Breast Cancer Health Article

Clinical staging, treatments, and prognosis

Staging

Once diagnosis is established, before treatment is rendered, more tests are done to determine if the cancer has spread beyond the breast. These tests include a chest x ray and blood count with liver function tests. Along with the liver function measured by the blood sample, the level of alkaline phosphatase, an enzyme from bone, is also determined. A radionuclear bone scan may be ordered. This test looks at the places in the body to which breast cancer usually metastasizes. A CT scan may also be ordered. The physician will do a careful examination of the axilla to assess likelihood of regional metastasis but unfortunately this exam is not very accurate. Since the axillary node status is the best reflection of possible widespread disease, these nodes in part or all will be removed at the time of surgical treatment.

Using the results of these studies, clinical stage is defined for the patient. This helps define treatment protocol and prognosis. After surgical treatment, the final, or pathologic, stage is defined as the true axillary lymph node status is known. Detailed staging criteria are available from the American Joint Commission on Cancer Manual and are generalized here:

• Stage 1—The cancer is no larger than 2 cm (0.8 in) and no cancer cells are found in the lymph nodes.
• Stage 2—The cancer is between 2 cm and 5 cm, and the cancer has spread to the lymph nodes.
• Stage 3A—Tumor is larger than 5 cm (2 in) or is smaller than 5 cm, but has spread to the lymph nodes, which have grown into each other.
• Stage 3B—Cancer has spread to tissues near the breast, (local invasion), or to lymph nodes inside the chest wall, along the breastbone.
• Stage 4—Cancer has spread to skin and lymph nodes beyond the axilla or to other organs of the body.

Treatment

Surgery, radiation, and chemotherapy are all utilized in the treatment of breast cancer. Depending on the stage, they will be used in different combinations or sequences to effect an appropriate strategy for the type and stage of the disease being treated.

SURGERY.

Historically, surgical removal of the entire breast and axillary contents along with the muscles down to the chest wall was performed as the lone therapy, (radical mastectomy). In the last twenty-five years, as it has been appreciated that breast cancer is often systemic early in its course, the role of surgery is still primary but of less and less magnitude.

Today, surgical treatment is best thought of as a combination of removal of the primary tumor and staging of the axillary lymph nodes. If the whole breast is removed along with the entire axillary contents, but the muscles of the chest wall are not, the modified radical mastectomy has been performed.

If the tumor is less than 4 cm (1.5 in) in size and located so that it can be removed without destroying a reasonable cosmetic appearance of the residual breast, just the primary tumor and a rim of normal tissue will be removed. The axillary nodes will still be removed for staging purposes, usually through a separate incision. Because of the risk of recurrence in the remaining breast tissue, radiation is used to lessen the chance of local recurrence. This type of primary therapy is known as lumpectomy, (or segmental mastectomy), and axillary dissection.

Currently the necessary extent of the axillary dissection is being questioned. Sentinel lymph node biopsy, a technique for identifying which nodes in the axilla drain the tumor, has been developed to provide selective sampling and further lessen the degree of surgical trauma the patient experiences.

When patients are selected appropriately based on the preoperative clinical stage, all of these surgical approaches have been shown to produce similar results. In planning primary surgical therapy, it is imperative that the operation is tailored to fit the clinical circumstance of the patient.

The pathologic stage is determined after surgical treatment absolutely defines the local parameters. In addition to stage, there are other tests that are very necessary to aid in decisions regarding treatment. Handling of the surgical specimen is thus very important. The tissue needs to be analyzed for the presence or absence of hormone receptors and a receptor called HER-2. The presence of these receptors will influence additional therapies. Microscopic evaluation may also include the assessment of lymphatic or blood vessel invasion as these predict a worse outcome. The DNA of the tumor cells is quantitatively analyzed to help decide the biologic aggressiveness of the tumor. These parameters will be utilized collectively along with the axillary lymph node status to define the anticipated aggressiveness of the cancer. This assessment, along with the age and general condition of the patient, will be considered when planning the adjuvant therapies. Adjuvant therapies are treatments utilized after the primary treatment to help ensure that no microscopic disease exists and to help prolong patients' survival time.

RADIATION.

Like surgical therapy, radiation therapy is a local modality—it treats the tissue exposed to it and not the rest of the body. Radiation is usually given post-operatively after surgical wounds have healed. The pathologic stage of the primary tumor is now known and this aids in treatment planning. The extent of the local surgery also influences the planning. Radiation may not be needed at all after modified radical mastectomy for stage I disease, but is almost always utilized when breast-preserving surgery is performed. If the tumor was extensive or if multiple nodes were involved, the field of tissue exposed will vary accordingly. Radiation is utilized as an adjunct to surgical therapy and is considered an important modality in gaining local control of the tumor. The use of radiation therapy does not affect decisions for adjuvant treatment. In the past, radiation was used as an alternative to surgery on occasion. However, now that breast-preserving surgical protocols have been developed, primary radiation treatment of the tumor is no longer performed. Radiation also has an important role in the treatment of the patient with disseminated disease, particularly if it involves the skeleton. Radiation therapy can effect pain control and prevention of fracture in this circumstance.

