Breast cancer treatment

The mainstay of breast cancer treatment is surgery when the tumor is localized, with possible adjuvant hormonal therapy (with tamoxifen or an aromatase inhibitor), chemotherapy, and/or radiotherapy. At present, the treatment recommendations after surgery (adjuvant therapy) follow a pattern. This pattern is subject to change, as every two years, a worldwide conference takes place in St. Gallen, Switzerland, to discuss the actual results of worldwide multi-center studies. Depending on clinical criteria (age, type of cancer, size, metastasis) patients are roughly divided to high risk and low risk cases, with each risk category following different rules for therapy. Treatment possibilities include radiation therapy, chemotherapy, hormone therapy, and immune therapy.

urgery

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Lumpectomy techniques are increasingly utilized for breast-conservation cancer surgery. Prior to a lumpectomy, a needle-localization of the lesion with placement of a guidewire may be performed, sometimes by a radiologist if the area being removed was detected by mammography or ultrasound, and sometimes by the surgeon if the lesion can be directly palpated.

However, mastectomy may be the preferred treatment in certain instances:
* Two or more tumors exist in different areas of the breast (a "multifocal" cancer).
* The breast has previously received radiotherapy.
* The tumor is large relative to the size of the breast.
* The patient has had scleroderma or another disease of the connective tissue, which can complicate radiotherapy.
* The patient lives in an area where radiotherapy is inaccessible.
* The patient is apprehensive about the risk of local recurrence after lumpectomy.

Standard practice requires the surgeon to establish that the tissue removed in the operation has margins clear of cancer, indicating that the cancer has been completely excised. If the removed tissue does not have clear margins, further operations to remove more tissue may be necessary. This may sometimes require removal of part of the pectoralis major muscle, which is the main muscle of the anterior chest wall.

During the operation, the lymph nodes in the axilla are also considered for removal. In the past, large axillary operations took out 10 to 40 nodes to establish whether cancer had spread. This had the unfortunate side effect of frequently causing lymphedema of the arm on the same side, as the removal of this many lymph nodes affected lymphatic drainage. More recently, the technique of sentinel lymph node (SLN) dissection has become popular, as it requires the removal of far fewer lymph nodes, resulting in fewer side effects. The sentinel lymph node is the first node that drains the tumor, and subsequent SLN mapping can save 65-70% of patients with breast cancer from having a complete lymph node dissection for what could turn out to be a negative nodal basin. Advances in Sentinel Lymph Node mapping over the past decade have increased the accuracy of detecting Sentinel Lymph Node from 80% using blue dye alone to between 92% and 98% using combined modalities.cite journal | author = | title = Sentinel Lymph Node Biopsy for Breast Cancer and Melanoma | journal = Oncology Issues | year = 2006 | volume = March/April | pages = 22&ndash;5 | url = http://www.accc-cancer.org/onis/articles/marapr06/bennett.pdf| format = dead link|date=June 2008 &ndash; ^{[http://scholar.google.co.uk/scholar?hl=en&lr=&q=author%3A+intitle%3ASentinel+Lymph+Node+Biopsy+for+Breast+Cancer+and+Melanoma&as_publication=Oncology+Issues&as_ylo=2006&as_yhi=2006&btnG=Search Scholar search]} ] dead link|date=April 2008 SLN biopsy is indicated for patients with T1 and T2 lesions (<5cm) and carries a number of recommendations for use on patient subgroups.

Radiation therapy

Radiation therapy is standard of care for women who have undergone lumpectomy or mastectomy surgery. In these cases the purpose of radiation is to reduce the chance that the cancer will recur. Radiation therapy involves using high-energy X-rays or gamma rays that target a tumor or post surgery tumor site. This radiation is very effective in killing cancer cells that may remain after surgery or recur where the tumor was removed. The X-rays are delivered by a machine called a Linear Accelerator or Linac. In addition to this treatment implanted radioactive catheters (brachytherapy), similar to those used in prostate cancer treatment, can be used. However this treatment option has been superseded by Electron beam radiotherapy to the breast scar. Radiation therapy for breast cancer is usually performed after surgery and is an integral component of breast-conserving therapy.

Radiation therapy eliminates the microscopic cancer cells that may remain near the area where the tumor was surgically removed. The dose of radiation must be strong enough to ensure the elimination of cancer cells. However, radiation affects normal cells and cancer cells alike, causing some damage to the normal tissue around where the tumor was. Healthy tissue can repair itself, while cancer cells do not repair themselves as well as normal cells. For this reason, radiation treatments are given over an extended period, enabling the healthy tissue to heal. Treatments are typically given over a period of five to seven weeks, performed five days a week. Each treatment takes about 15 minutes.

