INTRODUCTION — Breast cancer is the most common female cancer in the United States, the second most common cause of cancer death in women (after lung cancer), and the main cause of death in women ages 45 to 55. Every year, approximately 205,000 American women are diagnosed with breast cancer and more than 40,000 die from this disease.
UpToDate contains a number of patient information topic reviews that discuss breast cancer. The purpose of this overview is to provide a guide to the issues and questions that arise in women with newly diagnosed breast cancer. This topic can serve as a "road map" to the patient information topic reviews that are relevant to your particular situation.
This guide will focus only on the diagnosis and treatment of breast cancer. The reader is referred to other patient information materials for a discussion of the risk factors for breast cancer and methods to prevent breast cancer in women who are at high risk. (See "Patient information: Risk factors for breast cancer" and see "Patient information: Postmenopausal hormone therapy and breast cancer" and see "Patient information: Tamoxifen and raloxifene for the prevention of breast cancer").
IMPROVEMENTS IN CANCER CARE — While the number of new cases of breast cancer is rising over time, the death rate from breast cancer has declined about 20 percent over the past decade, in part because increased screening for breast cancer is catching the disease at an earlier stage when the chances of successful recovery are higher. (See "Patient information: Screening for breast cancer"). Early detection and treatment of breast cancer clearly improve survival because the breast tumor is removed before it has a chance to spread (metastasize).
The other factor that has improved outcomes in breast cancer is the early use of systemic (bodywide) anticancer treatment. The term "adjuvant systemic therapy" refers to additional anticancer treatment that is given after a cancer is removed surgically in order to eliminate any remaining tumor cells in the body (often termed micrometastases). Such therapy significantly decreases the chance that the cancer will return (or recur), and also improves the likelihood of surviving breast cancer. As a result, systemic adjuvant therapy has become an important component of treatment. The systemic treatments used for breast cancer include hormone therapy, chemotherapy, and antibody therapy.
DIAGNOSING BREAST CANCER
Mammogram — Breast cancer is often suspected because of an abnormal mammogram. An example of an abnormal finding is shown in radiograph 1 (show radiograph 1). In other cases, a woman (or her clinician) feels a lump or discovers a change in the breast. Changes may include dimpling of the skin, a change in the size or shape of one breast, inversion (inward turning) of the nipple when it previously pointed outward, or a discoloration of the skin of the breast.
A suspicious lump should not be ignored, even if the mammogram is negative. Up to 20 percent of new breast cancers are not visible on a mammogram.
Breast MRI — Magnetic resonance imaging (MRI) uses a strong magnet to create a detailed image of a part of the body. It does not use x-rays or radiation. Breast MRI may be recommended to aid in the diagnosis of breast cancer in selected situations. MRI is not recommended to detect breast cancer in all women because it is not as good as mammogram for certain breast conditions, such as ductal carcinoma in situ. The role of breast MRI in the diagnosis and management of breast cancer is evolving. Most experts restrict the use of breast MRI for diagnosis to the following situations: Breast cancer screening for young women (particularly those with dense breasts) who have an inherited susceptibility to breast cancer (eg, mutations in BRCA1 or BRCA2). Evaluation for breast cancer in a woman who is diagnosed with cancer of the lymph nodes (glands) under the arm. In this case, the breast MRI is done to determine if the cancer first developed in the breast. Evaluation of a woman with newly diagnosed breast cancer who has dense breasts. Evaluation of a woman with a small abnormality on mammogram who has a biopsy that indicates a large area of cancer. In this case, the MRI is often helpful to better define the size of the abnormal area (show radiograph 2), which can guide treatment (complete removal of the breast versus removal of the cancerous area). Evaluation of a woman with newly diagnosed breast cancer in one breast who has no evidence of breast cancer (based upon examination and mammography) in the opposite breast.
Breast biopsy — If breast cancer is suspected, the next step is to remove a small piece of the abnormal area (called a biopsy) to confirm the diagnosis. The biopsy technique depends upon whether a lump is present in the breast. If the physician feels a lump, a biopsy can often be performed in the office.
If the abnormality is only found on the mammogram and the breast feels normal, then the biopsy will need to be done using a test to guide where to perform the biopsy. A mammogram is often used for this purpose. The area of abnormality is visualized by the radiologist on the mammogram, and its location marked, often with a wire. A surgeon uses the wire to know which area to remove. This procedure is called a needle localization biopsy.
Types of breast cancer — Although there are several different types of breast cancer, they are treated similarly, with some exceptions.
