Breast cancer

 ICD9        = 174-175|

}} Breast cancer is cancerof breasttissue. Worldwide, it is the most common form of cancer in females, affecting approximately 1 out of 11-12 womenat some stage of their life in the Western world. Although significant efforts are made to achieve early detection and effective treatment, about 20% of all women with breast cancer will die from the disease, and it is the second most common cause of cancer deaths in women.

Epidemiologic risk factors

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 given the underlying cause. By analogy in peptic ulcer disease, the cause is Helicobacter pylori, a co-factor is stomach acidity, a promoter may be aspirin which altogether produce a stomach ulcer. Each is a risk factor associated with disease, and one is the primary cause. The cause of breast cancer is not known.

Age

The risk of getting breast cancer increases with age. For a woman who lives to the age of 90 the chancesof getting breast cancer her entire lifetime is about 12.5% or 1 in 8. Men can also develop breast cancer, but their risk is less than 1 in 1000 (see sex and illness). This risk is modified by many different factors. In a very small (~ 5%) proportion of breast cancer cases, there is a strong inherited familial risk. [1]Some racial groups have a higher risk of developing breast cancer - notably, women of Europeanand Africandescent have been noted to have a higher rate of breast cancer than women of Asianorigin. (figures from breastcancer.org) However, these apparent racial differences diminish when geography is altered, as Asian women migrating to the western world, gradually acquire risk approaching that of western women.

The probability of breast cancer rises with age but breast cancer tends to be more aggressive when it occurs in younger women. One type of breast cancer that is especially aggressive and disproportionately occurs in younger women is inflammatorybreast 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 mammographyor ultrasound. It presents with the signs and symptoms of a breast infection like mastitis.

Genes

Two genes, BRCA1 and BRCA2, have been linked to the rare familial form of breast cancer. Women in families expressing mutations in these genes have a much higher risk of developing breast cancer than women who do not. Not all people who inherit mutations in these genes will develop breast cancer. Together with Li-Fraumeni syndrome(p53mutations), these genetic aberrations determine around 5% of all breast cancer cases, suggesting that the remainder is sporadic. Genetic counselingand genetic testingshould be considered for families who may carry a hereditary form of cancer.

Alcohol

Alcohol is another risk factor for the development of breast cancer. Women who drink half a glass of wine every day have 6% increased risk of developing breast cancer.

Hormones

The International Agency for Research on Cancer(IARC) in Lyon, France invited 21 scientists from eight countries in June 2005, to evaluate the risk of cancer for humans of combined estrogen-progesterone contraceptives and combined estrogen-progesterone menopausal therapy. The working groupfound that there is a small increase in the relative risk of breast cancer in current and recent users of combined oral contraceptives.

The risk decreases to that of those who have never used such combined therapy ten years after cessation of use. The scientists described combined oral estrogen-progesterone contraceptives as "carcinogenic to humans." [2]They also found an increased risk of breast cancer in women under treatment with combined menopausal therapy, which is confined mostly to current or recent users, increases with duration of use and exceeds that in women taking estrogen-only therapy.

Other

Other established risk factors include not having children, delaying first childbirth, not breastfeeding, early menarche(the first menstrual period), late menopause, obesityand taking hormone replacement therapy.

Etiology

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 promotors have been identified, the majority of breast cancer incidence remains unattributable, and the primary cause is unknown.

Dietary influences have been proposed and examined, but these are small effects, and do not distinguish differences in risk within populations, as well as they do between populations.

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.

Screening

Due to the high incidence of breast cancer among older women, screening is now recommended in many countries. Screening methods suggested include breast self-examinationand mammography. Only mammography has been proven to reduce mortality from breast cancer. In some countries routine (annual) mammography of older women is encouraged as a screening method to diagnose early breast cancer.

Mammography is still the modality of choice for screening of early breast cancer. 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 more sensitive, it is less specific than mammography. This causes mammography to yield many false positivesthat that have undesirable financial and psychological costs. It is also a relatively expensive procedure, and one which requires the injection of a chemical agent to be effective. It may be valuable for younger women, whose breasts contain less fat and more connective tissue, making it harder to spot cancers on mammograms. Ultrasoundalone is not adequate as a screening tool but it is a useful additional investigation, especially for the characterisation of benign tumours.

