Breast Cancer

The breasts are made of fat, glands, and connective (fibrous) tissue. The breast has several lobes, which split into lobules that end in the milk glands. Tiny ducts run from the many tiny glands, connect together, and end in the nipple.

• These ducts are where 80% of breast cancers occur. Ductal cancer is breast cancer that arises in the ducts.
• Cancer developing in the lobules is termed lobular cancer. About 10%-15% of breast cancers are of this type.
• Other less common types of breast cancer include inflammatory breast cancer, medullary cancer, phyllodes tumor, angiosarcoma, mucinous (colloid) carcinoma, mixed tumors, and a type of cancer involving the nipple termed Paget's disease.

Precancerous changes, called in situ changes, are common.

• In situ is Latin for "in place" or "in site" and means that the changes haven't spread from where they started (also called non-invasive cancer).
• Ductal carcinoma in situ (DCIS) is the medical term for in situ changes that occur in the ducts. Routine mammography may identify DCIS.
• Lobular carcinoma in situ (LCIS) refers to abnormal-appearing cells in the milk-producing lobules of the breast. This is considered a non-cancerous condition that increases a woman's risk for breast cancer.

When cancers spread into the surrounding tissues, they are termed infiltrating cancers. Cancers spreading from the ducts into adjacent spaces are termed infiltrating ductal carcinomas. Cancers spreading from the lobules are infiltrating lobular carcinomas.

The most serious and dangerous cancers are metastatic cancers. Metastasis means that the cancer has spread from the place where it started into other tissues distant from the original tumor site. The most common place for breast cancer to metastasize is into the lymph nodes under the arm or above the collarbone on the same side as the cancer. Other common sites of breast cancer metastasis are the brain, the bones, and the liver. Cancers that have spread only into the lymph nodes under the arm are still curable. Those that spread to distant lymph nodes or other organs are not usually curable with available treatments today. Treatments can extend lives for years even in these cases.

Many women who develop breast cancer have no risk factors other than age and gender.

• Gender is the biggest risk because breast cancer occurs mostly in women.
• Age is another critical breast cancer risk factor. Breast cancer may occur at any age, though the risk of breast cancer increases with age. The average woman at 30 years of age has one chance in 280 of developing breast cancer in the next 10 years. This chance increases to one in 70 for a woman 40 years of age, and to one in 40 at 50 years of age. A 60-year-old woman has a one in 30 chance of developing breast cancer in the next 10 years.
• White women are slightly more likely to develop breast cancer than African-American women in the U.S.
• A woman with a personal history of cancer in one breast has a three- to fourfold greater risk of developing a new cancer in the other breast or in another part of the same breast. This refers to the risk for developing a new tumor and not a recurrence (return) of the first cancer.

Genetic Causes of Breast Cancer

Family history is a risk factor for breast cancer. Both maternal and paternal relatives are important. The risk is highest if the affected relative developed breast cancer at a young age, had cancer in both breasts, or if she is a close relative. First-degree relatives (mother, sister, and daughter) are most important in estimating risk. Several second-degree relatives (grandmother, aunt) with breast cancer may also increase risk. Breast cancer in a male increases the risk for all his close female relatives. Having relatives with both breast and ovarian cancer also increases a woman's risk of developing breast cancer.

There is great interest in genes linked to breast cancer. About 5%-10% of breast cancers are believed to be hereditary, because of mutations, or changes, in certain genes that are passed along in families.

• BRCA1 and BRCA2 are abnormal genes that, when inherited, markedly increase the risk of breast cancer to a lifetime risk estimated between 45%-65%. Women with these abnormal genes also have an increased likelihood of developing ovarian cancer. Women who have the BRCA1 gene tend to develop breast cancer at an early age.
• BRCA2 mutations are associated with a lifetime male breast cancer risk of about 6.8%.
• Testing for these genes is expensive and is not always covered by insurance.
• The issues around testing are complicated, and women who are interested in testing should discuss their risk factors with their health care providers and may want to talk to a genetic counselor.