In situ — The earliest breast cancers are called "in situ" cancers. If they arise in the ducts of the breast (the tubes that carry milk to the nipple when a woman is breastfeeding), and are limited to the ducts themselves, the tumor is called ductal carcinoma in situ, abbreviated DCIS.
Other in situ cancers arise in the lobules of the breast (where breast milk is made) and are referred to as lobular carcinoma in situ (LCIS). In situ carcinomas, which are the earliest recognizable breast cancers, seldom spread beyond the breast tissue. Thus, evaluation for evidence of tumor spread beyond the breast is usually unnecessary and adjuvant systemic therapy is not recommended.
The optimal local treatment for in situ cancers is controversial. Conservative surgery alone may be an option for some women, while others have surgery followed by radiation therapy, or even a mastectomy.
Invasive — The majority of breast cancers are referred to as invasive breast cancers because they have invaded beyond the ducts or lobules of the breast. Several varieties of invasive breast cancers are identified (eg, ductal, lobular, medullary, tubular, metaplastic) In general they are treated similarly.
Hormone receptors — About 50 to 70 percent of breast cancers require the female hormone estrogen to grow, while other breast cancers are able to grow without estrogen. Estrogen-dependent breast cancer cells produce hormone receptors, which can be estrogen receptors (ER), progesterone receptors (PR), or both.
If hormone receptors are present within a breast cancer, women are significantly more likely to benefit from treatments that lower estrogen levels or block the actions of estrogen. These treatments are referred to as endocrine or hormone therapies, and such tumors are referred to as hormone-responsive. In contrast, women whose tumors do not contain any ER or PR do not benefit from adjuvant hormone therapy, and it is not recommended. (See "Patient information: Adjuvant systemic therapy for hormone-responsive early stage breast cancer in premenopausal women")
HER2 — HER2 is a protein that is present in about one-third of breast cancers. The presence of HER2 can help to determine if adjuvant chemotherapy is needed. In particular, benefit from the drug trastuzumab (Herceptin) appears to be limited to women whose breast cancers express very high levels of this marker. The level of HER2 within a tumor can be determined by the pathologist. (See "Patient information: Adjuvant chemotherapy and trastuzumab (Herceptin) for early stage breast cancer")
HAS THE BREAST CANCER SPREAD? — Once a diagnosis of breast cancer is established, the next important questions to be answered are the following: How extensive is the cancer involvement within the breast? Is there evidence that the tumor has spread outside of the breast?
The extent of cancer involvement within the breast is usually determined by the findings on the biopsy and the results of the mammogram (both breasts need to be studied because there is a small risk of having cancer in both breasts).
Although by definition, breast cancer starts within the breast, tiny microscopic cells or pieces of the cancer may break off from the breast tumor at any point and travel to other places through the bloodstream or the lymph channels; this process is called metastasis.
When these metastases lodge themselves in a lymph node (also called glands) or an organ, they grow, eventually producing a mass or lump that can sometimes be felt (eg, if it involves the skin or the lymph nodes in the armpit). In other cases, metastases may only be evident on an x-ray such as a CT scan. The use of studies such as CT scans to evaluate the extent of breast cancer spread is discussed below. (See "Staging and the staging workup" below).
The importance of the axillary lymph nodes — One of the first sites breast cancer spreads is the lymph nodes located in the armpit (axilla). These nodes can become enlarged and can be felt during a clinician's examination. However, the only way to determine if they contain cancer is for the surgeon to remove them so that they can be examined under the microscope.
The presence or absence of lymph node involvement by a breast cancer is one of the most important factors in determining the long-term outcome of the cancer (prognosis), and it often guides the selection of adjuvant systemic therapy. If the axillary lymph nodes are involved with cancer (positive nodes), there is a higher chance that the tumor has spread elsewhere, and all of these women should receive adjuvant systemic therapy. Even if these nodes are negative (no cancer cells detected), there is a small chance that the tumor has spread elsewhere in the body.
Because of this, adjuvant therapy is recommended for some women with node-negative breast cancer. A further discussion of factors that affect the choice of breast cancer treatment is presented elsewhere. (See "Patient information: Localized breast cancer evaluation, mastectomy, and breast conserving therapy", section on Factors affecting treatment).
Sentinel node biopsy — Removal of the axillary lymph nodes can be done by removing all of the axillary lymph nodes (called axillary lymph node dissection, or ALND), or with a less invasive sentinel lymph node biopsy. The pros and cons of these two approaches to evaluating the possibility of spread of cancer to the axillary lymph nodes are discussed in detail elsewhere. (See "Patient information: Localized breast cancer evaluation, mastectomy, and breast conserving therapy", sections on How is breast cancer staged? and Management of axillary lymph nodes).
