less than a centimeter in diameter. Adjuvant hormonal or chemotherapy is now commonly recommended for stage Ib and Ic patients. The toxicity of the treatment must be weighed individually for the patient as patients with stage I disease have a survivorship of over 80% without adjuvant chemotherapy.

If patients are diagnosed with stage IV disease or, in spite of treatment, progress to a state of widespread disease, systemic chemotherapy is utilized in a more aggressive fashion. In addition to the adriamycin-containing regimens, docetaxel and paclitaxel) have been found to be effective in inducing remission.

On the basis of certain prognostic factors, some patients with stage II or III disease can be predicted to do poorly. If their performance status allows, they may be considered for treatment with highly aggressive chemotherapy. The toxicity is such that bone marrow failure will result. To get around this anticipated side effect of the aggressive therapy, either the patients will be transplanted with their own stem cells, (the cells that will give rise to new marrow), or an allogeneic bone marrow transplantation will be required. This therapy can be a high-risk procedure for patients. It is given with known risk to patients predicted to do poorly and then only if it is felt they can tolerate it. Most patients who receive this therapy receive it as part of a clinical trial.

For patients who are diagnosed with advanced local disease, surgery may be preceded with chemotherapy and radiation therapy. The disease locally regresses allowing traditional surgical treatment to those who could not receive it otherwise. Chemotherapy and sometimes radiation therapy will continue after the surgery. The regimens of this type are referred to as neo-adjuvant therapy. This has been proven to be effective in stage III disease. Neo-adjuvant therapy is now being studied in patients with large tumors that are stage II in an effort to be able to offer breast preservation to these patients.

A drug known as Herceptin (trastuzumab), a monoclonal antibody, is now being used in the treatment of those with systemic disease. The product of the Human Epidermal Growth Factor 2 gene, (HER-2) is overexpressed in 25%–30% of breast cancers. Herceptin binds to the HER-2 receptors on the cancer, resulting in the arrest of growth of these cells.

Prognosis

The prognosis for breast cancer depends on the type and stage of cancer. Over 80% of stage I patients are cured by current therapies. Stage II patients survive overall about 70% of the time; those with more extensive lymph nodal involvement do worse than those with disease confined to the breast. About 40% of stage III patients survive five years, and about 20% of stage IV patients do so.

Coping With Cancer Treatment

Surgery for breast cancer is physically well-tolerated by the patient, especially those undergoing minimal surgery in the axilla. Most patients can return to a normal lifestyle within a month or so after surgery. Exercises can help the patient regain strength and flexibility. Arm, shoulder, and chest exercises help, and complete recovery of activity is to be expected.

About 5%–7% of patients undergoing complete axillary lymph node resection as part of their therapy may develop clinically significant lymphedema, or swelling in the arm on the side of involvement. If present, elevation and massage may be needed intermittently. Though usually not serious, on occasion this complication may interfere with complete physical recovery. The incidence of lymphedema is less with less axillary surgery. This is the reason for the enthusiasm for sentinel node biopsy as the surgical staging procedure in the axilla.

It is common after breast cancer treatment to be depressed or moody, to cry, lose appetite, or feel unworthy or less interested in sex. The breast is involved with a woman's identity and loss of it may be disturbing. For some, counseling or a support group can help. Many women have found a support group of breast cancer survivors to be an invaluable help during this stage. Involvement with volunteers from the local chapter of the Reach to Recovery program may be very helpful.

Nearly all patients undergo some form of adjuvant therapy for breast cancer. The magnitude of the toxicity of these adjuvant therapies is usually small and many patients receiving chemotherapy on this basis are capable of normal activity during this time. Certainly, those who progress to advanced disease are treated with more toxic chemotherapeutic regimens in an attempt to induce remission.

Clinical Trials

The use of tamoxifen and other agents that alter the hormone status of the patient are under study. The National Surgical Adjuvant Breast and Bowel Project (NSABP) with support from the National Cancer Institute began a study in 1992 (called the Breast Cancer Prevention Trial, or BCPT). It researched the use of tamoxifen as a breast cancer preventive for high-risk women. The results yielded from the study showed that tamoxifen significantly reduced breast cancer risk, and the U.S. Food and Drug Administration approved the use of tamoxifen to reduce breast cancer risk for high-risk patients in 1998. Another NSABP study, known as STAR, has sought to understand if another drug, raloxifene, is as effective as tamoxifen in reducing breast cancer risk in high-risk patients. A number of clinical trials continue on the prevention and treatment of breast cancer. Numerous breast cancer organizations and the National Cancer Institute can provide information on participating in clinical trials.

Immune therapies have not been helpful to date though there are vaccines being developed against proteins such as that produced by HER-2 that may be beneficial in the future.

High-dose chemotherapy with bone marrow rescue remains controversial. Factors can be identified that predict certain patients will develop metastatic disease. This treatment has been offered to this select group of patients but the toxicity is such that defining a clear indication for this treatment remains under study.

Prevention

While most breast cancer can't be prevented, it can be diagnosed from a mammogram at an early stage when it is most treatable. The results of awareness and routine screening have allowed earlier diagnosis, which results in a better prognosis for those discovered.

Special Concerns

Though breast-preserving therapy is being done more frequently than in years past, modified radical mastectomy remains an option when selecting therapy for the primary

Questions to Ask the Doctor

• Has my cancer spread?
• What is the stage of my cancer? What does that mean?
• What treatment choices do I have?
• What treatment do you recommend? Why?
• What are the advantages and disadvantages of this treatment?
• Will I lose my hair? If so, what can be done about it?
• What are the chances my cancer will come back after this treatment?
• What should I do to be ready for treatment?

tumor. This option may allow treatment without radiation in earlier stage patients, or may be necessary if the presentation of the tumor does not allow breast preservation. Loss of the breast is disfiguring and many patients so treated desire reconstruction of the breast. Breast reconstruction is performed either at the time of initial surgery (immediate) or it may be delayed. Alternatives include placement of implants or the rotation of muscle flaps from the abdomen or back. Most agree that breast preservation gives superior results to any form of reconstruction. When the breast is removed as part of primary therapy, these reconstructions are available and produce reasonable results. In 2003, research showed that young women who choose breast-conserving surgery are at higher risk for local recurrence and should receive indefinite follow-up care from their physicians.

Resources

Books

Abelhoff, Armitage, Lichter, Niederhuber. Clinical Oncology Library. Philadelphia: Churchill Livingstone 1999.

Schwartz, Spencer, Galloway, Shires, Daly, and Fischer. Principles of Surgery. New York: McGraw Hill, 1999.

Periodicals

Esteva and Hortobagyi. "Adjuvant Systemic Therapy for Primary Breast Cancer." Surgical Clinics of North America 79, no. 5 (October 1999): 1075-1090.

"HRT Linked to Higher Breast Cancer Risk, Later Diagnosis, Abnormal Mammograms." Women's Health Weekly July 17, 2003: 2.

Margolese, R. G., M.D. "Surgical Considerations For Invasive Breast Cancer." Surgical Clinics of North America 79, no. 5 (October 1999): 1031-1046.

Munster and Hudis. "Adjuvant Therapy for Resectable Breast Cancer." Hematology Oncology Clinics of North America 13, no. 2 (April 1999): 391-413.

"New Human Breast and Ovarian Cancer Gene Described." Biotech Week December 31, 2003: 89.

Pennachio, Dorothy L. "Letrozole Improves Breast Cancer Outlook." Patient Care December 2003: 4.

"Revised Guidelines Show Changes for Breast Cancer Treatment." Biotech Week December 24, 2003: 296.

"Sentinel Lymph Node Biopsy is Accurate for Staging." Women's Health Weekly June 5, 2003: 4.

