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Breast Cancer

According to the CDC, breast cancer is the leading cause of cancer and cancer death among women in the U.S. In 2016, roughly 300,000 women in the U.S. will be diagnosed with invasive or in-situ breast cancer. Roughly 1 in 8 women will develop invasive breast cancer over a lifetime. However, today, 9 out of 10 women with breast cancer are still alive five years after their diagnosis

What is Breast Cancer?

Cancer is a group of many related diseases that begin in cells, the body's basic unit of life. The body is made up of many types of cells, and normally, cells grow and divide to produce more cells only when the body needs them. Sometimes, however, cells keep dividing when new cells are not needed. These extra cells form a mass of tissue, called a growth or tumor. There are two types of tumor: benign and malignant.

Benign tumors are not cancer. They can usually be removed, and, in most cases, they do not come back. Cells from benign tumors do not spread to other parts of the body, and are not a threat to life.

Malignant tumors are cancer. Cells in these tumors are abnormal; they divide without control or order, and can invade and damage nearby tissues and organs. Cancer cells can break away from a malignant tumor and enter the bloodstream or the lymphatic system, which is how cancer spreads from the original cancer site to form new tumors in other organs. The spread of cancer is called metastasis.

When cancer arises in breast tissue and spreads outside the breast, cancer cells are often found in the lymph nodes under the arm. If the cancer has reached these nodes, it means that cancer cells may have spread to other parts of the body, including other lymph nodes and other organs, such as the bones, liver, or lungs. When cancer spreads from its original location to another part of the body, the new tumor has the same kind of abnormal cells and the same name as the primary tumor. For example, if breast cancer spreads to the brain, the cancer cells in the brain are actually breast cancer cells. The disease is called metastatic breast cancer.

What Causes Breast Cancer?

The exact causes of breast cancer are not known. However, studies show that the risk of breast cancer increases with age. The disease is very uncommon in women under the age of 35. Most breast cancers occur in women over the age of 50, and the risk is especially high for women over age 60. Breast cancer occurs more often in white women than African-American or Asian women.

Women with the following conditions have an increased risk for breast cancer:

  • Personal history of breast cancer - Women who have had breast cancer face an increased risk of getting breast cancer in the other breast.
  • Family history - Risk for developing breast cancer increases if a close relative (mother, sister, or daughter) has had breast cancer, especially at a young age. In families where many women have had the disease, gene testing can sometimes show the presence of specific genetic changes that increase the risk of breast cancer. Doctors may suggest ways to try to delay or prevent breast cancer, or to improve the detection of this disease in women who have these changes in their genes.
  • Certain breast changes - Having a diagnosis of atypical hyperplasia or lobular carcinoma in situ (LCIS) may increase the risk of breast cancer.

Other factors associated with an increased risk for breast cancer include:

  • Estrogen - Evidence suggests that the longer a woman is exposed to estrogen (made by the body, taken as a drug, or delivered by a patch), the higher the risk of developing breast cancer. The risk is somewhat increased among women who began menstruation at an early age (before age 12), experienced late menopause (after age 55), never had children, or took Hormone Replacement Therapy (HRT) for extended periods of time.
  • Late childbearing - Women who have their first child late (after about age 30) have a greater chance of developing breast cancer than women who have a child at a younger age.
  • Breast density - Breast cancers nearly always develop in lobular or ductal (dense) tissue rather than in fatty tissue. Breast cancer is more likely to occur in breasts that have a lot of dense tissue. It is also more difficult to see abnormal areas on a mammogram when breasts are dense.
  • Radiation therapy - Women whose breasts were exposed to radiation during radiation therapy before age 30 are at an increased risk for developing breast cancer. Studies show that the younger a woman was when she received treatment, the higher the risk for developing breast cancer later in life.
  • Alcohol - Some studies suggest a slightly higher risk of breast cancer among women who drink alcohol.

It is important to know that many of the women who develop breast cancer have none of the risk factors listed above, other than the risk that comes with growing older.

