Stages of Breast Cancer

Key Points for This Section

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After breast cancer has been diagnosed, tests are done to find out if cancer cells have spread within the breast or to other parts of the body. There are three ways that cancer spreads in the body. The following stages are used for breast cancer: Stage 0 (carcinoma in situ) Stage I Stage II Stage IIIA Stage IIIB Stage IIIC Stage IV

After breast cancer has been diagnosed, tests are done to find out if cancer cells have spread within the breast or to other parts of the body.
The process used to find out whether the cancer has spread within the breast or to other parts of the body is called staging. The information gathered from the staging process determines the stage of the disease. It is important to know the stage in order to plan treatment. The following tests and procedures may be used in the staging process:

Sentinel lymph node biopsy : The removal of the sentinel lymph node during surgery. The sentinel lymph node is the first lymph node to receive lymphatic drainage from a tumor. It is the first lymph node the cancer is likely to spread to from the tumor. A radioactive substance and/or blue dye is injected near the tumor. The substance or dye flows through the lymph ducts to the lymph nodes. The first lymph node to receive the substance or dye is removed. A pathologist views thetissue under a microscope to look for cancer cells. If cancer cells are not found, it may not be necessary to remove more lymph nodes. Chest x-ray : An x-ray of the organs and bones inside the chest. An x-ray is a type of energy beam that can go through the body and onto film, making a picture of areas inside the body.

CT scan (CAT scan): A procedure that makes a series of detailed pictures of areas inside the body, taken from different angles. The pictures are made by a computer linked to an xray machine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography. Bone scan : A procedure to check if there are rapidly dividing cells, such as cancer cells, in the bone. A very small amount of radioactive material is injected into a vein and travels through the bloodstream. The radioactive material collects in the bones and is detected by a scanner. PET scan (positron emission tomography scan): A procedure to find malignant tumor cells in the body. A small amount of radioactive glucose (sugar) is injected into a vein. The PET scanner rotates around the body and makes a picture of where glucose is being used in the body. Malignant tumor cells show up brighter in the picture because they are more active and take up more glucose than normal cells do.

There are three ways that cancer spreads in the body.

The three ways that cancer spreads in the body are:

Through tissue. Cancer invades the surrounding normal tissue. Through the lymph system. Cancer invades the lymph system and travels through the lymph vessels to other places in the body. Through the blood. Cancer invades the veins and capillaries and travels through the blood to other places in the body. When cancer cells break away from the primary (original) tumor and travel through the lymph or blood to other places in the body, another (secondary) tumor may form. This process is called metastasis. The secondary (metastatic) tumor is the same type of cancer as the primary tumor. For example, ifbreast cancer spreads to the bones, the cancer cells in the bones are actually breast cancer cells. The disease is metastatic breast cancer, not bone cancer.

The following stages are used for breast cancer:

This section describes the stages of breast cancer. The breast cancer stage is based on the results of testing that is done on the tumor and lymph nodes removed during surgery and other tests.

Stage 0 (carcinoma in situ)

There are 3 types of breast carcinoma in situ:

Ductal carcinoma in situ (DCIS) is a noninvasive condition in which abnormal cells are found in the lining of a breast duct. The abnormal cells have not spread outside the duct to other tissues in the breast. In some cases, DCIS may become invasive cancer and spread to other tissues. At this time, there is no way to know which lesions could become invasive. Enlarge

Ductal carcinoma in situ (DCIS). Abnormal cells are found in the lining of a breast duct.

Lobular carcinoma in situ (LCIS) is a condition in which abnormal cells are found in the lobules of the breast. This condition seldom becomes invasive cancer. However, having LCIS in one breast increases the risk of developing breast cancer in either breast.

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Lobular carcinoma in situ (LCIS). Abnormal cells are found in the lobules of the breast.

Paget disease of the nipple is a condition in which abnormal cells are found in the nipple only.

Stage I

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Stage I breast cancer. In stage IA, the tumor is 2 centimeters or smaller and has not spread outside the breast. In stage IB, no tumor is found in the breast or the tumor is 2 centimeters or smaller. Small clusters of cancer cells (larger than 0.2 millimeter but not larger than 2 millimeters) are found in the lymph nodes.

