Breast cancer

Breast cancer
Specialty	Oncology

Breast cancer is a cancer of the breast tissue. Worldwide, it is the most common form of cancer in females - affecting, at some time in their lives, approximately one out of thirty-nine to one out of three women who reach age ninety in the Western world. It is the second most fatal cancer in women (after lung cancer), and the number of cases has significantly increased since the 1970s, a phenomenon partly blamed on modern lifestyles in the Western world. Because the breast is composed of identical tissues in males and females, breast cancer also occurs in males, and as statistics show, it is on a massive increase, hence the mass TV promotions aimed at men at present.

History of breast cancer

Breast cancer may be one of the oldest known forms of cancer tumors in humans. The oldest description of cancer (although the term cancer was not used) was discovered in Egypt and dates back to approximately 1600 BC. The Edwin Smith Papyrus describes 8 cases of tumors or ulcers of the breast that were treated by cauterization, with a tool called "the fire drill." The writing says about the disease, "There is no treatment." At least one of the described cases is male. For centuries, physicians described similar cases in their practises, with the same sad conclusion. It wasn't until doctors achieved greater understanding of the circulatory system in the 17th century that they could establish a link between breast cancer and the lymph nodes in the armpit. The French surgeon Jean Louis Petit (1674-1750) and later the Scottish surgeon Benjamin Bell (1749-1806) were the first to remove the lymph nodes, breast tissue, and underlying chest muscle. Their successful work was carried on by William Stewart Halsted who started performing mastectomies in 1882. He became known for his Halsted radical mastectomy, a surgical procedure that remained popular up to the 1970s.

Types of breast cancer

• Ductal carcinoma 65-90%
• Lobular carcinoma 10%
• Inflammatory breast cancer
• Medullary carcinoma 5%
• Colloid carcinoma 2%
• Papillary carcinoma 1%
• Metaplastic carcinoma

Epidemiologic risk factors and etiology

It is important to have a model of causation of a disease in order to distinguish epidemiological risk factors or associations with disease, from the biological etiology and primary cause, secondary co-factors, and simple promoters of the disease. The first work on breast cancer epidemiology was done by Janet Lane-Claypon, who published a comparative study in 1926 of 500 breast cancer cases and 500 control patients of the same background and lifestyle for the British Ministry of Health.

Today, breast cancer, like other forms of cancer, is considered to be a result of damage to DNA. How this mechanism may occur comes from several known or hypothesized factors (such as exposure to ionizing radiation). Some factors lead to an increased rate of mutation (exposure to estrogens) and decreased repair (the BRCA1, BRCA2 and p53 genes). Although many epidemiological risk factors, and biological co-factors and promoters have been identified, the majority of breast cancer incidence remains unattributable, and the primary cause is unknown.

Dietary influences have been proposed and examined, and recent research suggests that low fat diets may significantly decrease the risk of breast cancer as well as the recurrence of breast cancer.

A significant environmental effect was revealed by the large difference in breast cancer incidence between countries and continents, and a migration effect which slowly increases the risk of breast cancer even across generations after migration from a country of lower incidence to a country of higher incidence, such as moving from China or Japan to the United States.

Humans are not the only mammal prone to breast cancer. Some strains of mice, namely the house mouse (Mus domesticus) are prone to breast cancer which is caused by infection with the mouse mammary tumour virus (MMTV or "Bittner virus" for its discoverer Hans Bittner), by random insertional mutagenesis. Suspicion of MMTV or other viruses in human breast cancer is controversial, and the idea is not generally accepted for lack of direct and definitive evidence. There is much more research in diagnosis and treatment of breast cancer than in its cause.

Age

The risk of getting breast cancer increases with age. For someone who lives to the age of 90, the chances of getting breast cancer is about 14.3% or one in seven during their lifetime. Men can also develop breast cancer, but their risk is less than one in 1000 (see sex and illness). This risk is modified by many different factors. In a very small 5% of breast cancer cases, there is a strong inherited familial risk.

The probability of breast cancer rises with age but breast cancer tends to be more aggressive when it occurs in younger people. One type of breast cancer that is especially aggressive and disproportionately occurs in younger people is inflammatory breast cancer. It is initially staged as Stage IIIb or Stage IV. It also is unique because it often does not present with a lump so that it often is not detected by mammography or ultrasound. It presents with the signs and symptoms of a breast infection like mastitis.