Hormonal Causes of Breast Cancer

Hormonal influences play a role in the development of breast cancer.

• Women who have early onset of menstruation (early menarche -- 12 or younger) or experience a late menopause (55 or older) have a slightly higher risk of developing breast cancer. Conversely, being older at the time of the first menstrual period and early menopause tend to protect one from breast cancer.
• Having a child before 30 years of age may provide some protection, and having no children may increase the risk for developing breast cancer.
• Using oral contraceptive pills means that a woman has a slightly increased risk of breast cancer than women who have never used them. This risk appears to decrease and return to normal with time once a woman stops taking the pills.
• A large study conducted by the Women's Health Initiative showed an increased risk of breast cancer in postmenopausal women who were on a combination of estrogen and progesterone for several years. Therefore, women who are considering hormone therapy for menopausal symptoms need to discuss the risk versus the benefit with their health care providers. Patients should weigh quality of life concerns against the relative risks of such medications.

Lifestyle and Dietary Causes of Breast Cancer

Breast cancer seems to occur more frequently in countries with high dietary intake of fat, and being overweight or obese is a known risk factor for breast cancer, particularly in postmenopausal women.

• This link is thought to be an environmental influence rather than genetic. For example, Japanese women, at low risk for breast cancer while in Japan, increase their risk of developing breast cancer after coming to the United States.
• Several studies comparing groups of women with high- and low-fat diets, however, have failed to show a difference in breast cancer rates.

Alcohol consumption is also an established risk factor for the development of breast cancer. The risk increases with the amount of alcohol consumed. Women who consume two to five alcoholic beverages per day have a risk about one and a half times that of nondrinkers for the development of breast cancer. Consumption of one alcoholic drink per day results in a slightly elevated risk.

Studies are also showing that regular exercise may reduce a woman's risk of developing breast cancer. Studies have not definitively established how much activity provides a significant reduction in risk. One study from the Women's Health Initiative (WHI) showed that as little as one and a quarter to two and a half hours per week of brisk walking reduced a woman's breast cancer risk by 18%.

Benign Breast Disease

• Fibrocystic breast changes are very common. Fibrocystic breasts are lumpy with some thickened tissue and are frequently associated with breast discomfort, especially right before the menstrual period. This condition does not lead to breast cancer.
• However, certain other types of benign breast changes, such as those diagnosed on biopsy as proliferative or hyperplastic, do predispose women to the later development of breast cancer.

Environmental Causes of Breast Cancer

Radiation treatment increases the likelihood of developing breast cancer but only after a long delay. For example, women who received radiation therapy to the upper body for treatment of Hodgkin's disease before 30 years of age have a significantly higher rate of breast cancer than the general population.

Early stage breast cancer usually has no symptoms or signs, although sometimes it's possible to feel a lump in the breast. It is usually not painful.

Most people discover breast cancer before symptoms appear, either by finding an abnormality on mammography or feeling a breast lump. A lump in the armpit or above the collarbone that does not go away may be a sign of cancer. Other possible symptoms are breast discharge, nipple inversion, or changes in the skin overlying the breast.

• Most breast lumps are not cancerous. A doctor should evaluate all breast lumps.
• Breast discharge is a common problem. Discharge is most concerning if it is from only one breast or if it is bloody. In any case, a doctor should evaluate all breast discharge.
• Nipple inversion is a common variant of normal nipples, but nipple inversion that is a new development needs to be of concern.
• Changes in the skin of the breast include redness, changes in texture, and puckering. Skin diseases usually cause these changes but occasionally can be associated with breast cancer.

Breast cancer develops over months or years. Once identified, however, a certain sense of urgency is felt about the treatment, because breast cancer is much more difficult to treat as it spreads. You should see your health care provider if you experience any of the following:

• Finding a breast lump
• Finding a lump in your armpit or above your collarbone that does not go away in two weeks or so
• Developing nipple discharge
• Noticing new nipple inversion or skin changes over the breast

Redness or swelling in the breast may suggest an infection of the breast.

