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Breast Cancer

What Treatment Is Available For Breast Cancer?

Tuesday, March 20, 2012 - 11:06

Contributing Author: Guy Slowik FRCS

The treatment of breast cancer is determined by many factors, such as

  • tumor stage
  • tumor type
  • tumor characteristics
  • the person's general health
  • medical conditions that may influence treatment.

After breast cancer has been staged, a comprehensive treatment plan will be developed by a team of physicians, including an oncologist (cancer specialist). The treatment plan typically involves some form of

  • surgery (see also Surgery) to remove as much of the cancer as possible.

In addition to surgery, the treatment plan may call for adjuvant (assisting) therapy such as

Other treatment options that may be used for aggressive or late-stage breast cancers are

Finally, the physician team will try to predict the likelihood of breast cancerrecurrence (coming back). Specific tumor characteristics that help to determine the risk of recurrence include breast cancer

  • size
  • estrogen and progesterone (ER/PR) receptor status (presence or absence of hormone 'receptors' [lock-like molecules] - in cancer cells)
  • phase (whether or not tumor cells are actively dividing)
  • HER2/neu protein status (presence or absence of an oncogene-related protein found in some aggressive breast cancers),
  • grade (indicator of malignant change in the tumor), and
  • ploidy (number of sets of genetic material within tumor cells).

Surgery

A number of surgical procedures are used to treat breast cancer. Apart from removal of the tumor itself, operations may be performed to improve the appearance of the chest after breast surgery, to discover whether or not cancer has spread to the lymph nodes, or to relieve some of the symptoms of late-stage disease.

The most recent trend in breast cancer surgery is the use of breast-saving lumpectomy (removal of the tumor and its margins) plusradiation therapy for the treatment of early breast cancer. This method has been found to be as effective as mastectomy (complete removal of the breast), while sparing the breast. In addition, sentinel lymph node biopsy - a more exacting, less invasive form of lymph node biopsy - is becoming an acceptable alternative to axillary (armpit) dissection during surgical staging.

The most common surgeries for breast cancer are listed below:

  • Lumpectomy

    Lumpectomy removes the cancer, a surrounding border of cancer-free tissue (roughly 3/4 in), and the nearby lymph nodes. Lumpectomy is, by definition, a form of breast-conserving surgery (BCS).

  • Partial mastectomy

    Partial mastectomy is a non-specific term for surgery in which part of the breast is removed. If the tumor is located in the upper breast, the incision often is made in a curved line, close to the areola (dark, circular area around the nipple). If the tumor is located in the outer breast near the armpit, the tumor and nearby lymph nodes may be taken out through the same incision. If the tumor is located in the lower breast, the surgeon usually makes a radial incision (one that extends from the center of the breast outward towards the edges). The axillary (underarm) lymph nodes are removed through the original incision or via a separate incision in the armpit itself. In general, between 10 and 15 lymph nodes are removed during partial mastectomy.

    Quadrantectomy (also known as segmentectomy or tylectomy) is the term used to for a partial mastectomy in which about one-quarter of the breast is removed together with the tumor.

  • Total (simple) mastectomy

    Total mastectomy - also known as simple mastectomy - removes the entire breast, without removing the underam lymph nodes or muscular tissue beneath the breast. This procedure is being used increasingly for women who have carcinoma in situ (for example, DCIS) that has not yet spread to surrounding tissues.

  • Modified radical mastectomy

    Modified radical mastectomy (also known as Patey mastectomy) removes the entire breast and some of the underarm lymph nodes. In certain cases, the pectoralis minor (an upper chest muscle) may be removed if it is cancerous or if it hampers the removal of lymph nodes. This procedure is now the most frequently performed breast cancer surgery in the U.S., since it has a record of the best long-term results with the fewest complications.

  • Radical mastectomy

    Radical mastectomy, also known as the Halsted procedure, is a very invasive surgical procedure that involves extensive removal of chest tissue. In addition to the entire breast and axillary lymph nodes, this operation removes the chest muscles under the breast and the surrounding skin. After radical mastectomy, the natural contour of the chest is deformed, arm movement may be impaired, breast reconstruction is complicated, and skin grafting may be needed. Radical mastectomy is rarely justified or performed, since modified radical mastectomy has proven to be an equally effective technique with less disfigurement.

  • Skin-sparing mastectomy

    Skin-sparing mastectomy - a new surgical procedure - is a variation of total mastectomy. During this operation, the breast tissue is removed through a tiny circular incision that is made around the nipple. This technique, which minimizes disfigurement, leaves the skin undamaged and enables immediate breast reconstruction by means of an implant or natural tissue. Skin-sparing mastectomy is now being performed at a number of cancer centers throughout the U.S.