Alcohol

Alcohol generally appears to increase the risk of breast cancer. The UK's [5] Review of Alcohol: Association with Breast Cancer concludes that "studies confirm previous observations that there appears to be an association between alcohol intake and increased risk of breast cancer in women. On balance, there was a weak association between the amount of alcohol consumed and the relative risk."

The National Institute on Alcohol Abuse and Alcoholism (NIAAA) concludes that "Chronic alcohol consumption has been associated with a small (averaging 10 percent) increase in a woman's risk of breast cancer (Friedenreich et al.; Longnecker; Nasca). According to these studies, the risk appears to increase as the quantity and duration of alcohol consumption increases. Other studies, however, have found no evidence of such a link (Chu et al. ; Schatzkin et al.; Webser et al)."

The Committee on Carcinogenicity of Chemicals in Food, Consumer Products Non-Technical Summary concludes, "the new research estimates that a woman drinking an average of two units of alcohol per day has a lifetime risk of developing breast cancer 19% higher than a woman who drinks an average of one unit of alcohol per day. The risk of breast cancer further increases with each additional drink consumed per day. The research also concludes that approximately 6% (between 3.2% and 8.8%) of breast cancers reported in the UK each year could be prevented if drinking was reduced to a very low level (i.e. less than 1 unit/week)."

It has been reported that "two drinks daily increase the risk of getting breast cancer by about 25 percent" (NCI), but the evidence is inconsistent. The Framingham study has carefully tracked individuals since the 1940s. Data from that research found that drinking alcohol moderately did not increase breast cancer risk (Wellness Facts). Similarly, research by the Danish National Institute for Public Health found that moderate drinking had virtually no effect on breast cancer risk (Petri, et al).

Breast cancer constitutes about 7.3% of all cancers. Among women, breast cancer comprises 60% of alcohol-attributable cancers. One study suggests that women who frequently drink red wine may have an increased risk of developing breast cancer.

"Folate intake counteracts breast cancer risk associated with alcohol consumption" and "women who drink alcohol and have a high folate intake are not at increased risk of cancer." Those who have a high (200 micrograms or more per day) level of folate (folic acid or Vitamin B9) in their diet are not at increased risk of breast cancer compared to those who abstain from alcohol. Foods rich in folate include citrus fruits, citrus juices, dark green leafy vegetables (such as spinach), dried beans, and peas. Vitamin B9 can also be taken in a multivitamin pill.

Environmental causes

All women and men are at risk for breast cancer, regardless of hereditary factors. In fact, 85 to 90 percent of breast cancer incidences cannot be explained by inherited genetic predisposition. Other known risk factors and personal characteristics include personal or family history of breast cancer, high breast tissue density, earlier onset of menstruation (12 years or younger), later menopause (55 years or older), late first-term pregnancy (35 years or older), no children or no breast-feeding, early or recent use of oral contraceptives, more than four years use of hormone replacement therapy, postmenopausal obesity, alcohol consumption, exposures to secondhand cigarette smoke and exposure to ionizing radiation.

When all known risk factors and characteristics are added together including genetics and family history, as much as 50 percent of breast cancer cases remain unexplained.

Although environmental exposures are not generally cited as risk factors for the disease (except for diet, pharmaceuticals and radiation), a substantial and growing body of evidence indicates that exposures to certain toxic chemicals and hormone-mimicking compounds including chemicals used in pesticides, cosmetics and cleaning products contribute to the development of breast cancer.

A recent Canadian study concluded that female farm workers are three times more likely to have breast cancer.

Genes

Two autosomal dominant genes, BRCA1 and BRCA2, have been linked to the rare familial form of breast cancer. People in families expressing mutations in these genes have a 60% to 80% risk of developing breast cancer according to Robbins Pathological Basis of Disease. If a mother or a sister was diagnosed breast cancer, the risk is about 2-fold higher than those women without a familial history.

Hormones

Persistently increased blood levels of estrogen are associated with an increased risk of breast cancer, as are increased levels of the androgens androstenedione and testosterone (which can be directly converted by aromatase to the estrogens estrone and estradiol, respectively). Increased blood levels of progesterone are associated with a decreased risk of breast cancer in premenopausal women. A number of circumstances which increase exposure to endogenous estrogens including not having children, delaying first childbirth, not breastfeeding, early menarche (the first menstrual period) and late menopause are suspected of increasing lifetime risk for developing breast cancer.