The U.S. National Cancer Instituterecommends 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 a family history of breast cancer should start screening mammography at an earlier age, and it is usually suggested to start screening at an age that is 10 years less than the age at which a relative was diagnosed with breast cancer.

Breast cancers detected by mammography are usually smaller than those detected clinically, and women who undergo mammography are more likely to be eligible for breast-conserving therapy.

Diagnosis

Many breast cancers are diagnosed now by mammography before they are large enough to be palpated, but despite screening efforts, many women are diagnosed with breast cancer after they notice a lump or when experiencing symptoms due to metastatic disease.

Breast cancer can be suspected after a cautious clinical history, physical examinationand imaging (either mammographyor ultrasound). The diagnosis can only be established when a suspicious lump is biopsiedfor histological confirmation of whether it is malignant or not. The biopsy is usually performed either with a fine needle guided by ultrasound or with a larger "core" needle. Some cases require an open biopsy after wire localization under x-ray.

A pathology report will usually contain a description of cell typeand grade. Other useful information derived from the pathology laboratory include estrogen receptor and progesterone receptors status and HER2/neustatus; these can help to guide treatment.

The most common invasive breast cancer cell type is infiltrating ductal carcinoma(M8500/3). Other types include:

• (M8500/2): the noninvasive ductal carcinoma in situ(DCIS)
• (M8520/2): lobular carcinoma in situ(LCIS)
• infiltrating lobular carcinoma
• (M8510/3): medullary carcinoma

After diagnosis, the next phase is tumour staging - this aims to assess the extent of the tumour and whether it has metastasized(spread to distant sites).

Staging

For suspicious, high risk cases, other investigations which include CT scans, nuclear medicine studies (e.g. bone scans or PET imaging), magnetic resonance imaging (MRI), chest X-rays, and blood tests may be done to look for any metastasisor secondary cancer that has spread a long way from the site of the primary tumour.

The standard way of categorising tumour is by stagingit using the TNM(Tumour, Nodes and Metastasis) system, which in turn determines treatment recommendations. The TNM system is specific for each type of cancer. Some biological features of the cancer such as estrogen receptorand HER2/neuoncogeneexpression are also determined as they also affect treatment recommendations.

TNM classification

The TNM classification of breast cancer:

• Tumor size:
  • T0 no primary tumor found
  • Tis in situ
  • T1 =< 2 cm
    • T1mic ≤ 0.1 cm (microinvasive)
    • T1a > 0.1 to 0.5 cm
    • T1b > 0.5 to 1 cm
    • T1c > 1 to 2 cm
  • T2 > 2 to 5 cm
  • T3 > 5 cm
  • T4 Chest wall /skin
    • T4a Chest wall
    • T4b Skin oedema (peau d'orange), ulceration, or satellite skin modules
    • T4c Both 4a and 4b
    • T4d Inflammatory carcinoma
• Lymph nodes:
  • N0 No lymph nodes
  • N1 Movable axillary
  • N2a Fixed axillary
  • N2b Internal mammary clinically apparent
  • N3a Infraclavicular
  • N3b Internal mammary clinically apparent with axillary lymph node involvement
  • N3c Supraclavicular lymph nodes
• Distant metastasis:
  • M0 No
  • M1 Yes

Stage grouping

• Stage 0: Tis
• Stage I: T1,N0,M0
• Stage IIA: T0-1,N1,M0 or T2,N0,M0
• Stage IIB: T2,N1,M0 or T3,N0,M0
• Stage IIIA: T3,N1,M0 or T0-3,N2,M0
• Stage IIIB: T4,any N,M0
• Stage IIIC: any T,N3,M0
• Stage IV: any T,any N,M1

Staging depends on factors which include the size of the tumour, whether there is lymph node involvement or not and whether there is distant spread of cancer cells (metastasis). Stages are a composite of the TNM. Stage I is small tumor (T1) without any spread, while stage IV is metastatic disease. Stages correlate with long-term prognosis, and treatment decisions are often made on the basis of the stage.

