Treatment of Breast cancer by Staging

Surgery

Almost all women with breast cancer will have some type of surgery in the course of their treatment. The purpose of surgery is to remove as much of the cancer as possible, and there are many different ways that the surgery can be carried out. Some women will be candidates for what is called breast conservation therapy (BCT). In BCT, surgeons perform a lumpectomy which means they remove the tumor with a little bit of breast tissue around it but do not remove the entire breast. BCT always needs to be combined with radiation therapy to make it an option for treating breast cancer. At the time of the surgery, the surgeon may also dissect the lymph nodes under the arm so the pathologist can review them for signs of cancer. Some patients will have a sentinel lymph node biopsy procedure first to determine if a formal lymph node dissection is required. Sometimes, the surgeon will remove a larger part (but not the whole breast), and this is called a segmental or partial mastectomy. This needs to be combined with radiation therapy as well. In early stage cancers (like stage I and II), BCT is as effective as removal of the entire breast via mastectomy. Most patients with DCIS that have a lumpectomy are treated with radiation therapy to prevent the local recurrence of DCIS (although some of these DCIS patients may be candidates for close observation after surgery). The advantage of BCT is that the patient will not need a reconstruction or prosthesis to appear like she did before the procedure.

More advanced breast cancers are usually treated with a modified radical mastectomy. Modified radical mastectomy means removing the entire breast and dissecting the lymph nodes under the arm. Patients with DCIS that have a mastectomy do not need to have the lymph nodes removed from under the arm. Some patients are candidates for BCT but choose modified radical mastectomy for personal reasons. Your surgeon can discuss your options and the pros and cons of either procedure. Most women who have modified radical mastectomies choose to undergo a reconstruction. There are many different procedures for creating a new breast mound, and you should talk to your plastic surgeon before your surgery to discuss your options and decide on how you would like to proceed.

Stage 0 (Ductal Carcinoma in Situ [DCIS] or Lobular Carcinoma in Situ [LCIS]): The two types of stage 0 breast cancer, DCIS and LCIS, are treated quite differently.

No immediate or active treatment is recommended for most women with LCIS because this condition is not a true cancer. But because having LCIS increases your risk of developing invasive cancer later on, close follow-up is essential. This usually includes a yearly mammogram and a clinical breast exam. Close follow-up of both breasts is important because women with LCIS in one breast have an equal risk of developing breast cancer on the same or opposite side.

These women may wish to consider taking tamoxifen or participating in a clinical trial for breast cancer prevention (with tamoxifen or raloxifene, for example). They may also wish to discuss other possible prevention strategies (such as optimizing their body weight, an exercise program, or preventive surgery) with their doctor.

Some medical centers have clinical trials to test the value of magnetic resonance imaging (MRI) for patients with LCIS. Some women with LCIS may choose to have a bilateral simple mastectomy (removal of both breasts but not axillary lymph nodes), especially if they have other risk factors such as strong family history, in an attempt to prevent invasive cancer from developing. Depending on the woman's preference, she may consider immediate or delayed breast reconstruction.

Treatment of DCIS depends on mammogram and biopsy results. In most cases, a woman can choose between breast-conserving therapy (lumpectomy, usually followed by radiation therapy) and simple mastectomy. Lymph node removal (axillary dissection) is usually not necessary. Lumpectomy without radiation therapy is usually considered an option only for women with small areas of low-grade DCIS with surgical margins around the DCIS of at least 1 cm. Mastectomy may be necessary if the area of DCIS is very large, if the breast has several areas of DCIS, or if lumpectomy cannot completely remove the DCIS (that is, the lumpectomy specimen and re-excision specimens have positive margins).

After a lumpectomy, a mammogram should be done to ensure that the disease has been removed. The surgical specimen is also x-rayed to make sure it contains all the abnormalities, such as calcifications, seen on the original mammogram.

Women having mastectomy for DCIS may have immediate or delayed reconstruction. Studies have shown that 5 years of treatment with tamoxifen can lower the risk of another DCIS or invasive cancer developing in either breast after treatment of DCIS with lumpectomy and radiation therapy, but only if the original DCIS had estrogen receptors.

Invasive Breast Cancer

If the cancer is small enough, breast-conserving surgery is appropriate. If it is too large, a mastectomy will be needed, unless preoperative chemotherapy can shrink the tumor enough. In either case, the lymph nodes will need to be checked and removed if they contain cancer. Radiation will be needed for almost all patients who have breast-conserving surgery and some who have mastectomy. Adjuvant therapy after surgery will also be recommended for all cancers larger than 1 cm (0.4 inches) and some that are smaller.