• You should see your health care provider within the next 24 hours to begin treatment.
• If you have redness, swelling, or severe pain in the breast and are unable to reach your health care provider, this warrants a trip to the nearest emergency department.

If your mammogram spots an abnormality, you should see your health care provider right away to make a plan for further evaluation.

Diagnosis of breast cancer usually is comprised of several steps, including examination of the breast, mammography, possibly ultrasonography or MRI, and, finally, biopsy. Biopsy (taking a piece of breast tissue) is the only definitive way to diagnose breast cancer.

Examination of the Breast

• A complete breast examination includes visual inspection and careful palpation (feeling) of the breasts, the armpits, and the areas around your collarbone.
• During that exam, your health care provider may palpate a lump or just feel a thickening.

Mammography

• Mammograms are X-rays of the breast that may help define the nature of a lump. Medical professionals recommend mammograms for screening to find early cancer.
• Usually, it is possible to tell from the mammogram whether a lump in the breast is abnormal, but no test is 100% reliable. Mammograms may miss as many as 10%-15% of breast cancers.
• A false-positive mammogram is one that suggests malignancy (cancer) when a biopsy finds no malignancy.
• A false-negative mammogram is one that appears normal when in fact cancer is present.
• A mammogram alone is often not enough to evaluate a lump. Your health care provider will probably request additional tests.
• Health care providers need to clearly define all breast lumps as benign or biopsy them.

Ultrasound

• Medical professionals often perform an ultrasound of the breast to evaluate a breast lump.
• Ultrasound waves create a "picture" of the inside of the breast.
• It can demonstrate whether a mass is filled with fluid (cystic) or solid. Cancers are usually solid, while many cysts are benign.
• Health care professionals may use ultrasound to guide a biopsy or the removal of fluid.

MRI

• MRI may provide additional information and may clarify findings that have been seen on mammography or ultrasound.
• MRI is not routine for screening for cancer, but health care providers may recommend it in special situations.

Biopsy

• The only way to diagnose breast cancer with certainty is to biopsy the tissue in question. Biopsy means to take a very small piece of tissue from the body for examination under the microscope and testing by a pathologist to determine if cancer is present. A number of biopsy techniques are available.
• Fine-needle aspiration consists of placing a needle into the breast and sucking out some cells for examination by a pathologist. It is common for doctors to use this technique after finding a fluid-filled mass and cancer is not likely.
• A physician performs a core-needle biopsy with a special needle that takes a small piece of tissue for examination. Usually, a physician directs the needle into the suspicious area with ultrasound or mammogram guidance. Medical professionals use this technique more and more because it is less invasive than surgical biopsy. It obtains only a sample of tissue rather than removing an entire lump. Occasionally, if a physician can feel the mass easily, cells may be removed with a needle without additional guidance.
• A medical professional performs a surgical biopsy by making an incision in the breast and removing the piece of tissue. Certain techniques allow removal of the entire lump.
• Regardless of how the biopsy is taken, a pathologist will review the tissue. These are physicians specially trained in diagnosing diseases by looking at cells and tissues under a microscope.
• If a physician diagnoses a cancer on biopsy, the tissue will be tested for hormone receptors. Receptors are sites on the surface of tumor cells that bind to estrogen or progesterone. In general, the more receptors, the more sensitive the tumor will be to hormone therapy. There are also other tests (for example, measurement of HER2/neu receptors) that may be performed to help characterize a tumor and determine the type of treatment that will be most effective for a given tumor. Genomic testing (tests that evaluate gene expression in the tumor) is also often performed on the tissue sample to determine how likely it is that an individual tumor will recur and to predict whether a patient with an estrogen receptor-positive tumor will benefit from adding chemotherapy to the hormonal therapy regimen.

