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Treatment of invasive breast cancer, by stage

 东那个东 2013-01-31

Treatment of invasive breast cancer, by stage

Breast-conserving surgery (BCS) is often appropriate for earlier-stage invasive breast cancers if the cancer is small enough, although mastectomy is also an option. If the cancer is too large, a mastectomy will be needed, unless pre-operative (neoadjuvant) chemotherapy (chemo) can shrink the tumor enough to allow BCS. In either case, one or more underarm lymph nodes will need to be checked for cancer. Radiation will be needed for almost all patients who have BCS and some who have mastectomy. Adjuvant systemic therapy after surgery is typically recommended for all cancers larger than 1 cm (about 1/2 inch) across, and also sometimes for smaller tumors.

Stage I

These cancers are still relatively small and either have not spread to the lymph nodes (N0) or have a tiny area of cancer spread in the sentinel lymph node (N1mi).

Local therapy: Stage I cancers can be treated with either BCS (lumpectomy, partial mastectomy) or mastectomy. The lymph nodes will also need to be evaluated, with a sentinel lymph node biopsy or an axillary lymph node dissection. Breast reconstruction can be done either at the same time as surgery or later.

Radiation therapy is usually given after BCS. Women may consider BCS without radiation therapy if ALL of the following are true:

  • They are age 70 years or older.
  • The tumor was 2 cm or less across and it has been completely removed.
  • The tumor contains hormone receptors and hormone therapy is given.
  • None of the lymph nodes that were removed contained cancer.

Some women who do not meet these criteria may be tempted to avoid radiation, but studies have shown that not getting radiation increases the chances of the cancer coming back.

Adjuvant systemic therapy: Most doctors will discuss the pros and cons of adjuvant hormone therapy (either tamoxifen, an aromatase inhibitor, or one following the other) with all women who have a hormone receptor–positive (estrogen or progesterone) breast cancer, no matter how small the tumor. Women with tumors larger than 0.5 cm (about 1/4 inch) across may be more likely to benefit from it.

If the tumor is smaller than 1 cm (about 1/2 inch) across, adjuvant chemo is not usually offered. Some doctors may suggest chemo if a cancer smaller than 1 cm has any unfavorable features (such as being high-grade, hormone receptor–negative, HER2-positive, or having a high score on one of the gene panels like Oncotype Dx). Adjuvant chemo is usually recommended for larger tumors.

For HER2-positive cancers, adjuvant trastuzumab (Herceptin) is usually recommended as well.

See below for more information on adjuvant therapy.

Stage II

These cancers are larger and/or have spread to a few nearby lymph nodes.

Local therapy: Surgery and radiation therapy options for stage II tumors are similar to those for stage I tumors, except that for stage II, radiation therapy to the chest wall may be considered even after mastectomy if the tumor is large (more than 5 cm across) or cancer cells are found in several lymph nodes.

Adjuvant systemic therapy: Adjuvant systemic therapy is recommended for women with stage II breast cancer. It may involve hormone therapy, chemo, trastuzumab, or some combination of these, depending on the patient's age, estrogen-receptor status, and HER2/neu status. See the following section for more information on adjuvant therapy.

Neoadjuvant therapy: An option for some women who would like to have BCS, but the surgeon thinks the tumor is too large to have a good result, is to have neoadjuvant (before surgery) chemo, hormone therapy, and/or trastuzumab to shrink the tumor.

If the neoadjuvant treatment shrinks the tumor enough, women may then be able to have BCS (such as lumpectomy) followed by radiation therapy. More adjuvant therapy after surgery may also be given.

If the tumor does not shrink enough for BCS, then mastectomy may be required. Adjuvant therapy may also be given after surgery, but would likely be with different drugs, since the tumor did not shrink with the first set given. Radiation therapy may be given after surgery, as well.

A woman's chance for survival from breast cancer does not seem to be affected by whether she gets chemo before or after her breast surgery.

Stage III

For a cancer to be a stage III, the tumor must be large (greater than 5 cm or about 2 inches across) or growing into nearby tissues (the skin over the breast or the muscle underneath), or the cancer has spread to many nearby lymph nodes. Local treatment for some stage III breast cancers is largely the same as that for stage II breast cancers. Tumors that are small enough (and have not grown into nearby tissues) may be removed by BCS (such as lumpectomy) which is followed by radiation therapy. Otherwise, the breast is treated with mastectomy (with or without breast reconstruction). Sentinel lymph node biopsy may be an option for some patients, but most require an axillary lymph node dissection. Surgery is usually followed by adjuvant systemic chemotherapy, and/or hormone therapy, and/or trastuzumab. Radiation after mastectomy is often recommended.

Often, stage III cancers are treated with neoadjuvant chemo (chemo before surgery). This may shrink the tumor enough that BCS may be done. Otherwise, a mastectomy is done. Usually an axillary lymph node dissection is done as well. Immediate reconstruction may be an option for some, but reconstruction is often delayed until after radiation therapy, which is often given even if a mastectomy is done. Adjuvant chemo may also be given, and adjuvant hormone therapy is offered to all women with hormone receptor–positive breast cancers.