In stage I, cancer has formed. Stage I is divided into stages IA and IB.

In stage IA, the tumor is 2 centimeters or smaller. Cancer has not spread outside the breast. In stage IB, small clusters of breast cancer cells (larger than 0.2 millimeter but not larger than 2 millimeters) are found in the lymph nodes and either: no tumor is found in the breast; or the tumor is 2 centimeters or smaller.

Stage II
Stage II is divided into stages IIA and IIB.
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In stage IIA: no tumor is found in the breast or the tumor is 2 centimeters or smaller. Cancer (larger than 2 millimeters) is found in 1 to 3 axillary lymph nodes or in the lymph nodes near thebreastbone (found during a sentinel lymph node biopsy); or

the tumor is larger than 2 centimeters but not larger than 5 centimeters. Cancer has not spread to the lymph nodes. Enlarge

Stage IIA breast cancer. No tumor is found in the breast and cancer is found in 1 to 3 axillary lymph nodes or lymph nodes near the breastbone (left panel); OR the tumor is 2 centimeters or smaller and cancer is found in 1 to 3 axillary lymph nodes or lymph nodes near the breastbone (middle panel); OR the tumor is larger than 2 centimeters but not larger than 5 centimeters and has not spread to the lymph nodes (right panel). o

In stage IIB, the tumor is: larger than 2 centimeters but not larger than 5 centimeters. Small clusters of breast cancercells (larger than 0.2 millimeter but not larger than 2 millimeters) are found in the lymph nodes; or larger than 2 centimeters but not larger than 5 centimeters. Cancer has spread to 1 to 3axillary lymph nodes or to the lymph nodes near the breastbone (found during a sentinel lymph node biopsy); or larger than 5 centimeters. Cancer has not spread to the lymph nodes.

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Stage IIB breast cancer. The tumor is larger than 2 centimeters but not larger than 5 centimeters and small clusters of cancer cells are found in the lymph nodes (left panel); OR the tumor is larger than 2 centimeters but not larger than 5 centimeters and cancer is found in 1 to 3 axillary lymph nodes or lymph nodes near the breastbone (middle panel); OR the tumor is larger than 5 centimeters and has not spread to the lymph nodes (right panel).

Stage IIIA

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Stage IIIA breast cancer. No tumor is found in the breast or the tumor may be any size and cancer is found in 4 to 9 axillary lymph nodes or lymph nodes near the breastbone (left panel); OR the tumor is larger than 5 centimeters and small clusters of cancer cells (larger than 0.2 millimeter but not larger than 2 millimeters) are found in the lymph nodes (middle panel); OR the tumor is larger than 5 centimeters and cancer is found in 1 to 3 axillary lymph nodes or lymph nodes near the breastbone (right panel).

In stage IIIA:

no tumor is found in the breast or the tumor may be any size. Cancer is found in 4 to 9 axillary lymph nodes or in the lymph nodes near the breastbone (found during imaging tests or a physical exam); or the tumor is larger than 5 centimeters. Small clusters of breast cancer cells (larger than 0.2millimeter but not larger than 2 millimeters) are found in the lymph nodes; or the tumor is larger than 5 centimeters. Cancer has spread to 1 to 3 axillary lymph nodes or to the lymph nodes near the breastbone (found during a sentinel lymph node biopsy).

Stage IIIB

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Stage IIIB breast cancer. The tumor may be any size and cancer has spread to the chest wall and/or to the skin of the breast and caused swelling or an ulcer. Cancer may have spread to axillary lymph nodes or lymph nodes near the breastbone. Cancer that has spread to the skin of the breast may be inflammatory breast cancer.

In stage IIIB, the tumor may be any size and cancer has spread to the chest wall and/or to the skin of the breast and caused swelling or an ulcer. Also, cancer may have spread to:

up to 9 axillary lymph nodes; or the lymph nodes near the breastbone. Cancer that has spread to the skin of the breast may also be inflammatory breast cancer. See the section on Inflammatory Breast Cancer for more information.

Stage IIIC

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Stage IIIC breast cancer. No tumor is found in the breast or the tumor may be any size and may have spread to the chest wall and/or the skin of the breast. Also, cancer has spread to 10 or more axillary lymph nodes (left panel); OR to lymph nodes above or below the collarbone (middle panel); OR to axillary lymph nodes and lymph nodes near the breastbone (right panel).