Combined oral contraceptive pills may produce a slight increase in breast cancer risk among long-term users, but this appears to be a short-term effect. The largest meta-analysis (1996) of data from 54 studies identified a relative risk (RR) of 1.24 for current users; 10 or more years after stopping, no difference was seen. Further, the cancers diagnosed in women who had ever used hormonal contraceptives were less advanced than those in nonusers, raising the possibility that the small excess among users was due to increased detection. Breast cancer risk associated with hormonal contraceptive use did not appear to vary with family history of breast cancer.

Data exist from both observational and randomized clinical trials regarding the association between postmenopausal hormone replacement therapy (HRT) and breast cancer. The largest meta-analysis (1997) of data from 51 observational studies, indicated a relative risk of breast cancer of 1.35 for women who had used HRT for 5 or more years after menopause. The estrogen-plus-progestin arm of the Women's Health Initiative (WHI), a randomized controlled trial, which randomized more than 16,000 postmenopausal women to receive combined hormone therapy or placebo, was halted early (2002) because health risks exceeded benefits. One of the adverse outcomes prompting closure was a significant increase in both total and invasive breast cancers (RR = 1.24) in women randomized to receive estrogen and progestin for an average of 5 years. HRT-related breast cancers had adverse prognostic characteristics (more advanced stages and larger tumors) compared with cancers occurring in the placebo group, and HRT was also associated with a substantial increase in abnormal mammograms. Short-term use of hormones for treatment of menopausal symptoms appears to confer little or no breast cancer risk.

Light levels

Researchers at the National Cancer Institute and National Institute of Environmental Health Sciences have concluded a study that suggests that artificial light can be a factor for breast cancer.

Obesity

Gaining weight after the menopause can increase a woman's or man's risk. Putting on 9.9kg (22lbs) increased the risk of developing breast cancer by 18%.

Unproven

• It has been hypothesized that abortion may increase the risk of breast cancer because of hormones in early pregnancy. Recent large studies do not support this association.
• Although not well quantified there has long been a concern about risk associated with environmental estrogenic compounds, such as dioxins, or phytoestrogens such as found in soy beans.
• Aluminum salts such as those used in anti-perspirants have recently been classified as metalloestrogens. In research published in the Journal of Applied Toxicology, Dr. Philippa D. Darbre of the University of Reading has shown that aluminium salts increase estrogen-related gene expression in human breast cancer cells grown in the laboratory.

Prevention in high-risk individuals

Prophylactic oophorectomy (removal of ovaries), post-child-bearing, reduces the risk of developing breast cancer by 60%, as well as reducing the risk of developing ovarian cancer by 96%. The side effects of Oophorectomy may be alleviated by medicines other than hormonal replacement. Non-hormonal biphosphonates (such as Fosamax and Actonel) increase bone strength and are available as once-a-week pills. Low-dose Selective Serotonin Reuptake Inhibitors (e.g. Paxil, Prozac) alleviate vasomotor menopausal symptoms, i.e. "hot flashes".

Prevention of Environmental Causes

Fewer than 20% percent of breast cancers are genetic. When all known risk factors and characteristics are added together, including family history, genetics, smoking and obesity, more than 50 percent of breast cancer cases remain unexplained. According to State of the Evidence 2006 - What Is the Connection Between the Environment and Breast Cancer?”, a report which reviews and analyzes nearly 350 journal-published scientific studies on environmental links to breast cancer:

• Over 100,000 synthetic chemicals are registered for use today in the United States, with an additional 1,000 new chemicals added each year, yet less than 10 percent of these chemicals have been tested for their effects on human health. Large numbers of these chemicals are found in products we come into contact with every day and compelling scientific evidence points to these chemicals as contributing to the development of breast cancer, either by altering hormone function or gene expression
• Many toxic chemicals are now credibly linked to serious chronic diseases including breast cancer. Furthermore, new science demonstrates that even very small amounts of some chemicals can have adverse health effects, particularly in pregnant mothers, infants and small children. (See State of the Evidence)

The Breast Cancer Fund suggests the following environmental prevention methods:

• Practice Healthy Purchasing: Don’t bring toxic chemicals home from the store. Choose chlorine-free paper products to reduce dioxin, a carcinogen released when chlorinated products are incinerated. Read food labels, and choose pesticide-free, organic produce and hormone-free meats and dairy products. Replace harmful household cleaners that contain bleach with cheaper, nontoxic alternatives like baking soda, borax soap and vinegar. Look for alternatives to chemical weed and bug killers— many contain toxic chemicals that accumulate in our bodies.