  • Subcutaneous mastectomy

    Subcutaneous mastectomy removes most, but not all, breast tissue via a small surgical incision that leaves the breast skin and nipple unchanged. This operation is rarely performed, since breast cancer often recurs due to cancerous tissue that has been left behind in the breast and nipple.

  • Axillary dissection

    Axillary dissection is used to determine whether or not cancer has spread to the lymph nodes under the arm. During this procedure, a section of underarm fat and adjoining lymph nodes are removed for microscopic analysis by a histopathologist (specialist in diseases of tissues). Axillary dissection may be conducted as part of a modified radical mastectomy or as a separate underarm incision that is made during lumpectomy.

  • Sentinel lymph node biopsy

    Sentinel lymph node biopsy uses a radioactive substance to target the lymph nodes that are likely to be affected by breast cancer. A radioactive tracer is injected into the tumor and is eventually carried by the lymph to the first 'sentinel' node in the tumor's lymphatic pathway. If the cancer has spread, this node is most likely to contain cancer cells. Therefore, the surgeon will biopsy the sentinel node and have it analyzed for malignancy. If it does not contain cancer cells, the removal of additional lymph nodes may be unnecessary.

  • Reconstructive or breast implant surgery

    Strictly speaking, breast reconstruction is NOT a breast cancer treatment. It is a surgical procedure that is performed to restore a woman's appearance after breast surgery. To ensure the best results, a person should decide about breast reconstruction before mastectomy. This enables the surgeon to plan for reconstruction or even perform reconstruction at the time of mastectomy. The advantages of immediate reconstruction include:

    • lessening of grief over breast loss,
    • completion of both procedures with one anesthetic risk, and
    • preservation and immediate use of uninvolved breast skin.

    Delayed reconstruction is preferable if:

    • the person is unsure about having the operation,
    • prolonged anesthesia will increase the risk of the operation, or
    • postoperative radiation therapy is being considered.

    A reconstructed breast may differ in shape and/or size from the remaining normal breast. Therefore, some women choose to have plastic surgery performed on the normal breast so that both breasts appear similar.

Breast implants (artificial cushions that are filled with a soft, breast-like substance - usually saline [salt water] or gel) have been used extensively for breast reconstruction. Breast implants are not placed under the skin, but rather are inserted under the pectoral (chest) muscle in a surgically-made pouch. Sometimes the chest muscle must be pre-stretched by a temporary device before placement of the permanent implant.

The major advantage of using an implant is that it can be inserted easily and quickly. The disadvantages are the continual risk of implant failure in the form of infection, rupture, breakdown, capsular contraction (tissue hardening around an implant), and the need for tissue pre-stretching. The lifespan of implants beyond 10 to 20 years is still unknown, as is the relationship - if any - to autoimmune disease.

For these reasons, the use of the woman's own tissue has become the method of choice for breast reconstruction. Specifically, surgeons have begun to use skin and fat from elsewhere in the woman's body (e.g., the abdomen) to create a more natural-looking breast.

In some cases - especially if the chest muscles have been removed during radical surgery - myocutaneous (skin and muscle) "flaps" may be transferred from a donor site to the chest wall. Such flaps include the

  • latissimus dorsi (back muscle), or "LD" flap,
  • transverse rectus abdominis (abdominal muscle)myocutaneous, or "TRAM" flap, and
  • gluteus maximus flap, which is a "free" or unattached flap made from the tissue of the buttocks or thigh.

Nipple and areola reconstruction usually is conducted a few months after breast reconstruction so that the nipple can be positioned correctly. A variety of methods are used to create the nipple projection and areola. The tissue often is darkened by tattooing to achieve a good color match.

For more specific information about breast surgery or mastectomy, contact the American Cancer Society or the National Cancer Institute.

Radiation Therapy

Radiation therapy, also known as radiotherapy, uses high-energy rays

(x-rays, gamma rays) to destroy cancer cells. Cancer cells are targeted by radiation therapy because, unlike normal cells, they are unable to repair radiation-induced damage. Radiation therapy is delivered by means of linear accelerators - machines that generate x-rays and electrons and direct them as an external beam. Another device, the cobalt machine, gives off gamma rays from a radioactive source of cobalt. Radiation therapy usually is given after breast-conserving surgery, that is, after

  • lumpectomy or
  • partial mastectomy for early-stage cancers.

