Prevention[edit]
Women may reduce their risk of breast cancer by maintaining a healthy weight, drinking less alcohol, being physically active and breastfeeding their children.[84] These modifications might prevent 38% of breast cancers in the US, 42% in the UK, 28% in Brazil and 20% in China.[84] The benefits with moderate exercise such as brisk walking are seen at all age groups including postmenopausal women.[84][85] Marine omega-3 polyunsaturated fatty acids appear to reduce the risk.[86] Strategies that encourage regular physical activity and reduce obesity could also have other benefits, such as reduced risks of cardiovascular disease and diabetes.[25]
Removal of both breasts before any cancer has been diagnosed or any suspicious lump or other lesion has appeared (a procedure known as prophylactic bilateral mastectomy) may be considered in people with BRCA1 and BRCA2 mutations, which are associated with a substantially heightened risk for an eventual diagnosis of breast cancer.[87][88]Evidence is not strong enough to support this procedure in anyone but those at the highest risk.[89] BRCA testing is recommended in those with a high family risk after genetic counseling. It is not recommended routinely.[90] This is because there are many different forms of changes in BRCA genes, ranging from harmless polymorphisms to obviously dangerous frameshift mutations. The effect of most of identifiable changes in the genes is uncertain. Testing in an average-risk person is particularly likely to return one of these indeterminate, useless results. It is unclear if removing the second breast in those who have breast cancer in one is beneficial.[89]
The selective estrogen receptor modulators (such as tamoxifen) reduce the risk of breast cancer but increase the risk of thromboembolism and endometrial cancer.[91][91] There is no overall change in the risk of death.[91][92] They are thus not recommended for the prevention of breast cancer in women at average risk but may be offered for those at high risk.[93] The benefit of breast cancer reduction continues for at least five years after stopping a course of treatment with these medications.[94]
Screening[edit]
Main article: Breast cancer screening
Breast cancer screening refers to testing otherwise-healthy women for breast cancer in an attempt to achieve an earlier diagnosis under the assumption that early detection will improve outcomes. A number of screening tests have been employed including: clinical and selfbreast exams, mammography, genetic screening, ultrasound, and magnetic resonance imaging.
A clinical or self breast exam involves feeling the breast for lumps or other abnormalities. Clinical breast exams are performed by health care providers, while self breast exams are performed by the person themselves.[96] Evidence does not support the effectiveness of either type of breast exam, as by the time a lump is large enough to be found it is likely to have been growing for several years and thus soon be large enough to be found without an exam.[7][97] Mammographic screening for breast cancer uses X-rays to examine the breast for any uncharacteristic masses or lumps. During a screening, the breast is compressed and a technician takes photos from multiple angles. A general mammogram takes photos of the entire breast, while a diagnostic mammogram focuses on a specific lump or area of concern.[98]
A number of national bodies recommend breast cancer screening. For the average woman, the U.S. Preventive Services Task Forcerecommends mammography every two years in women between the ages of 50 and 74,[7] the Council of Europe recommends mammography between 50 and 69 with most programs using a 2-year frequency,[99] and in Canada screening is recommended between the ages of 50 and 74 at a frequency of 2 to 3 years.[100] These task force reports point out that in addition to unnecessary surgery and anxiety, the risks of more frequent mammograms include a small but significant increase in breast cancer induced by radiation.[101]
The Cochrane collaboration (2013) states that the best quality evidence neither demonstrates a reduction in cancer specific, nor a reduction in all cause mortality from screening mammography.[5] When less rigorous trials are added to the analysis there is a reduction in mortality due to breast cancer of 0.05% (a decrease of 1 in 2000 deaths from breast cancer over 10 years or a relative decrease of 15% from breast cancer).[5] Screening over 10 years results in a 30% increase in rates of over-diagnosis and over-treatment (3 to 14 per 1000) and more than half will have at least one falsely positive test.[5][102][103] This has resulted in the view that it is not clear whether mammography screening does more good or harm.[5][103][needs update] Cochrane states that, due to recent improvements in breast cancer treatment, and the risks of false positives from breast cancer screening leading to unnecessary treatment, "it therefore no longer seems reasonable to attend for breast cancer screening" at any age.[104] Whether MRI as a screening method has greater harms or benefits when compared to standard mammography is not known.[105]
Management[edit]
Main article: Breast cancer management
The management of breast cancer depends on various factors, including the stage of the cancer and the age of the patient. Increasingly aggressive treatments are employed in accordance with the poorer the patient's prognosis and the higher the risk of recurrence of the cancer following treatment.