• Use Caution with Plastics: Some plastics leach hormone-disrupting chemicals called phthalates into the substances they touch. Polyvinyl chloride (PVC) plastics release carcinogens into our air and water during the production process. PVC plastics are especially dangerous in toys that children put in their mouths, so keep an eye out for nontoxic toys. Further, never put plastic or plastic wrap in the microwave, as this can release phthalates into food and beverages.

• Advocate for Clean Air: The soot and fumes released by factories, automobiles, diesel trucks and tobacco products contain chemicals called polycyclic aromatic hydrocarbons (PAHs) that are linked to breast cancer. Indeed, breathing these compounds from secondhand tobacco smoke may increase your risk for breast cancer more than active smoking. Stay away from secondhand smoke, and advocate for stronger clean air protections.

• Avoid Unnecessary Radiation: Ionizing radiation is a known cause of breast cancer. Radiation damage to genes is cumulative over a lifetime—thus many low doses may have the same effect as a single high dose. Mammograms, other X-rays and CT scans expose you to radiation. While mammography screening may benefit postmenopausal women, mammography for women in their 30s and 40s remains controversial. Whenever you have an X-ray or scan, request a lead shield to protect the areas of your body not being X-rayed.

• Explore Alternatives to Artificial Estrogens: Women who have prolonged exposure to estrogens are at higher risk for breast cancer, and major studies continue to show an increased risk when postmenopausal women use hormone replacement therapy (HRT). Women who use both birth control pills and—later in life—HRT face an even greater risk of breast cancer than those who use neither. Explore your options with healthcare professionals.

• Advocate for Safe Cosmetics: Chemicals linked to cancer and birth defects do not belong in cosmetics, period. However, some popular brands of shampoo, deodorant, face cream and other everyday products contain these dangerous chemicals. The Breast Cancer Fund demands safer products and smarter laws by letting cosmetics companies know they need a makeover. The public can join BCF in asking cosmetic companies to sign the Compact for Safe Cosmetics, a pledge to substitute chemicals linked to birth defects, infertility, cancer, brain damage and other serious health consequences with safer alternatives.

Symptoms

Early breast cancer can in some cases be painful. Usually breast cancer is discovered before any symptoms are present, either on mammography or by feeling a breast lump. A lump under the arm or above the collarbone that does not go away may be present. Other possible symptoms include breast discharge, nipple inversion and changes in the skin overlying the breast .

Screening

Due to the high incidence of breast cancer among older women, screening is now recommended in many countries, the same also applies to men. Screening methods suggested include breast self-examination and mammography. Mammography has been shown to reduce breast cancer-related mortality by 20-30%. Routine (annual) mammography of women older than 40 is encouraged as a screening method to diagnose early breast cancer and has demonstrated a protective effect in multiple clinical trials.

Normal (left) versus cancerous (right) mammography image.

Mammography is still the modality of choice for screening of early breast cancer, and breast cancers detected by mammography are usually smaller than those detected clinically.

Magnetic resonance imaging (MRI) has been shown to detect cancers that are not visible on mammograms, but it has several disadvantages. For example, although it is 27-36% more sensitive, it is less specific than mammography. As a result, MRI studies will have more false positives (up to 5%), which may have undesirable financial and psychological costs. It is also a relatively expensive procedure, and one which requires the intravenous injection of a chemical agent to be effective. Proposed Indications for using MRI for screening include:

• Strong family history of breast cancer
• Patients with BRCA-1 or BRCA-2 oncogene mutations
• Evaluation of women with breast implants
• History of previous lumpectomy or breast biopsy surgeries
• Axillary metastasis with an unknown primary tumor
• Very dense or scarred breast tissue

Ultrasound alone is not adequate as a screening tool but it is a useful additional for the characterization of palpable tumours and directing image-guided biopsies.