Detecting Breast Cancer

Breast cancer screening has shown to decrease the risk of dying from breast cancer. Women can take an active part in the early detection of breast cancer by having regularly scheduled screening mammograms and clinical breast exams (performed by health professionals). Women should also perform breast self-exams themselves.

A screening mammogram is the best tool available for finding breast cancer early, before symptoms appear. Mammograms can often detect a breast lump before it can be felt. If an area of the breast looks suspicious on the screening mammogram, additional (diagnostic) mammograms may be needed. Depending on the results, the doctor may advise the woman to have a biopsy.

Symptoms of Breast Cancer

Early breast cancer usually does not cause pain, and when breast cancer first develops, there may be no symptoms at all. As the cancer grows, it can cause changes that women should watch for; breast cancer signs or symptoms may include:

  • A lump or thickening in or near the breast or in the underarm area
  • A change in the size or shape of the breast
  • Nipple discharge or tenderness, or the nipple pulled back (inverted) into the breast
  • Ridges or pitting of the breast (the skin looks like the skin of an orange); or
  • A change in the way the skin of the breast, areola, or nipple looks or feels (for example, warm, swollen, red, or scaly).

Any symptoms such as those listed should be reported to a doctor. Most often, they are not cancer, but it's important to check with the doctor so that any problems can be diagnosed and treated as early as possible.

Diagnosing Breast Cancer

A doctor may perform one or more breast examinations:

  • Clinical breast exam - involves the doctor carefully feeling the lump and the tissue around it. Benign lumps often feel different from cancerous ones. The doctor can examine the size and texture of the lump and determine whether the lump moves easily.
  • Mammography - X-rays of the breast can give the doctor important information about a breast lump.
  • Ultrasonography - can often show whether a lump is a fluid-filled cyst (not cancer) or a solid mass (which may or may not be cancer). This exam may be used along with mammography.
  • Biopsy - involves the removal of fluid or tissue from the breast so the doctor can make a diagnosis.
  • Fine-needle aspiration - A thin needle is used to remove fluid and/or cells from a breast lump. If the fluid is clear, it may not need to be checked by a lab.
  • Needle biopsy - A needle is used to remove tissue from an area that looks suspicious on a mammogram. The tissue is sent to a lab to be checked by a pathologist for cancer cells.
  • Surgical biopsy - Incisional biopsy involves cutting out a sample of a lump or suspicious area. Excisional biopsy involves removing all of the lump or suspicious area and an area of healthy tissue around the edges. A pathologist then examines the tissue under a microscope to check for cancer cells.

When Cancer Is Found

The most common type of breast cancer is ductal carcinoma, which begins in the lining of the ducts. Lobular carcinoma arises in the lobules. The pathologist is able to tell if the cancer is ductal or lobular, and whether it has invaded nearby tissues in the breast (invasive).

Hormone receptor tests of the tissue looking for estrogen (ER+) and progesterone receptors (PR+) can determine the potential response of the cancer to hormonal therapy. About 2 out of every 3 breast cancers are hormone receptor-positive. HER2 (the human epidermal growth factor receptor-2 or HER-2 gene) is a specialized protein found on breast cancer cells that controls cancer growth. The test for this gene determines the risk of the breast cancer returning and can help to determine the best treatment. Other tests (lab tests and x-rays) are sometimes performed to predict the progression of the cancer. Examinations of the bones, liver or lungs may be performed because the breast cancer may spread to these areas.

Methods of Treatment and Side Effects

Breast cancer may be treated with local therapy, systemic therapy, or both.

Local therapies, such as surgery and radiation, are used to remove or destroy breast cancer in a specific area. If the breast cancer has spread to other parts of the body, local therapy may be used to control cancer in those specific areas, such as in the lung or bone.

Systemic therapies, such as chemotherapy, hormonal therapy and biological therapy, are used to destroy or control cancer throughout the body. Sometimes, systemic therapy is used to shrink the tumor before local therapy. Systemic therapy is also used to prevent the cancer from coming back, or to treat cancer that has spread.