Shuster, et al. "Multidisciplinary Care For Patients With Breast Cancer." Surgical Clinics of North America 80, no. 2 (April, 2000): 505-533.

"Young Women Who Choose Lumpectomies Need Indefinite Follow-up, Study Says." Clinical Oncology Week November 24, 2003: 11.

Organizations

American Cancer Society. (800) ACS-2345. .American Cancer Society's Reach to Recovery Program: .

Cancer Care, Inc. (800) 813-HOPE. .

Cancer Information Service of the NCI. (1-800-4-CANCER). .

National Alliance of Breast Cancer Organizations. 9 East 37th St., 10th floor, New York, NY 10016. (888) 80-NABCO.

National Coalition for Cancer Survivorship. 1010 Wayne Ave., 5th Floor, Silver Spring, MD 20910. (301) 650-8868.

National Women's Health Resource Center. 2425 L St. NW, 3rd floor, Washington, DC 20037. (202) 293-6045.

Other

Breast Cancer Online..

National Alliance of Breast Cancer Organizations..

National Cancer Institute..

—Richard A. McCartney, M.D.; Carol A. Turkington

Definition

Breast cancer is the abnormal growth and uncontrolled division of cells in the breast. Cancer cells invade and destroy surrounding normal tissue, and can spread throughout the body via blood or lymph fluid (clear fluid bathing body cells) to start a new cancer in another part of the body.

Description

Every woman is at risk for breast cancer and the disease was diagnosed more than 200,000 times in 2002 in the United States. When a woman lives to be 85, there is a one out of nine chance that she will develop the condition sometime during the rest of her life. As a woman ages, her risk of developing breast cancer rises dramatically regardless of her family history. The breast cancer risk of a 25-year-old woman is only one out of 19,608; by age 45, it is one in 93. In fact, 80% of all breast cancers are found in women over age 50.

Causes & Symptoms

There are a number of risk factors for the development of breast cancer, including:

• family history of breast cancer in mother or sister
• early onset of menstruation and late menopause
• reproductive history (women who had no children or have children late in life and women who have never breastfed have increased risk)
• history of abnormal breast biopsies

However, more than 70% of women who get breast cancer have no known risk factors. While a breast cancer gene was discovered in 1994, only about 5% of breast cancers are believed to be related to the gene.

In addition, some studies suggest that high fat diets, bottle feeding instead of breastfeeding, or consuming alcohol may contribute to the risk profile. Other aspects of nutrition and lifestyle in Western countries may be responsible for higher rates of breast cancer in our societies. For example, aromatic hydrocarbons in tobacco and certain hydrocarbons in well-done meat may act as carcinogens. While some studies had suggested a link between hormone replacement therapies (HRTs) contributing to breast cancer, many did not take them seriously. However, a landmark study released in 2003 proved the risk was greater than thought. The Women's Health Initiative found that even relatively short-term use of estrogen plus progestin is associated with increased risk of breast cancer, diagnosis at a more advanced stage of the disease, and a higher number of abnormal mammograms. The longer a woman used HRT, the more her risk increased.

It is important to realize that not all lumps detected in the breast are cancerous. Many are benign and require only the removal of the lump. While having several risk factors may boost a woman's chances of having breast cancer, the interplay of factors is complex. The best way to assess breast cancer risk is by doing monthly self examinations to detect any lump at an early stage. The second is to have a regular mammogram, an x ray of the front and side of the breast that will detect cysts or tumors at the earliest possible stage. Seeking risk assessment consultation at one of the many breast cancer centers located throughout the United States is also helpful.

Changes in the breast that may indicate breast cancer include:

• lump or thickening in breast or armpit
• changes in a nipple (thickening, pulling in, bleeding, or discharge)
• dimpled or reddened skin over the breast
• change in size or shape
• abnormality on a mammogram

Diagnosis

More than 90% of all breast cancers are detected by mammogram (a low-dose x ray of the breast). Mammograms should be done to evaluate a suspicious lump. Screening mammograms should be ordered according to the doctor's guidelines. Despite the controversy about the cost-effectiveness of mammograms for women in their 40s, most doctors agree with the current American Cancer Society guidelines that recommend screening mammograms every year or two for women between 40 and 49, and every year after age 50. Women with a family history of breast cancer may want to have a mammogram every year after age 40.

A typical mammography screening includes two views of each breast (one from above, and one from the side). Normally, the technologist examines the x-ray films immediately to make sure views are complete. A radiologist determines if further views or follow-up ultrasound studies are needed.

If anything irregular is detected, such as a mass, changes from earlier mammograms, abnormalities of the skin, or enlargement of the lymph nodes, further testing may be recommended. This could include an ultrasound of the breast, a biopsy or needle sampling, or consultation with a breast surgeon.

Biopsy of the breast is a removal of breast tissue for examination by a pathologist. An excisional biopsy is a surgical procedure in which the entire lump area and some surrounding tissue is removed for examination. If the mass is very large, an incisional biopsy is done where only a portion of the area is removed and analyzed. Needle biopsy can be done in two methods. An aspiration needle biopsy uses a very fine needle to withdraw cells and fluid from the mass for analysis. A large core needle biopsy uses a larger diameter needle to remove small pieces of tissue from the mass that can be analyzed. These analyses can determine whether the mass is benign (noncancerous) or cancerous and therefore, whether further treatment is required.

To find out if the cancer has spread to other parts of the body (metastasized), doctors remove some underarm lymph nodes to test for cancer cells that have spread and to assist in making decisions for treatment. A newer technique, called sentinel lymph node biopsy, allows physicians to check the sentinel node, or the one that first receives fluid drained from the cancerous area, to preserve as many lymph nodes as possible. If this node is free of cancer cells, the cancer should not have spread any further than locally. Checking to see if there are cancer cells in the lymph nodes is also a way to tell how advanced the cancer is ("staging" cancer). Breast cancer is rated from Stage 0 to Stage IV. Staging uses the diagnostic information to tell the cancer physician (oncologist) how widespread the disease is and includes:

• Stage I. The cancer is no larger than 2 cm and no cancer cells are found in the lymph nodes.
• Stage II. The cancer is no larger than 2 cm but has spread to the lymph nodes or is larger than 2 cm but has not spread to the lymph nodes.
• Stage IIIA. Tumor is larger than 5 cm and has spread to the lymph nodes or is smaller than 5 cm, but has spread to the lymph nodes, which have grown into each other.
• Stage IIIB. Cancer has spread to tissues near the breast or to lymph nodes inside the chest wall, along the breastbone.
• Stage IV. Cancer has spread to skin and lymph nodes near the collarbone or to other organs of the body.

Treatment

The best chance for successful treatment is to find breast cancer early. Breast cancer is a life-threatening disease, and a correct diagnosis and appropriate treatment with surgery, chemotherapy, and/or radiation is critical to controlling the illness.

Acupuncture and guided imagery may be useful tools in treating pain symptoms and side effects of chemotherapy associated with breast cancer. Acupuncture involves the placement of a series of thin needles into the skin at targeted locations on the body, known as acupoints, in order to harmonize the energy flow within the human body.

Guided imagery involves creating a visual mental image of pain. Once the pain can be visualized, the patient can adjust the image to make it more pleasing, and thus more manageable, to them.

A number of herbal remedies are also available to lessen pain symptoms and chemotherapy side effects, and to promote relaxation and healing. However, breast cancer patients should consult with their healthcare professional before taking them. Depending on the preparation and the type of herb, these remedies may interact with or enhance the effects of other prescribed medications.

