Breast Cancer

This article was last reviewed on

May 15, 2015.

This article waslast modified on July 27, 2018.

What is breast cancer?

Breast cancers are malignant tumors that arise from the uncontrolled growth of cells in the breast. They occur primarily in the ducts that transport milk to the nipple during breast feeding (lactation) and secondarily in the lobules, the glands that produce milk.

Each breast cancer will have its own characteristics. Some are slow-growing; others can be aggressive. Some are sensitive to the hormones estrogen and progesterone, while others can over-express certain proteins. The cancer's characteristics can affect treatment choices and the potential for the cancer to recur.

Each year, more women in the United States are diagnosed with breast cancer than with any other cancer, with the exception of skin cancer. About 1 in 8 American women will develop invasive breast cancer in their lifetime. The American Cancer Society (ACS) estimates that about 230,000 new cases of invasive breast cancer will be diagnosed in women in the U.S. in 2015 and that about 40,000 women will die from the disease. Men can also develop the disease. ACS estimates that about 2,300 men will be diagnosed with breast cancer in 2015, and about 440 men will die. The rest of this article will focus on breast cancer in women. It is recommended that men who have been diagnosed with breast cancer speak to their healthcare provider for information specific to them and see the ACS's web site about Breast Cancer in Men.

About Breast Cancer

Risk Factors
Breast cancer can develop at any age, but the risk of developing it increases as women get older. The majority of cases develop for reasons we do not yet understand. Some of those at higher risk of developing breast cancer include women:

With close relatives (mother, sister, aunt) who have had the disease

Who have had a cancer in the other breast

Who have not had children

Who had their first child after the age of 30

With an inherited mutation in breast cancer genes, usually either BRCA1 or BRCA2. About 5% to 10% of breast cancers are related to these mutations. BRCA1 and BRCA2 are two tumor suppressor genes that help prevent cancer by producing proteins that suppress abnormal cell growth. Mutations in these genes can affect their normal function, potentially allowing uncontrolled cell growth and increasing the risk of cancer. Women with inherited BRCA1 or BRCA2 mutations have up to an 85% lifetime risk of developing breast cancer.

A healthy lifestyle that includes regular exercise, maintaining a healthy body weight, and avoiding alcohol may help to minimize the risk of developing breast cancer. Research studies continue to identify factors that are associated with an increased or decreased risk of developing the disease, but there is no single set of actions that will cause or prevent breast cancer. Family history (genetics) and exposure to estrogen are among the most important factors in breast cancer risk. Women should work with their healthcare provider to determine their personal risk factors and how to best address them. For example, a woman may choose to avoid long-term use of hormone replacement therapy (HRT).

Women who are at high risk of developing breast cancer may be able to take the drugs tamoxifen or raloxifene to reduce their risk. However, tamoxifen can increase the risk of developing blood clots, endometrial (uterine) cancer, and possibly cardiovascular disease, so the decision to take the medication needs to be weighed carefully. A health practitioner can help assess the risks and benefits of such treatment.

For those women who have a gene mutation such as BRCA1 and BRCA2 that is frequently associated with breast cancer, prophylactic mastectomy is an option. Women electing this option choose to have both breasts removed before developing cancer rather than run the high risk of developing the disease later in their lifetime. Studies have shown that such surgery can reduce the risk of developing breast cancer by up to 97%. Other women elect to have a prophylactic mastectomy on their cancer-free breast after developing cancer in the other breast. A health practitioner can help advise and work with a woman who is considering prophylactic mastectomy.
Signs and Symptoms
It is important to remember that most lumps found in the breast are not cancerous but are benign and that the symptoms and signs associated with breast cancer may be due to other causes. Some signs and symptoms include:

Mass or lump in the breast

Breast skin dimpling, reddening, or thickening

Nipple retraction

Breast swelling or pain

Nipple pain and/or discharge

Swelling or lumps in adjacent underarm lymph node

Pigmented, peeling, scaling or flaking skin in the area around the nipple

Changes in size, shape or appearance of the breast

A rare form of breast cancer, inflammatory breast cancer (IBC), does not form a lump. Some of the symptoms of this condition can be similar to those of a breast infection, with warmth, tenderness, breast swelling, itching, and ridged thickened skin.
Screening
Early breast cancer detection has a strong influence on breast cancer survival. For example, when breast cancer is found in the early, localized stage, 98.5% of those people survive for at least five years after diagnosis. The primary early detection tool is a mammogram.

The medical community recognizes the value of breast cancer screening and mammography, but there is no universal consensus on how often it should be done or when it should be started. Most health organizations agree, however, that women should work with their healthcare provider to assess their personal risk of developing breast cancer and to determine what is best for them. Considerations can be given to the benefits of screening as well as the harms. While screening can detect cancer early when it is most treatable, it may also lead to false-positive results and unnecessary follow-up procedures, such as biopsies.