Although radiation therapy can reduce the chance of breast cancer recurrence, it is much less effective in prolonging patient survival. According to a review of six studies by the National Cancer Institute, none of them found a survival benefit for radiation therapy. [ [http://www.cancer.gov/cancertopics/pdq/treatment/breast/HealthProfessional/page7#Section_251 cancer.gov] ] Patients who are unable to have radiation therapy after lumpectomy should consult with a surgeon who understands this research and who believes that lumpectomy (or partial mastectomy) alone is a reasonable treatment option.

Indications for radiation

Indications for radiation treatment are constantly evolving. Patients treated in Europe have been more likely in the past to be recommended adjuvant radiation after breast cancer surgery. Radiation therapy is usually recommended for all patients who had (lumpectomy, quadrant-resection). Radiation therapy is usually not indicated in patients with advanced (stage IV disease) except for palliation of symptoms like bone pain, fungating lesion.

In general recommendations would include:
*As part of breast conserving therapy when the whole breast is not removed (lumpectomy or wide local excision)
*After mastectomy: Patients with higher chances of cancer recurring because of conditions such as a large primary tumor or substantial involvement of the lymph nodes.

Other factors which may influence adding adjuvant radiation therapy:
*Tumor close to or involving the margins on pathology specimen
*Multiple areas of tumor (multicentric disease)
*Microscopic invasion of lymphatic or vascular tissues
*Microcopic invasion of the skin, nipple/areola, or underlying pectoralis major muscle
*Patients with extension out of the substance of a LN
*Inadequate numbers of axillary LN sampled

Types of radiotherapy

Radiotherapy can be delivered in many ways but is most commonly produced by a linear accelerator.

This usually involves treating the whole breast in the case of breast lupectomy or the whole chest wall in the case of mastectomy.

Improvements in computers and treatment delivery technology have led to more complex radiotherapy treatment options. One such new technology is using IMRT (intensity modulated radiation therapy), which can change the shape and intensity of the radiation beam at different points across and inside the breast. This allows for better dose distribution within the breast while minimizing dose to healthy organs such as the lung or heart. However there is yet to be a demonstrated difference in treatment outcomes (both tumor recurrence and level of side effects) for IMRT in breast cancer when compared to ordinary radiotherapy treatment. In addition, ordinary radiotherapy can also deliver similar dose distributions utilizing modern computer dosimetry planning and equipment.

Another new procedure involves a type of brachytherapy, where a radioactive source is temporarily placed inside the breast in direct contact with the tumor bed (area where tumor was removed). This technique is called a Mammosite and is currently undergoing clinic trials.

New technology has also allowed more precise delivery of radiotherapy in a portable fashion &mdash; for example in the operating theatre. Targeted intraoperative radiotherapy (TARGIT) [cite web | author=Vaidya J |title = TARGIT (TARGeted Intraoperative radioTherapy) | url = http://www.dundee.ac.uk/surgery/targit/targitpapers.htm | accessdate = 2007-03-11] is a method of delivering therapeutic radiation from within the breast using a portable X-ray generator called Intrabeam. It is undergoing clinical trials in several countries to test whether it can replace the whole course of radiotherapy in selected patients.cite web | title = Protocol 99PRT/47 Targeted Intraoperative radiotherapy (Targit) for breast cancer | author=Vaidya J, Tobias J, Baum M, Houghton J | url = http://www.thelancet.com/journals/lancet/misc/protocol/99PRT-47 | accessdate = 2007-03-11] It may also be able provide a much better boost dose to the tumor bed and appears to provide superior control.cite journal |author=Vaidya J, Baum M, Tobias J, Massarut S, Wenz F, Murphy O, Hilaris B, Houghton J, Saunders C, Corica T, Roncadin M, Kraus-Tiefenbacher U, Melchaert F, Keshtgar M, Sainsbury R, Douek M, Harrison E, Thompson A, Joseph D |title=Targeted intraoperative radiotherapy (TARGIT) yields very low recurrence rates when given as a boost |journal=Int J Radiat Oncol Biol Phys |volume=66 |issue=5 |pages=1335&ndash;8 |year=2006 |pmid=17084562] This will be tested in a TARGIT-B trial. [ [http://www.dundee.ac.uk/surgery/targit/targitpapers.htm Targit literature Website] ]

ide effects of radiation therapy

External beam radiation therapy is a non-invasive treatment with some short term and some longer term side effects. Patients undergoing some weeks of treatment usually experience fatigue caused by the healthy tissue repairing itself and aside from this there can be no side effects at all. However many breast cancer patients develop a suntan-like change in skin color in the exact area being treated. As with a suntan, this darkening of the skin usually returns to normal in the one to two months after treatment. In some cases permanent changes in color and texture of the skin is experienced. Other side effects sometimes experienced with radiation can include:
*muscle stiffness
*mild swelling
*tenderness in the area