Results of a clinical trial performed at the National Cancer Institute of Milan, Italy, have indicated that homeopathic remedies of belladonna (Atropa belladonna) can be useful in relieving the discomfort, warmth, and swelling of the skin associated with radiotherapy for breast cancer (i.e., radiodermatitis). As with all homeopathic remedies, the prescription of belladonna depends on an individual's overall symptom picture, mood, and temperament, and should be prepared by a trained homeopathic professional. When used as a homeopathic remedy, belladonna is administered in a highly diluted form to trigger the body's natural healing response without risk of belladonna poisoning or overdose. There are many other herbs that help in relieving the nausea that accompanies chemotherapy, including ginger (Zingiber officinale).

Allopathic Treatment

Treatment options include surgery, chemotherapy, and radiation. Breast cancer is treated in two ways: locally to eliminate tumor cells from the breast by surgery and radiation, and to systemically destroy cancer cells that have traveled to other parts of the body. Systemic therapy includes the use of drugs in chemotherapy and hormonal treatments to reduce the amount of estrogen circulating in the blood.

Surgery

The extent of surgery depends on the type of breast cancer, whether the disease has spread, and the patient's age and health. If the tumor is less than about 1.6 in (4.1 cm) or there is not much chance it will return, then the patient and doctor may opt for removal of the tumor alone (lumpectomy) followed by radiation therapy.

Studies have shown that conservative treatment (a lumpectomy or partial mastectomy) offers the same odds of survival as does removal of the entire breast (total mastectomy) in someone with a small breast tumor that has not spread into the nearby lymph nodes. New studies suggest that after lumpectomy, a combination of chemotherapy and radiation offers the best chance of long–term survival. Recent studies also show that breast conserving surgery leads to better quality of life following breast cancer for women of all ages.

If the tumor is larger, a total (or simple) mastectomy may be needed. If the cancer has spread to the chest muscles, most doctors believe a radical mastectomy is the best solution. This operation is now used only when the cancer has spread to the chest muscle.

In a lumpectomy, the doctor removes:

• the lump
• some of the tissue around the lump
• some of the lymph nodes under the arm may be removed (auxillary dissection) and tested to see if the cancer has spread there

Even if no cancer is found in the nodes, radiation always follows lumpectomy and treatment may include chemotherapy.

In a modified radical mastectomy, the doctor removes:

• the entire breast
• the underarm lymph nodes
• the lining over the chest muscle (but not the muscles themselves)

A radical mastectomy is almost never done, but if necessary the doctor removes:

• the breast
• the chest muscles
• all of the lymph nodes under the arm

Surgery can be combined with breast reconstruction (creating a new breast-shaped mound), either right away or later on. Patients who want breast reconstruction should tell the doctor before surgery, since this could change the way the surgeon operates.

Removing the tumor and a border of normal tissue around it will remove the cancer while saving most of the breast tissue. However, the longer a tumor has been growing in the breast, the more likely it will be that the cancer cells have spread to the lymph nodes. These nodes under the arm or in the chest are a common place for breast cancer cells to spread. During surgery, some of the nodes are removed to check for cancer cells.

The presence of cancer cells in the lymph nodes may require more extensive surgery. If the cancer has spread to the nodes, the patient will need either radiation, chemotherapy, hormone therapy, or a combination of all three after surgery. This is called "adjuvant therapy."

Radiation

Once the cancer has been removed, the doctor may recommend radiation to destroy or shrink any remaining breast cancer cells. Radiation stops the cancer cells from dividing. It works especially well on fast-growing tumors. Unfortunately, it also stops some types of healthy cells from dividing. Healthy cells that divide quickly, like those of the skin and hair, are affected the most. This is why radiation can cause fatigue, skin problems, and hair loss.

Chemotherapy

Breast cancer surgery may be followed by chemotherapy in even the earliest stages. Chemotherapy is administered either orally or by injection into a blood vessel. It is usually given in cycles, followed by a period of time for recovery, followed by another course of drugs. Treatment time may range between four to nine months.

There may be significant side effects with some types of chemotherapy, including nausea and vomiting, temporary hair loss, mouth or vaginal sores, fatigue, weakened immune system, and infertility. However, chemotherapy for early breast cancer uses medications that cause fewer side effects.

Hormone Therapy

The growth of some breast cancer cells may be slowed by the drug tamoxifen, an anti-estrogen medication. Given each day as a pill, tamoxifen travels throughout the bloodstream, slowing or stopping cancer cell growth. Tamoxifen treatment lasts at least two years, and often as long as five. Research suggests that tamoxifen may lower the chance that a breast cancer can return by between 25% and 35%.

Side effects of tamoxifen may include a slightly higher risk of cancer of the lining of the uterus (endometrial cancer). The risk increases if the drug is taken for more than five years. Other side effects include menopause-like symptoms, such as weight gain, hot flashes, and mood swings.

In rare cases, the surgeon may suggest removal of the ovaries (oophorectomy) in premenopausal women as a way of eliminating the main source of estrogen, which can boost the growth of some breast tumors.

Stem Cell Treatment

Stem cell treatment is used to treat advanced breast cancer. By first removing a woman's stem cells from her bone marrow or blood, the doctor can use very high doses of chemotherapy or radiation to kill cancer cells. Because this also kills healthy white blood cells, leaving the woman vulnerable to infection, the stem cells are then replaced, where they restore the body's ability to fight infection.

Expected Results

The prognosis for breast cancer depends on the type and stage of cancer. Most patients can return to a normal lifestyle within a month or so after surgery. Exercises can help the patient regain strength and flexibility, and avoid building up too much fluid. Arm, shoulder, and chest exercises may aid in the patient's recovery.

It is normal after breast cancer treatment to be depressed or moody, to cry, lose appetite, or feel unworthy or less interested in sex. If these problems last for an extended time, individual counseling is appropriate. Many women have also found that attending a support group of breast cancer survivors to be an invaluable help during this stage.

Prevention

While breast cancer cannot be prevented, it can be diagnosed from a mammogram at an early stage when it is most treatable. Despite recent questions about the effectiveness of mammography in preventing breast cancer, it remains effective in screening for and detecting signs of breast cancer. A baseline mammogram should be done by age 35, so that a normal x ray can be used to compare future mammograms, even when there is no reason to believe there is a lump or cyst. In addition, women should check their own breasts at the same time each month. The American Cancer Society (ACS) publishes guidelines recommending how often and at what ages women should have screening mammograms. The ACS updated its guidelines in 2003 to recommend annual screening mammograms for women beginning at age 40.

In 1998, the National Surgical Adjuvant Breast and Bowel Project (NSABP) released the results of a six-year study called the Breast Cancer Prevention Trial (BCPT) that analyzed the breast cancer prevention qualities of the drug tamoxifen (Novadex). The study concluded that tamoxifen reduced the incidence of breast cancer in women at high risk of developing this disease. Researchers reported a 49% reduction in diagnoses of invasive breast cancer among women who took tamoxifen, and a 50% decrease in diagnoses of noninvasive breast tumors, such as ductal or lobular carcinoma in situ. More recent studies suggest that tamoxifen also helps prevent breast cancer in women over age 60. However, the drug has also been associated with blood clotting problems and an increased risk of uterine cancer in some patients.

A clinical study comparing tamoxifen and raloxifene, an osteoporosis drug, began in 1999. Raloxifene is thought to have breast cancer prevention properties similar to tamoxifen, but with fewer harmful side effects.

Resources

Books

Lauersen, Niels, and Eileen Stukane. The Complete Book of Breast Care. New York: Fawcett Columbine, 1998.

Porter, Margit Esser. Hope is Contagious: The Breast Cancer Treatment Survival Handbook. New York: Simon & Schuster, 1997.