The U.S. National Cancer Institute recommends screening mammography with a baseline mammogram at age 35, mammograms every two years beginning at age 40, and then annual mammograms beginning at age 50. In the UK, women are invited to attend for screening once every three years beginning at age 50. Women with one or more first degree relatives (mother, sister, daughter) with premenopausal breast cancer should begin screening at an earlier age. It is usually suggested to start screening at an age that is 10 years less than the age at which the relative was diagnosed with breast cancer. More and more men are being propted to undertake breast screening due to the rise of Breast Cancer in Men.

Diagnosis

The diagnosis of breast cancer is established by the pathological examination of removed breast tissue. Such tissue is generally obtained at the time of surgical treatment. A number of procedures have been devised to obtain tissue or cells prior to the treatment for histological or cytological examination. Such procedures include fine-needle aspiration, nipples aspirates, ductal lavage, core needle biopsy, and local surgical biopsy. Most of these diagnostic steps, however, have some limitations as they may not yield enough tissue or miss the cancer, while the surgical biopsy already becomes an invasive procedure. Imaging tests are used to detect metastasis and include chest x-ray, bone scan, CT, MRI, and PET scanning. Ca 15.3 (carbohydrate antigen 15.3, epithelial mucin) is a tumor marker determined in blood which can be used to follow up disease activity.

Breast cancer is staged. Not only will this allow for better understanding of the disease process, but it will also facilitate interpretation of data, and determine treatment. Prognosis is closely linked to results of staging.

Summary of stages:

• Stage 0 - Carcinoma in situ
• Stage I - Tumor (T) does not exceed 2 cm, no axillary lymph nodes (N) involved.
• Stage IIA – T 2-5 cm, N negative, or T <2 cm and N positive.
• Stage IIB – T > 5 cm, N negative, or T 2-5 cm and N positive (< 4 axillary nodes).
• Stage IIIA – T > 5 cm, N positive, or T 2-5 cm with 4 or more axillary nodes
• Stage IIIB – T has penetrated chest wall or skin, and may have spread to < 10 axillary N
• Stage IIIC – T has > 10 axillary N, 1 or more supraclavicular or infraclavicular N, or internal mammary N.
• Stage IV – Distant metastasis (M)

Breast lesions are examined for certain markers, notably sex steroid hormone receptors. About two thirds of postmenopausal breast cancers are estrogen receptor positive (ER+) and progesterone receptor positive (PR+). Receptor status modifies the treatment as, for instance, ER+ lesions are more sensitive to hormonal therapy.

The breast lesion will also be tested for the presence of human epidermal growth factor a protein also known as HER2, neu or erbB2. HER2 is a cell-surface protein involved in cell development. In normal cells, HER2 controls aspects of cell growth and division. When activated in cancer cells, HER2 accelerates tumor formation. About 20-30% of breast cancers overexpress HER2. Those patients may be candidates for the drug Herceptin.

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 may be adapted 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 which follow different rules for therapy. Treatment possibilities include Radiation Therapy, Chemotherapy, Hormone Therapy, and Immune Therapy.

An online resource for helping to quantify the relative risks and benefits of chemotherapy v. hormonal therapy is Adjuvant! Online (see below).

In planning treatment, doctors can also use PCR tests like Oncotype DX or microarray tests like MammaPrint that predict breast cancer recurrence risk based on gene expression. In February 2006, the MammaPrint test became the first breast cancer predictor to win formal approval from the Food and Drug Administration. This is a new gene test to help predict whether women with early stage breast cancer will relapse in five or 10 years, this could help influence how aggressively they fight the initial tumor.

The emotional impact of cancer diagnosis, symptoms, treatment, and related issues can be severe. Most larger hospitals are associated with cancer support groups which can help patients cope with the many issues that come up in a supportive environment with other people with experience with similar issues. Online cancer support groups are also very beneficial to cancer patients, especially in dealing with uncertainty and body-image problems inherent in cancer treatment.

Surgery

Depending on the staging and type of the tumor, just a lumpectomy (removal of the lump only) may be all that is necessary or removal of larger amounts of breast tissue may be necessary. Surgical removal of the entire breast is called mastectomy.

Standard practice requires that the surgeon must establish that the tissue removed in the operation has margins clear of cancer, indicating that the cancer has been completely excised. If the tissue removed does not have clear margins, then 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 ten to forty 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. SLN biopsy is indicated for patients with T1 abd T2 lesions (<5cm) and carries a number of recommendations for use on patient subgroups.