After surgery, radiation and other treatments are complete many patients notice the affected breast seems smaller or seems to have shrunk. This is basically due to the removal of tissue during the lumpectomy operation.

The use of adjuvant radiation has significant potential effects if the patient has to later undergo breast reconstruction surgery. Fibrosis of chest wall skin from radiation negatively affects skin elasticity and makes tissue expansion techniques difficult. Traditionally most patients are advised to defer immediate breast reconstruction when adjuvant radiation is planned and are most often recommended surgery involving autologous tissue reconstruction rather than breast implants.

ystemic therapy

Systemic therapy uses medications to treat cancer cells throughout the body. Any combination of systemic treatments may be used to treat breast cancer. Systemic treatments include chemotherapy, immune therapy, and hormonal therapy.

Chemotherapy

Chemotherapy (drug treatment for cancer) may be used before surgery, after surgery, or instead of surgery for those cases in which surgery is considered unsuitable.

"See breast cancer chemotherapy."

Hormonal treatment

Patients with estrogen receptor positive tumors will typically receive hormonal therapy after chemotherapy is completed. Typical hormonal treatments include:

*Tamoxifen is typically given to premenopausal women to inhibit the estrogen receptors
*Aromatase inhibitors are typically given to postmenopausal women to lower the amount of estrogen in their systems
*GnRH-analogues are used in premenopausal women for ovarian ablation or suppression

Targeted therapy

In patients whose cancer expresses an over-abundance of the HER2 protein, a monoclonal antibody known as trastuzumab (Herceptin) is used to block the activity of the HER2 protein in breast cancer cells, slowing their growth. In the advanced cancer setting, trastuzumab use in combination with chemotherapy can both delay cancer growth as well as improve the recipient's survival. [cite journal |author=Slamon DJ, Leyland-Jones B, Shak S "et al" |title=Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2 |journal=N Engl J Med |volume=344|issue=11|pages=783&ndash;92 |year=2001 |pmid=11248153|doi=] More recently, several clinical trials have also confirmed that in the adjuvant setting i.e. postoperative following breast cancer surgery, the use of trastuzumab for up to one year also delays the recurrence of breast cancer and improves survival. [cite journal |author=Piccart-Gebhart MJ, Procter M, Leyland-Jones B "et al" |title=Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer |journal=N Engl J Med |volume=353|issue=16 |pages=1659&ndash;72 |year=2005 |pmid=16236737 |doi=] [cite journal |author=Joensuu H, Kellokumpu-Lehtinen PL, Bono P "et al" |title=Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer |journal=N Engl J Med |volume=354 |issue=8|pages=809&ndash;20 |year=2006 |pmid=16495393 |doi=] [cite journal |author=Romond EH, Perez EA, Bryant J "et al" |title=Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer |journal=N Engl J Med |volume=353|issue=16|pages=1673&ndash;1684 |year=2005 |pmid=16236738 |doi=]

Antiangiogenic therapy

A commercially available monoclonal antibody that blocks the activation of the VEGF receptor, bevacizumab, underwent testing in a randomized clinical trial whose preliminary results were announced by the National Cancer Institute in 2005. [cite press release | title=Bevacizumab Combined With Chemotherapy Improves Progression-Free Survival for Patients With Advanced Breast Cancer | publisher=National Cancer Institute | date=2005-04-14 | url=http://www.cancer.gov/newscenter/pressreleases/AvastinBreast | accessdate=2007-08-15] The preliminary data indicated that bevacizumab delays disease progression for up to five months over conventional chemotherapy, but survival was no better. Genentech, manufacturer of bevacizumab, has filed a supplemental biological application with the FDA for approval of bevacizumab in the setting of metastatic breast cancer, on the strength of the improvement in progression-free survival.