In general, the major benefit of sentinel lymph node procedure is that it can provide the necessary information while causing fewer long-term side effects (particularly arm swelling, also called lymphedema). (See "Patient information: Lymphedema after breast cancer surgery").
Staging and the staging workup — For all cancers, treatment and prognosis depend upon the "stage" of the cancer (how far it has spread). The stage of a breast cancer is based upon tumor size, involvement of the skin, chest wall, or local lymph nodes, and whether the cancer has spread to other organs (metastasis). Staging studies are done to determine if the cancer has spread, which may include: A complete physical examination, including a neurologic exam, to evaluate for signs of distant metastatic disease Blood tests, including a complete blood count and liver function tests Bone scan Chest X-ray or CT scan CT scan of the abdomen and pelvis CT scan or magnetic resonance imaging (MRI) of the brain A PET scan
Oncologists use a standard system, called the TNM staging system to describe the stage of individual cancers. "T" stands for the primary tumor, "N" reflects for the status of the regional lymph nodes, and "M" designates the presence of absence of metastases to other organs.
In general, the size and extent of the breast tumor, involvement of adjacent lymph nodes, and the presence or absence of spread to other organs are grouped together to form the stage grouping of a breast cancer, which ranges from stage I to IV. Table 1 describes these stages (show table 1). Treatment differs according to stage.
Stage I and II breast cancer — Women with either stage I or II breast cancers are referred to as having early stage localized breast cancer. Stage I breast cancer means that the tumor is less than 2 cm in size, and is node-negative.
Stage II tumors are those that are node-positive (but the axillary lymph nodes are small and either nonpalpable or movable on physical examination), or the tumor size is larger than 2 cm but not larger than 5 cm. A tumor that is larger than 5 cm must be node-negative to be considered early stage (show table 1).
Stage III breast cancers — Stage III tumors are referred to as locally advanced breast cancer. They consist of large breast cancers (greater than 5 cm across), those with extensive axillary nodal involvement, or nodal involvement of the soft tissues above or below the collarbone (termed the infraclavicular and supraclavicular nodes, show table 1).
A tumor is also designated stage III if the tumor extends to underlying muscles of the chest wall or the overlying skin. Stage III breast cancer also includes inflammatory breast cancer, a rapidly growing type of cancer that makes the breast appear red and swollen (hence the term inflammatory).
Stage IV breast cancer — Stage IV breast cancer includes tumors that have metastasized to areas outside the breast, including the brain, bones, skin, or other organs. The primary tumor may be any size, and there may be any number of affected lymph nodes. This is referred to as metastatic breast cancer (show table 1)
OVERVIEW OF TREATMENT — The treatment of breast cancer must be individualized and is based upon several factors. Optimal management in most cases requires collaboration between surgeons (breast cancer surgeons and reconstructive surgeons, who are typically plastic surgeons) and physicians who specialize in radiation and medical oncology. Each woman should carefully discuss the available treatment options with her doctors to determine which is the best choice for her.
Early stage localized breast cancer — Women with stage I and II breast cancer are treated similarly with minor exceptions. Two surgical options are available for treating localized breast cancer: mastectomy (removal of the breast) and breast conserving therapy. The latter consists of removal of the cancerous tissue (designated "lumpectomy", wide excision, quadrantectomy, or partial mastectomy, show figure 1).
Several studies have confirmed that unless the breast tissue removal is extensive, radiation to the breast should be given postoperatively. The combination of carefully performed excision and judiciously applied radiation frequently results in cosmetically satisfactory breast preservation without compromising overall survival.
In centers that specialize in breast cancer treatment, approximately 75 percent of women with early stage breast cancer are considered appropriate candidates for breast conserving therapy, while the remainder undergo mastectomy. (See "Patient information: Localized breast cancer evaluation, mastectomy, and breast conserving therapy").
Breast reconstruction is an important option for women who undergo mastectomy, and may be considered at the time of the mastectomy or at a later date. Consultation with a plastic surgeon prior to the mastectomy is essential.
Adjuvant therapy — As noted above, adjuvant systemic therapy is recommended to the vast majority of women with stage II breast cancer, and to selected women with stage I disease. Adjuvant hormone therapy is recommended for all women with hormone receptor-positive breast cancer, while selected women also receive chemotherapy. (See "Patient information: Adjuvant systemic therapy for hormone-responsive early stage breast cancer in premenopausal women" and see "Patient information: Adjuvant systemic therapy for hormone-responsive early stage breast cancer in postmenopausal women").