Such treatment helps to eliminate any cancer cells that may remain in the breast. Radiotherapy is used to preventlocal recurrence (regrowth of breast cancer at the original site) and to avoid the need for mastectomy. Recent follow-up studies indicate that women who undergo lumpectomy with radiotherapy survive as long as women who undergo mastectomy. Unfortunately, women who develop a local recurrence usually require mastectomy, because a cancerous breast cannot be irradiated twice without damaging side effects (for example, death of normal breast tissue, skin ulceration, or radiation-induced cancer).

Radiation therapy usually is not needed after a complete mastectomy. Some exceptions include breast cancer that is:

  • advanced, with a high risk of recurrence in the chest wall (for example, cancer with four or more cancerous lymph nodes),
  • very large (> 5 cm),
  • not able to be removed with awide enough margin, and
  • recurrent after mastectomy (for example, a small cancer that returns to grow upon the skin).

In such cases, radiotherapy may be employed to destroy cancer cells in a wider area of the chest and to prevent recurrence. Chemotherapy and/or hormone therapy may be given before or after radiotherapy.

Computer simulation is used to establish the fields (parts of the body to receive radiation) and angles of radiation that will be used. The simulator helps to ensure that radiation therapy is limited to the breast, with little exposure of other tissues. To confirm the treatment area for radiation therapy, the person's skin is marked with indelible ink or small tattoos.

External beam radiation therapy - which usually delivers a total dose of about 4500-5000 rad (a unit of absorbed dose of radiation) - often is performed in an outpatient facility. A typical schedule is 5 days of therapy per week over a period of about 6 weeks. Each session lasts a few minutes and is painless. A boost dose (another type of radiation specifically directed at the tumor site) may be given over a period of 5 to 14 days.

An internal boost of radiotherapy may be used as an alternative treatment. During this procedure, a radioactive isotope like iridium (Ir192) is implanted into the breast cancer by means of hollow plastic tubes. The implants remain in place for about 2 days, after which they are removed. In some cases (for example, cancers deep within the breast), the internal boost may be given during the removal of the tumor, before the surgical incision is closed.

Lymph nodes may be treated by external beam radiation under certain circumstances. For example, if breast cancer has spread to the axillary (armpit) lymph nodes, then the supraclavicularlymph nodes (above the collarbone) are at high risk and may need to be irradiated. Also, if breast cancer is located near the middle of the body, then the internal mammary lymph nodes may require radiation therapy. Radiation therapy should NOT be performed upon the axillary lymph nodes if surgery has been conducted in the underarm region, since it is likely that lymphedema (swelling of the arm caused by fluid retention) will occur after the operation or at some time in the future.

Radiation therapy can cause side effects such as:

  • fatigue,
  • sunburn-like reddening and peeling of the breast skin,
  • loss of underarm hair, and
  • 'pins and needles' sensation in the treatment area.

After a while, the 'sunburn' effect usually fades into a light tan. Temporary relief from mild burning sensations may be provided by gentle creams, the use of baby powder, and the wearing of light, non-binding cotton clothing. The breast skin may thicken, causing the breast to become firmer to the touch and slightly smaller in size. Occasionally, the breast may become larger if fluid builds up within the breast tissue due to a damaged lymphatic system. Other uncommon side effects are costochondritis (arthritic pain in the rib/breastbone junction), hairline fractures in ribs made brittle by radiation, radiation pneumonitis (lung inflammation), and radiation damage of the nerves, muscles, or heart.

Radiotherapy is NOT RECOMMENDED for women who have connective tissue diseases such as scleroderma or systemic lupus erythematosus (SLE. Their tissues respond abnormally to radiation and may form considerable scars or non-healing skin ulcers. Radiotherapy also may be problematic for women with large breasts. If radiation equipment cannot be adjusted to deliver the radiation dose required for a large tissue mass, the woman may need to be referred to another facility that has suitable equipment.

Chemotherapy

Chemotherapy is the use of anticancer drugs to destroy cancer cells. Chemotherapeutic drugs are given with the hope that micrometastases (small groups of cancer cells) will be eliminated before they spread to other tissues. Many chemotherapeutic drugs interfere with cell division or other metabolic processes. Therefore, they are most harmful to rapidly-dividing cancer cells, although normal cells also may be damaged.

Chemotherapy typically is delivered in the form of shots or pills. It may be the only treatment used if breast cancer has spread to other parts of the body. More commonly, though, chemotherapy is given as an adjuvant (assisting therapy) to reduce the chance of cancer recurring after surgery, radiation therapy, or both. Adjuvant chemotherapy, like hormone therapy, usually is started about 4 weeks after surgeryNeoadjuvant chemotherapy is given before surgery to shrink the breast tumor and make it easier to remove. Specific schedules are followed during chemotherapy, so that periods of treatment are accompanied by periods of recovery. Most treatment schedules are completed within 3 to 6 months.

