Breast cancer guide to diagnosis and treatment

Patient information: Breast cancer guide to diagnosis and treatment
Author
Christine Laronga, MD, FACS
Section Editors
Daniel F Hayes, MD
Anees B Chagpar, MD, MSc, MA, MPH, FACS, FRCS(C)
Deputy Editor
Susan E Pories, MD, FACS
Disclosures

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 found 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: Medications 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 as well as earlier and improved treatment for breast cancer. Screening usually detects the disease at an earlier stage when the chances of successful treatment are higher. Early detection and treatment of breast cancer improve survival because the breast tumor can be removed before it has a chance to spread (metastasize). In addition, other treatments, called adjuvant systemic therapies (described below) can be used to prevent cancer cells that have escaped the breast from growing in other organs. (See “Patient information: Breast cancer screening”.)

Adjuvant systemic therapy — Systemic (body-wide) anti-cancer treatment that is given before or after surgery is called adjuvant systemic therapy. Adjuvant systemic therapy prevents cancer cells that may have escaped from the breast before detection from growing into metastases, which are usually not curable. Thus, adjuvant systemic therapy also contributes to the decline in mortality due to breast cancer.

Three types of anticancer agents are used for breast cancer adjuvant therapy:

Endocrine therapy (Anti-estrogen treatment)
Chemotherapy
Molecularly targeted therapy against a protein (termed HER2)
The goal of adjuvant systemic therapy is to eliminate or prevent the growth of any cancer cells that may have escaped the breast and that might grow in other organs. Areas of breast cancer growth outside the breast or axillary lymph nodes are called “metastases.” Patients with metastases or cancer cells in organs such as liver, lung, bone are rarely cured. However, adjuvant systemic therapy may prevent metastases in a large fraction of patients and thus cure many women who would not be cured otherwise. Adjuvant systemic therapy, therefore, has become an important component of breast cancer treatment because it significantly decreases the chance that a cancer will return. This in turn improves the chances of surviving breast cancer.

DIAGNOSING BREAST CANCER

Abnormal lump — Breast cancer can be discovered when a lump or other change in the breast or armpit is found by a 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 (pulling in) of the nipple when it previously pointed outward, or a discoloration of the skin of the breast.

To evaluate a breast lump, a mammogram and a breast ultrasound are usually recommended. 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. The breast tissue is compressed for the x-ray, which decreases the thickness of the tissue and holds the breast in position, so the radiologist can find abnormalities more accurately. Each breast is compressed between 2 panels and x-rayed from two directions (top-down and side-to-side) to make sure all the tissue is examined.

Breast cancer is often diagnosed with 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 ultrasound — An ultrasound uses sound waves to look at breast tissue and can tell if a lump is a fluid filled cyst or a solid lump. An ultrasound is only used to examine a limited area of the breast and is not used as a screening test of the entire breast.

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, but does require injection of a contrast agent into a vein. 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 most 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). In addition MRI testing is more likely to identify suspicious findings that turn out not to be cancer (false positives).

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 with extremely dense breasts on mammograms, because the density makes the mammograms difficult to interpret.
Breast biopsy — If breast cancer is suspected, the next step is to sample the abnormal area with a core needle biopsy to confirm the diagnosis. If the physician feels a lump, the biopsy can be performed in the office. If possible, the technique should be performed using x-ray guidance, with mammography, ultrasound, or MRI. Core needle biopsies are performed with local anesthesia and do not require sedation.

After the breast biopsy, a tiny metal clip is usually placed into the breast lump or imaging abnormality to mark the spot. If the diagnosis of breast cancer or atypical cells is made, the metal clip is targeted with a thin wire inserted into the abnormal area under x-ray guidance. A surgeon then uses the wire to guide the operation and remove the proper area of the breast. This procedure is called a needle localization excisional breast biopsy if the surgery is being done for diagnosis or lumpectomy if the surgery is done for cancer.

Types of breast cancer — Although there are several different types of breast cancer, they are treated similarly, with some exceptions (figure 1).

In situ breast cancer — The earliest breast cancers are called “in situ” cancers.

Ductal carcinoma in situ (DCIS) — If cancers 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). DCIS cancers do not spread beyond the breast tissue. However DCIS may develop into invasive cancers if not treated.

The best local treatment for DCIS will depend on the size of the area of disease, the grade of the disease, and overall health of the woman. Most women are treated with removal of the cancerous area (lumpectomy) followed by radiation therapy. Surgical removal of the cancerous area alone may be an option, particularly for older women with a very small area of low grade disease that is completely removed. Women with small areas of DCIS who are being treated with lumpectomy do not need their lymph nodes checked for spread of tumor.