Surgery is the most common treatment for breast cancer, and there are several types:

  • Breast-sparing (or breast-conserving) surgery removes the cancer but not the breast. Examples are lumpectomy and segmental (partial) mastectomy. Radiation therapy is usually given after breast-sparing surgery to destroy remaining cancer cells the area.
  • Mastectomy is an operation to remove the breast (or as much of the breast as possible). Breast reconstruction is often an option at the same time or after the mastectomy.

In most cases, the surgeon also removes lymph nodes under the arm to help determine whether cancer cells have entered the lymphatic system. This is called an axillary lymph node dissection.

Surgery causes short-term pain and tenderness in the area of the operation and also carries a risk of infection, poor wound healing, bleeding, or a reaction to the anesthesia used during surgery. Removal of a breast can cause a weight imbalance, which can result in discomfort in the neck and back. Skin in the area where the breast was removed may be tight, the muscles of the arm and shoulder may feel stiff, and nerves that may be injured or cut during surgery can cause numbness and tingling in the chest, underarm, shoulder, and upper arm.

These feelings usually go away within a few weeks or months.

Radiation therapy (radiotherapy) is the use of high-energy rays to kill cancer cells. The radiation may be directed at the breast by a machine (external radiation), or may come from radioactive material placed in thin plastic tubes that are placed directly in the breast (implant radiation). Sometimes, both types of radiation therapy are used.

Before surgery, radiation therapy, alone or with chemotherapy or hormonal therapy, is sometimes used to destroy cancer cells and shrink tumors. This approach is most often used in cases in which the breast tumor is large or not easily removed by surgery.

During radiation therapy, patients may become extremely tired, especially after several treatments. It is also common for the skin in the treated area to become red, dry, tender, and itchy. The breast may feel heavy and hard, but these conditions will clear up with time. Toward the end of treatment, the skin may become moist and weepy but exposing this area to air as much as possible will help the healing process.

Chemotherapy is the use of drugs to kill cancer cells. Chemotherapy for breast cancer is usually a combination of drugs given in a pill or by injection.

The side effects of chemotherapy depend mainly on the specific drugs and the dose. In general, anti-cancer drugs affect rapidly dividing cells. These include blood cells, which fight infection, help the blood to clot, and carry oxygen to all parts of the body. When blood cells are affected, patients are more likely to get infections, may bruise or bleed easily, and may feel unusually weak and very tired. Rapidly dividing cells in hair roots and cells that line the digestive tract may also be affected. As a result, side effects may include loss of hair, poor appetite, nausea and vomiting, diarrhea, or mouth and lip sores.

Many of these side effects can now be controlled, thanks to new or improved drugs. Side effects generally are short-term and gradually go away. Hair grows back, but it may be different in color and texture.

Hormonal therapy prevents the growth of hormone dependent cancer cells. This treatment may include the use of drugs, or surgery to remove the ovaries, which make female hormones.

The side effects of hormonal therapy depend largely on the specific drug or type of treatment. Tamoxifen is the most common hormonal treatment. Tamoxifen may cause hot flashes, vaginal discharge or irritation, nausea, and irregular periods.

Biological therapy is a treatment designed to enhance the body's natural defenses against cancer. For example, monoclonal antibodies can target breast cancer cells that have too much of a protein known as human epidermal growth factor receptor-2 (HER-2). Blocking HER-2 slows or stops the growth of these cells.

The side effects of biological therapy differ with the types of substances used, and from patient to patient. Rashes or swelling where the biological therapy is injected are common. Flu-like symptoms also may occur.

Avastin (bevacizumab) Indication for Breast Cancer Revoked

In February 2008, FDA approved bevacizumab to be used in combination with the cancer drug paclitaxel for patients with HER2-negative metastatic breast cancer who had not been treated with chemotherapy. However, in November, 2011, the FDA revoked bevacizumab's breast cancer approval because the drug had not been shown to be safe and effective for that use. Prior to the FDA decision, an FDA advisory committee voted unanimously to recall the approval of the drug for breast cancer treatment.