Some inflammatory breast cancers are stage III. They are treated with neoadjuvant chemo, sometimes with radiation. This is followed by a mastectomy and axillary lymph node dissection. Then adjuvant treatment with chemo (and trastuzumab if the cancer is HER2-positive), radiation therapy (if it wasn’t given before surgery), and hormone therapy (if the cancer is hormone receptor?positive) is given.

Adjuvant drug therapy for stages I to III breast cancer

Adjuvant drug therapy may be recommended, based on the tumor's size, spread to lymph nodes, and other prognostic features. If it is, you may get chemotherapy, trastuzumab (Herceptin), hormone therapy, or some combination of these.

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 the size of the tumor 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 block the effects of estrogen being made by the ovaries. Some doctors also give a luteinizing hormone-releasing hormone (LHRH) analog, which makes the ovaries temporarily stop functioning. Another (permanent) option is surgical removal of the ovaries (oophorectomy). Still, it is not clear that removing the ovaries or stopping them from working helps tamoxifen work better for cancers that have been removed completely. If the woman becomes post-menopausal within 5 years of starting tamoxifen (either naturally or because her ovaries are removed), she may be switched from tamoxifen to an aromatase inhibitor.

Sometimes a woman will stop having periods after chemotherapy or while on tamoxifen. But this does not necessarily mean she is truly post-menopausal. The woman's doctor can test for certain hormones to determine her menopausal status. This is important because the aromatase inhibitors will only benefit post-menopausal women.

Women no longer having periods, or who are known to be in menopause at any age, and who have hormone receptor–positive tumors will generally get adjuvant hormone therapy either with an aromatase inhibitor (typically for 5 years), or with tamoxifen for 2 to 5 years followed by an aromatase inhibitor for 3 to 5 more years. For women who can't take aromatase inhibitors, an alternative is tamoxifen for 5 years.

As mentioned before, there are still many unanswered questions about the best way to use these drugs. For example, it's not clear if starting adjuvant therapy with one of these drugs is better than giving tamoxifen for some length of time and then switching to an aromatase inhibitor. Nor has the optimal length of treatment with aromatase inhibitors been determined. Studies now under way should help answer these questions. You might want to discuss these newer treatments with your doctor.

If chemo is to be given as well, hormone therapy is usually not started until after chemo is completed.

Chemotherapy: Chemo is usually recommended for all women with an invasive breast cancer whose tumor is hormone receptor-negative, and for women with hormone receptor?positive tumors who might additionally benefit from having chemo along with their hormone therapy, based on the stage and characteristics of their tumor.

Adjuvant chemo can decrease the risk of the cancer coming back, but it does not remove the risk completely. Before deciding if it's right for you, it is important to understand the chance of your cancer returning and how much adjuvant therapy will decrease that risk.

Your doctor should discuss what specific drug regimens are best for you based on your cancer, its stage, your other health issues, and your preferences. The typical chemo regimens are listed in the chemotherapy section. The length of these regimens usually ranges from 3 to 6 months. In some cases, dose-dense chemo may be used (see the Chemotherapy section for an explanation of dose-dense chemo).

Trastuzumab (Herceptin): Women who have HER2-positive cancers are usually given trastuzumab along with chemo as part of their treatment.

A common chemo regimen is doxorubicin (Adriamycin) and cyclophosphamide together for about 3 months (or 2 months if dose-dense chemo is used), followed by paclitaxel (Taxol) and trastuzumab. The paclitaxel is given for about 3 months (2 months if dose-dense treatment is used), while the trastuzumab is given for a total of about 1 year.

A concern among doctors is that giving the trastuzumab so soon after doxorubicin may lead to heart problems, so heart function is watched closely during treatment with tests such as echocardiograms or MUGA scans.

To try to lessen the possible effects on the heart, doctors are also looking for effective chemotherapy combinations that don't contain doxorubicin. One such regimen is called TCH. It gives the chemotherapy drugs docetaxel (Taxotere) and carboplatin every 3 weeks along with weekly trastuzumab (Herceptin) for 6 cycles. This is followed by trastuzumab every 3 weeks for a year.

Gene pattern tests: Some doctors may use newer gene pattern tests to help decide whether to give adjuvant chemotherapy to women with certain stage I or II breast cancers. Examples of such tests include Oncotype DX and MammaPrint, which are described in more detail in the section "How is breast cancer diagnosed?" These tests are done on a sample of your breast cancer tissue. They look at the function of several genes within the cancer to help predict its risk of returning after treatment. The tests will not tell your doctor which hormone therapy or chemotherapy is best for you. They can help your doctor decide how useful adjuvant treatment may be for you. Large clinical trials are now being done to see how helpful these tests may be in situations where doctors are often uncertain, such as in women with small tumors and clear lymph nodes.

Online tools to help make decisions: To decide if adjuvant therapy is right for you, you might want to visit the Mayo Clinic Web site at www. and type "adjuvant therapy for breast cancer" into the search box. You will find a page that will help you to understand the possible benefits and limits of adjuvant therapy.