The following drugs are commonly used for breast cancer chemotherapy:

Brand name

Generic (common) name

Cytoxan®

Cyclophosphamide

(Methotrexate)

Methotrexate

5-Fluorouracil (5-FU)

5-Fluorouracil

Adriamycin®

Doxorubicin

(Prednisone)

Prednisone

Nolvadex®

Tamoxifen

Taxol®

Paclitaxel

(Leucovorin)

Leucovorin

Oncovin®

Vincristine

Thioplex®

Thiotepa

Arimidex®

Anastrozole

Taxotere®

Docetaxel

Navelbine®

Vinorelbine tartrate

Gemzar®

Gemcitabine

 

As illustrated by the table above, many anticancer drugs are available to treat breast cancer. Combination chemotherapy - a mix of two or more drugs - often is more effective than a single medication. Some proven, first-line drug combinations include:

Drug

Combination

CMF

cyclophosphamide, methotrexate, and 5-fluorouracil. This mixture, which has been studied for more than 20 years, is very effective in mastectomy patients who have cancerous lymph nodes. Both premenopausal and postmenopausal women respond well to CMF therapy.

'classic' CMF

oral cyclophosphamide plus methotrexate and 5-fluorouracil

CAF

cyclophosphamide, adriamycin® (doxorubicin), and 5-fluorouracil. When the dose of adriamycin is increased, this regimen is called FAC.

AC

Adriamycin® and cyclophosphamide

ACT

Adriamycin® plus cyclophosphamide and tamoxifen

AC taxol

Adriamycin® plus cyclophosphamide and paclitaxel (Taxol®)

FACT

5-fluorouracil plus adriamycin®, cyclophosphamide, and tamoxifen

A-CMF

4 cycles of adriamycin® followed by 8 cycles of CMF; also known as Adria/CMF or the Milan regimen.

CMFP

CMF plus prednisone.

CMFVP

CMF plus vincristine and prednisone.

CAFMV

CAF plus methotrexate and vincristine.

CMFVATN

CMF plus vincristine, adriamycin®, thiotepa, and tamoxifen.

MF

methotrexate plus 5-fluorouracil and leucovorin (a B-vitamin relative used to temper the activity of antimetabolite drugs).

Chemotherapy may cause significant side effects, depending upon the

type of medication taken, the dose, and the length of treatment. Some temporary conditions include:

  • nausea and vomiting
  • hair loss
  • diarrhea
  • mouth sores
  • fatigue
  • excess stomach acid
  • bone marrow damage
  • leukopenia (shortage of white blood cells)
  • infection

Less common, but notable side effects are:

  • heart muscle damage
  • phlebitis (vein inflammation)
  • neuropathy (nerve damage)
  • arthritic pain
  • increased blood sugar
  • changes in skin color
  • bladder wall damage
  • prolonged fever
  • thrombocytopenia (shortage of blood-clotting cells)

Medicines are available to help relieve some of the side effects caused by chemotherapy. These include anti-nausea drugs (for example, reglan), anti-anemia drugs (for example, epoetin alfa [Procrit®, Epogen®] - a synthetic hormone that stimulates the manufacture of red blood cells), and cell-protecting drugs like amifostin (Ethyol®), which lessens some of the toxic effects of cisplatin chemotherapy.

Most temporary side effects disappear after chemotherapy has ended. Unfortunately, the permanent side effects of chemotherapy in premenopausal women are:

  • impaired function of the ovaries, and
  • sterility.

Some oncologists believe that no chemotherapeutic program should last for more than 6 months; however, longer programs have been effective in some women, particularly when combined with hormone therapy (e.g., tamoxifen).

Nice To Know:

Chemotherapy medications and examples

Medication Type and Activity

Examples

Alkylating agents

Prevent cell growth

Cyclophosphamide (Cytoxan®)

Ifosphamide (Ifex®)

Melphalan (L-Pam®)

Thiotepa (Thioplex®)

Cisplatin (Cisplatinum®, Platinol®)Carboplatin (Paraplatin®)

Carmustine (BCNU; BiCNU®)

Antimetabolites

Interfere with the manufacture of genetic material (DNA, RNA) and with nutrition in tumor cells

5-Fluorouracil (5-FU)

Methotrexate

Antitumor antibiotics

Kill tumor cells and interfere with cell genetics (DNA manufacture)

Doxorubicin (Adriamycin®)