Breast cancer is usually treated with surgery, which may be followed by chemotherapy or radiation therapy, or both. A multidisciplinary approach is preferable.[106] Hormone receptor-positive cancers are often treated with hormone-blocking therapy over courses of several years. Monoclonal antibodies, or other immune-modulating treatments, may be administered in certain cases of metastatic and other advanced stages of breast cancer.
Surgery[edit]
Surgery involves the physical removal of the tumor, typically along with some of the surrounding tissue. One or more lymph nodes may be biopsied during the surgery; increasingly the lymph node sampling is performed by a sentinel lymph node biopsy.
Standard surgeries include:
- Mastectomy: Removal of the whole breast.
- Quadrantectomy: Removal of one quarter of the breast.
- Lumpectomy: Removal of a small part of the breast.
Once the tumor has been removed, if the patient desires, breast reconstruction surgery, a type of plastic surgery, may then be performed to improve the aesthetic appearance of the treated site. Alternatively, women use breast prostheses to simulate a breast under clothing, or choose a flat chest. Nipple/areola prostheses can be used at any time following the mastectomy.
Medication[edit]
Drugs used after and in addition to surgery are called adjuvant therapy. Chemotherapy or other types of therapy prior to surgery are called neoadjuvant therapy. Aspirin may reduce mortality from breast cancer.[107]
There are currently three main groups of medications used for adjuvant breast cancer treatment: hormone-blocking agents, chemotherapy, and monoclonal antibodies.
- Hormone blocking therapy
- Some breast cancers require estrogen to continue growing. They can be identified by the presence of estrogen receptors (ER+) and progesterone receptors (PR+) on their surface (sometimes referred to together as hormone receptors). These ER+ cancers can be treated with drugs that either block the receptors, e.g. tamoxifen, or alternatively block the production of estrogen with an aromatase inhibitor, e.g. anastrozole[108] or letrozole. The use of tamoxifen is recommended for 10 years.[109] Aromatase inhibitors are only suitable for women after menopause; however, in this group, they appear better than tamoxifen.[110] This is because the active aromatase in postmenopausal women is different from the prevalent form in premenopausal women, and therefore these agents are ineffective in inhibiting the predominant aromatase of premenopausal women.[111]
- Chemotherapy
- Chemotherapy is predominantly used for cases of breast cancer in stages 2–4, and is particularly beneficial in estrogen receptor-negative (ER-) disease. The chemotherapy medications are administered in combinations, usually for periods of 3–6 months. One of the most common regimens, known as "AC", combines cyclophosphamide withdoxorubicin. Sometimes a taxane drug, such as docetaxel (Taxotere), is added, and the regime is then known as "CAT". Another common treatment is cyclophosphamide,methotrexate, and fluorouracil (or "CMF"). Most chemotherapy medications work by destroying fast-growing and/or fast-replicating cancer cells, either by causing DNA damage upon replication or by other mechanisms. However, the medications also damage fast-growing normal cells, which may cause serious side effects. Damage to the heart muscle is the most dangerous complication of doxorubicin, for example.
- Monoclonal antibodies
- Trastuzumab, a monoclonal antibody to HER2 (a cell receptor that is especially active in some breast cancer cells), has improved the 5-year disease free survival of stage 1–3 HER2-positive breast cancers to about 87% (overall survival 95%).[112] When stimulated by certain growth factors, HER2 causes cellular growth and division; in the absence of stimulation by the growth factor, the cell will normally stop growing. Between 25% and 30% of breast cancers overexpress the HER2 gene or its protein product,[113] and overexpression of HER2 in breast cancer is associated with increased disease recurrence and worse prognosis. When trastuzumab binds to the HER2 in breast cancer cells that overexpress the receptor, trastuzumab prevents growth factors from being able to bind to and stimulate the receptors, effectively blocking the growth of the cancer cells. Trastuzumab, however, is very expensive, and its use may cause serious side effects (approximately 2% of patients who receive it suffer significant heart damage).[114]Further, trastuzumab is only effective in patients with HER2 amplification/overexpression.