Women with extensive DCIS may need a mastectomy which may be done with or without reconstruction. A sentinel lymph node biopsy, a special technique to identify and remove only the most important lymph nodes in the armpit is usually recommended for women who are having a mastectomy for DCIS. Large areas of DCIS have an increased chance of being associated with hidden invasive cancer and if the lymph nodes are involved this will affect treatment decisions. It is not possible to perform sentinel node biopsy after a mastectomy. (See “Patient information: Surgery for breast cancer — Mastectomy and breast conserving therapy”.)

Chemotherapy is not necessary for women with DCIS but endocrine (also called hormonal therapy) treatment with tamoxifen may be recommended for prevention of recurrence if the DCIS tests positive for responsiveness to estrogen (estrogen receptor positive), particularly if they did not have a mastectomy. The tamoxifen reduces the chances that the cancer will come back in the treated breast and also decreases the chances of developing a new breast cancer in the other breast.

Lobular carcinoma in situ (LCIS) — If abnormal cells arise in the lobules of the breast (where breast milk is made), and they do not extend outside of the breast lobule, this are referred to as lobular carcinoma in situ (LCIS). LCIS is not considered a true cancer but instead is considered a risk factor for developing cancer in the future in either breast. Women with LCIS should see a high risk specialist and discuss risk reduction strategies, such as medication to reduce the risk of breast cancer. In some cases preventive mastectomies are considered for women with a strong family history of breast cancer, who are diagnosed with LCIS. Women with LCIS should have yearly mammograms and report any changes in their breasts to their physicians. (See “Patient information: Risk factors for breast cancer” and “Patient information: Medications for the prevention of breast cancer”.)

Invasive breast cancer — 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 into the surrounding tissue (figure 1). 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 (estrogen and progesterone receptors) and HER2. These proteins are important for selecting medical treatment. These tests are performed by the pathologist, the doctor responsible for examining the breast cancer tissue under the microscope and making the diagnosis. The pathologist will also grade the cancer. Grade is assigned to the tumor cells based on how aggressive the individual cancer cells look 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 a woman’s breast cancer, she is 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. Drugs that target the HER2 protein include trastuzumab (Herceptin) and lapatinib (Tykerb®). The benefit from trastuzumab and lapatinib appears to be limited to women whose breast cancers make very high levels of this protein. (See “Patient information: Adjuvant medical therapy for HER2 positive 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 (figure 1).

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 because they cause symptoms such as bone pain and can be seen 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 contain cancer (positive nodes), there is a higher chance that cancer cells have spread elsewhere, and most of these women are advised to have adjuvant systemic therapy.
Systemic therapy, especially chemotherapy, 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 or other prognostic factors are all favorable. Adjuvant endocrine therapy is usually recommended to all patients with estrogen receptor positive breast cancer, even if the lymph nodes are negative, because it generally has less toxicity than chemotherapy.
Even if the axillary lymph nodes are negative, there is a modest chance (up to 30 percent) that the tumor has spread elsewhere in the body, and adjuvant therapy is recommended for some of these women.

21 gene test (Oncotype DX) — A 21 gene test called Oncotype DX can be performed on the tumor tissue to help with decision making about chemotherapy. The 21 gene test evaluates the genetic make-up of the tumor and provides a number score to help predict the chance of recurrence. The score is called the “recurrence score” and the results range from 1 to 100. Women with estrogen receptor positive, node negative breast cancer that have low recurrence scores will not need chemotherapy while women with high scores may benefit from chemotherapy. This test is only appropriate for women with estrogen receptor positive tumors. A further discussion of factors that affect the choice of breast cancer treatment is presented elsewhere. (See “An overview of breast cancer”.)

Examination of the axillary lymph nodes — The axillary lymph nodes should be examined for tumor spread. This is done first by physical exam and, sometimes with ultrasound. If the nodes are enlarged or feel suspicious, a needle biopsy can be performed. If the needle biopsy is positive and the nodes contain cancer cells then surgical removal of additional axillary lymph nodes may be performed. This is called axillary lymph node dissection, or ALND.

In cases where the axillary lymph nodes are not enlarged, the ultrasound is negative, or if the needle biopsy of the lymph node is negative, a surgical procedure called a sentinel lymph node biopsy is performed. In this procedure, one, or at most a few, of the most important nodes are removed. The major benefit of the sentinel lymph node procedure is that it provides important staging information, while causing fewer problems such as arm swelling (also called lymphedema) than a more extensive axillary lymph node dissection. (See “Patient information: Lymphedema after breast cancer surgery”.)