The American Cancer Society (ACS) recommends that:

Women age 40 be given the option to begin screening with a mammogram

Women age 45 to 54 have a yearly mammogram

Women age 55 and older have the option to switch to screening with a mammogram every other year or continue with mammograms every year and for as long as they are healthy and expected to live more than 10 years

Women at high risk for breast cancer may choose to have an MRI in addition to an annual mammogram beginning at age 30 and for as long as they are in good health

The U.S. Preventive Services Task Force:

Recommends routine mammography every 2 years for women ages 50-74

Recommends against screening mammograms for women under the age of 50

Discourages teaching breast self examination

Concludes that there is insufficient evidence for or against recommending MRI screening

The American College of Obstetricians and Gynecologists (ACOG) recommends that:

Mammography screening be offered annually to women starting at age 40

Women age 40 and older have an annual clinical breast exam by a health practitioner

Women in their 20s and 30s have a clinical breast exam every one to three years

Women may consider doing a breast self-exam; they should know how their breasts normally appear and feel and should report any changes to their healthcare provider.

The American Medical Association adopted the policy that says that women age 40 and older should have access to screening mammography if they choose and their healthcare providers agree. That replaced their early guidance that supported screening mammograms in all asymptomatic women older than 40.

Women with certain risk factors may be advised to begin screening at an earlier age and may be advised to be screened more frequently, with additional testing such as imaging scans.

Tests

The goals of breast cancer testing are to:

Identify genetic risk in high-risk women
Detect and diagnose breast cancer in its earliest stages
Determine how far it has spread
Evaluate the cancer's characteristics in order to guide treatment
Monitor the effectiveness of treatment and monitor the person over time to detect and address any cancer recurrences

The table below summarizes various breast cancer tests. The tissue samples required for some of the tests may involve a needle biopsy, in which cells from the breast are aspirated through a needle into a syringe, or by surgically removing some breast tissue or a tumor (open biopsy). Detailed discussions of the tests follow the table.

Tests for Breast Cancer

Test	Description	Test Sample
Mammogram	Highly-sensitive digital X-ray technology that may detect small lumps that otherwise would not be detected through self-exam.	N/A
BRCA1 / BRCA2	Genetic mutations, if present, suggest a likelihood of breast cancer occurrence as high as 80%.	Blood
HER2/neu	A test for the overexpression of HER2 proteins or the amplification of the gene that codes for the protein; tumors that are positive may respond well to a medication that targets HER2, such as Herceptin^®.	Tissue
HER2 (blood)	After an initial diagnosis of metastatic breast cancer is made, this blood test may be performed and, if the initial level is greater than 15 ng/mL, the test may be used to monitor treatment.	Blood
Estrogen Receptor/ Progesterone Receptor	Increased levels suggest a good response to hormonal therapy. Hormonal therapy is not the same as hormone replacement therapy (HRT) and presence of these receptors does not indicate that HRT caused the cancer.	Tissue
CA15-3/ CA27.29	This test measures a specific cancer antigen. Elevated blood levels may indicate recurrence of cancer.	Blood
Oncotype DX^®	A genetic test that may assist in determining risk of recurrence and predict who will benefit from hormone therapy or chemotherapy.	Tissue
MammaPrint^®	A genetic test that may assist in determining whether a woman is at risk of recurrence of cancer, to help guide treatment.	Tissue

Laboratory Tests

Laboratory tests for breast cancer can be broken down into groups, based on the purpose of testing.

Genetic risk:

BRCA1 or BRCA2 gene mutation – Women who are at high risk because of a personal or strong family history of early onset breast cancer or ovarian cancer can find out if they have a BRCA gene mutation. A mutation in either gene indicates that the person is at significantly higher lifetime risk (between 50-80%) for developing the disease. It is important to remember, however, that only about 5% to 10% of breast cancer cases occur in women with a BRCA gene mutation. Genetic counseling should be considered both before testing takes place and after receiving positive test results.

Diagnosis: cytology and surgical pathology

When a radiologist detects a suspicious area, such as hardened tissue (calcifications) or a non-palpable mass on a mammogram, or if a lump has been found during a clinical or self-exam (see Non-Laboratory Tests below), a health practitioner will frequently order a needle or surgical biopsy or a fine needle aspiration. In each case, a small sample of tissue is taken from the suspicious area of the breast so that a pathologist can examine the cells microscopically for signs of cancer. This pathological examination is done to determine whether the lesion is benign or malignant.

Malignant cells show changes or deviations from normal cells. Signs include changes in the size, shape, and appearance of cell nuclei and evidence of increased cell division. Malignant cells can also distort the normal arrangement of cells within breast tissue. Pathologists can diagnose cancer based upon the observed changes, determine how abnormal the cells appear, and see whether there is a single type of change or a mixture of changes. These results help guide breast cancer treatment.