Stage I: This can be treated with either breast-conserving surgery sometimes called lumpectomy (removal of the cancer and a narrow margin of surrounding normal breast tissue), or mastectomy. The lymph nodes will need to be evaluated. Sentinel lymph node sampling may be used instead of standard axillary lymph node dissection. Radiation therapy is usually given after lumpectomy. Breast reconstruction can be done after a mastectomy, either at the time of surgery or later.

If the tumor is less than 1 cm (nearly 1/2 inch) in diameter, adjuvant systemic chemotherapy is not usually offered. Some doctors suggest adjuvant chemotherapy if a cancer smaller than 1 cm has any unfavorable features (microscopic study shows high grade, the estrogen-receptor assay is negative, or the tumor is HER2/neu positive). If the tumor is larger, depending on the features mentioned above, adjuvant chemotherapy or hormone therapy, or both, may be recommended. Most doctors will discuss the pros and cons of adjuvant hormone therapy (either tamoxifen or an aromatase inhibitor) with all women who have an estrogen receptor positive breast cancer no matter how small the tumor.

Stage II: Surgery and radiation therapy options for stage I and stage II tumors are similar, except that in stage II, radiation therapy may be considered even after mastectomy if the tumor is large (over 5 cm) or has spread to many lymph nodes (four or more). Adjuvant systemic therapy is also recommended. Adjuvant therapy may involve hormone therapy, chemotherapy, or both, depending on the patient's age and estrogen-receptor assay results.

An option for some women who would like to have breast-conserving therapy for tumors larger than 2 cm (4/5 inch – T2 or T3) is to have neoadjuvant (before surgery) chemotherapy to shrink the tumor. The size of these tumors relative to some women's breasts may make lumpectomy difficult or impossible.

If the neoadjuvant chemotherapy shrinks their tumors enough, women may then be able to have lumpectomy, which is followed by radiation therapy and hormone therapy if the hormone receptor is positive. If the tumor does not shrink enough to permit lumpectomy, then mastectomy followed by different chemotherapy, radiation therapy, and hormone therapy is the usual treatment. A woman's survival from breast cancer is not affected by whether she gets her chemotherapy before or after her breast surgery.

Stage III: Smaller stage IIIA breast cancers may be removed by lumpectomy. Modified radical mastectomy (with or without reconstruction) is another option. Surgery is usually followed by adjuvant systemic chemotherapy and/or hormone therapy and radiation therapy.

Larger stage IIIA as well as stage IIIB and IIIC cancers may be treated with neoadjuvant (before surgery) chemotherapy. Then a modified radical mastectomy is done, with or without reconstruction. A lumpectomy may be an option. In any case, surgery is followed by radiation therapy even if a total mastectomy is done. Hormone therapy will be discussed with all women with estrogen receptor positive breast cancers.

Adjuvant therapy for stage I - III breast cancer: Adjuvant drug therapy may be recommended, based on the tumor's size, spread to lymph nodes, and/or prognostic features. If it is, you may receive chemotherapy and/or hormone therapy.

Hormone therapy: Hormone therapy is not likely to be effective for women with hormone receptor-negative tumors. Hormone therapy is frequently offered to all women with hormone receptor-positive invasive breast cancer regardless of size or the number of lymph nodes involved.

Women who are still having periods and have hormone receptor-positive tumors can be treated with tamoxifen, which blocks the effects of estrogen being made by the ovaries or with luteinizing hormone-releasing hormone (LHRH) analogs, which medically make the ovaries temporarily nonfunctional. Another alternative is surgical removal of their ovaries.

Women not having periods or who are known to be in menopause at any age and have hormone receptor-positive tumors will generally receive hormone therapy with an aromatase inhibitor. If the aromatase inhibitor is given alone, the period of treatment is five years. An alternative is tamoxifen for five years as adjuvant therapy.

Some women may benefit from receiving both drugs (although not at the same time). Recent studies have shown that postmenopausal women who take the aromatase inhibitor letrozole after taking tamoxifen for five years may further lower the risk that their breast cancer will come back. It is not known exactly how long the letrozole should be taken. Other aromatase inhibitors may be equally effective. Another recent study has shown a benefit for the aromatase inhibitor exemestane, given after tamoxifen. In that study, postmenopausal women were given exemestane for two to three years after receiving tamoxifen for two to three years. These women had a lower cancer recurrence rate, both local and distant, than did women who took tamoxifen for the full five-year period. Similar benefits have also recently been reported when switching from tamoxifen to anastrozole after two years of tamoxifen for a total of five years of hormone therapy. You might want to discuss these new treatments with your doctor.