Surgery is the mainstay of therapy for breast cancer. The choice of which type of surgery is based on a number of factors, including the size and location of the tumor, the type of tumor and the person's overall health and personal wishes. Breast-sparing surgery is often possible and can be equally effective when combined with other treatment as compared to whole breast removal or mastectomy.

A doctor stages the cancer using the information from surgery and from other tests. Staging is a classification that reflects the extent and spread of a cancer at the time of its diagnosis and has an impact on treatment decisions and the prognosis for recovery.

• Staging in breast cancer is based on the size of the tumor, which parts of the breast are involved, how many and which lymph nodes are affected, and whether the cancer has metastasized to another part of the body.
• Physicians may refer to cancers as invasive if they spread to other tissues. Cancer that does not spread to other tissues is noninvasive. Carcinoma in situ is a noninvasive cancer.

Breast cancer is staged from 0 to IV. You might see a TNM staging system based on the tumor size, lymph node involvement, and whether metastasis has occurred. This TNM system is used to determine the final staging from 0 to IV.

• Stage 0 is noninvasive breast cancer, that is, carcinoma in situ with no affected lymph nodes or metastasis. This is the most favorable stage of breast cancer.
• Stage I is breast cancer that is less than 2 cm (3/4 in) in diameter and has not spread from the breast.
• Stage II is breast cancer that is fairly small in size but has spread to lymph nodes in the armpit or cancer that is somewhat larger but has not spread to the lymph nodes.
• Stage III is breast cancer of a larger size, greater than 5 cm (2 in), with greater lymph node involvement, or of the inflammatory type.
• Stage IV is metastatic breast cancer: a tumor of any size or type that has metastasized to another part of the body. This is the least favorable stage.

Surgery is generally the first step after the diagnosis of breast cancer. The type of surgery is dependent upon the size and type of tumor and the patient's health and preferences. Discuss the choice of procedures with your health care team as any approach has advantages and disadvantages.

• Lumpectomy involves removal of the cancerous tissue and a surrounding area of normal tissue. This is not considered curative and should usually be done in association with other therapy such as radiation therapy with or without chemotherapy or hormonal therapy. This is breast-conserving surgery.
• At the time of lumpectomy, the axillary lymph nodes (the glands in the armpit) need to be evaluated for the spread of cancer. This can be done by either removing the lymph nodes or by sentinel node biopsy (biopsy of the closest lymph node to the tumor).
• If a sentinel node biopsy is done at the time of lumpectomy, it may allow the surgeon to remove only some of the lymph nodes. In this procedure, a dye is injected into the area of the tumor. The path of the substance is then followed as it travels to the lymph nodes. The first node reached is the sentinel node. This node is considered most important to biopsy when evaluating the spread of the tumor.
• If the sentinel node biopsy is positive, the surgeon will usually remove of all of the lymph nodes found in the axilla (armpit).
• Simple mastectomy removes the entire breast but no other structures. If the cancer is invasive, this surgery alone will not cure it. It is a common treatment for DCIS, a noninvasive type of breast cancer.
• Nipple-sparing mastectomy is a surgical procedure that leaves the nipple and skin in place.
• Modified radical mastectomy removes the breast and the axillary (underarm) lymph nodes but does not remove the underlying muscle of the chest wall. Although additional chemotherapy or hormonal therapy is almost always offered, surgery alone is considered adequate to control the disease if it has not metastasized.
• Radical mastectomy involves removal of the breast and the underlying chest-wall muscles, as well as the underarm contents. This surgery is no longer done because current therapies are less disfiguring and have fewer complications.

Many women have treatment in addition to surgery, which may include radiation therapy, chemotherapy, or hormonal therapy. The decision about which additional treatments are needed is based upon the stage and type of cancer, the presence of hormone (estrogen and progesterone) and/or HER2/neu receptors, and patient health and preferences.

Radiation Therapy for Breast Cancer

Radiation therapy is used to kill tumor cells if there are any left after surgery.