Needle aspiration evaluations are limited due to the small sample that is obtained. A tissue biopsy is often needed to determine if a cancer is early stage or invasive. When a breast cancer is surgically removed (see Treatment), cells from the tumor and sometimes from adjacent tissue and lymph nodes are examined by the pathologist to help determine how far the cancer has spread.

For more on this, see the article on Anatomic Pathology.

Determine treatment options:

If the pathologist's diagnosis is breast cancer, there are several tests that may be performed on the tissue cancer cells. The results of these tests provide a prognosis and help the oncologist (cancer specialist) guide the woman's treatment. The most useful of these are HER-2/neu and estrogen and progesterone receptors.

HER2/neu is an oncogene associated with cell growth. Normal epithelial cells contain two copies of the HER2/neu gene and produce low levels of the HER2 protein on the surface of their cells. In about 20-30% of invasive breast cancers, the HER2/neu gene is amplified and its protein is over-expressed. These tumors are susceptible to treatment that specifically binds to this over-expressed protein. Drugs that target HER2 include, for example, trastuzumab (Herceptin^®) and lapatinib. Women with amplified HER2/neu gene respond well to these drugs and have a good prognosis.
Estrogen and progesterone receptor (ER and PR) status are important for predicting the course of the disease and helping to guide treatment. Breast cancer cells that have estrogen and/or progesterone receptors can bind estrogen and progesterone. These female hormones promote cell growth and can "feed" ER- and PR-positive cancers. The higher the percentage of cancer cells that are positive, as well as the greater the intensity (the number of receptors per cell), the better the prognosis. This is because hormone-dependant cancers frequently respond well to hormonal therapy that blocks estrogen or lowers estrogen levels.

Breast cancer cells that are negative for HER2/neu amplification and negative for estrogen and progesterone receptors are called "triple-negative." This type of breast cancer occurs more often in younger women and in women of African or Hispanic descent. Women with triple negative breast cancer may be predisposed to BRCA mutations.

Triple negative breast cancers tend to grow and spread more quickly than other types and have a worse prognosis. Because the cells do not have amplified HER2/neu, they will not respond to treatment with trastuzumab (Herceptin®) or lapatinib. Likewise, they do not have receptors for estrogen and progesterone and cannot be treated with therapy that blocks the hormones. However, they may be treated with other types of chemotherapy.

Monitor treatment:

Cancer antigen 15-3 (CA 15-3) – this is a protein that is produced by normal breast cells. There is an increased production of CA 15-3 and the related cancer antigen 27.29 in many women with breast cancer. CA 15-3 does not cause cancer. Rather, the protein is shed by tumor cells and enters the blood, making it useful as a tumor marker to follow the course of the cancer. CA 15-3 is elevated in only about 10% of women with early localized breast cancer but is elevated in about 80% of those with metastatic breast cancer. Blood tests for CA 15-3 (or CA 27.29) may be ordered at intervals after treatment to help monitor a woman for breast cancer recurrence. They are not used as screens for breast cancer but can be used to follow it in some women once it has been diagnosed.

Other tests:

There are several tests available, and many others being researched, that evaluate large numbers of genetic patterns in breast cancer tumor tissue. These tests are being investigated as predictive tests for the recurrence of breast cancer and therapy outcome. The American Society of Clinical Oncology (ASCO) mentioned several of them in its "2007 Update of Recommendations for the Use of Tumor Markers in Breast Cancer." In most cases, the tests were deemed promising, but data to support their routine clinical use were still thought to be insufficient. Examples of these tests being ordered by some health practitioners include:

Oncotype DX^® – ASCO indicates that this test, which measures 21 genes, can be used to predict risk of cancer recurrence in those who have been newly diagnosed with early breast cancer, have cancer-negative lymph nodes, have estrogen receptor positive tumors, and are taking the drug tamoxifen. Oncotype DX is included in the National Comprehensive Cancer Network's 2015 Breast Cancer Treatment Guidelines.
MammaPrint^® test – in use in Europe and cleared by the FDA for use in the U.S. This test evaluates gene activity patterns in 70 tumor genes. It may be used to help predict whether a breast cancer will recur and/or metastasize in women who have early stage cancer, are under the age of 61, and have cancer-negative lymph nodes.

There are additional tests that may be used in some breast cancer cases, such as DNA ploidy, Ki-67, or other proliferation markers. However, most authorities believe that HER2/neu, estrogen and progesterone receptor status are the most important to evaluate first. The other tests do not have therapeutic implications and, when compared with grade and stage of the disease, are not independently significant with respect to prognosis. Some medical centers use these tests for additional information in evaluating patients, making it important to discuss the value of these tests with a cancer management team.