Other online guides, such as www., are designed to be used by health care professionals. This Web site provides information about your risk of the cancer returning within the next 10 years and what benefits you might expect from hormone therapy and/or chemotherapy. You may want to ask your doctor if he or she uses this site.

Stage IV

Stage IV cancers have spread beyond the breast and lymph nodes to other parts of the body. Breast cancer most commonly spreads to the bones, liver, and lung. As the cancer progresses, it may spread to the brain, but it can affect any organ, even the eye.

Although surgery and/or radiation may be useful in some situations (see below), systemic therapy is the main treatment. Depending on many factors, this may consist of hormone therapy, chemotherapy, targeted therapies, or some combination of these treatments. Treatment can shrink tumors, improve symptoms, and help patients live longer, but it isn’t able to cure these cancers (make the cancer go away and stay away).

Trastuzumab may help women with HER2-positive cancers live longer if it is given with the first chemo for stage IV disease. Giving pertuzumab with chemo and trastuzumab may help even more. Trastuzumab can also be given with the hormone therapy drug letrozole. It is not clear how long treatment with trastuzumab or pertuzumab should continue.

All of the systemic therapies given for breast cancer—hormone therapy, chemo, and targeted therapies—have possible side effects, which were described in previous sections. Your doctor will explain to you the benefits and risks of these treatments before prescribing them.

Radiation therapy and/or surgery may also be used in certain situations, such as:

  • When the breast tumor is causing an open wound in the breast (or chest)
  • To treat a small number of metastases in a certain area
  • To prevent bone fractures
  • When an area of cancer spread is pressing on the spinal cord
  • To treat a blockage in the liver
  • To provide relief of pain or other symptoms
  • When the cancer has spread to the brain

If your doctor recommends such local treatments, it is important that you understand their goal—whether it is to try to cure the cancer or to prevent or treat symptoms.

In some cases, regional chemo (where drugs are delivered directly into a certain area, such as the fluid around the brain or into the liver) may be useful as well.

Treatment to relieve symptoms depends on where the cancer has spread. For example, pain from bone metastases may be treated with external beam radiation therapy and/or bisphosphonates such as pamidronate (Aredia) or zoledronic acid (Zometa). Most doctors recommend bisphosphonates or denosumab (Xgeva), along with calcium and vitamin D, for all patients whose breast cancer has spread to their bones. (For more information about treatment of bone metastases, see our document, Bone Metastasis.)

Advanced cancer that progresses during treatment: Treatment for advanced breast cancer can often shrink the cancer or slow its growth (often for many years), but after a time, it stops working. Further treatment at this point depends on several factors, including previous treatments, where the cancer is located, and a woman's age, general health, and desire to continue getting treatment.

For hormone receptor–positive cancers that were being treated with hormone therapy, switching to another type of hormone therapy sometimes helps. If either letrozole (Femara) or anastrozole (Arimidex) were given, using everolimus (Affinitor) with exemestane may be an option. If hormone drugs stop working, chemo is usually the next step.

If the cancer is no longer responding to one chemo regimen, trying another may be helpful. Many different drugs and combinations can be used to treat breast cancer. However, each time a cancer progresses during treatment it becomes less likely that further treatment will have an effect.

HER2-positive cancers that no longer respond to trastuzumab might respond to lapatinib Lapatinib also attacks the HER2 protein. This drug is often given along with the chemotherapy drug capecitabine (Xeloda), but it can be used with other chemo drugs, with trastuzumab, or even alone (without chemo).

Because current treatments are very unlikely to cure advanced breast cancer, patients in otherwise good health are encouraged to think about taking part in clinical trials of other promising treatments.

Recurrent breast cancer

Cancer is called recurrent when it come backs after treatment. Recurrence can be local (in the same breast or in the mastectomy scar) or in a distant area. Rarely, breast cancer comes back in nearby lymph nodes. This is called regional recurrence. Cancer that is found in the opposite breast is not a recurrence—it is a new cancer that requires its own treatment.

Local recurrence: Treatment of women whose breast cancer has recurred locally depends on their initial treatment. If the woman had breast-conserving surgery, a 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. This is followed by radiation therapy, but only if none had been given after the original surgery. (Radiation can't be given to the same area twice.) In either case, hormone therapy, trastuzumab, chemo, or some combination of these may be used after surgery and/or radiation therapy.

Regional recurrence: When breast cancer comes back in nearby lymph nodes (such as those under the arm or around the collar bone), it is treated by removing those lymph nodes. This may be followed by radiation treatments aimed at the area. Systemic treatment (like chemo or hormone therapy) may be considered after the local treatment as well.

Distant recurrence: In general, women whose cancer comes back in organs like the bones, lungs, brain, etc., are treated the same way as those found to have stage IV breast cancer in these organs when they were first diagnosed (see treatment for stage IV). The only difference is that treatment may be affected by previous treatments a woman has had.

Should your cancer come back, our document, When Your Cancer Comes Back: Cancer Recurrence can provide you with more general information on how to manage and cope with this phase of your treatment.


Last Medical Review: 08/23/2012
Last Revised: 01/17/2013

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