Periodicals

Balzarini, A., et al. "Efficacy of Homeopathic Treatment of Skin Reactions During Radiotherapy for Breast Cancer: A Randomised, Double-Blind Clinical Trial." British Homeopathic Journal 89, no. 1 (January 2000): 8–12.

"Does Tamoxifen Prevent Breast Cancer?" Journal of Family Practice 50, no. 12 (December 2001): 1023.

"Early Detection Saves Lives." Women's Health Weekly (November 14, 2003):13.

"HRT Linked to Higher Breast Cancer Risk, Later Diagnosis, Abnormal Mammograms." Women's Health Weekly (July 17, 2003):2.

"Nutrition and Lifestyle Factors Affect the Risk of Developing Breast Cancer." Health & Medicine Week (July 28, 2003): 48.

"Quality of Life Seems to be Better After Conservative Treatment of Breast Cancer." Women's Health Weekly (July 17, 2003):22.

"Sentinel Lymph Node Biopsy is Accurate for Staging." Women's Health Weekly (June 5, 2003):4.

Smith, Robert A., et al. "American Cancer Society Guidelines for Breast Cancer Screening: Update 2003." Cancer (May-June 2003):141.

Zoler, Michael L. "Mammograhpy Analysis Slammed (No Change in Recommendations)." Internal Medicine News 34, no. 23 (December 1, 2001): 1.

Organizations

American Cancer Society. (800) ACS-2345. .

Cancer Care, Inc. 275 7th Ave., New York, NY, 10001. (800) 813-HOPE. info@cancercare.org. .

CancerNet. (800) 4-CANCER. .

National Alliance of Breast Cancer Organizations. 9 East 37th St., 10th floor, New York, NY 10016. (888) 80-NABCO. .

[Article by: Paula Ford-Martin; Teresa G. Odle]

Breast cancer is the most common malignancy in American women, accounting for approximately 30 percent of their new cancer cases. It is the second leading cause of cancer death in women, following lung cancer. In the year 2000, it was estimated that there were more than 180,000 new cases of breast cancer diagnosed, and over 41,000 breast cancer deaths in the United States. Breast cancer incidence rates were steady through the 1990s, although the number of breast cancer deaths declined, decreasing an average of 1.8 percent per year between 1990 and 1996.

Breast cancer can be divided into invasive and noninvasive forms. Noninvasive breast cancer is almost always cured through local control measures (surgery and radiation therapy). Tamoxifen (a selective estrogen-receptor modulator), is used to reduce the risk of a local recurrence in patients treated with breast conservation. Early-stage invasive disease is limited to the breast and axillary lymph nodes, while metastatic disease includes tumors that have spread outside the breast and local lymph nodes. Early-stage invasive breast cancer is curable, although less so than noninvasive disease.

The first step in the management of early-stage breast cancer is surgical removal of the tumor. This can be accomplished by lumpectomy (removal of the tumor and a margin of surrounding normal breast tissue) or mastectomy (removal of the entire affected breast). Following lumpectomy, patients should receive radiation to the remaining breast tissue to decrease the risk of recurrence. Studies have shown that patients with small tumors who are treated with breast conservation therapy (lumpectomy and radiation) have equivalent survival rates to patients treated with mastectomy. Ipsilateral axillary lymph nodes are removed in order to determine whether the tumor has spread via the lymphatic drainage. Involvement of the ipsilateral lymph nodes is a marker for increased risk of later distant spread of the tumor.

Once the tumor is removed, the size of the tumor, hormonal status (estrogen and progesterone receptor), and lymph node involvement is considered in aggregate to determine the overall risk of distant spread of disease. Patients at high risk for recurrent disease can be given systemic therapy in order to decrease the odds of relapse. Systematic therapy circulates throughout the entire body in order to kill microscopic tumor cells. Conventionally this therapy can consist of chemotherapy, hormonal therapy (if the tumor is estrogen- or progesterone-receptor positive), or both. Chemotherapy is typically given to patients with invasive tumors greater than 1 centimeter in largest diameter or with involved (positive) lymph nodes. Patients with hormone receptor—positive tumors or tumors in which the receptor status is unknown benefit from treatment with tamoxifen for five years. Both of these interventions have been shown to decrease both the patient's annual risk of recurrence and the risk of mortality from breast cancer. Tamoxifen also decreases the risk of a second primary breast cancer in the preserved contralateral breast.

Breast cancer can metastasize to other organs in the body. Once breast cancer has been detected in distant sites, it is no longer curable. At that stage, the goal of the treatment is to prolong survival while maintaining quality of life. Patients with hormone receptor—positive tumors who are minimally symptomatic and who have predominantly bone disease can frequently be treated with hormonal therapy. This treatment is taken orally and is generally well tolerated. Patients who have hormone receptor—negative tumors, those who have failed hormone therapy, and those who have symptomatic or rapidly progressive disease are frequently treated with chemotherapy. The specific decisions regarding hormone therapy, chemotherapy, and supportive measures require skill, compassion, and a detailed understanding of the numerous treatment options.

Established risk factors for breast cancer include older age (women over fifty have a 6.5 times higher risk of developing breast cancer than younger women), a family history of breast cancer (especially the presence of a documented genetic abnormality), early age of menarche (less than 12 versus equal to or greater than 14), late age of menopause (equal to or greater than 55 versus less than 55), age at first live birth (greater than 30 versus less than 20), history of benign breast disease, and a history of hormone replacement use. Some studies also suggest an increased breast-cancer risk associated with increased alcohol and dietary fat intake, excess body weight, and limited exercise. Further studies are needed to establish the benefit of lifestyle modification in the prevention of breast cancer.

Randomized trials have shown the benefit of chemoprevention in reducing the risk of breast cancer for women at increased risk. The National Surgical Adjuvant Breast and Bowel Project Tamoxifen Prevention Trial (NSABP-1) evaluated the benefits of tamoxifen in the prevention of breast cancer. More than three thousand women at increased risk for breast cancer (defined as a five-year risk of breast cancer of 1.66 percent or more) were followed for approximately four years. Treatment with tamoxifen reduced the overall odds of developing both invasive and noninvasive breast cancer by approximately 50 percent. This decrease in breast cancer risk was seen across all age groups. Side effects of tamoxifen include hot flashes, an increased risk of thromboembolic events, and increased risk of endometrial cancer.

Newer antiestrogens, such as raloxifene, may have fewer side effects than tamoxifen. The MORE (Multiple Outcomes of Raloxifene Evaluation) trial was a trial of 7,705 postmenopausal women who received raloxifene for the treatment of osteoporosis. Raloxifene was found to reduce the risk of invasive breast cancer by 76 percent, with no increased risk of endometrial cancer. Raloxifene is being compared directly to tamoxifen for prevention in high-risk patients in the STAR (Study of Tamoxifen and Raloxifene) trial.

(SEE ALSO: Breast Cancer Screening; Breast Self-Examination; Cancer; Clinical Breast Examination; Gender and Health; Mammography; Tamoxifen)

Bibliography

Armstrong, K.; Eisen, A.; and Weber, B. (2000). "Assessing the Risk of Breast Cancer." New England Journal of Medicine 342:564–571.

Cummings, S. R.; Eckert, S.; Krueger, K. A. et al. (1999). "The Effect of Raloxifene on Risk of Breast Cancer in Postmenopausal Women: Results from the MORE Randomized Trial. Multiple Outcomes of Raloxifene Evaluation." Journal of American Medical Association 281:2189–2197. (Published erratum appears in Journal of American Medical Association 282:2124.)

Early Breast Cancer Trialists' Collaborative Group (1998). "Tamoxifen for Early Breast Cancer: An Overview of the Randomized Trials." Lancet 351: 1451–1467.