• Radiation is a local treatment and therefore works only on tumor cells that are directly in its beam.
• Radiation is used most often in people who have undergone conservative surgery such as lumpectomy. Conservative surgery is designed to leave as much of the breast tissue in place as possible.
• Radiation therapy is usually given five days a week over five to six weeks. Each treatment takes only a few minutes.
• Radiation therapy is painless and has relatively few side effects. However, it can irritate the skin or cause a burn similar to a bad sunburn in the area.
• Radiation therapy in breast cancer is usually external beam radiation, where the radiation is pointed at a specific area of the breast from the outside. Rarely internal radiation therapy is used, where radioactive pellets are implanted close to the cancer. Newer techniques of rapid partial breast radiation have been developed and may be appropriate in certain circumstances. The use of radiation treatment at the same time as surgery is done more in other countries that here, but continues to be explored.

Chemotherapy for Breast Cancer

Chemotherapy consists of the administration of medications that kill cancer cells or stop them from growing. In breast cancer, three different chemotherapy strategies may be used:

1. Adjuvant chemotherapy is given to some people who have had potentially curative treatment for their breast cancer, such as surgery and for whom radiation may be planned. The possibility that breast cancer cells may have spread microscopically away from the area operated upon or to be radiated is thought to be what results in the metastases developing at a later date. Adjuvant therapy is given to try to eliminate these hidden, but potentially still present cells to reduce the risk of relapse. The characteristics of the primary cancerous tumor both grossly, microscopically, and on genomic analysis help the doctor to judge what risk there is that such hidden cells could be present. Adjuvant chemotherapy is typically given in the case of triple-negative breast cancer, HER2-positive breast cancer, or other cancers that are deemed to be at high risk.
2. Presurgical chemotherapy (known as neoadjuvant chemotherapy) is given to shrink a large tumor and/or to kill stray cancer cells. This increases the chances that surgery will get rid of the cancer completely.
3. Therapeutic chemotherapy is routinely administered to women with metastatic breast cancer that has spread beyond the confines of the breast or local area.

• Most chemotherapy agents are given through an IV line, but some are given as pills.
• Chemotherapy is usually given in "cycles." Each cycle includes a period of intensive treatment lasting a few days or weeks followed by a week or two of recovery. Most people with breast cancer receive at least two, more often four, cycles of chemotherapy to begin with. Tests are then repeated to see what effect the therapy has had on the cancer.
• Chemotherapy differs from radiation in that it treats the entire body and thus may target stray tumor cells that may have migrated from the breast area.
• The side effects of chemotherapy are well known. Side effects depend on which drugs are used. Many of these drugs have side effects that include loss of hair, nausea and vomiting, loss of appetite, fatigue, and low blood cell counts. Low blood counts may cause patients to be more susceptible to infections, to feel sick and tired, or to bleed more easily than usual. Medications are available to treat or prevent many of these side effects.

Hormonal Therapy for Breast Cancer

Hormonal therapy may be given because breast cancers (especially those that have ample estrogen or progesterone receptors) are frequently sensitive to changes in hormones. Hormonal therapy may be given to prevent recurrence of a tumor or for treatment of existing disease.

• In some cases, it is beneficial to suppress a woman's natural hormones with drugs; in others, it is beneficial to add hormones.
• In premenopausal women, ovarian ablation (removal of the hormonal effects of the ovary) may be useful. This can be accomplished with medications that block the ovaries' ability to produce estrogens or by surgically removing the ovaries, or less commonly with radiation.
• Until recently, tamoxifen (Nolvadex), an antiestrogen (a drug that blocks the effect of estrogen), has been the most commonly prescribed hormone treatment. It is used both for breast cancer prevention and for treatment.
• Fulvestrant (Faslodex) is another drug that acts via the estrogen receptor, but instead of blocking it, this drug eliminates it. It can be effective if the breast cancer is no longer responding to tamoxifen. Fulvestrant is only given to women who are already in menopause and is approved for use in women with advanced breast cancer.
• Palbociclib (Ibrance) is a drug that has been shown to improve survival in women with metastatic estrogen receptor-positive breast cancer.
• Toremifene (Fareston) is another anti-estrogen drug closely related to tamoxifen.
• Aromatase inhibitors, which block the effect of a key hormone affecting the tumor, may be more effective than tamoxifen in the adjuvant setting. The drugs anastrozole (Arimidex), exemestane (Aromasin), and letrozole (Femara) have a different set of side effects and risks than tamoxifen.
• Aromatase inhibitors also are frequently used after two or more years of tamoxifen therapy.
• Megace (megestrol acetate) is a drug similar to progesterone which may also be used as hormonal therapy.