Preclinical

Protein tyrosine phosphatase 1B (PTP1B)

In the March 2007, edition of the scientific journal, "Nature Genetics", researchers from Canada's McGill University reported that they have developed a potential drug target for treating up to 40 percent of breast cancers by blocking an enzyme called protein tyrosine phosphatase 1B (PTP1B), which has been implicated in the onset of breast cancer in mouse models of the disease. [cite journal |author=Julien SG, Dubé N, Read M, "et al" |title=Protein tyrosine phosphatase 1B deficiency or inhibition delays ErbB2-induced mammary tumorigenesis and protects from lung metastasis |journal=Nat. Genet. |volume=39 |issue=3 |pages=338&ndash;46 |year=2007 |pmid=17259984 |doi=10.1038/ng1963] Elevated levels of PTP1B have also been found in diabetes and obesity. A drug to block the activity of PTP1B is under development by Merck, and was found to delay the development of breast tumors and prevent lung cancer up to two months from the administration of the drug. The researchers hope to continue further research in mouse models which are also HER-2 positive (responsive to Herceptin) so that the drug could benefit a significant population of women. [ [http://news.bbc.co.uk/2/hi/health/6646193.stm Breast tumour drug target found] , BBC News, 20 May 2007]

Flax

Testing of flaxseed (the highest source of mammalian lignans) on rats led to reduction and regression of tumours. This led to a formal randomized, placebo-controlled, double-blind study involving 32 postmenopausal patients confirming that 25g flaxseed daily intake significantly reduced cell proliferation, increased apoptosis and reduced c-erbB2 expression of human breast cancer cells [cite journal | last = Thompson | first = L. U. | authorlink = L. U. Thompson | coauthors = Chen, J.M., Li, T., Strasser-Weippl, K., Goss, P.E. | title = Dietary flaxseed alters tumor biological markers in postmenopausal breast cancer | journal = Clinical Cancer Research | volume = 11 | issue = 10 | pages = 3828&ndash;3835 | publisher = American Association for Cancer Research | location = New Milford, CT | issn = 1078-0432 | doi = 10.1158/1078-0432.CCR-04-2326 | year = 2005] . The preliminary research into flax seeds indicates that flax can significantly change breast cancer growth and metastasis, and enhance the inhibitory effect of tamoxifen on estrogen-dependent tumors. [cite journal|author=Wang, L et al|title=The inhibitory effect of flaxseed oil on the growth and metastasis of estrogen receptor negative human breast cancer xenografts is attributed to both its lignan and oil components|journal=International Journal of Cancer|volume=116|issue=5|pages=793&ndash;8|year=2005|pmid=15849746|doi=10.1002/ijc.21067] [cite journal|author=Thompson, LU et al|title=Dietary flaxseed alters tumor biological markers in postmenopausal breast cancer|journal=Clinical Cancer Research|volume=11|issue=10|pages=3828&ndash;35|year=2005|pmid=15897583|doi=10.1158/1078-0432.CCR-04-2326] [cite journal|author=Chen, J et al|title=Dietary flaxseed enhances the inhibitory effect of tamoxifen on the growth of estrogen-dependent human breast cancer (mcf-7) in nude mice|journal=Clinical Cancer Research|year=2004|volume=10|issue=22|pages=7703&ndash;11|pmid=15570004|doi=10.1158/1078-0432.CCR-04-1130] [cite journal|author=Chen, J et al|title=Dietary flaxseed inhibits human breast cancer growth and metastasis and downregulates expression of insulin-like growth factor and epidermal growth factor receptor|journal=Nutrition and Cancer|volume=43|issue=2|pages=187&ndash;92|year=2002|pmid=12588699|doi=10.1207/S15327914NC432_9]

Alternative treatments

A wide range of alternative medical treatments of breast cancer have been proposed.

Personalization with gene expression profiling

Recently, the acceleration of gene expression profiling research has made available additional markers to predict disease recurrence. Beyond conventional TNM staging, doctors can now order a gene expression profile on tumors to predict whether a breast cancer patient will have a high chance of developing breast cancer again. There are currently 2 commercial tests on the market, MammaPrint and Oncotype DX. Oncotype DX is not used in every clinical setting; for example, in a patient with positive lymph nodes who is a candidate for chemotherapy, the test would not change therapy decisions. The most useful setting for Oncotype DX testing is where there are negative lymph nodes, and the benefit of chemotherapy is felt to be small. In up to 10% of patients, there will be disease recurrences, but treating every patient with chemotherapy is overkill. In this setting, a high-risk score on the Oncotype DX can help doctors decide whether to recommend chemotherapy.

Attribution

*"The original version of this article incorporated text from the Wikipedia article Breast cancer."

References

External links

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