Fisher, B.; Constantino, J. P.; Wickerman, D. L.; et al. (1998). "Tamoxifen for Prevention of Breast Cancer: Report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study." Journal of the National Cancer Institute 90:1371–1388.

Fisher, B.; Redmond, C.; Poisson, P. et al. (1989). "Eight-Year Results of a Randomized Clinical Trial Comparing Total Mastectomy and Lumpectomy With or Without Irradiation in the Treatment of Breast Cancer." New England Journal of Medicine 320:822–828.

Greenlee, R. T.; Murray, T.; Bolden, S.; and Wingo, P. A. (2000). "Cancer Statistics, 2000." CA Cancer J Clin 50:7–33.

— CLIFFORD HUDIS; ARTI HURRIA

Breast cancer remains the most common cause of cancer among women in the United States, and it results in more deaths from cancer among women than any other type of cancer, except lung cancer. Over 40,000 women die from breast cancer in the United States each year. A long history of research, now coupled with the new information emerging from the field of molecular genetics, is beginning to explain the basic steps leading to breast cancer, and it will enable the development of novel treatment and prevention strategies.

Almost all breast cancers begin in the glandular structures in the breast that, during lactation, produce milk. These mammary glands are under the control of reproductive hormones that stimulate the monthly cycle of gland expansion and shrinkage, which is a feature of the regular menstrual cycle. Many of the factors associated with the development of breast cancer appear to have their effect through interaction with the hormonal stimulation of these glands.

The risk of developing breast cancer increases throughout a woman's lifetime, and the disease is relatively rare in very young women. The overall association of breast cancer incidence with increasing age may be explained by a model of breast cancer in which a progressive and cumulative series of genetic changes within the cells of the glands is necessary for the initiation of cancer. The longer a woman lives, the more opportunities there are for these genetic changes to accumulate and reach a stage where cells can become cancerous.

One of the most consistent epidemiological observations is the association of reproductive events with risk of breast cancer. Women who have one or more full-term pregnancies have a lower risk for breast cancer, especially if they are pregnant before age twenty. Pregnancy at an early age may help to stabilize the mammary glands and make them less vulnerable to genetic changes later in life. The risk for breast cancer is also significantly decreased among women undergoing surgical removal of the ovaries, particularly if the surgery is performed before age thirty-five. This surgery removes the major source of reproductive hormones and therefore results in less stimulation of the glands in the breast.

Conversely, the greater number of years a woman has regular menstrual cycles, the higher the risk of breast cancer. There is also a modest increase in risk associated with postmenopausal estrogen replacement therapy (especially when used more than 15 years), and with exposure to the synthetic estrogen diethylstilbestrol during pregnancy. Studies have found a significant correlation between breast cancer and levels of hormones—estradiol, estrone, estrone sulfate, prolactin, and dehydroepiandrosterone sulfate. A drug used to treat breast cancer, tamoxifen, blocks estrogen receptors.

Taken together, a significant body of research shows that reproductive hormones—produced internally and taken as medicines—are major determinants of breast cancer risk. Other factors—including genetic predisposition, environmental exposure, and lifestyle choices—may increase cancer risk via hormone regulation.

There are striking racial and ethnic differences in breast cancer incidence and resulting deaths. Overall, rates are highest for Caucasian women and lowest for Native American and Korean women. The general international pattern of breast cancer incidence reveals higher rates for Western, industrialized nations, and lower rates for less industrialized and Asian countries. Even within the United States, there is significant geographic diversity in breast cancer rates, with mortality rates highest in the Northeast and lowest in the South. Much of this variation is thought to be due to regional differences in reproductive events, such as the age when women start having children and their use of hormone medications.

There is also considerable evidence from international comparisons, migration studies, and time trends to support an important role for dietary fat in the causation of breast cancer. However when the diets of specific population groups are followed over time, no definite causal link can be demonstrated. The data on fiber and vitamins and minerals is also contradictory. Dietary studies also show a fairly consistent but weak increase in breast cancer risk with moderate to heavy alcohol consumption. Alcohol may act by stimulating the production of more internal hormones. Among postmenopausal women, body weight has also been positively correlated with both breast cancer incidence and mortality. Although exposure to large amounts of radiation is associated with an increased risk for breast cancer, there does not appear to be any risk associated with routine diagnostic imaging, such as chest X rays and mammograms.

Finally, there is limited data to support a protective role for physical activity, both during leisure time and at work, in terms of breast cancer risk. The effect is most pronounced among premenopausal and younger postmenopausal women. The known association of vigorous physical activity with decreased circulating levels of ovarian hormones may explain this finding, which could have significant public health implications.

Women undergoing breast biopsies whose tissue shows no evidence of cancer, but whose cells have atypical features or faster-than-normal rates of growth have an increased risk of breast cancer, with risks up to eightfold higher in some cases. It is thought that these atypical cells may be a precursor to the development of breast cancer, or they may act as markers for genetic instability within the glandular cells.

Population studies have documented that a history of breast cancer in first-, second-, or third-degree relatives increases cancer risk between twofold and fourfold. Recently two genes, BRCA1 and BRCA2, have, when inherited in a mutated form, been associated with a hereditary form of breast cancer. This form is characterized by early age at onset (5 to 15 years earlier than noninherited cases), cancer in both breasts, and association in the family with tumors of other organs, particularly of the ovary in women and prostate gland in men. Among the normal functions of these genes are the control of the cell cycle and the maintenance of stability of the genes. Both genes are tumor suppressor genes whose proteins help both to control the cell cycle and to repair damaged DNA. Mutations interfere with this vital function, causing damaged cells to reproduce and become cancerous.

The frequency of mutations in BRCA1 in the general population has been estimated to be 1 in 800. Carrier rates are not distributed evenly, however, and mutations tend to concentrate in families with multiple cases of breast or ovarian cancer. Different ethnic groups have unique BRCA1 and BRCA2 mutations. Most notably, three specific mutations are common in Ashkenazic Jews. Additional founder mutations have been described in Sweden and Iceland.

Individuals who have inherited a mutated BRCA1-2 gene face an estimated 36 percent to 85 percent lifetime risk for breast cancer and an estimated 16 percent to 60 percent lifetime risk for ovarian cancer. Among female BRCA1 carriers who have already developed a primary breast cancer, estimates for a second breast cancer in the opposite breast are as high as 64 percent by age seventy. Men who test positive for a mutation in the BRCA2 gene also have a higher lifetime risk for breast cancer.

The identification and location of these breast cancer genes will now permit further investigation of the precise role they play in cancer progression and, specifically, how they interact with reproductive hormones.

Bibliography

Brody, Larry, and Barbara Biesecker. "Breast Cancer Susceptibility Genes BRCA1 and BRCA2." Medicine 77 (1998): 208-226.

Kelsey, Jennifer, and Leslie Bernstein. "Epidemiology and Prevention of Breast Cancer." Annual Review of Public Health 17 (1996): 47-67.

Weber, Barbara L. "Genetic Testing for Breast Cancer." Scientific American Science and Medicine 3, no. 1 (1996): 12-21.

—Mary B. Daly

For more information on breast cancer, visit Britannica.com.

• Sylvie Fortin's Breast Cancer Victory Creating breast cancer awareness
• The breast cancer blog Helping women who with breast cancer

Breast cancer
Classification and external resources
Mammogram showing breast cancer (indicated by arrow)
ICD-10	C50.
ICD-9	174-175,V10.3
OMIM	114480
DiseasesDB	1598
MedlinePlus	000913
eMedicine	med/2808  med/3287 radio/115 plastic/521
MeSH	D001943

Breast cancer is a cancer that starts in the breast, usually in the inner lining of the milk ducts or lobules.^[1].

