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. When caught and treated early, breast cancer is often curable.

UpToDate contains a number of patient information articles 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 articles that are relevant to your particular situation.

This guide will focus only on the diagnosis and treatment of breast cancer. Other articles within UpToDate discuss 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 "Patient information: Tamoxifen and raloxifene for the prevention of breast cancer".)

IMPROVEMENTS IN CANCER CARE

Increased screening — The death rate from breast cancer has declined about 20 percent over the past decade. This is due in part to increased screening for breast cancer, which usually detects the disease at an earlier stage when the chances of successful treatment are higher. Early detection and treatment of breast cancer clearly improve survival because the breast tumor can be removed before it has a chance to spread (metastasize). (See "Patient information: Breast cancer screening".)

Adjuvant systemic therapy — Systemic (body-wide) anti-cancer treatment that is given after surgery is called adjuvant systemic therapy. Three types of anticancer agents are used for breast cancer adjuvant therapy:

• Endocrine therapy
• Chemotherapy
• Molecularly targeted therapy against a protein (termed HER2)

The goal of adjuvant systemic therapy is to eliminate any tumor cells that might remain in the body after surgery. Adjuvant systemic therapy has become an important component of breast cancer treatment because it significantly decreases the chance that a cancer will return, and it improves the chances of surviving breast cancer.

DIAGNOSING BREAST CANCER

Abnormal lump — Some women's breast cancer is discovered when a lump or other change in the breast is found by the woman herself or by her healthcare provider. In addition to a lump, other abnormal 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.

To evaluate the breast, a mammogram or breast ultrasound is usually recommended first. A breast biopsy may also be recommended (see 'Breast biopsy' below). A suspicious lump should never be ignored, even if a mammogram is negative. Up to 20 percent of new breast cancers are not visible on a mammogram.

Mammogram — A mammogram is an x-ray of the breast. It is done by compressing the breast tissue between two panels, which allows the radiologist to more easily see abnormalities. Increasingly, breast cancer is diagnosed after a routine mammogram, before a lump or other change in the breast develops.

Even if the mammogram is performed because a lump was felt in one breast, both breasts need to be examined because there is a small risk of having cancer in both breasts.

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 a mammogram for certain breast conditions, such as ductal carcinoma in situ (a type of noninvasive or early breast cancer).

The role of breast MRI for the diagnosis and management of breast cancer is evolving, and there is disagreement as to which women should undergo breast MRI in addition to mammography. Many experts restrict the use of breast MRI to the following situations:

• Breast cancer screening for young women (particularly those with dense breasts) who have an increased risk of breast cancer (eg, mutations in the genes BRCA1 or BRCA2). (See "Patient information: Genetic testing for breast and ovarian cancer".)
• Evaluation for breast cancer in a woman who is diagnosed with cancer of the lymph nodes (glands) under the arm but who has a no sign of breast cancer on physical examination or mammogram of the breast on that side. Sometimes the breast MRI can be used to determine if the cancer first developed in the breast and its location.
• Evaluation of a woman with newly diagnosed breast cancer who has dense breasts that are difficult to image on a mammogram.
• Evaluation of a woman with a small abnormality on mammogram who has a biopsy that indicates an unexpectedly large area of cancer. In this case, the MRI is often helpful to better define the size of the abnormal area. This can help guide the decision about the best type of treatment; complete removal of the breast (mastectomy) versus removal of just the cancerous area (lumpectomy).

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, the biopsy can often be performed in the office.

If the abnormality is only seen on the mammogram and the breast feels normal, then a test is needed 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 thin wire that is inserted into the abnormal area. A surgeon then uses the wire to know which area to biopsy. 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 do not grow outside of the ducts, 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 they do not extend outside of the breast lobule. These types of cancers are referred to as lobular carcinoma in situ (LCIS).

In situ cancers seldom spread beyond the breast tissue. Thus, it is not usually necessary to do further testing to determine if the tumor has spread beyond the breast. In addition, adjuvant systemic therapy is not generally recommended.

However, the best local treatment for an in situ cancer is controversial. Surgical removal of the cancerous area alone may be an option for some women, while others have removal of the cancerous area followed by radiation therapy of the entire breast. Still others recommend a mastectomy. (See "Patient information: Surgery for breast cancer — Mastectomy and breast conserving therapy".)

Invasive — The majority of breast cancers are referred to as invasive breast cancers because they have grown or "invaded" beyond the ducts or lobules of the breast. Several varieties of invasive breast cancers are possible (eg, ductal, lobular, medullary, tubular, metaplastic). In general, they are all treated similarly.

Features of a breast cancer that influence the choice of treatment — At the time breast cancer is diagnosed and/or treated, the cancer should be studied for the presence of two types of proteins; hormone receptors and HER2. These proteins are important for selecting treatment. These tests are generally performed by the pathologist who examines the breast cancer tissue under the microscope.