DRUG THERAPY.

Many breast cancers, particularly those originating in post-menopausal women, are responsive to hormones. These cancers have receptors on their cells for estrogen and progesterone. Part of primary tumor assessment after removal of the tumor is the evaluation for the presence of these estrogen and progesterone receptors. If they are present on the cancer cells, altering the hormone status of the patient will inhibit tumor growth and have a positive impact on survival. The drug tamoxifen binds up these receptors on the cancer cells so that the hormones can't have an effect and, in so doing, inhibits tumor growth. If the patient has these receptors present, tamoxifen is commonly prescribed for five years as an adjunct to primary treatment. Adjuvant hormonal therapy with tamoxifen has few side effects but they have to be kept in mind, particularly the need for yearly evaluation of the uterus. Other agents directed at altering hormone environment are under study. Because of these agents, there is rarely any need for surgical removal of hormone-producing glands, such as the ovary or adrenal gland, that was sometimes necessary in the past.

Shortly after the modified radical mastectomy replaced the radical mastectomy as primary surgical treatment, it was appreciated that survival after local treatment in stage II breast cancer was improved by the addition of chemotherapy. Adjuvant chemotherapy for an interval of four to six months is now standard treatment for patients with stage II disease. The addition of systemic therapy to local treatment in patients who have no evidence of disease is performed on the basis that some patients have metastasis that are not currently demonstrable because they are microscopic. By treating the whole patient early, before widespread disease is diagnosed, the adjuvant treatment improves survival rates from roughly 60% for stage II to about 75% at five years after treatment. The standard regimen of cytoxan, methotrexate, and fluorouracil (CMF), is given for six months and is well tolerated. The regimen of cytoxan, adriamycin (doxorubicin), and floururacil, (CAF), is a bit more toxic but only requires four months. (Adriamycin and cytoxin may also be used alone, without the fluorouracil.) The two methods are about equivalent in results. Adjuvant hormonal therapy may be added to the adjuvant chemotherapy as they work through different routes.

As one would expect, the encouraging results from adjuvant therapy in stage II disease have led to the study of similar therapy in stage I disease. The results are not as dramatic, but they are real. Currently, stage I disease is divided into categories a, b, and c on the basis of tumor size. Stage Ia is less than a centimeter in diameter. Adjuvant hormonal or chemotherapy is now commonly recommended for stage Ib and Ic patients. The toxicity of the treatment must be weighed individually for the patient as patients with stage I disease have a survivorship of over 80% without adjuvant chemotherapy.

If patients are diagnosed with stage IV disease or, in spite of treatment, progress to a state of widespread disease, systemic chemotherapy is utilized in a more aggressive fashion. In addition to the adriamycin-containing regimens, docetaxel and paclitaxel have been found to be effective in inducing remission.

On the basis of prognostic factors such as total number of involved nodes over 10, aneuploid DNA with a high synthesis value, or aggressive findings on microscopic evaluation, some patients with stage II or III disease can be predicted to do poorly. If their performance status allows, they can be considered for treatment with highly aggressive chemotherapy. The toxicity is such that bone marrow failure will result. To get around this anticipated side effect of the aggressive therapy, either the patients will be transplanted with their own stem cells, (the cells that will give rise to new marrow), or an allogeneic bone marrow transplantation will be required. This therapy can be a high-risk procedure for patients. It is given with known risk to patients predicted to do poorly and then only if it is felt they can tolerate it. Most patients who receive this therapy receive it as part of a clinical trial. At present, it is unclear that such aggressive therapy can be justified and it is under study.

For patients who are diagnosed with advanced local disease, surgery may be preceded with chemotherapy and radiation therapy. The disease locally regresses allowing traditional surgical treatment to those who could not receive it otherwise. Chemotherapy and sometimes radiation therapy will continue after the surgery. The regimens of this type are referred to as neo-adjuvant therapy. This has been proven to be effective in stage III disease. Neo-adjuvant therapy is now being studied in patients with large tumors that are stage II in an effort to be able to offer breast preservation to these patients.

A drug known as Herceptin (trastuzumab), a monoclonal antibody, is now being used in the treatment of those with systemic disease. The product of the Human Epidermal Growth Factor 2 gene, (HER-2) is overex-pressed in 25%-30% of breast cancers. Herceptin binds to the HER-2 receptors on the cancer, resulting in the arrest of growth of these cells.

Prognosis

The prognosis for breast cancer depends on the type and stage of cancer. Over 80% of stage I patients are cured by current therapies. Stage II patients survive overall about 70% of the time, those with more extensive lymph nodal involvement doing worse than those with disease confined to the breast. About 40% of stage III patients survive five years, and about 20% of stage IV patients do so.