Radiation therapy

Radiation therapy consists of the use of high powered X-rays or gamma rays (XRT) that precisely target the area that is being treated. These X-rays or gamma rays are very effective in destroying the cancer cells that might recur where the tumor was removed. These X-rays are delivered by a machine called a linear Accelerator or LINAC. Alternatively, the use of implanted radioactive catheters (brachytherapy), similar to those used in prostate cancer treatment, is being evaluated. The use of radiation therapy for breast cancer is usually given after surgery has been performed and is an essential component of breast conserving therapy. The purpose of radiation is to reduce the chance that the cancer will recur.

Radiation therapy works for breast cancer by eliminating the microscopic cancer cells that may remain near the area where the tumor was removed during surgery. Since by the nature of radiation and its effects on normal cells and cancer cells alike the dose that is given is to ensure that the cancer cells are eliminated. However, the dose cannot be given in one sitting. Radiation causes some damage to the normal tissue around where the tumor was but normal healthy tissue can repair itself. The treatments are given typically over a period of five to seven weeks, performed five days a week. Each treatment session takes about fifteen minutes per day. Breaking the treatments up over this extended period of time gives the healthy normal tissue a chance to repair itself. Cancer cells do not repair themselves as well as normal cells, which explains the efficacy of radiation therapy.

Although radiation therapy can reduce the chance that breast cancer will recur in the breast, it is much less effective in prolonging patient survival. The National Cancer Institute reviews this information. in a paragraph that begins:“Breast-conserving surgery alone without radiation therapy . . .” The NCI includes six studies; none of them found a survival benefit for radiation therapy. Abstracts from all six studies are available for review. 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.

In general recommendations would include:

• As part of breast conserving therapy of breast cancer when the whole breast is not removed (lumpectomy or wide local excision)
• After mastectomy: Patients with higher chances of cancer recurring such as : large primary tumor and involvement of 4 or more lymph nodes.

Other factors which may influence adding adjuvant

• Tumor close to or to 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 <4 LN involved, but extension out of the substance of a LN
• Inadequate numbers of axillary LN sampled

Types of radiotherapy

Radiotherapy can be delivered in many ways. Most commonly this is done using radiation from linear accelerators. Since this is delivered from outside, one needs to restrict the amount of dose that can be given at one time so that normal tissues are not harmed. So the course usually lasts for several days, typically every day for 5 to 6 weeks.

New technology has allowed more precise delivery of radiotherapy in a portable fashion - for example in the operating theatre. Targeted intraoperative radiotherapy (TARGIT) (coined by Dr Jayant S Vaidya in 1999) 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 at present to test whether it can replace the whole course of radiotherapy in selected patients. It may also be able provide a much better boost dose to the tumour bed and appears to provide superior control. This will be tested in a Targit-B trial.

Side effects of radiation therapy

The side effects of radiation have improved considerably over the past decades. Aside from general fatigue caused by the healthy tissue repairing itself there will probably be no side effects at all. Some patients do develop a suntan-like change in skin color in the exact area being treated. As with a suntan, this darkening of the skin will fade with time. Other side effects experienced with radiation include the fact that radition therapy can and often does cause permanent changes in the color and texture of skin, in addition to :

• reddening of the skin
• muscle stiffness
• mild swelling
• tenderness in the area
• long-term shrinking of the irradiated breast

Along with improved cosmetic outcome of treatment with radiation there are also other techniques for delivering radiation to the breast. One such new technology is using IMRT (intensity modulated radiation therapy) which the radiation oncologist can change the shape and intensity of the radiation beam at different points across and inside the breast. This allows for an even more focused beam of radiation directed at the tumor cells and leaving most of the healthy tissue unaffected by the radiation

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.

Systemic 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 can be given both before and after surgery. Neo-adjuvant chemotherapy is used to shrink the size of a tumor prior to surgery. Adjuvant chemotherapy is given after surgery to reduce the risk of recurrence.