Worldwide, breast cancer is the second most common type of cancer after lung cancer (10.4% of all cancer incidence, both sexes counted)^[2] and the fifth most common cause of cancer death.^[3] In 2004, breast cancer caused 519,000 deaths worldwide (7% of cancer deaths; almost 1% of all deaths).^[3]

Breast cancer is about 100 times as frequent among women as among men, but survival rates are equal in both sexes.^[4][5][6]

Contents 1 Classification 2 Signs and symptoms 3 Causes 4 Pathophysiology 5 Diagnosis 6 Screening 7 Treatment 8 Prognosis 8.1 Psychological aspects 9 Epidemiology 9.1 United States 9.1.1 Racial disparities 9.2 UK 10 History 11 Prevention 12 Cultural references 13 Gallery 14 See also 15 References 16 External links

Classification

Main article: Breast cancer classification

Breast cancers are described along four different classification schemes, or groups, each based on different criteria and serving a different purpose:

• Pathology - Each tumor is classified by its histological (microscopic anatomy) appearance and other criteria.^[7]
• Grade of tumor - The histological grade of a tumor is determined by a pathologist under a microscope. A well-differentiated (low grade) tumor resembles normal tissue. A poorly differentiated (high grade) tumor is composed of disorganized cells and, therefore, does not look like normal tissue. Moderately differentiated (intermediate grade) tumors are somewhere in between.
• Protein & gene expression status - Currently, all breast cancers should be tested for expression, or detectable effect, of the estrogen receptor (ER), progesterone receptor (PR) and HER2/neu proteins. These tests are usually done by immunohistochemistry and are presented in a pathologist's report. The profile of expression of a given tumor helps predict its prognosis, or outlook, and helps an oncologist choose the most appropriate treatment. More genes and/or proteins may be tested in the future.
• Stage of a tumor - The currently accepted staging scheme for breast cancer is the TNM classification. This considers the Tumor itself, whether it has spread to lymph Nodes, and whether there are any Metastases to locations other than the breast and lymph nodes.

Breast cancer is usually, but not always, primarily classified by its histological appearance. Rare variants are defined on the basis of physical exam findings. For example, inflammatory breast cancer (IBC), a form of ductal carcinoma or malignant cancer in the ducts, is distinguished from other carcinomas by the inflamed appearance of the affected breast.^[8] In the future, some pathologic classifications may be changed.

Signs and symptoms

The first symptom, or subjective sign, of breast cancer is typically a lump that feels different from the surrounding breast tissue. According to the The Merck Manual, more than 80% of breast cancer cases are discovered when the woman feels a lump.^[9] According to the American Cancer Society, the first medical sign, or objective indication of breast cancer as detected by a physician, is discovered by mammogram.^[10] Lumps found in lymph nodes located in the armpits^[9] can also indicate breast cancer.

Indications of breast cancer other than a lump may include changes in breast size or shape, skin dimpling, nipple inversion, or spontaneous single-nipple discharge. Pain ("mastodynia") is an unreliable tool in determining the presence or absence of breast cancer, but may be indicative of other breast health issues.^[9][10][11]

When breast cancer cells invade the dermal lymphatics—small lymph vessels in the skin of the breast—its presentation can resemble skin inflammation and thus is known as inflammatory breast cancer (IBC). Symptoms of inflammatory breast cancer include pain, swelling, warmth and redness throughout the breast, as well as an orange-peel texture to the skin referred to as peau d'orange.^[9]

Another reported symptom complex of breast cancer is Paget's disease of the breast. This syndrome presents as eczematoid skin changes such as redness and mild flaking of the nipple skin. As Paget's advances, symptoms may include tingling, itching, increased sensitivity, burning, and pain. There may also be discharge from the nipple. Approximately half of women diagnosed with Paget's also have a lump in the breast.^[12]

Occasionally, breast cancer presents as metastatic disease, that is, cancer that has spread beyond the original organ. Metastatic breast cancer will cause symptoms that depend on the location of metastasis. Common sites of metastasis include bone, liver, lung and brain.^[13] Unexplained weight loss can occasionally herald an occult breast cancer, as can symptoms of fevers or chills. Bone or joint pains can sometimes be manifestations of metastatic breast cancer, as can jaundice or neurological symptoms. These symptoms are "non-specific", meaning they can also be manifestations of many other illnesses.^[14]

Most symptoms of breast disorder do not turn out to represent underlying breast cancer. Benign breast diseases such as mastitis and fibroadenoma of the breast are more common causes of breast disorder symptoms. The appearance of a new symptom should be taken seriously by both patients and their doctors, because of the possibility of an underlying breast cancer at almost any age.^[15]

Causes

The primary risk factors that have been identified are sex,^[16] age,^[17] childbearing, hormones,^[18] a high-fat diet,^[19] alcohol intake,^[20][21] obesity,^[22] and environmental factors such as tobacco use, radiation^[23] and shiftwork.^[24]

No etiology is known for 95% of breast cancer cases, while approximately 5% of new breast cancers are attributable to hereditary syndromes.^[25] In particular, carriers of the breast cancer susceptibility genes, BRCA1 and BRCA2, are at a 30-40% increased risk for breast and ovarian cancer, depending on in which portion of the protein the mutation occurs.^[26]

• Personal history of breast cancer: A woman who had breast cancer in one breast has an increased risk of getting cancer in her other breast.
• Family history: A woman's risk of breast cancer is higher if her mother, sister, or daughter had breast cancer. The risk is higher if her family member got breast cancer before age 40. Having other relatives with breast cancer (in either her mother's or father's family) may also increase a woman's risk.
• Certain breast changes: Some women have cells in the breast that look abnormal under a microscope. Having certain types of abnormal cells (atypical hyperplasia and lobular carcinoma in situ [LCIS]) increases the risk of breast cancer.
• Race: Breast cancer is diagnosed more often in Caucasian women than Latina, Asian, or African American women.
• No physical activity: Women who are physically inactive throughout life may have an increased risk of breast cancer. Being active may help decrease risk.

• Tamoxifen may interact unfavorably with certain antidepressants when used for prevention of breast cancer recurrence.^[27]

Pathophysiology

Main article: Carcinogenesis

Breast cancer, like other forms of cancer, is the outcome of multiple environmental and hereditary factors. Some of these factors include:

1. Lesions to DNA such as genetic mutations. Mutations that can lead to breast cancer have been experimentally linked to estrogen exposure.^[28]
2. Failure of immune surveillance, a theory in which the immune system removes malignant cells throughout one's life.^[29]
3. Abnormal growth factor signaling in the interaction between stromal cells and epithelial cells can facilitate malignant cell growth.
4. Inherited defects in DNA repair genes, such as BRCA1, BRCA2^[23] and TP53.^[30] People in less-developed countries report lower incidence rates than in developed countries.

Experts believe that 95 percent of inherited breast cancer can be traced to one of two genes, which they call Breast Cancer 1 (BRCA1) and Breast Cancer 2 (BRCA2). Hereditary breast cancers can take the form of a site-specific hereditary breast cancer- cancers affecting the breast only- or breast- ovarian and other cancer syndromes. Breast cancer can be inherited both from female and male relatives. ^[31]

Diagnosis

This section does not cite any references or sources. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. (October 2007)

While screening techniques discussed above are useful in determining the possibility of cancer, a further testing is necessary to confirm whether a lump detected on screening is cancer, as opposed to a benign alternative such as a simple cyst.