Adjuvant chemotherapy is recommended for women with hormone receptor-negative breast cancer. Adjuvant trastuzumab is generally reserved for women with HER2-positive breast cancer, regardless of hormone receptor status. (See "Patient information: Adjuvant chemotherapy and trastuzumab (Herceptin) for early stage breast cancer").
Locally advanced and inflammatory breast cancer — The term locally advanced breast cancer is used to describe a breast cancer that has progressed locally but has not yet spread beyond the breast and regional lymph nodes. inflammatory breast cancer, a rapidly growing type of cancer that makes the breast appear red and swollen (hence the term inflammatory).
Although the likelihood of curing locally advanced and inflammatory breast cancer is lower than it would be if the cancer were small and confined to the breast, cure is possible with aggressive treatment using a combination of chemotherapy, radiation therapy and surgery. In most cases, chemotherapy is given before surgery. (See "Patient information: Locally advanced and inflammatory breast cancer")
Metastatic breast cancer — Metastatic breast cancer can be treated with surgery, radiation therapy, chemotherapy, endocrine therapy, trastuzumab, or some combination of these options. Although these treatments only occasionally lead to long-term survival without disease recurrence (termed relapse-free survival), they can prolong life, delay the progression of the cancer, relieve cancer-related symptoms, and improve quality of life. Cure is possible, but it is very uncommon in women with metastatic breast cancer. (See "Patient information: General principles of treatment for metastatic breast cancer").
The choice of treatment for metastatic breast cancer depends upon many individual factors, including features of the woman's breast cancer, the extent and location of metastases, the expected response of the cancer to various therapies, treatment-related side effects, and a woman's personal preferences. Each woman should discuss the available treatment options with her physician to determine which is the best choice for her. (See "Patient information: Chemotherapy and Herceptin (trastuzumab) for metastatic breast cancer" and see "Patient information: Endocrine therapy for metastatic breast cancer").
SUMMARY Early detection and treatment of breast cancer improve a woman's chance of survival. (See "Improvements in cancer care" above). Breast cancer can be diagnosed if a woman or her doctor/nurse notices a lump in the breast. Some women with cancer have changes in their breast's skin, such as dimpling or color changes. Mammograms (x-ray of the breast tissue) can also help to diagnose breast cancer (show radiograph 1). (See "Diagnosing breast cancer" above). The earliest breast cancers are called "in situ" cancers. If the cancer develops in the ducts of the breast (the tubes that carry milk to the nipple when a woman is breastfeeding), it is called ductal carcinoma in situ (DCIS). Other in situ cancers develop in the lobules of the breast (where breast milk is made); this is called lobular carcinoma in situ (LCIS). (See "In situ" above). In situ cancers rarely spread beyond the breast. Whole body treatments (eg, chemotherapy) are usually not needed for in situ cancer. If the cancer spreads outside the ducts, it is called invasive ductal carcinoma. Cancer that spreads outside the lobules is called invasive lobular carcinoma. Treatment is similar for most types of invasive breast cancer. (See "Invasive" above). In a woman with breast cancer, tests will be done to determine the best type of treatment. Tests will also be done to see if the cancer has spread outside the breast. One of the most common places for breast cancer to spread first is the lymph nodes (glands). (See "Hormone receptors" above). Most women with breast cancer require surgery to remove the part of the breast that contains cancer; this is called breast conserving surgery (show figure 2). Some women need to have the entire breast removed; this is called a mastectomy. After the breast tumor is removed, there is a lower chance that the cancer will spread to other areas. (See "Overview of treatment" above). A number of whole body treatments may be given to some women with breast cancer, include hormone therapy, chemotherapy, and antibody therapy. Some of these treatments are taken as pills while others are given into a vein. Most women require treatment for several months to years. (See "Adjuvant therapy" above). Whole body treatments reduce the risk that the cancer will spread to areas outside the breast. Whole body treatments also improve a woman's chance of surviving the cancer. Women with more advanced types of breast cancer, or breast cancer that has spread, can also be treated. Although cure is less likely with advanced breast cancer, treatment can prolong life and improve comfort. (See "Locally advanced and inflammatory breast cancer" above).
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Cancer Institute
1-800-4-CANCER
(www.nci.nih.gov)
People Living With Cancer: The official patient information
website of the American Society of Clinical Oncology
(www.plwc.org/portal/site/PLWC)
National Comprehensive Cancer Network
(www.nccn.org/patients/patient_gls.asp)
American Cancer Society
1-800-ACS-2345
(www.cancer.org)
Susan G. Komen Breast Cancer Foundation
(www.komen.org)
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