In stage IIIC, no tumor is found in the breast or the tumor may be any size. Cancer may have spread to the skin of the breast and caused swelling or an ulcer and/or has spread to the chest wall. Also, cancer has spread to:

10 or more axillary lymph nodes; or lymph nodes above or below the collarbone; or axillary lymph nodes and lymph nodes near the breastbone. Cancer that has spread to the skin of the breast may also be inflammatory breast cancer. See the section on Inflammatory Breast Cancer for more information. For treatment, stage IIIC breast cancer is divided into operable and inoperable stage IIIC.

Stage IV

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Stage IV breast cancer. The cancer has spread to other parts of the body, most often the bones, lungs, liver, or brain.

In stage IV, cancer has spread to other organs of the body, most often the bones, lungs, liver, or brain.

Breast Cancer
There is no single, specific cause of breast cancer; rather, a combination of hormonal, genetic, and possibly environmental events may contribute to its development.

Etiology
Hormones produced by the ovaries have an important role in breast cancer. Two key ovarian hormones, estradiol and progesterone, are altered in the cellular environment by a variety of factors, and these may affect growth factors for breast cancer. HORMONES The role of hormones and their relationship to breast cancer remain controversial. Research suggests that a relationship exists between estrogen exposure and the development of breast cancer. In laboratory studies, tumors grow much faster when exposed to estrogen, and epidemiologic research suggests that women who have longer exposure to estrogen have a higher risk for breast cancer. Early menarche, nulliparity, childbirth after 30 years of age, and late menopause are known but minor risk factors. The assumption is that these factors are all associated with prolonged exposure to estrogen because of menstruation. The theory is that each cycle (which has high levels of endogenous estrogen) provides the cells of the breast another chance to mutate, increasing the chance for cancer to develop. Estrogen itself does not cause breast cancer, but it is associated with its development. GENETICS Growing evidence indicates that genetic alterations are associated with the development of breast cancer. These genetic alterations include changes or mutations in normal genes and the influence of proteins that either promote or suppress the development of breast cancer. Genetic alterations may be somatic (acquired) or germline (inherited). To date, two gene mutations have been identified that may play a role in the development of breast cancer. A mutation in the BRCA-1 gene has been linked to the development of breast and ovarian cancer, whereas a mutation in the BRCA-2 gene identifies risk for breast cancer, but less so for ovarian cancer (Houshmand, Campbell, Briggs et al., 2000). These gene mutations may also play a role in the development of colon, prostate, and pancreatic cancer, but this is far from clear at present. It has been estimated that 1 of 600 women in the general population has either a BRCA-1 or BRCA-2 gene mutation. For women who carry either mutation, the risk for developing breast cancer can range from 50% to 90% (Kauff, Satagopan, Robson et al., 2002). At present, only 5% to 10% of all breast cancers are estimated to be associated with the BRCA-1 or BRCA-2 gene mutations. It is thought, however, that breast cancer is genetic and that up to 80% of women diagnosed with breast cancer before age 50 years have a genetic component to their disease (Boyd, 1996). This is believed to be linked to either unidentified BRCA-1 or BRCA-2 carriers or less penetrating genes that have yet to be identified

through genetics research. A womans risk for either BRCA-1 or BRCA-2 should be interpreted with caution and with an exhaustive look at all her other risk factors; this is usually carried out by a genetics counselor. Abnormalities in either of the two genes can be identified by a blood test; however, women should be counseled about the risks and benefits before actually undergoing genetic testing. The risks and benefits of a positive or negative result should be explored. Treatment options for a positive result are long-term surveillance, bilateral prophylactic mastectomy, or chemoprevention with tamoxifen, as discussed previously. A positive result can cause tremendous anxiety and fear, can unleash potential discrimination in employment and insurability, and can cause a woman to search for answers that may not be available. A negative result can produce survivor guilt in a person with a strong family history of cancer. For these women, the risk for breast cancer is similar to that of the general population, and routine screening guidelines should be followed. The decision to pursue genetic testing must be made carefully, and women should be asked what they will do differently after they know the results. Furthermore, because testing is relatively new and health care providers have yet to determine a true benefit from a positive or negative result, genetic testing should be done under the auspices of clinical research protocols to protect the patient (because these data are kept separate from the patients medical record). Nurses play a role in educating patients and their family members about the implications of genetic testing. Ethical issues related to genetic testing include possible employment discrimination, bias in insurability and possibly with insurance rates, and family members concerns (eg, effect on siblings, children).

