is
Cancer of
Breast tissue. Worldwide, it is the most common form of cancer in females, affecting approximately one out of eleven to twelve
Women at 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.
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.
The risk of getting breast cancer increases with age. For a woman who lives to the age of 90 the ) . 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.
Zmagsite
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 ''
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 .
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 (
P53 mutations), these genetic aberrations determine around 5% of all breast cancer cases , suggesting that the remainder is sporadic.
Genetic Counseling and
Genetic Testing should be considered for families who may carry a hereditary form of cancer.
Alcohol is another risk factor for the development of breast cancer. Boffetta P. et al. (
2006-03-23 ) Int J Cancer.
The burden of cancer attributable to alcohol drinking. Women who frequently drink red wine may have an increased risk of developing breast cancer. Maggiolini M. et al. (2005) J Mol Endocrinol.
The red wine phenolics piceatannol and myricetin act as agonists for estrogen receptor alpha in human breast cancer cells.
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 Group found 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."
Mdconsult.com 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 established risk factors include not having children, delaying first childbirth, not breastfeeding, early .
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, 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.
Due to the high incidence of breast cancer among older women, screening is now recommended in many countries. Screening methods suggested include
Breast Self-examination and
Mammography . Only mammography has been proved 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. As a result, MRI studies will have more
False Positives , 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. It may be valuable for younger women, whose breasts are denser with less fat and more connective tissue, making it harder to spot cancers on mammograms.
Ultrasound alone is not adequate as a screening tool but it is a useful additional investigation, especially for the characterization of benign tumours.
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 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.
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).
The emotional impact of cancer diagnosis, symptoms, treatment, and related issues can be severe. Most larger hospitals are associated with
Cancer Support Group s 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 Group s are also very beneficial to cancer patients, especially in dealing with uncertainty and body-image problems inherent in cancer treatment.
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 dissection has become popular as it requires the removal of far fewer lymph nodes, resulting in fewer side effects.
Radiation Therapy is recommended for all patients who had (lumpectomy, quadrant-resection). 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.
Radiation therapy consists of the use of high powered X-rays or
Gamma Rays 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. 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.
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. Like with a suntan this darkening of the skin will fade with time. Other side effects that have been experienced with radiation are:
- 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 the 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 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 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 which regimen will be used 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:
- (brand name Cytoxan), methotrexate, and 5-fluorouracil (5-FU)
- FAC:
- ) and Cyclophosphamide (brand name Cytoxan)
- AC with paclitaxel (brand name Taxol ) administered after the AC
- TAC : docetaxel (brand name Taxotere), Adriamycin, Cytoxan
- FEC for three cycles followed by Taxotere for three cycles
- Dose dense AC: Adriamycin and Cytoxan followed by Taxol
Since chemotherapy effects the production of white blood cells a growth factor e.g.
Pegfilgrastim is sometimes administered along with chemotherapy.
Chemotherapy has increasing side effects as the patient's age passes 65.
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 estrogen the reception of estrogen by breast cancer cells
- Aromatase Inhibitors are typically given to postmenopausal women to lower the amount of estrogen in their systems
- GnRH-analogues
In patients whose cancer expresses an over-abundance of the HER2 protein the drug
Trastuzumab (brand name 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.
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/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.
Prevention of breast cancer in high-risk women is probably more important than treatment of breast cancer. Many women who may have inherited genetic mutations in breast cancer related genes (called BRCA1 and BRCA2) might have very high risk of developing breast cancer. In these women and other women who have very strong family history of breast cancer, the chance of developing breast cancer may be decreased by hormonal treatment . Classic drug for breast cancer prevention is (FDA) approved for breast cancer prevention.
Because the breast is composed of identical tissues in males and females, breast cancer can also occur in males. The .
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 men and women face when battling the cancer.