Targeted Therapy for Breast Cancer

• Targeted therapy is a type of treatment that has been developed to directly work against some of the cellular changes that have been identified in breast cancers. Examples of targeted therapies include monoclonal antibodies against cancer cell-specific proteins.

HER2- positive breast cancer is any breast cancer that expresses the HER2 protein (sometimes referred to as HER2/neu), a protein responsible for cancer cell growth. About 15%-25% of breast cancers are HER2-positive. Because the treatment for HER2-positive breast cancers is different, all breast cancer tissue is tested for the presence of HER2. This is done on the surgically removed tissue sample, which is tested for hormone receptor status (estrogen and progesterone receptors), as well.

There are two approved tissue testing methods for HER2 status. In 2013, the American Society of Clinical Oncologists (ASCO) and the College of American Pathologists (CAP) issued an updated joint clinical practice guideline about HER2 testing for breast cancer. The two approved methods currently used in the U.S. to test for HER2 are immunohistochemistry (IHC) and in-situ hybridization (ISH). IHC testing uses specially labeled antibodies to show how much of the HER2 protein is present on the cancer cell surface, while ISH testing measures the number of copies of the HER2 gene inside each cell. There are two main types of ISH tests: fluorescence and bright-field ISH. Fluorescence in situ hybridization is referred to as FISH. Both of these tests are performed on the tumor sample that is removed at the time of surgery.

Signs and symptoms of HER2-positive breast cancer are the same as those of all breast cancers. It is not possible to determine HER2 presence by the clinical signs and symptoms.

Specialized breast cancer treatments, known as targeted therapies, have been developed to treat breast cancers that express the HER2 protein. Targeted therapies are newer forms of cancer treatment that specifically attack cancer cells and do less damage to normal cells than traditional chemotherapy. Targeted therapies for HER2-positive breast cancer include the following:

• Trastuzumab (Herceptin) is an antibody against the HER2 protein Adding treatment with trastuzumab to chemotherapy given after surgery has been shown to lower the recurrence rate and death rate in women with HER2-positive early breast cancers. Using trastuzumab along with chemotherapy has become a standard adjuvant treatment for these women.
• Pertuzumab (Perjeta) also works against HER2-positive breast cancers by blocking the cancer cells' ability to receive growth signals from HER2.
• Lapatinib (Tykerb) is another drug that targets the HER2 protein and may be given combined with chemotherapy. It is used in women with HER2-positive breast cancer that is no longer helped by chemotherapy and trastuzumab.
• T-DM1 or ado-trastuzumab emtansine (Kadcyla) is a combination of Herceptin and the chemotherapy medication emtansine. Kadcyla was designed to deliver emtansine to cancer cells by attaching it to Herceptin.

People who have been diagnosed with breast cancer need careful follow-up care for life. Initial follow-up care after completion of treatment is usually every three to six months for the first two to three years.

• This follow-up protocol is based on the individual circumstances and treatments received.

The most important risk factors for the development of breast cancer are gender, age, and genetics. Because women can do nothing about these risks, regular screening is recommended in order to allow early detection and thus prevent death from breast cancer.