There are several different chemotherapy regimens that may be used. The determination of the appropriate regimen depends on many factors including the character of the tumor, lymph node status, and the age and health of the patient. Possible chemotherapy regimens include:

• CMF: cyclophosphamide, methotrexate, and 5-fluorouracil
• FAC: 5-fluorouracil, doxorubicin, cyclophosphamide
• AC: doxorubicin and cyclophosphamide
• AC with paclitaxel administered after the AC
• TAC: docetaxel , doxorubicin, and cyclophosphamide
• FEC: 5-fluorouracil, epirubucin and cyclophosphamide for 6 cycles
• FEC for three cycles followed by docetaxel for three cycles
• Dose dense AC: doxorubicin and cyclophosphamide followed by paclitaxel
• TC: Taxotere (docetaxel) and cyclophosphamide

Since chemotherapy affects the production of white blood cells, a growth factor e.g. pegfilgrastim is sometimes administered along with chemotherapy. This has been shown to reduce, though not completely prevent the rate of infection and low white cell count.

Chemotherapy has increasing side effects as the patient's age passes 65.

Hormonal treatment

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

• Tamoxifen is typically given to premenopausal women to block the estrogen receptor on cells to prevent the transport of estrogen into the cell
• Aromatase inhibitors are typically given to postmenopausal women to lower the amount of estrogen in their systems
• GnRH-analogues
• ovarian ablation or suppression is used in premenopausal women

However, a recent statistic data shows breast cancer rate dropped dramatically in 2003 and the declining use of hormone could be the reason [6].

Targeted therapy

In patients whose cancer expresses an over-abundance of the HER2 protein the drug trastuzumab (Herceptin ®) is used to block the HER2 protein in breast cancer cells slowing their growth. This drug was originally used only in the treatment of patients with metastatic disease, however in the summer of 2005 two large clinical trials published results suggesting that patients with early-stage disease also benefit significantly from Herceptin.

Preclinical

Flax seeds

Preliminary research into flax seeds indicate that flax can significantly inhibit breast cancer growth and metastasis, and enhance the inhibitory effect of tamoxifen on estrogen-dependent tumors.

Alternative medicine

The use of traditional Chinese medicine to treat breast cancer has been claimed, but no successful clinical trials have yet been reported.

Prognosis

There are several prognostic factors associated with breast cancer. Stage is the single most important prognostic factor in breast cancer, as it will take into consideration local involvement, lymph node status and whether metastatic disease is present or not. The higher the stage at the time of diagnosis, the worse the prognosis of breast cancer is. Node negative breast cancer patients have a much better prognosis compared to node positive patients.

Presence of estrogen and progesterone receptors in the cancer cell is another important prognostic factor, and may guide treatment. Hormone receptor positive breast cancer is usually associated with much better prognosis compared to hormone negative breast cancer.

HER2/neu status has also been described as a prognostic factor. Patients whose cancer cells are positive for HER2/neu have more aggressive disease and may be treated with trastuzumab, a monoclonal antibody that targets this protein.

Ashkenazi Jewish women and black women tend to have higher rates of fatalities.

Breast cancer in males

Less than 1% of breast cancers occur in men and incidence is about 1 in 100,000. Men with gynaecomastia do not have a higher risk of developing breast cancer. There may be an increased incidence of breast cancer in men with prostate cancer. The prognosis, even in stage I cases, is worse in men than in women. The treatment of men with breast cancer is similar to that in older women. Since the male breast tissue is confined to the area directly behind the nipple, treatment for males has usually been a mastectomy with axillary surgery. This may be followed by adjuvant radiotherapy, hormone therapy (such as tamoxifen), or chemotherapy.

Breast Cancer spreading elsewhere in the body

Most people understand breast cancer as something that happens in the breast. However it can spread via lymphatics to nearby lymph nodes usually those under the arm. That is why surgery for breast cancer always involves some type of surgery for the glands under the arm- either axillary clearance, sampling or sentinel node biopsy.

Breast cancer can also spread to other parts of the body via blood vessels. So it can spread to the lungs, pleura (the lining of the lungs), the liver, the brain and most commonly to the bones.

Seventy percent of the time that breast cancer spreads to other locations, it spreads to bone, especially the vertebrae and the long bones of the arms, legs and ribs. Breast cancer cells "set up housekeeping" in the bones and form tumors. When breast cancer is found in bones, it has usually spread to more than one site. At this stage, it is treatable, often for many years, but it is not curable.

Like normal breast cells, these tumors in the bone often thrive on female hormones, especially estrogen. Therefore, the doctor often treats the patient with medicines that lower her estrogen levels.