Risk Factors
Although there are no specific known causes of breast cancer, researchers have identified a cluster of risk factors (Chart 48-3). These factors are important in helping to develop prevention programs. However, nearly 60% of women diagnosed with breast cancer have no identifiable risk factors other than their hormonal environment (Vogel, 2000). Thus, all women are considered at risk for developing breast cancer during their lifetime. Nonetheless, identifying risk factors provides a means for identifying women who may benefit from increased surveillance and early treatment. In addition, further research into risk factors will help in developing strategies to prevent or modify breast cancer in the future. A high-fat diet was once thought to increase the risk of breast cancer. Epidemiologic studies of American and Japanese women showed that American women had a fivefold higher rate of breast cancer. Japanese women who moved to the United States were shown to have breast cancer rates similar to their Caucasian counterparts. Recent cohort studies show only weak or inconclusive relationships between a high-fat diet and breast cancer (Brown et al., 2001). Because fat intake is implicated in colon cancer and heart disease, however, women may benefit from lowering their intake of fat. Oral contraceptives were once thought to increase the risk for breast cancer. Currently, no association is thought to exist in

women in the general population, but there are no data about the effect on women considered to be at high risk. The role of smoking in breast cancer remains unclear. Most studies suggest that smoking does not increase a womans risk for breast cancer. Some studies, however, suggest that smoking does increase the risk for breast cancer and that the earlier a woman begins smoking, the higher her risk. Smoking does increase the risk for lung cancer, which is the leading cause of death in women with cancer (breast cancer is second). Smoking cessation is part of a healthy lifestyle, and nurses have a key role in providing women with information about smoking cessation programs. Silicone breast implants can be associated with fibrous capsular contraction, and some women and medical professionals have claimed an association with certain immune disorders. There is no evidence, however, that breast implants are associated with an increased risk of breast cancer.

Protective Factors
Certain factors may be protective in relation to the development of breast cancer. Regular, vigorous exercise has been shown to decrease risk, perhaps because it can delay menarche, suppress menstruation, and, like pregnancy, reduce the number of ovulatory menstrual cycles. Also, exercise decreases body fat, where estrogens are stored and produced from other steroid hormones. Thus, decreased body fat can decrease extended exposure to estrogen. Breastfeeding is also thought to decrease risk because it prevents the return of menstruation, again decreasing exposure to endogenous estrogen. Having had a full-term pregnancy before the age of 30 years is also thought to be protective. Protective hormones are released after delivery of the fetus, with the purpose of reverting to normal the proliferation of cells in the breast that occur with pregnancy.

Clinical Manifestations
Breast cancers occur anywhere in the breast, but most are found in the upper outer quadrant, where most breast tissue is located. Generally, the lesions are nontender rather than painful, fixed rather than mobile, and hard with irregular borders rather than encapsulated and smooth. Complaints of diffuse breast pain and tenderness with menstruation are usually associated with benign breast disease. Marked pain at presentation, however, may be associated with breast cancer in the later stages. With the increased use of mammography, more women are seeking treatment at an earlier stage of disease. These women may have no symptoms and no palpable lump, but abnormal lesions are detected on mammography. Unfortunately, many women with advanced disease seek initial treatment only after ignoring symptoms. For example, they may seek attention for dimpling or for a peau dorange (orange-peel) appearance of the skin (a condition caused by swelling that results from obstructed lymphatic circulation in the dermal layer). Nipple retraction and lesions fixed to the chest wall may also be evident. Involvement of the skin is manifested by ulcerating and fungating lesions. These classic signs and symptoms characterize breast cancer in the late stages. A high index of suspicion should be maintained with any breast abnormality, and abnormalities should be promptly evaluated.