Chemotherapy: Chemotherapy is frequently discussed with all women with an invasive breast cancer whose tumor is hormone receptor-negative, or with those women with hormone receptor positive tumors who may receive additional benefit from receiving chemotherapy in addition to their hormone therapy. The specific drug regimens and the length of therapy are frequently determined by the size of the cancer, the aggressiveness of the cancer, and the number of involved lymph nodes. The specific chemotherapy regimens usually discussed are listed above in the chemotherapy section. As a general rule, CMF (cyclophosphamide, fluoruracil, and methotrexate) given for six months is equivalent to AC (adriamycin and Cyclophosphamide) given for three months. Patients with more aggressive tumors or those women with lymph node involved cancers will frequently be offered a taxane (paclitaxel or Docetaxel), in addition to adriamyclin and cyclophosphamide either in sequence or all at the same time. The length of these regimens ranges from four months to six months.

Most doctors recommend that hormone therapy be started after the chemotherapy is completed.

Women who have HER2/neu positive cancers should receive trastuzumab (Herceptin) as part of their program. In general the chemotherapy regimen that has been used is doxorubicin and cyclophosphamide together for four treatments followed by paclitaxel for 12 weekly treatments or every three weeks for four treatments. The trastuzumab, which is given weekly for about one year, may be slightly more effective if it is started at the same time as the paclitaxel. But doctors worry that giving the trastuzumab so soon after doxorubicin can lead to heart problems. Clinical trials of non-doxorubicin chemotherapy combinations along with trastuzumab are in progress.

Another aid that is being used by doctors to help determine the benefits of hormone therapy and chemotherapy for women with lymph node negative, hormone receptor positive invasive breast cancer is called Oncotype DX. This test is performed on a sample of your breast cancer and tests for the function of 21 specific genes within your cancer. How these genes are functioning in relation to one another can predict the risk of your cancer returning somewhere else in your body, as well as your expected benefit from hormone therapy or chemotherapy. The test will not yet tell your doctor which is the best hormone therapy or chemotherapy to recommend.

Stage IV: Systemic therapy is the main treatment, using chemotherapy, hormone therapy, or both. Immunotherapy with trastuzumab (Herceptin) alone or in combination with chemotherapy is an option for women whose cancer cells have high levels of the HER2/neu protein. Trastuzumab may allow women to live longer if it is given with the first chemotherapy for stage IV disease. It is not yet known whether it also should be given at the same time as hormone therapy, or how long a woman should remain on therapy. Another new form of therapy has also recently been shown to be of benefit for women with advanced cancer receiving chemotherapy. This class of drugs is called anti-VEGF therapy. They work by blocking factors made by cancers (VEGF—vascular endothelial growth factor), which stimulate a new blood supply to the cancer. These drugs seem to be able to block the cancer's ability to provide itself a health blood supply. Recently, results of a study were reported using a drug called bevacizumab (Avastin) along with paclitaxel. Women who received both of these drugs together had a doubling of the amount of time their cancer was under control versus just receiving the chemotherapy alone.

None of the systemic therapies given for breast cancer is without side effects including hormone therapy, chemotherapy, or the newer biologic therapies Herceptin or Avastin. Your doctor will explain to you the benefits and risks of all of these therapies before prescribing them.

Radiation and/or surgery may also be used to provide relief of certain symptoms. Treatment to relieve symptoms depends on where the cancer has spread. For example, pain due to bone metastases may be treated with external beam radiation therapy and/or bisphosphonates such as pamidronate (Aredia). Bisphosphonates are drugs that can help prevent bone damage or fractures caused by metastatic breast cancer. These are recommended for all patients whose breast cancer has spread to their bones. (For more information about treatment of bone metastases, see the American Cancer Society document, "Bone Metastasis.")

Patients in otherwise good health are encouraged to take part in clinical trials of other promising treatments being studied.

Recurrent breast cancer: Breast cancer can come back locally (in the breast or near the mastectomy scar) or in a distant area.

Treatment of women whose breast cancer has recurred locally depends on their initial treatment. If the woman had breast conservation therapy, local recurrence in the breast is usually treated with mastectomy. If the initial treatment was mastectomy, recurrence near the mastectomy site is treated by removing the tumor whenever possible, usually followed by radiation therapy, if none had been given after the original surgery. In either case, hormone therapy and/or chemotherapy may be used after surgery and/or radiation therapy.

Women who have a distant recurrence involving organs such as the bones, lungs, brain, etc., are treated the same as those found to have stage IV breast cancer involving these organs at the time of initial diagnosis.

Treatment of breast cancer during pregnancy: Breast cancer is diagnosed in about 1 pregnant woman out of 3,000. Radiation therapy during pregnancy is known to increase the risk of birth defects, so it is not recommended for pregnant women with breast cancer.

For this reason, breast conservation therapy (lumpectomy and radiation therapy) is not considered an option if treatment cannot be delayed until it is safe to deliver the baby. However, breast biopsy procedures and even modified radical mastectomy are safe for the mother and fetus.

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