Originally, FDA had approved bevacizumab under an accelerated approval program to allow access to promising drugs for serious or life-threatening conditions while researchers conducted clinical trials to confirm the drug's safety and benefits. However, after reviewing thousands of pages of data and several clinical trials, FDA regulators determined that bevacizumab use in women with metastatic breast cancer could lead to life-threatening side effects without evidence that a delay in tumor growth, survival or enhanced quality of life would occur. Side effects noted by the FDA included: severe high blood pressure; bleeding and hemorrhaging; heart attack and heart failure; and the development of perforations in the nose, stomach, intestines and other parts of the body.

Drugs Used in the Treatment of Breast Cancer

Breast Cancer Prevention in Women at High Risk

Medications like tamoxifen (Nolvadex) and raloxifene (Evista) have been shown to help reduce the risk of breast cancer if a woman has a higher than average risk of getting breast cancer. To determine the risk, a doctor can assess the risk factors for an individual women, such as her family history, age, genetic profile (BRCA mutation), and other risk factors. Clinicians use a tool known as the The Breast Cancer Risk Assessment Tool to estimate the risk of getting breast cancer in the next 5 years or over a lifetime, based on many of these risk factors. It is important to weigh the risk of taking a lifetime of medication versus the predicted risk for getting breast cancer. Most women who have one or more risk factors will never develop breast cancer, and this is important to discuss with a doctor.

Both tamoxifen and raloxifene are selective estrogen receptor modulators (or SERMs), and act to block estrogen, a female hormone, in some tissues. Estrogen can boost breast cancer cell growth, and both tamoxifen and raloxifene block the estrogen hormone in breast cells. To lower the risk of breast cancer, these drugs are taken for 5 years, or possibly longer.

Studies are evaluating an investigational agent known as fenretinide for chemoprevention. Fenretinide is in a class of drugs known as retinoids (drugs related to vitamin A). As reported by the American Cancer Society, this drug reduced breast cancer risk as much as tamoxifen in preliminary research.

Aromatase inhibitors (drugs taken as a pill once daily that lower estrogen levels) are also being studied to reduce the risk of breast cancer. Current studies have shown that taking either exemestane or anastrozole for 3 to 5 years lowered the risk of breast cancer by about half (47%) in post-menopausal, high risk women.

Women with a very high risk of breast cancer, for example with BRCA gene mutations, may decide to have their breasts and/or ovaries surgically removed to help prevent the occurrence of breast cancer and ovarian cancer. This is a drastic decision that should be made in conjunction with a genetic specialist, oncologist and surgeon.

Research in Treatment of Breast Cancer

Many studies of new approaches for patients with breast cancer are under way. Current areas of research and treatment advances include:

  • Research evaluating best practice with genetic testing and treatments for BRCA1 and BRCA2 mutations
  • Research looking at environmental causes of breast cancer
  • Prevention with aromatase inhibitors
  • Investigation into certain dietary supplements to reduce the risk of breast cancer although published data is scarce.
  • Further studies evaluating
  • Immunotherapy and targeted drugs for treatment of breast cancer.
Women who are interested in learning about ongoing breast cancer clinical trials should speak to their doctor and call 1-855-216-0127 or visit http://www.cancerresearch.org/cancer-immunotherapy/clinical-trial-finder.

The Sister Study

Genetics can play a large role in breast cancer, and studying families can lead to a better understanding of these genetic variables. The National Institute of Environmental Health Sciences (NIEHS) has recruited over 50,000 women between the ages 35–74 for The Sister Study, which is now closed for enrollment. These women, whose sister had breast cancer, will provide data for identifying risk factors that may boost breast cancer prevention. Researchers believe the Sister Study will help us better understand genetic and environmental factors linked with breast cancer.

Another genetic study called The Two Sister Study was launched by the NIEHS in 2008 and looked at women who developed breast cancer at a young age; enrollment for this study is also closed. NIEHS researchers are comparing the sisters with and without breast cancer and also looking for possible genetic and environmental links. To learn more about either study, visit www.sisterstudy.org or call 1-877-4SISTER (1-877-474-7837).

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Last updated: 2016-04-26 by L. Anderson, PharmD

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