Radiation[edit]
Radiotherapy is given after surgery to the region of the tumor bed and regional lymph nodes, to destroy microscopic tumor cells that may have escaped surgery. It may also have a beneficial effect on tumor microenvironment.[115][116] Radiation therapy can be delivered asexternal beam radiotherapy or as brachytherapy (internal radiotherapy). Conventionally radiotherapy is given after the operation for breast cancer. Radiation can also be given at the time of operation on the breast cancer- intraoperatively. The largest randomised trial to test this approach was the TAR-GIT-A Trial[117] which found that targeted intraoperative radiotherapy was equally effective at 4-years as the usual several weeks' of whole breast external beam radiotherapy.[118] Radiation can reduce the risk of recurrence by 50–66% (1/2 – 2/3 reduction of risk) when delivered in the correct dose[119] and is considered essential when breast cancer is treated by removing only the lump (Lumpectomy or Wide local excision).
Prognosis[edit]
Prognosis is usually given for the probability of progression-free survival (PFS) or disease-free survival (DFS). These predictions are based on experience with breast cancer patients with similar classification. A prognosis is an estimate, as patients with the same classification will survive a different amount of time, and classifications are not always precise. Survival is usually calculated as an average number of months (or years) that 50% of patients survive, or the percentage of patients that are alive after 1, 5, 15, and 20 years. Prognosis is important for treatment decisions because patients with a good prognosis are usually offered less invasive treatments, such as lumpectomy and radiation or hormone therapy, while patients with poor prognosis are usually offered more aggressive treatment, such as more extensive mastectomy and one or more chemotherapy drugs.
Prognostic factors[edit]
Prognostic factors are reflected in the classification scheme for breast cancer including stage, (i.e., tumor size, location, whether disease has spread to lymph nodes and other parts of the body), grade, recurrence of the disease, and the age and health of the patient. TheNottingham Prognostic Index is a commonly used prognostic tool.
The stage of the breast cancer is the most important component of traditional classification methods of breast cancer, because it has a greater effect on the prognosis than the other considerations. Staging takes into consideration size, local involvement, lymph node status and whether metastatic disease is present. The higher the stage at diagnosis, the poorer the prognosis. The stage is raised by the invasiveness of disease to lymph nodes, chest wall, skin or beyond, and the aggressiveness of the cancer cells. The stage is lowered by the presence of cancer-free zones and close-to-normal cell behaviour (grading). Size is not a factor in staging unless the cancer is invasive. For example, Ductal Carcinoma In Situ (DCIS) involving the entire breast will still be stage zero and consequently an excellent prognosis with a 10-year disease free survival of about 98%.[120]
- Stage 1 cancers (and DCIS, LCIS) have an excellent prognosis and are generally treated with lumpectomy and sometimes radiation.[121] HER2+ cancers should be treated with the trastuzumab (Herceptin) regime.[122] Chemotherapy is uncommon for other types of stage 1 cancers.
- Stage 2 and 3 cancers with a progressively poorer prognosis and greater risk of recurrence are generally treated with surgery (lumpectomy or mastectomy with or without lymph node removal), chemotherapy (plus trastuzumab for HER2+ cancers) and sometimes radiation (particularly following large cancers, multiple positive nodes or lumpectomy).
- Stage 4, metastatic cancer, (i.e. spread to distant sites) has poor prognosis and is managed by various combination of all treatments from surgery, radiation, chemotherapy and targeted therapies. Ten-year survival rate is 5% without treatment and 10% with optimal treatment.[123]
The breast cancer grade is assessed by comparison of the breast cancer cells to normal breast cells. The closer to normal the cancer cells are, the slower their growth and the better the prognosis. If cells are not well differentiated, they will appear immature, will divide more rapidly, and will tend to spread. Well differentiated is given a grade of 1, moderate is grade 2, while poor or undifferentiated is given a higher grade of 3 or 4 (depending upon the scale used). The most widely used grading system is the Nottingham scheme;[124] details are provided in the discussion of breast cancer grade.
The presence of estrogen and progesterone receptors in the cancer cell is important in guiding treatment. Those who do not test positive for these specific receptors will not be able to respond to hormone therapy, and this can affect their chance of survival depending upon what treatment options remain, the exact type of the cancer, and how advanced the disease is.