Mitomycin C (Mutamycin®)

Cytotoxics

Kill tumor cells and interfere with cell genetics (DNA manufacture)

Mitoxantrone (Novantrone®)

Natural products

Vinca alkaloids

Kill tumor cells; are extracts of the periwinkle plant

 

Vincristine (Oncovin®)

Vinblastine (Velban®)

Vinorelbine (Navelbine®)

Taxanes

Kill tumor cells; are extracts of Pacific and European yew trees

 

Paclitaxel (Taxol®)

Docetaxel (Taxotere®)

Retinoids

Vitamin A derivatives that affect cell growth, maturation, and immunologic function

Fenretinide

Hormone-related drugs

Corticosteroids

Enhance the tumor-killing effects of other chemotherapeutic drugs and, possibly, interfere with cell DNA

Prednisone

Antiestrogens

Interfere with the action of estrogen on cancer cells; inhibits tumor growth

Tamoxifen (Nolvadex®)

Male hormone

Inhibits tumor growth

Fluoxymesterone (Halotestin®)

Investigational drugs

 

Topoisomerase-I ("topo-I") compounds

Extracts of the Chinese tree Camptotheca acuminata

Toptecan

Irinotecan

9-amino-camptothecin [9-AC]

Anthrapyrazoles

Antitumor antibiotics that are less toxic relatives of doxorubicin; they kill tumor cells and interfere with cell genetics (DNA manufacture)

Biantrazole

Losoxantrone

Antimetabolites

Methotrexate-like compounds that interfere with the manufacture of genetic material (DNA, RNA) and with nutrition in tumor cells

Edatrexate

Epidophylotoxins

Kill tumor cells

Etoposide

Teniposide

Hormone Therapy

Hormone therapy for breast cancer is based on the observation that cancer cell growth is sped up by estrogen. 'Antiestrogen' medications like

tamoxifen (Nolvadex®) are used to counteract this effect.

Tamoxifen is an estrogen-like compound that binds to the breasts' estrogen receptors (ER) and makes them unavailable to estrogen's cancer-promoting activity. Tamoxifen also may prevent breast cancer by stopping angiogenesis - the blood vessel growth required by tumors.

Hormone therapy usually begins within 4 weeks of surgery. Tamoxifen is given in pill form and is most effective when administered on a daily basis for a period of five years. Recent studies indicate that tamoxifen benefits most women with early breast cancer.

Clinical trials are now underway to evaluate the effects of another antiestrogen, raloxifene. Raloxifene, like tamoxifen, may lessen the chance of developing breast cancer; however, it is not recommended for use in women who are already have breast cancer.

Tamoxifen is likely to be given if a woman's breast cancer is

  • 'ER/PR positive' - that is, it contains estrogen and progesterone receptors, or if a woman's breast cancer is
  • 'ER/PR positive' and shows metastasis or recurrence.

If tamoxifen is not effective against an aggressive tumor, other hormonal medications may be prescribed. Such drugs include

  • aromatase inhibitors (e.g., anastrozole [Arimidex®], aminoglutethimide [Cytadren®]), which block the estrogen-converting power of the enzyme aromatase and stop estrogen production
  • LHRH (luteinizing hormone-releasing hormone)-inhibiting compounds (e.g., goserelin [Zoladex®], leuprolide (Lupron®), which suppress the production of pituitary hormones that cause the ovaries to make estrogen
  • progestins (e.g., megestrol acetate [Megace®], medroxyprogesterone acetate [Provera®]), which are synthetic progestational (pregnancy-enhancing, abortion-preventing) drugs, and
  • androgens (e.g., fluoxymesterone [Halotestin®], testolactone [Teslac®], testosterone enanthate [Delatestryl®]) synthetic male hormones that suppress the estrogen supplied to the breasts

Along with breast cancer prevention, tamoxifen has other beneficial effects such as increased bone production and the prevention of plaque buildup within the blood vessels. Tamoxifen usually is well tolerated. However, reported side effects, which are related to its estrogen-like properties, include hot flashes, nausea, vomiting, endometrial hyperplasia (overgrowth of the tissue lining the womb), and early or temporary menopause in premenopausal women.

Unlike tamoxifen, the aromatase inhibitor aminoglutethamide can cause relatively toxic side effects, such as sluggishness, ataxia (lack of motor coordination), orthostatic hypotension (low blood pressure when standing), dizziness, weakness, blood abnormalities, elevated liver enzymes, and nausea. By contrast, the progestins medroxyprogesterone acetate and megestrol acetate cause few side effects and are particularly useful in postmenopausal women (age 60+ years) who have experienced a recurrence of cancer. Androgens can cause masculinization (development of male secondary sex characteristics like a low voice and facial hair) in some women. Fortunately, fluoxymesterone (Halotestin®) is not as likely to produce masculinization as some of the other androgens. There are reports that it may be particularly effective in women who have bone metastases.