Most patients do not have cancer in their sentinel lymph nodes and will not need additional surgery. Some studies have shown that there are patients for whom an axillary lymph node dissection is not necessary even if the sentinel lymph nodes are positive. This issue remains controversial and should be discussed with your oncology team. This is discussed in more detail elsewhere. (See “Patient information: Surgery for breast cancer — Mastectomy and breast conserving therapy”, section on ‘Management of lymph nodes’.)

Staging and the staging workup — 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 stands for the status of the regional lymph nodes, and the “M” status stands for 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 “stage” of the cancer is an indication of whether and how far it has spread. The following table describes these stages (table 1).

Tumor size (T) and nodes (N) — To establish the stage of a breast cancer, the first step is to evaluate the size of the cancer (T) and establish whether the lymph nodes have cancer in them or not (N). This is accomplished with:

A complete physical, including careful examination of the breast and lymph nodes
Mammogram (and if indicated, other means of breast imaging such as ultrasound or breast MRI)
Pathologic examination of the cancer and lymph nodes after they are removed
Metastases (M) — If any cancer is detectable outside of the breast and axillary lymph nodes, these deposits are called metastases (M).

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

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. Indeed for most women, including those who have no suspicious symptoms and who have small tumors with negative or only a few positive lymph nodes, no staging is needed other than physical exam and routine blood tests. The components of the staging evaluation are covered in more detail elsewhere. (See “Patient information: Surgery for breast cancer — Mastectomy and breast conserving therapy”.)

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 with spread to the axillary lymph nodes and/or a tumor size larger than 2 cm but not larger than 5 cm (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 and lymph nodes to 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 surgery (removal of the cancerous tissue, called lumpectomy).

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

In centers that specialize in breast cancer treatment, approximately 60 percent of women with early stage breast cancer are candidates for BCT. In 25 to 50 percent of women, there are medical, cosmetic, and/or social and emotional reasons for having a mastectomy rather than BCT. Survival outcomes are the same whether BCT or mastectomy is performed. (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 if immediate reconstruction is desired.

Adjuvant therapy — Adjuvant systemic therapy is recommended for the vast majority of women with stage II breast cancer and for some women with stage I disease. (See “Patient information: Early stage breast cancer treatment in premenopausal women” and “Patient information: Early stage breast cancer treatment in postmenopausal women”.)

The selection of the type of adjuvant therapy depends on several factors:

Hormone receptor-positive breast cancer – Adjuvant endocrine therapy is recommended for most women with hormone receptor-positive breast cancer, while selected women also receive chemotherapy. The need for chemotherapy among women with hormone receptor-positive breast cancer depends on the characteristics of the tumor, whether the axillary lymph nodes are positive, the results of the recurrence score (if done), the overall health of the woman, and whether she is pre- or postmenopausal. The 21 gene recurrence score has permitted identification of women who have such a favorable prognosis that the benefits of chemotherapy do not outweigh the risks (see ’21 gene test (Oncotype DX)’ above).
Hormone receptor-negative breast cancer – Adjuvant chemotherapy is generally recommended for women who have hormone receptor-negative invasive breast cancers.
HER2-positive breast cancer – For women with HER2-positive breast cancer, trastuzumab (Herceptin) plus chemotherapy is generally recommended. (See “Patient information: Adjuvant medical therapy for HER2 positive breast cancer”.)
Locally advanced and inflammatory breast cancer — 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, but is still possible with appropriate treatment. Treatment generally includes a combination of chemotherapy, endocrine therapy (if the tumor is hormone receptor-positive), trastuzumab (if the tumor is HER2-positive), radiation therapy, and surgery. 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 is generally treated with “systemic therapy” that treats the whole body, such as chemotherapy, endocrine therapy, trastuzumab, or some combination of these options. Surgery and radiation therapy that are more localized can sometimes be added to control disease in certain areas. While metastatic disease is often aggressive, treatment 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”.)

CLINICAL TRIALS — There are many unanswered questions about the evaluation and treatment of breast cancer. Many advances have been made that have led to more effective and less toxic treatments over the last several decades. Ask your doctor if you are eligible for a clinical trial and then decide if participation is right for you.

WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem.

 

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: Medications 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 medical therapy for HER2 positive 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 stage 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
Breast conserving therapy
Breast imaging: Mammography and ultrasonography
Breast lumps and other common breast problems
Diagnostic evaluation of women with suspected breast cancer
General principles of management of early breast cancer in older women
Genetic testing for hereditary breast and ovarian cancer syndrome
Management of hereditary breast and ovarian cancer syndrome and patients with BRCA mutations
Mastectomy
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
(file://breastcancer.about.com/forum)