In addition to hormone receptors, there are other cell surface proteins that may affect prognosis and treatment. HER2 status directs the course of treatment. Patients whose cancer cells are positive for HER2 have a more aggressive disease and may be treated with the 'targeted therapy', trastuzumab (Herceptin), a monoclonal antibody that targets this protein and improves the prognosis significantly.
Younger women tend to have a poorer prognosis than post-menopausal women due to several factors. Their breasts may change with their menstrual cycles, they may be nursing infants, and they may be unaware of changes in their breasts. Therefore, younger women are usually at a more advanced stage when diagnosed. There may also be biologic factors contributing to a higher risk of disease recurrence for younger women with breast cancer.[125]
High mammographic breast density, which is a marker of increased risk of developing breast cancer, may not mean an increased risk of death among breast cancer patients, according to a 2012 report of a study involving 9232 women by the National Cancer Institute (NCI).[126] On the other hand, more recent research has shown that women with extremely low mammographic densities (<10%) hold a significantly worse prognosis compared to women with other densities, irrespective of all possible confounding factors. [127]
Since breast cancer in males is usually detected at later stages, outcomes are typically worse.[128]
Psychological aspects[edit]
The emotional impact of cancer diagnosis, symptoms, treatment, and related issues can be severe. Most larger hospitals are associated with cancer support groups which provide a supportive environment to help patients cope and gain perspective from cancer survivors.
Not all breast cancer patients experience their illness in the same manner. Factors such as age can have a significant impact on the way a patient copes with a breast cancer diagnosis. Premenopausal women with estrogen-receptor positive breast cancer must confront the issues of early menopause induced by many of the chemotherapy regimens used to treat their breast cancer, especially those that use hormones to counteract ovarian function.[129]
On the other hand, a small 2007 study conducted by researchers at the College of Public Health of the University of Georgia suggested a need for greater attention to promoting functioning and psychological well-being among older cancer survivors, even when they may not have obvious cancer-related medical complications.[130] The study found that older breast cancer survivors showed multiple indications of decrements in their health-related quality of life, and lower psychosocial well-being than a comparison group. Survivors reported no more depressive symptoms or anxious mood than the comparison group, however, they did score lower in measures of positive psychosocial well-being, and reported more depressed mood and days affected by fatigue. As the incidence of breast cancer in women over 50 rises and survival rates increase, breast cancer is increasingly becoming a geriatric issue that warrants both further research and the expansion of specialized cancer support services tailored for specific age groups.[130]
Epidemiology[edit]
Main article: Epidemiology of breast cancer
Worldwide, breast cancer is the most common invasive cancer in women. (The most common form of cancer is non-invasive non-melanoma skin cancer; non-invasive cancers are generally easily cured, cause very few deaths, and are routinely excluded from cancer statistics.) Breast cancer comprises 22.9% of invasive cancers in women[132] and 16% of all female cancers.[133] In 2012, it comprised 25.2% of cancers diagnosed in women, making it the most common female cancer.[134]
In 2008, breast cancer caused 458,503 deaths worldwide (13.7% of cancer deaths in women and 6.0% of all cancer deaths for men and women together).[132] Lung cancer, the second most common cause of cancer-related death in women, caused 12.8% of cancer deaths in women (18.2% of all cancer deaths for men and women together).[132]
The incidence of breast cancer varies greatly around the world: it is lowest in less-developed countries and greatest in the more-developed countries. In the twelve world regions, the annual age-standardized incidence rates per 100,000 women are as follows: in Eastern Asia, 18; South Central Asia, 22; sub-Saharan Africa, 22; South-Eastern Asia, 26; North Africa and Western Asia, 28; South and Central America, 42; Eastern Europe, 49; Southern Europe, 56; Northern Europe, 73; Oceania, 74; Western Europe, 78; and in North America, 90.[135]
The number of cases worldwide has significantly increased since the 1970s, a phenomenon partly attributed to the modern lifestyles.[136][137] Breast cancer is strongly related to age with only 5% of all breast cancers occurring in women under 40 years old.[138]There were more than 41,000 newly diagnosed cases of breast cancer registered in England in 2011, around 80% of these cases were in women age 50 or older [139]
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