Usually when breast cancer spreads to bone, it eats away healthy bone causing weak spots. The bones break easily at these weak spots. That is why breast cancer patients are often seen wearing braces or using a wheel chair, and why they complain about aching bones. If a patient has had breast cancer in the past and notices pain in the bones, the patient should see a doctor.

Breast cancer awareness

Pink ribbon

In the month of October, breast cancer is recognized by survivors, family and friends of survivors and/or victims of the disease. A pink ribbon is worn to recognize the struggle that sufferers face when battling the cancer.

Pink for October is an initiative started by Matthew Oliphant, which asks that any sites willing to help make people aware of breast cancer, change their template or layout to include the color pink, so that when visitors view the site, they see that the majority of the site is pink. Then after reading a short amount of information about breast cancer, or being redirected to another site, they are aware of the disease itself.

See also

• List of notable breast cancer patients according to occupation
• List of notable breast cancer patients according to survival status
• List of breast carcinogenic substances
• Mammary tumor for breast cancer in other animals
• Breast reconstruction
• Alcohol and cancer
• Mammogram Quality Standards Act
• National Breast Cancer Coalition
• Breast Cancer Action
• Barron Lerner (Physician)
• William Stewart Halsted (Radical Masectomy)

References

• Chu, S.Y.; Lee, N.C.; Wingo, P.A.; and Webster, L.A. Alcohol consumption and the risk of breast cancer. American Journal of Epidemiology 130(5):867-877, 1989.
• Friedenreich, C.M.; Howe, G.R.; Miller, A.B.; and Jain, M.G. A cohort study of alcohol consumption and risk of breast cancer. American Journal of Edidemiology 137(5):512-520, 1993.
• Longnecker, M.P.; Berlin, J.A.; Orza, M.J.; and Chalmers, T.C. A meta-analysis of alcohol consumption in relation to risk of breast cancer. Journal of the American Medical Association 260(5):652-656, 1988.
• Longnecker, M.P. Alcohol consumption in relation to risk of cancers of the breast and large bowel. Alcohol Health & Research World 16(3)':223-229, 1992.
• Nasca, P.C.; Baptiste, M.S.; Field, N.A.; Metzger, B.B.; Black, M.; Kwon, C.S.; and Jacobson, H. An epidemiological case-control study of breast cancer and alcohol consumption. International Journal of Epidemiology 19(3):532-538, 1990.
• Petri, A.L., et al. Alcohol intake, type of beverage, and risk of cancer in pre- and postmenopausal women. Alcoholism: Clinical & Experimental Research, 2004, 28(7), 1084-1090).
• Schatzkin, A.; Piantadosi, S.; Miccozzi, M.; and Bartee, D. Alcohol consumption and breast cancer: A cross-national correlation study. International Journal of Epidemiology 18(1):28-31, 1989.
• Webster, L.A.; Layde, P.M.; Wingo, P.A.; and Ory, H.W. Alcohol consumption and risk of breast cancer. Lancet 2(8352):724-726, 1983.

External links

• Surgery Choices for Women with Early-Stage Breast Cancer, National Cancer Institute

• Step-by-step surgical details of sentinel lymph node biopsy From InsideSurgery.com
• Susan G. Komen for the Cure home page - One of the largest organizations and grassroots network of activists supporting breast cancer research.
• Breast Cancer Fund - This breast cancer organization sponsored California's Biomonitoring Bill and focusses on environmental issues such as chemical exposure and radiation.
• History of breast cancer treatment, courtesy of the Breast Cancer Campaign (Portable Document Format)
• International Agency for Research on Cancer home page
• Australia: Cancer Control Bulletin Alcohol and cancer risk (PDF format)
• The Breast -Neoplasms of the Breast. Bening Breast Disorders
• Johns Hopkins Avon Foundation Breast Center
• Abreast in the West - A quarterly newsletter for and about breast cancer. The newsletter provides a wide spectrum of content for health care professionals, patients, family and friends.
• Breast cancer incidence by country
• National Cancer Institute - Breast Cancer Home Page
• Mayo Clinic: How the grading system for cancerous tumors was developed.
• Cornell University Alcohol and the Risk of Breast Cancer
• Breast Cancer Treatment Information and Pictures
• Interviews with Breast Cancer Experts
• RadiologyInfo - The radiology information resource for patients: Breast Cancer
• Breast Cancer Quotes
• Mastectomy vs.n Lumpectomy: Who Decides?, National Research Center for Women & Families