In a clinical setting, breast cancer is commonly diagnosed using a "triple test" of clinical breast examination (breast examination by a trained medical practitioner), mammography, and fine needle aspiration cytology. Both mammography and clinical breast exam, also used for screening, can indicate an approximate likelihood that a lump is cancer, and may also identify any other lesions. Fine Needle Aspiration and Cytology (FNAC), which may be done in a GP's office using local anaesthetic if required, involves attempting to extract a small portion of fluid from the lump. Clear fluid makes the lump highly unlikely to be cancerous, but bloody fluid may be sent off for inspection under a microscope for cancerous cells. Together, these three tools can be used to diagnose breast cancer with a good degree of accuracy.

Other options for biopsy include core biopsy, where a section of the breast lump is removed, and an excisional biopsy, where the entire lump is removed.

Screening

Main article: Breast cancer screening

Mammograms showing a normal breast (left) and a breast cancer (right).

Breast cancer screening is an attempt to find cancer in otherwise healthy individuals. The most common screening method for women is a combination of x-ray mammography and clinical breast exam. In women at higher than normal risk, such as those with a strong family history of cancer, additional tools may include genetic testing or breast Magnetic Resonance Imaging.

Breast self-examination was a form of screening that was heavily advocated in the past, but has since fallen into disfavour since several large studies have shown that it does not have a survival benefit for women and often causes considerably anxiety. This is thought to be because cancers that could be detected tended to be at a relatively advanced stage already, whereas other methods push to identify the cancer at an earlier stage where curative treatment is more often possible.

X-ray mammography uses x-rays to examine the breast for any uncharacteristic masses or lumps. Regular mammograms is recommended in several countries in women over a certain age as a screening tool.

Genetic testing for breast cancer typically involves testing for mutations in the BRCA genes. This is not generally a recommended technique except for those at elevated risk for breast cancer.

Treatment

Main article: Breast cancer treatment

Chest appearance after right breast mastectomy.

The mainstay of breast cancer treatment is surgery when the tumor is localized, with possible adjuvant hormonal therapy (with tamoxifen or an aromatase inhibitor), chemotherapy, and/or radiotherapy. At present, the treatment recommendations after surgery (adjuvant therapy) follow a pattern. This pattern is subject to change, as every two years, a worldwide conference takes place in St. Gallen, Switzerland, to discuss the actual results of worldwide multi-center studies. Depending on clinical criteria (age, type of cancer, size, metastasis) patients are roughly divided to high risk and low risk cases, with each risk category following different rules for therapy. Treatment possibilities include radiation therapy, chemotherapy, hormone therapy, and immune therapy.

In planning treatment, doctors can also use PCR tests like Oncotype DX or microarray tests that predict breast cancer recurrence risk based on gene expression. In February 2007, the first breast cancer predictor test won formal approval from the Food and Drug Administration. This is a new gene test to help predict whether women with early-stage breast cancer will relapse in 5 or 10 years, this could help influence how aggressively the initial tumor is treated.^[32]

Radiation therapy is also used to help destroy cancer cells that may linger after surgery. Radiation can reduce the risk of recurrence by 50-66% (1/2 - 2/3rds reduction of risk) when delivered in the correct dose. ^[33]

Prognosis

This section does not cite any references or sources. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. (October 2007)

A prognosis is the medical team's "best guess" in how cancer will affect a patient. There are many prognostic factors associated with breast cancer: staging, tumor size and location, grade, whether disease is systemic (has metastasized, or traveled to other parts of the body), recurrence of the disease, and age of patient.

Stage is the most important, as it takes into consideration size, local involvement, lymph node status and whether metastatic disease is present. The higher the stage at diagnosis, the worse the prognosis. The stage is raised by the invasiveness of disease to lymph nodes, chest wall, skin or beyond, and the aggressiveness of the cancer cells. The stage is lowered by the presence of cancer-free zones and close-to-normal cell behaviour (grading). Size is not a factor in staging unless the cancer is invasive. Ductal Carcinoma in situ throughout the entire breast is stage zero.

Grading is based on how biopsied, cultured cells behave. The closer to normal cancer cells are, the slower their growth and the better the prognosis. If cells are not well differentiated, they will appear immature, will divide more rapidly, and will tend to spread. Well differentiated is given a grade of 1, moderate is grade 2, while poor or undifferentiated is given a higher grade of 3 or 4 (depending upon the scale used).

Younger women tend to have a poorer prognosis than post-menopausal women due to several factors. Their breasts are active with their cycles, they may be nursing infants, and may be unaware of changes in their breasts. Therefore, younger women are usually at a more advanced stage when diagnosed. There may also be biologic factors contributing to a higher risk of disease recurrence for younger women with breast cancer.^[34]

The presence of estrogen and progesterone receptors in the cancer cell, while not prognostic, is important in guiding treatment. Those who do not test positive for these specific receptors will not respond to hormone therapy.

Likewise, HER2/neu status directs the course of treatment. Patients whose cancer cells are positive for HER2/neu have more aggressive disease and may be treated with trastuzumab, a monoclonal antibody that targets this protein.

Elevated CA15-3, in conjunction with alkaline phosphatase, was shown to increase chances of early recurrence in breast cancer.^[35]

Psychological aspects

The emotional impact of cancer diagnosis, symptoms, treatment, and related issues can be severe. Most larger hospitals are associated with cancer support groups which provide a supportive environment to help patients cope and gain perspective from cancer survivors. Online cancer support groups are also very beneficial to cancer patients, especially in dealing with uncertainty and body-image problems inherent in cancer treatment.

Not all breast cancer patients experience their illness in the same manner. Factors such as age can have a significant impact on the way a patient copes with a breast cancer diagnosis. Premenopausal women with estrogen-receptor positive breast cancer must confront the issues of early menopause induced by many of the chemotherapy regimens used to treat their breast cancer, especially those that use hormones to counteract ovarian function. ^[36]

On the other hand, a recent study conducted by researchers at the College of Public Health of the University of Georgia showed that older women may face a more difficult recovery from breast cancer than their younger counterparts.^[37] As the incidence of breast cancer in women over 50 rises and survival rates increase, breast cancer is increasingly becoming a geriatric issue that warrants both further research and the expansion of specialized cancer support services tailored for specific age groups.^[37]

Epidemiology

Main article: Epidemiology and etiology of breast cancer

Epidemiological risk factors for a disease can provide important clues as to the etiology, or cause, of a disease. The first case-controlled study on breast cancer epidemiology was done by Janet Lane-Claypon, who published a comparative study in 1926 of 500 breast cancer cases and 500 control patients of the same background and lifestyle for the British Ministry of Health.^{[38][verification needed][39]}

Worldwide, breast cancer is by far the most common cancer amongst women, with an incidence rate more than twice that of colorectal cancer and cervical cancer and about three times that of lung cancer. However breast cancer mortality worldwide is just 25% greater than that of lung cancer in women.^[2] In 2004, breast cancer caused 519,000 deaths worldwide (7% of cancer deaths; almost 1% of all deaths).^[3] The number of cases worldwide has significantly increased since the 1970s, a phenomenon partly blamed on modern lifestyles in the Western world.^[40][41]

The incidence of breast cancer varies greatly around the world, being lower in less-developed countries and greatest in the more-developed countries. In the twelve world regions, the annual age-standardized incidence rates per 100,000 women are as follows: in Eastern Asia, 18; South Central Asia, 22; sub-Saharan Africa, 22; South-Eastern Asia, 26; North Africa and Western Asia, 28; South and Central America, 42; Eastern Europe, 49; Southern Europe, 56; Northern Europe, 73; Oceania, 74; Western Europe, 78; and in North America, 90.^[42]