Immunotherapy

Immunotherapy - treatment that works via the immune system - usually is begun if standard therapies (chemotherapy, hormone therapy) are no longer effective. Trastuzumab (Herceptin®) - a monoclonal antibody(immune system molecule) - is a drug that binds with the HER2/neu protein found on the surface of some breast cancer cells. Trastuzumab inactivates HER2/neu, which otherwise can promote cancer growth and metastasis.

Because of how it works, trastuzumab causes fewer side effects than traditional chemotherapy. The mild side effects that have been reported include flu-like symptoms such as fever and chills, weakness, nausea, vomiting, cough, diarrhea, and headache. Trastuzumab provides another treatment option for people with late-stage cancer, since it improves survival and the quality of life with minimal toxicity. Clinical studies are in progress to determine whether or not trastuzumab is beneficial when used during the first course of chemotherapy.

Transplantation Procedures

Chemotherapy for breast cancer often improves as the dose is increased. Because of this fact, oncologists (cancer specialists) have begun to practice a controversial treatment known as high-dose chemotherapy.

High-dose chemotherapy usually is given as a single, brief treatment with a dramatically increased amount of chemotherapeutic drugs. A typical program is cyclophosphamide plus cisplatin and BCNU (also called carmustine).

Unfortunately, high-dose chemotherapy temporarily destroys bone marrow - an organ essential for the production of oxygen-carrying red blood cells, clot-making platelets, and white blood cells needed to fight the serious infections that can develop following chemotherapy. Therefore, after high-dose chemotherapy, the bone marrow must be renewed by procedures such as

  • bone marrow transplant (BMT), or
  • peripheral blood stem cell transplant (PBSCT).

Stem cells ('mother' cells that can form many types of blood cells) are collected by BMT or PBSCT before chemotherapy. They are transplanted (transfused) back into the patient after chemotherapy to colonize the bone marrow with healthy, blood-making cells.

BMT requires a surgical procedure, whereas PBSCT does not. To perform BMT, a needle is used to extract stem cells from the bone marrow. To perform PBSCT, a technique known as leukapheresis(sometimes shortened to "pheresis") is conducted to separate stem cells from the peripheral (circulating) blood. Sometimes PBSCT is preceded by injections of a 'growth factor' (e.g., granulocyte-colony stimulating factor, or G-CSF) to spur the production of stem cells.

PBSCT is the newest form of transplantation. It has the advantage of being performable when cancer has spread to the bone marrow. Both BMT and PBSCT usually can be carried out in an outpatient setting without general anesthesia.

High-dose chemotherapy and transplantation have been used in clinical trials to treat women who have a high risk of cancer recurrence oradvanced disease. To date, there is no conclusive proof that this method is better than standard chemotherapy. Yet because there is no confirmed cure for metastatic breast cancer, many women and their physicians feel that it is an appropriate, although experimental, therapy.

Treatment By Stage

As previously noted, treatment options are directly related to the stage of breast cancer. Yet, before deciding upon a treatment plan, the individual and her physician team must consider a number of factors. These include overall health, personal preference for therapy, anticipated length of survival, risk of another cancer, and the ER/PR (estrogen receptor / progesterone receptor) status of the tumor.

Some women develop a combination of invasive and non-invasive breast cancer. The treatment of such cases is determined by the stage of the invasive tumor.

  • Stage 0 breast cancer

Ductal carcinoma in situ (DCIS) and lobular carcinoma in situ (LCIS) are both - by definition - stage 0 breast cancers. But, the similarity ends there, as these tumors are managed very differently.

LCIS

LCIS usually does not require surgery; however, it should be watched carefully, because LCIS is associated with an increased risk of cancer over time (20% incidence over 20 years). Both breasts are at risk.

  • Hormone therapy with tamoxifen or raloxifene (now being tested in clinical trials) may be beneficial, along with other
  • preventive measures such as exercise, dietary changes, and, in certain cases, preventive surgery (e.g., removal of both breasts in women with recurrent lumps, difficult-to-interpret mammograms, or a strong family history of breast cancer).

DCIS

DCIS is of greater concern than LCIS, since it is considered a direct forerunner of invasive breast cancer. Therefore, DCIS usually does require surgery in the form of

  • mastectomy or wide excision followed by
  • radiation therapy.