Non-Laboratory Tests

In addition to laboratory tests, there are non-laboratory tests that are equally important. These include the following:

Mammography is widely recommended as a screening tool. A screening mammogram uses X-ray technology to produce an image of the breasts and can reveal breast cancer up to two years before a lump is large enough to be felt during a clinical or self-exam.
Newer technologies, such as digital mammography and computer-aided detection, may yield a clearer image than a mammography in some cases. In particular, younger women, whose breast tissue is often too dense to show tumors clearly on the X-ray film used for a standard mammogram, may benefit from ultrasound exams or magnetic resonance imaging (MRI).

For more information on mammography and other imaging technologies, visit the National Cancer Institute's web site or RadiologyInfo.org.

Stages

Breast cancer may be divided into several stages, reflecting the size of the tumor and the extent to which the cancer has spread in the body. Generally, the lower the number of the stage, the less the cancer has spread. Determining the stage of a cancer can aid in treatment decisions and establishing a prognosis, i.e., predicting the course of the disease and the chances of remission and/or recurrence. For more detail, see the section on Biopsies and examination of tissues in the Anatomic Pathology feature article.

Stage	Size of the tumor	Location
Stage 0		Confined within the breast ducts (ductal carcinoma in situ, DCIS) or confined within the lobules (lobular carcinoma in situ, LCIS)
Stage I	Less than 2 cm (3/4 inch) across	Tumor has spread beyond the ducts but is still confined within the breast tissue
Stage II
Stage IIA	Less than 2 cm across or no tumor	Spread to one to three lymph nodes in the armpit (axilla)
	Between 2 and 5 cm (3/4 to 2 inches) across	No spread to the lymph nodes
Stage IIB	2 to 5 cm across	Spread to the lymph nodes
	Larger than 5 cm across	No spread to the lymph nodes
Stage III
Stage IIIA		Spread to lymph nodes in the armpit that are attached to each other or other structures and may have spread to lymph nodes behind the breast bone
Stage IIIB	Any size	Spread to chest wall or skin of the breast; may have spread to lymph nodes in the armpit and may have spread to behind the breast bone Inflammatory breast cancer, a rare type of cancer that does not form a lump, usually falls into this category because it is aggressive.
Stage IIIC	Any size	Spread to lymph nodes in the armpit and to lymph nodes either behind the breast bone or above the collar bone
Stage IV	Any size	Spread to distant organs such as bone or liver
Recurrent	Any size	Breast cancer that was undetected after treatment but is now detectable in any area of the body

Treatment

Most breast cancers are treated by surgically removing the cancer, or as much of the cancer as possible, and then using one or more other therapies to kill or control any remaining cancer cells. A lumpectomy removes the cancerous tissue while leaving the remaining breast tissue intact. A mastectomy is a more extensive surgical procedure but can vary in the amount of breast and surrounding tissue removed. While mastectomy was once the preferred treatment even in early stage breast cancer, more choices have become available.

Lumpectomy followed by radiation has been demonstrated to be as effective as a mastectomy in treating many early stage breast cancers. In performing either a lumpectomy or mastectomy, a health practitioner may remove some or all of the lymph nodes under the arm and submit them for pathological examination to determine if the cancer has spread.

The use of radiation, chemotherapy, and other drug therapies depends on the woman, on the cancer's characteristics, and on how far the cancer has spread. Drug therapies may include tamoxifen, aromatase inhibitors, and other anti-estrogen drugs that target hormone-sensitive cancers. Those who over-express the HER2/neu protein may benefit from therapy with drugs that target HER2 such as trastuzumab (Herceptin®) and lapatinib. These drugs can substantially improve survival in individuals with HER2-positive invasive breast cancer.

There is a great deal of new research being performed in the field of breast cancer treatment, and a healthcare provider is the best source of information about treatment options. New drugs with fewer side effects than existing therapies are being developed. There are also promising gene-targeting drugs and vaccines, some of which are already being used on a limited, or trial, basis. See the links in Related Content for more information on treatment.

See More About Breast Cancer See Less About Breast Cancer

Elsewhere On The Web

College of American Pathologists: How to Read Your Pathology Report
American Cancer Society: Breast Cancer Overview
National Cancer Institute: Breast Cancer
National Cancer Institute: What You Need to Know About Breast Cancer
National Cancer Institute: Breast Cancer Risk Assessment Tool
Genetic Health: Considering Genetic Testing
National Human Genome Research Institute: Learning About Breast Cancer
National Comprehensive Cancer Network: NCCN Guidelines for Patients, Breast Cancer
Centers for Disease Control and Prevention: Breast Cancer
Centers for Disease Control and Prevention: Know:BRCA Tool
Patient Power: Breast Cancer

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