United States

Women in the United States have the highest incidence rates of breast cancer in the world; 141 among white women and 122 among African American women.^[43][44] Among women in the US, breast cancer is the most common cancer and the second-most common cause of cancer death (after lung cancer).^[44] Women in the US have a 1 in 8 (12.5%) lifetime chance of developing invasive breast cancer and a 1 in 35 (3%) chance of breast cancer causing their death.^[44] In 2007, breast cancer was expected to cause 40,910 deaths in the US (7% of cancer deaths; almost 2% of all deaths).^[10] This figure includes 450-500 men who die annually in the U.S. out of approximately 2000 who contract it.^[45]

In the US, both incidence and death rates for breast cancer have been declining in the last few years in Native Americans and Alaskan Natives.^[10][46] Nevertheless, a US study conducted in 2005 by the Society for Women's Health Research indicated that breast cancer remains the most feared disease,^[47] even though heart disease is a much more common cause of death among women.^[48] Many doctors say that women exaggerate their risk of breast cancer.^[49]

Racial disparities

Several studies have found that black women in the U.S. are more likely to die from breast cancer even though white women are more likely to be diagnosed with the disease. Even after diagnosis, black women are less likely to get treatment compared to white women.^[50][51][52] Scholars have advanced several theories for the disparities, including inadequate access to screening, reduced availability of the most advanced surgical and medical techniques, or some biological characteristic of the disease in the African American population.^[53] Some studies suggest that the racial disparity in breast cancer outcomes may reflect cultural biases more than biological disease differences.^[54] Research is currently ongoing to define the contribution of both biological and cultural factors.^[51][55]

UK

45,000 cases diagnosed and 12,500 deaths per annum. 60% of cases are treated with Tamoxifen, of these the drug becomes ineffective in 35%.^[56]

History

Breast cancer may be one of the oldest known forms of cancerous tumors in humans. The oldest description of cancer was discovered in Egypt and dates back to approximately 1600 BC. The Edwin Smith Papyrus describes 8 cases of tumors or ulcers of the breast that were treated by cauterization.The writing says about the disease, "There is no treatment."^[57] For centuries, physicians described similar cases in their practises, with the same conclusion. It was not until doctors achieved greater understanding of the circulatory system in the 17th century that they could establish a link between breast cancer and the lymph nodes in the armpit. The French surgeon Jean Louis Petit (1674–1750) and later the Scottish surgeon Benjamin Bell (1749–1806) were the first to remove the lymph nodes, breast tissue, and underlying chest muscle. Their successful work was carried on by William Stewart Halsted who started performing mastectomies in 1882. The Halsted radical mastectomy often involved removing both breasts, associated lymph nodes, and the underlying pectoral muscles. This often led to long-term pain and disability, but was seen as necessary in order to prevent the cancer from recurring.^[58] Radical mastectomies remained the standard until the 1970s, when a new understanding of metastasis led to perceiving cancer as a systemic illness as well as a localized one, and more sparing procedures were developed that proved equally effective.

Prominent women who died of breast cancer include Empress Theodora, wife of Justinian; Anne of Austria, mother of Louis XIV of France; Mary Washington, mother of George, and Rachel Carson, the environmentalist.^[59]

Prevention

Regular exercise, weight loss, avoidance of alcohol, stressors, toxic chemicals and environmental pollutants are all helpful measures in the prevention of breast cancer. Dietary inclusion of dried beans, cruciferous vegetables, and whole grains have also proven beneficial. Brazil nuts, rich in the mineral selenium, when combined with natural vitamin E as found in almonds and walnuts are also highly effective in reducing cancer risk. ^[60][61]

In addition, there are three published studies with findings indicating that regular semen consumption is able to prevent breast cancer.^{[62] [63] [64]} This effect is attributed to its DHA, glycoprotein and selenium content.^[65]

Cultural references

In the month of October, breast cancer is recognized by survivors, family and friends of survivors and/or victims of the disease.^[66] A pink ribbon is worn to recognize the struggle that sufferers face when battling the cancer.^[67]

Pink for October is an initiative started by Matthew Oliphant, which asks that any sites willing to help make people aware of breast cancer, change their template or layout to include the color pink, so that when visitors view the site, they see that the majority of the site is pink. Then after reading a short amount of information about breast cancer, or being redirected to another site, they are aware of the disease itself.^[68]

The patron saint of breast cancer is Saint Agatha of Sicily.^[69]

The pink and blue ribbon was designed in 1996 by Nancy Nick, President and Founder of the John W. Nick Foundation to bring awareness that "Men Get Breast Cancer Too!"^[70]

Gallery

Wikimedia Commons has media related to: Breast cancer

This section looks like an image gallery. Wikipedia policy discourages galleries of random images of the article subject; please edit the section in accordance with the policy, moving freely licensed images to Wikimedia Commons if they are not already hosted there.

Breast self exam	Illustration of the early warning signs of breast cancer	Woman undergoing mammogram	Breastcancer in ultrasound
Breast prostheses used by some mastectomy patients	Patient with advanced local-regional recurrence of breast cancer with an ulcerating axillary mass	Mastectomy specimen containing a very large cancer of the breast (in this case, an invasive ductal carcinoma)	Typical macroscopic (gross) appearance of the cut surface of a mastectomy specimen containing a cancer, in this case, an invasive ductal carcinoma of the breast, pale area at the center
Excised human breast tissue, showing a stellate area of cancer 2cm in diameter. The lesion could be felt clinically as a hard mobile lump, not attached to skin or chest wall.	Benign granular cell tumor removed from a woman's breast. Granular cell tumors of the breast represent one of the few lesions that can impersonate an invasive breast cancer on gross examination.	Infiltrating ductal carcinoma of the breast	Infiltrating ductal carcinoma of the Breast assayed with anti Mucin 1 antibody
Breast cancer (Infiltrating ductal carcinoma of the breast) assayed with anti HER-2 (ErbB2) antibody	Invasive lobular carcinoma of the breast demonstrating a predominantly lobular growth pattern	Metaplastic (sarcomatoid) carcinoma of the breast.	Histopathologic image from ductal cell carcinoma in situ (DCIS) of breast. Hematoxylin-eosin stain.
Histopathology of invasive ductal carcinoma of the breast representing a scirrhous growth. Core needle biopsy. HER-2/neu oncoprotein expression by Ventana immunostaining system.

See also

• List of notable breast cancer patients according to occupation
• List of notable breast cancer patients according to survival status
• List of breast carcinogenic substances
• Mammary tumor for breast cancer in other animals
• Breast reconstruction
• Alcohol and cancer
• Mammography Quality Standards Act
• National Breast Cancer Coalition
• National Comprehensive Cancer Network
• Breast Cancer Action
• Breakthrough Breast Cancer
• Living Beyond Breast Cancer
• International Agency for Research on Cancer
• Susan G. Komen for the Cure
• Breast Cancer Network of Strength
• Your Disease Risk

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External links

Wikimedia Commons has media related to: Breast cancer

The Wikibook Sexual Health has a page on the topic of Cancer#Breast Cancer

• Breast cancer at the Open Directory Project
• Breast cancer at the Yahoo! Directory

v • d • e Breast cancer Main article · Epidemology and etiology · Screening · Treatment · Ductal carcinoma

v • d • e Tumors: breast cancer (C50/D24, 174-175/217) Fibroepithelial/stromal Fibroadenoma · Phyllodes tumor Ductal, lobular, and medullary Ductal Ductal carcinoma in situ (DCIS): Paget's disease of the breast · Comedocarcinoma Invasive ductal carcinoma (IDC) Lobular Lobular carcinoma in situ (LCIS) Invasive lobular carcinoma (ILC) Medullary Medullary carcinoma Other/ungrouped Inflammatory breast cancer Precursor lesions Atypical ductal hyperplasia see also noncongenital, congenital

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