Mastectomy ensures a near 100% success rate for the treatment of DCIS. If breast-saving excision is chosen instead, there is a low (1%) but acceptable risk of recurrence each year.

Paget's disease

Sometimes a tumor near the nipple will be found if there are changes in the areola or nipple surface. If Paget cells are detected during biopsy, it is likely that there is an underlying in situ or invasive ductal cancer in the breast. If the tumor affects only the nipple, Paget's disease may be treated by removing the nipple alone and performing reconstructive surgery to replace it. Invasive breast cancers require more aggressive treatment.

Stage I breast cancer

According to breast cancer specialists, most women with stage I or stage II disease may be treated appropriately with

  • breast-conserving surgery (lumpectomy, partial mastectomy) and
  • axillary dissection (removal of underarm lymph nodes) or sentinel lymph node biopsy (removal of targeted lymph nodes) (see alsoSurgery), followed by
  • radiation therapy.

Depending upon the individual's specific concerns (for example, more than one cancer in the breast or a tumor near the center of the breast)modified radical mastectomy may be a better alternative, possibly followed by breast reconstruction.

When breast cancer is very small - for example, an early stage I cancer that is 0.1 to 1.0 cm in size - the treatment plan MAY NOT include systemic therapy (therapy that is given through the bloodstream, such as chemotherapy, hormone therapy, or immunotherapy). However, hormone therapy (e.g., daily doses of tamoxifen over a 5-year period) can benefit some individuals who, despite having a small tumor, are more likely to have cancer return (for example, women who are at risk due to the S-phase, HER2/neu, or ploidy characteristics of their tumors).

Stage I cancers that are between 1.0 and 2.0 cm in size often requirecombinationchemotherapy. The following are typical drug combinations:

  • AC (adriamycin® and cyclophosphamide)
  • CMF (cyclophosphamide plus methotrexate and 5-fluorouracil)
  • classic CMF (oral cyclophosphamide plus methotrexate and 5-fluorouracil)
  • FAC (5-fluorouracil plus high-dose adriamycin® and cyclophosphamide)

Hormone therapy with tamoxifen may be added to the above treatments if the woman's tumor is positive for estrogen and progesterone receptors ("ER/PR positive"):

  • ACT (adriamycin® plus cyclophosphamide and tamoxifen)
  • CMFT (cyclophosphamide plus methotrexate, 5-fluorouracil, and tamoxifen)
  • classic CMF+T (oral cyclophosphamide plus methotrexate, 5-fluorouracil, and tamoxifen)
  • FACT (5-fluorouracil plus high-dose adriamycin®, cyclophosphamide, and tamoxifen)

Stage II breast cancer

Like women with stage I disease, most women with stage II disease initially are treated with

  • breast-conserving surgery (lumpectomy, partial mastectomy) and
  • axillary dissection (removal of underarm lymph nodes) or sentinel lymph node biopsy (removal of targeted lymph nodes; see alsoSurgery), followed by
  • radiation therapy.

If the cancer is large or has spread to many lymph nodes, the surgery of choice may be

  • modified radical mastectomy, followed by
  • radiation therapy.

Women who have been diagnosed with stage II breast cancer often need some form of adjuvant therapy, including chemotherapy, hormone therapy, or both.

  • Chemotherapy typically is an option for women who are in good health and are expected to survive for a long time.

If the person is 'ER/PR negative'- that is, if her breast cancer DOES NOT have estrogen or progesterone receptors - chemotherapy usually is given WITHOUT tamoxifen (hormone therapy).

  • Hormone therapy may be more suitable for women who are in poor health or who have a short projected survival time.

If the person is 'ER/PR positive' - that is, if her breast cancer DOES have estrogen or progesterone receptors - then 5-year tamoxifen therapy is advisable.

Combination chemotherapy for stage II breast cancer is comparable to that given for stage I cancer. Below are typical drug combinations:

  • AC (adriamycin® and cyclophosphamide; plus tamoxifen = ACT)
  • CMF (cyclophosphamide plus methotrexate and 5-fluorouracil; plus tamoxifen = CMFT)
  • classic CMF (oral cyclophosphamide plus methotrexate and 5-fluorouracil; plus tamoxifen = classic CMF+T)
  • FAC (5-fluorouracil plus high-dose adriamycin® and cyclophosphamide; plus tamoxifen = FACT)

Clinical trials may offer additional treatment options for some people. If a woman's breast cancer has spread to more than 10 lymph nodes, she may be eligible for a trial that uses high-dose chemotherapy withstem cell or bone marrow transplantation (see also Transplantation procedures).