Assessment and Diagnostic Findings

Techniques to determine the histology and tissue diagnosis of breast cancer include FNA, excisional (or open) biopsy, incisional biopsy, needle localization, core biopsy, and stereotactic biopsy (all described previously). In addition to the staging criteria described below, other pathologic features and prognostic tests are used to identify different patient groups that may benefit from adjuvant treatment. Histologic examination of the cancer cells helps determine the prognosis and leads to a better understanding of how the disease progresses.

Breast Cancer Staging

Staging involves classifying the cancer by the extent of disease (see Fig. 48-5). Staging of any cancer is important because it helps the health care team identify and recommend the best treatment available, offer a prognosis, and compare the results of various treatment regimens. Several diagnostic tests and procedures are performed in the staging of the disease. These may include chest x-rays, bone scans, and liver function tests. Clinical staging involves the physicians estimate of the size of the breast tumor and the extent of axillary node involvement by physical examination (palpable nodes may indicate progression of the disease) and mammography. After the diagnostic workup and the definitive surgical treatment, the breast cancer is staged according to the TNM system (Greene, Page, Fleming, et al., 2002), which evaluates the size of the tumor, number of nodes involved, and evidence of distant metastasis. Pathologic staging based on histology provides information for a more accurate prognosis. Table 48-2 lists typical treatment guidelines by stage at diagnosis (see the following management section for details regarding these treatments).

Prognosis
Several features of breast tumors contribute to the prognosis. Generally, the smaller the tumor, the better the prognosis. Carcinoma of the breast is not a pathologic entity that develops overnight. It starts with a genetic alteration in a single cell. It can take about 16 doubling times for a carcinoma to become 1 cm or larger, at which point it becomes clinically apparent. Assuming that it takes at least 30 days for each doubling time, it would take a minimum of 2 years for a carcinoma to become palpable. This
Stage I: Tumors are less than 2 cm in diameter and confined to breast. Stage II: Tumors are less than 5 cm, or tumors are smaller with mobile axillary lymph node involvement. Stage IIIa: Tumors are greater than 5 cm, or tumors are accompanied by enlarged axillary lymph nodes fixed to one another or to adjacent tissue. Stage IIIb: More advanced lesions with satellite nodules, fixation to the skin or chest wall, ulceration, edema, or with supraclavicular or intraclavicular nodal involvement.

Stage IV: All tumors with distant metastases.

FIGURE 48concept is important for nurses in teaching and counseling patients because once breast cancer is diagnosed, women have a safe period of several weeks to make a decision regarding treatment. The prognosis also depends on whether the cancer has spread. For example, the overall 5-year survival rate is greater than 98% when the tumor is confined to the breast (ACS, 2002). When the cancer cells have spread to the regional lymph nodes, however, the overall 5-year survival rate falls to 76%. The 5-year survival rate for women diagnosed with metastatic disease is 16%. At diagnosis, about 37% of patients have evidence of regional or distant spread or metastasis. The most common route of regional spread is to the axillary lymph nodes. Table 48-3 describes the relationship between positive axillary lymph nodes and the risk for breast cancer recurrence. Other sites of lymphatic spread include the internal mammary and supraclavicular nodes (Fig. 48-6). Distant metastasis can affect any organ, but the most common sites are bone (71%), lung (69%), liver (65%), pleura (51%), adrenals (49%), skin (30%), and brain (20%) (Winchester & Cox, 1998). In addition to tumor size, nodal involvement, evidence of metastasis, and histologic type, other measures help in determining prognosis. The presence of estrogen and progesterone receptor proteins indicates retention of regulatory controls of the mammary epithelium. The presence of both receptor proteins is associated with an improved prognosis; their absence is associated with a poorer prognosis. Similarly, a tumor with a high degree of differentiation is associated with a better prognosis than a poorly differentiated anaplastic tumor. The assessment of a tumors proliferative rate (S-phase fraction) and DNA content (ploidy) by laboratory assay may help to determine prognosis because these two factors are strongly correlated with other prognostic factors, and research is ongoing to examine how helpful these two factors may actually be. Tumors classified as diploid (normal DNA content) are associated with a better prognosis than are tumors classified as aneuploid (abnormal DNA content). Modified Radical Mastectomy. Modified radical mastectomy is removal of the entire breast tissue, along with axillary lymph nodes. The pectoralis major and pectoralis minor muscles remain intact. Before surgery, the surgeon plans an incision that will provide maximum opportunity to remove the tumor and the affected nodes. At the same time, efforts are made to avoid a scar that will be visible and restrictive. An objective of surgical treatment is to maintain or restore normal function to the hand, arm, and shoulder girdle on the affected side. Skin flaps and tissue are handled with great care to ensure proper viability, hemostasis, and drainage. If reconstructive surgery is planned, a consultation is made with a plastic surgeon before the mastectomy is performed. After the tumor is removed, bleeding points are ligated and the skin is closed over the chest wall. Skin grafting is performed if the skin flaps are too small to close the wound. A nonadherent dressing (Adaptic) may be applied and covered by a pressure dressing. Two drainage tubes may be placed in the axilla and beneath