Hormone receptors — More than one-half 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 proteins called hormone receptors, which can be estrogen receptors (ER), progesterone receptors (PR), or both.

If hormone receptors are present within her breast cancer, a woman is 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 endocrine therapy, and it is not recommended. (See "Patient information: Early stage breast cancer treatment in premenopausal women".)

HER2 — HER2 is a protein that is present in about one out of every five breast cancers. The presence of HER2 in the breast cancer identifies women who might benefit from treatments directed against the HER2 protein. This includes the drug trastuzumab (Herceptin). Benefit from this drug and another agent that also targets HER2, called lapatinib (Tykerb®), appears to be limited to women whose breast cancers make very high levels of this protein. (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, the results of the mammogram and, in some cases, the results of the breast MRI scan.

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 stray tumor cells lodge themselves in a lymph node (also called glands) or an organ such as the liver or the bones, 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, a bone scan, or a PET scan. The use of these studies is discussed below. (See 'Staging and the staging workup' below.)

The importance of the axillary lymph nodes — One of the first sites of breast cancer spread is to the lymph nodes located in the armpit (axilla). These nodes (referred to as axillary lymph nodes) can become enlarged and can sometimes be felt during a breast examination. However, even if the lymph nodes are enlarged, the only way to determine if they truly contain cancer is to examine a sample of the tissue under the microscope.

The presence or absence of lymph node involvement is one of the most important factors in determining the long-term outcome of the cancer (prognosis), and it often guides decisions about treatment.

• 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 are advised to have adjuvant systemic therapy.
• Systemic therapy is recommended less often for women who have no cancer cells detected in the axillary lymph nodes (node-negative breast cancer), particularly if the tumor is small.

However, even if the nodes are negative, there is a small chance that the tumor has spread elsewhere in the body, and adjuvant therapy is recommended for some of these women. A further discussion of factors that affect the choice of breast cancer treatment is presented elsewhere. (See "Patient information: Surgery for breast cancer — Mastectomy and breast conserving therapy", section on 'Factors affecting surgical treatment'.)

Sentinel node biopsy — The axillary lymph nodes can be examined for tumor spread using two different approaches:

• Surgical removal all of the nodes, called axillary lymph node dissection, or ALND.
• Use of a less invasive surgical procedure, called a sentinel lymph node biopsy. In this procedure, one, or at most a few, of the most important nodes are removed. In general, the major benefit of the 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".)

The pros and cons of these two approaches are discussed in detail elsewhere. (See "Patient information: Surgery for breast cancer — Mastectomy and breast conserving therapy", section on 'Breast cancer staging' and "Patient information: Surgery for breast cancer — Mastectomy and breast conserving therapy", section on 'Management of lymph nodes'.)

Staging and the staging workup — For all cancers, including breast cancer, the specific treatment and prognosis depend upon the "stage" of the cancer, which is an indication of how far it has spread. The stage of a breast cancer is based upon the size of the tumor in the breast, whether there is involvement of the skin, chest wall, or axillary lymph nodes, and whether there is evidence that the cancer has spread to other organs (distant metastasis).

Several "staging" studies may be carried out to help determine if the cancer has spread beyond the breast and axillary lymph nodes. These 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

Not all of these studies will be recommended during the staging process. The components of the staging evaluation are covered in more detail elsewhere. (See "Patient information: Surgery for breast cancer — Mastectomy and breast conserving therapy".)

Doctors who care for cancer patients (oncologists) use a standard set of abbreviations, called the TNM staging system, to describe the stage of individual cancers. The "T" status stands for the primary tumor, "N" status reflects the status of the regional lymph nodes, and the "M" status designates the presence or absence of metastases to other organs.

The T, N, and M designations are then grouped together to form the stage grouping of a breast cancer, which ranges from stage I (least advanced) to IV (most advanced). The following table describes these stages (table 1).

Treatment differs according to stage.

Stage I and II breast cancer — Women with stage I or II breast cancers are said to have early stage localized breast cancer. A stage I breast cancer refers to a tumor less than 2 cm in size that is node-negative.

Stage II tumors are those that are node-positive (but the axillary lymph nodes are small and either cannot be felt or are 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 (table 1).

Stage III breast cancers — Women with stage III tumors are referred to as having locally advanced breast cancer. These consist of large breast tumors (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 lymph nodes, (table 1).

A tumor is also designated stage III if it extends to underlying muscles of the chest wall or the overlying skin. Stage III breast cancer also includes inflammatory breast cancer, a rapidly growing form of cancer that makes the breast appear red and swollen (hence the term inflammatory).

Stage IV breast cancer — Stage IV breast cancer refers to 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 (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 discuss the available treatment options with her doctors to determine what treatment is best 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 (removal of the cancerous tissue, called lumpectomy).