Stage III breast cancer

Until recently, the treatment of women with stage III breast cancer began with mastectomy (surgical removal of the breast); since there is a high risk that cancer will return in such locally-advanced disease. Yet many oncologists now begin treatment with

  • neoadjuvant chemotherapy (chemotherapy before surgery) to increase the woman's options for breast-conserving surgery (BCS) (see also Surgery). Women with large or inflammatory cancers have a particular need for neoadjuvant chemotherapy.

As with less advanced tumors, if the person is 'ER/PR negative'- that is, if her breast cancer DOES NOT have estrogen or progesterone receptors - chemotherapy usually is given WITHOUT tamoxifen (hormone therapy). Alternatively, if the person is 'ER/PR positive' - that is, if her breast cancer DOES have estrogen or progesterone receptors - then 5-year tamoxifen therapy is recommended.

Combination chemotherapy programs for people with stage III cancers include:

  • AC (adriamycin® and cyclophosphamide; plus tamoxifen = ACT)
  • CMF (cyclophosphamide plus methotrexate and 5-fluorouracil; plus tamoxifen = CMFT)
  • classic CMF (oral cyclophosphamide plus methotrexate and 5-fluorouracil; plus tamoxifen = classic CMF+T)
  • FAC (5-fluorouracil plus high-dose adriamycin® and cyclophosphamide; plus tamoxifen = FACT)

Surgery - usually a modified radical mastectomy - is conducted after the tumor has shrunk.

Some individuals may be eligible to participate in clinical trials designed to lower the risk of cancer recurrence. Such trials may involve post-surgical (after surgery) therapy with high-dose chemotherapy andstem cell or bone marrow transplantation (see also Transplantation procedures). Women with inflammatory carcinomas should be considered for bone marrow transplantation after initial therapy has been completed.

Stage IV breast cancer

When a woman is faced with stage IV cancer, either her breast cancer has recurred (returned), or it has metastasized (spread) beyond the breast.

The primary treatment for stage IV cancer is systemic therapy using

  • chemotherapy, and/or
  • hormone therapy.

The goal of treatment for stage IV cancer is to prolong survival and maintain thequality of life. Women with stage IV disease are often told that, although long-term management of their cancer is possible, there is no cure. Yet more and more people with stage IV cancer are defying the odds of cancer survival.

Hormone therapy usually is recommended if the woman's tumor is

ER/PR positive and has spread only to the bones. Typical treatment involves

  • oophorectomy (surgical removal of one/both ovaries),
  • 5-year tamoxifen therapy, and
  • anastrozole (Arimidex®) therapy (see also Hormone therapy) to control metastatic disease.

If the woman's tumor is ER/PR negative and has spread to the viscera (liver, lungs, brain, etc.),

  • chemotherapy usually is given first if the person is able to tolerate it, followed by
  • hormone therapy.

Unhealthy individuals who are ER/PR negative may be offered hormone therapy alone, with additional medicine for comfort and symptoms.

Common chemotherapy/hormone therapy programs for people with stage IV cancers include:

  • ACT (Adriamycin® plus cyclophosphamide and tamoxifen)
  • classic CMF+T (oral cyclophosphamide plus methotrexate, 5-fluorouracil, and tamoxifen)
  • CMFT (cyclophosphamide plus methotrexate, 5-flurouracil, and tamoxifen)
  • FACT (5-fluorouracil plus high-dose Adriamycin®, cyclophosphamide, and tamoxifen)
  • Paclitaxel (Taxol®) plus tamoxifen
  • Docetaxel (Taxotere®) plus tamoxifen
  • Vinorelbine tartrate (Navelbine®) plus tamoxifen
  • Gemcitabine (Gemzar®) plus tamoxifen

If the woman's tumor is 'HER2/neu positive' (that is, it contains the HER2/neu protein), then

  • immunotherapy with trastuzumab (Herceptin®) may be started after or instead of hormone therapy (see also Immunotherapy). Ongoing studies hopefully will determine whether immunotherapy is more beneficial when given alone or in combination with
  • chemotherapy.

Women who are troubled by cancer-related symptoms may benefit from additional treatment with

  • radiation and/or
  • surgery.

Stage IV patients who otherwise are in good health may respond very well to the treatment offered in clinical trials. Such trials usually involve aggressive, high-dosechemotherapy with stem cell transplantation(see also Transplantation procedures). A small percentage of women actually may be cured of breast cancer or may remain disease-free for long periods of time. Because promising new therapies are continuously being developed, all eligible women should be considered for treatment in clinical trials.

Breast Cancer