the superior skin flap, and portable suction devices may be used; these remove the blood and lymph fluid that collect after surgery. The dressing may be held in place by wide elastic bandages or a surgical bra. CHEMOTHERAPY Chemotherapy is administered to eradicate the micrometastatic spread of the disease. An overview of chemotherapy is presented in Chapter 16. Although chemotherapy is generally initiated after breast surgery, no single standard exists for the sequencing of systemic chemotherapy and radiation therapy. Ongoing clinical trials may help to determine which treatment sequence produces the best outcomes. Chemotherapy regimens for breast cancer combine several agents to increase tumor cell destruction and to minimize medication resistance. The chemotherapeutic agents most often used in combination are cyclophosphamide (Cytoxan) (C), methotrexate (M), fluorouracil (F), and doxorubicin (Adriamycin) (A). Paclitaxel (Taxol) (T) has been recently introduced into the adjuvant chemotherapy setting, and the data from clinical trials suggest a slight survival benefit with its use (Norton, 2001). Additionally, a newer taxane, docetaxel (Taxotere) (T), is being used more frequently, but research remains limited on its difference. The combination regimen of CMF or CAF is a common treatment protocol. AC, ACT (AC given first followed by T), and ATC, with all three agents given together, are other regimens that may be used (Levine, 2001). A new anthracycline agent, epirubicin (Ellence), which has been used more in Europe, is being used in certain regimens and protocols. Decisions regarding the chemotherapeutic protocol are based on the patients age, physical status, and disease status and whether she is participating in a clinical trial. Chemotherapy treatment modalities are summarized in Table 48-5. Reactions to Chemotherapy. Anticipatory anxiety is a common response among patients facing chemotherapy. Today, however, side effects can be managed well, with many women continuing their daily work and routine schedules. This has occurred in large measure because of the meticulous educational and psychological preparation provided to patients and their families by oncology nurses, oncologists, social workers, and other members of the health care team. The other factor is the availability of medication regimens that can alleviate the side effects of nausea and vomiting. Common physical side effects of chemotherapy for breast cancer include nausea, vomiting, taste changes, alopecia (hair loss), mucositis, dermatitis, fatigue, weight gain, and bone marrow suppression. In addition, premenopausal women may experience temporary or permanent amenorrhea leading to sterility. Less common side effects include hemorrhagic cystitis and conjunctivitis. Although its cause is unknown, weight gain of more than 10 pounds occurs in about half of all patients. Aerobic exercise and its anxiety-alleviating effects may be helpful to decrease weight gain and elevate mood. Side effects may vary with the chemotherapeutic agent used. CMF is generally well tolerated with only minimal side effects. Doxorubicin can be toxic to tissue if it infiltrates the vein, so it is usually diluted and infused through a large vein. Nausea and vomiting can occur. Antiemetics

and tranquilizers may provide relief, as may visual imagery and relaxation exercises. Doxorubicin and paclitaxel usually cause alopecia, so obtaining a wig before hair loss occurs may prevent some of the associated emotional trauma. The patient needs reassurance that new hair will grow when treatment is completed, although the color and texture of the hair may differ. It is helpful to provide a list of wig suppliers in the patients geographic region and to become familiar with creative ways to use scarves and turbans to reduce the patients reactions to hair loss. The American Cancer Society offers a program called Look Good, Feel Better that provides useful tips for applying cosmetics during

chemotherapy.