Breast conserving therapy may also be referred to as wide excision, quadrantectomy, or partial mastectomy. Breast conserving therapy is usually recommended in conjunction with radiation therapy of the remainder of the affected breast. The combination of surgery and radiation frequently results in cosmetically acceptable preservation of the breast without compromising breast cancer outcomes.

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. Mastectomy may be necessary because of the location of the tumor, the size or shape of the underlying breast, or it may represent the patient's preference. (See "Patient information: Surgery for breast cancer — 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 for the vast majority of women with stage II breast cancer and for selected women with stage I disease. The selection of the type of adjuvant therapy depends on several factors:

• Adjuvant endocrine therapy is recommended for all women with hormone receptor-positive breast cancer larger than 0.5 cm, while selected women also receive chemotherapy. The need for chemotherapy among women with hormone receptor-positive, node-negative breast cancer is controversial, and discussed separately for postmenopausal and premenopausal women. (See "Patient information: Early stage breast cancer treatment in premenopausal women" and "Patient information: Early stage breast cancer treatment in postmenopausal women".)
• Adjuvant chemotherapy is recommended for women who have hormone receptor-negative breast cancers larger than 0.5 cm. (See "Patient information: Adjuvant chemotherapy and trastuzumab (Herceptin) for early stage breast cancer".)
• For women with node-positive, HER2-positive breast cancer and for women with node-negative HER2-positive tumors larger than 1.0 cm, trastuzumab (Herceptin) plus chemotherapy is generally recommended. (See "Patient information: Adjuvant chemotherapy and trastuzumab (Herceptin) for early stage breast cancer".)

Locally advanced and inflammatory breast cancer — 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. Treatment generally includes a combination of chemotherapy, radiation therapy, surgery, endocrine therapy (if the tumor is hormone receptor-positive) and trastuzumab (if the tumor is HER2-positive). In most cases, systemic therapy (chemotherapy, trastuzumab, and sometimes endocrine therapy) 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 a 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. (See "Patient information: Treatment of metastatic breast cancer".)

The choice of treatment for metastatic breast cancer depends upon many individual factors, including features of the woman's breast cancer (especially whether it produces hormone receptors and HER2), the expected response of the cancer to various therapies, treatment-related side effects, the extent and location of metastases, and a woman's personal preferences.

Each woman should discuss the available treatment options with her physician to determine which choice is best for her. (See "Patient information: Treatment of metastatic breast cancer".)

WHERE TO GET MORE INFORMATION

Your healthcare provider is the best source of information for questions and concerns related to your medical problem.

This article will be updated as needed every four months on our web site (www.uptodate.com/patients).

Related topics for patients, as well as selected articles written for healthcare professionals, are also available. Some of the most relevant are listed below.

Patient level information

Patient information: Risk factors for breast cancer
Patient information: Tamoxifen and raloxifene for the prevention of breast cancer
Patient information: Breast cancer screening
Patient information: Genetic testing for breast and ovarian cancer
Patient information: Surgery for breast cancer — Mastectomy and breast conserving therapy
Patient information: Early stage breast cancer treatment in premenopausal women
Patient information: Adjuvant chemotherapy and trastuzumab (Herceptin) for early stage breast cancer
Patient information: Lymphedema after breast cancer surgery
Patient information: Early stage breast cancer treatment in postmenopausal women
Patient information: Locally advanced and inflammatory breast cancer
Patient information: Treatment of metastatic breast cancer

Professional level information

Adjuvant chemotherapy and trastuzumab for HER2-positive early breast cancer
Adjuvant endocrine therapy for postmenopausal women with early stage breast cancer
Adjuvant endocrine therapy for premenopausal women with early stage breast cancer
Adjuvant systemic therapy for older women with early stage breast cancer
An overview of breast cancer and treatment for early stage disease
An overview of treatment for locally recurrent and metastatic breast cancer
Breast imaging: Mammography and ultrasonography
Breast lumps and other common breast problems
Clinical decisions in systemic adjuvant therapy for early breast cancer
Diagnostic evaluation of women with suspected breast cancer
General principles of management of early breast cancer in older women
Genetic testing for breast and ovarian cancer
Mastectomy and breast conserving therapy for invasive breast cancer
Options for women with a genetic predisposition to breast and ovarian cancer
Tumor node metastasis (TNM) staging classification for breast cancer

The following organizations also provide reliable health information.

• National Cancer Institute

       1-800-4-CANCER
       (www.nci.nih.gov)

• American Society of Clinical Oncology

      (www.cancer.net/portal/site/patient)

• National Comprehensive Cancer Network

      (www.nccn.com)

• American Cancer Society

       1-800-ACS-2345
      (www.cancer.org)

• Susan G. Komen Breast Cancer Foundation

       (www.komen.org)

Patient support — There are a number of online forums where patients can find information and support from other people with similar conditions.

• About.com Breast Cancer Forum

      (http://breastcancer.about.com/forum)