Clinical breast examination: The American Cancer Society historically recommended a breast examination by a trained health care provider once every three years starting at 20 years of age and then yearly after age 40 years. More recent recommendations have called this recommendation into question, since there is no evidence to show any benefit of breast self-examination or breast examination by a physician. Currently, these practices are not recommended, but it is recommended that women be familiar with the look and feel of their breasts and report any changes to a health care provider.

Controversy has also arisen regarding when to begin mammograms for breast cancer screening. Screening truly refers to studies done in people with average risk and no symptoms in order to look for hidden cancers. The American Cancer Society recommends the following screening practice for women at average risk:

• Women ages 40 to 44 should have the choice to start annual mammograms if they wish to do so. The risks of screening as well as the potential benefits should be considered.
• Women age 45 to 54 should get mammograms every year.
• Women age 55 and older should switch to mammograms every two years or have the choice to continue yearly screening.

Screening should continue as long as a woman is in good health and is expected to live 10 more years or longer.

For women at high risk for the development of breast cancer, mammogram testing may start earlier, generally 10 years prior to the age at which the youngest close relative developed breast cancer. Genetic testing should be considered.

Obesity after menopause and excessive alcohol intake may increase the risk of breast cancer slightly. Physically active women may have a lower risk. All women are encouraged to maintain normal body weight, especially after menopause, to limit excess alcohol intake, and to get regular exercise. Hormone replacement should be limited in duration if it is medically required.

In women who are genetically at high risk for the development of breast cancer, estrogen-blocking drugs (Tamoxifen) have shown to decrease the incident of breast cancer. Side effects should be carefully discussed with your health care provider prior to embarking on therapy. A second drug, raloxifene (Evista), which is now being used for the treatment of osteoporosis, also blocks the effects of estrogen and appears to prevent breast cancer. Initial studies showed that both tamoxifen and raloxifene were able to reduce the risk of invasive breast cancer, but raloxifene did not have this protective effect against noninvasive cancer. Studies are ongoing to further characterize the effectiveness and indications for use of raloxifene as a breast cancer preventive drug.

Occasionally, a woman at very high risk for development of breast cancer will decide to have a preventive or prophylactic mastectomy to avoid developing breast cancer. Additionally, removal of the ovaries has shown to reduce the risk of developing breast cancer in women who have the BRCA1 or BRCA2 mutations and who have their ovaries surgically removed before they reach age 40.

Research is ongoing to help clarify the precise causes of breast cancer and the cellular mechanism by which certain lifestyle factors cause development of cancer. A long-term ongoing study is looking at 50,000 women whose sisters had breast cancer and will collect information from these women over a period of 10 years. The influence of diet and lifestyle factors that may influence cancer development or progression is of particular interest to researchers. Clinical trials for breast cancer are always ongoing to evaluate new therapies or combinations of therapies.

Other types of research are directed at identification of additional cellular targets (such as the HER2 protein) that may be useful for the development of new therapies for breast cancer. The development of new chemotherapy agents is being studied as well as the effectiveness of newer and different radiotherapy regimens.

Surgical therapies are also being improved and advances in surgical technique are being investigated to improve both surgical removal of breast cancers and breast reconstruction following tumor removal.

Due to improved screening and awareness of breast cancer coupled with advances in therapy, death rates from breast cancer have been continuously declining since 1990. In particular, noninvasive (in situ) cancers are associated with a very high cure rate, but even advanced tumors have been successfully treated. It is important to remember that breast cancer is a highly treatable disease and that screening for breast cancer often enables the detection of tumors at their earliest stages when treatment has the best chance for success.

HER2-positive tumors tend to grow faster than tumors that do not express the HER2 protein. However, recurrence rates vary and depend upon more than simply the HER2 status of the tumor. Like other breast cancers, recurrence rates depend upon the extent of spread of the tumor at the time of diagnosis (stage) of the tumor along with other characteristics of the tumor. The development of anti-HER2 therapies (discussed previously) has significantly improved the outlook for patients with HER2-positive breast cancer.

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