Treatment

The mainstay of breast cancer treatment is surgerywhen the tumor is localized, with possible adjuvant hormonal therapy (with tamoxifenor an aromatase inhibitor), chemotherapy, and/or radiotherapy.

Surgery

Depending on the staging and type of the tumour, 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 musclewhich is the main muscle of the anterior chest wall.

During the operation, the lymph nodesin the axillaare also considered for removal. In the past, large axillary operations took out 10-40 nodes to establish whether cancer had spread - this had the unfortunate side effect of frequently causing lymphedemaof the arm on the same side as the removal of this many lymph nodes affected lymphatic drainage. More recently the technique of sentinel lymph nodedissection has become popular as it requires the removal of far fewer lymph nodes, resulting in fewer side effects.

Adjuvant therapy

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. The following list is a compilation of possibilities:

1. After a breast conserving therapy (lumpectomy, quadrant-resection), the high local recurrence risk (~40%) is reduced by radiation therapyto the breast
2. If the lymph nodes are positive, the high mortality risk (30-80%) is reduced by systemic treatment (either anti-hormones or chemotherapy).
3. In younger patients, the most useful systemic therapy is chemotherapy (usually older regimens such as CMF, FAC, ACand/or Taxol) and now the FDA approved regimen TAC (Taxotere, Adriamycin, Cytoxan) or FEC for 3 cycles followed by Taxotere for 3 cycles. Another standard regimen includes dose dense AC (Adriamycinand cyclophosphamide) followed by Taxol. This is given on a two week cycle with growth factor support, e.g. pegfilgrastim.
4. In older patients with estrogen receptor positive tumors, the most useful systemic therapy is anti-hormone therapy (tamoxifen, aromatase inhibitors, GnRH-analogues)
5. Chemotherapy has increasing side effects as the patient's age passes 65
6. In patients with estrogen receptor negative tumours, the most useful systemic therapy is chemotherapy
7. In patients with estrogen receptor positive tumours, the most effective systemic therapy is hormone therapy with medications such as tamoxifenor an aromatase inhibitor(in postmenopausal women)
8. Two large clinical trials published in the summer of 2005 demonstrated that patients with positive nodes and HER2/neupositive breast cancer should be treated with trastuzumab(brand name Herceptin) in addition to traditional adjuvant chemotherapy

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

Radiation therapy is recommended in all patients who had lumpectomy, however radiation therapy after mastectomy is recommended only if four or more lymph nodes are involved with cancer. Radiation therapy is usually not indicated in patients with advanced (stage IV disease) except for palliation of symptoms like bone pain.

The emotional impact of cancer diagnosis, symptoms, treatment, and related issues can be severe. Most larger hospitals are associated with cancer support groupswhich 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 groupsare also very beneficial to cancer patients, especially in dealing with uncertainty and body-image problems inherent in cancer treatment.

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, lymphnode 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/neustatus 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 antibodythat targets this protein.

Breast cancer awareness

Image:Pink ribbon.png In the month of October, breast cancer is recognized by survivors, family and friends of survivors and/or victims of the disease. A pink ribbonis worn to recognize the struggle that men and women face when battling the cancer.

See also

List of famous people with breast cancer

External links

• Detailed Guide: Breast Cancer
• Keeping Abreast: Dedicated to providing only the most interesting Breast Cancer News links and sumaries
• Inflammatory Breast Cancer Organization
• Y-ME National Breast Cancer Organization
• Breast cancer incidence by country
• National Cancer Institute - Breast Cancer Home Page
• Cancer Research UK - Information Resource Centre- contains in-depth Breast cancer information, statistics and up-to-date news provided by the UK's leading cancer charity.
• The Susan G Komen Breast Cancer Foundation
• Adjuvant! Online. Widely used online resource for calculating relative benefits of adjuvant antihormonal therapy v. chemotherapy for early stage breast cancer. Described further in PMID 11181660.
• Imaginis - Histologic grades of breast cancer
• RadiologyInfo - The radiology information resource for patients: Breast Cancer

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It uses material from the http://en.wikipedia.org/wiki/Breast+cancer Wikipedia article Breast cancer.