Breast cancer
Breast cancer is a cancer that develops from breast tissue. Signs of breast cancer may include: a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or a red or scaly patch of skin. In those with distant spread of the disease, there may be bone pain, swollen lymph nodes, shortness of breath, or yellow skin.
Risk factors for developing breast cancer include obesity, a lack of physical exercise, alcohol consumption, hormone replacement therapy during menopause, ionizing radiation, an early age at first menstruation, having children late in life, older age, having a prior history of breast cancer, and a family history of breast cancer. About five to ten percent of cases are the result of an inherited genetic predisposition, including BRCA mutations among others. Breast cancer most commonly develops in cells from the lining of milk ducts and the lobules that supply these ducts with milk. Cancers developing from the ducts are known as ductal carcinomas, while those developing from lobules are known as lobular carcinomas. There are more than 18 other sub-types of breast cancer. The diagnosis of breast cancer is confirmed by taking a biopsy of the concerning tissue. Once the diagnosis is made, further tests are carried out to determine if the cancer has spread beyond the breast and which treatments are most likely to be effective.
Breast cancer screening can be instrumental, given that the size of a breast cancer and its spread are among the most critical factors in predicting the prognosis of the disease. Breast cancers found during screening are typically smaller and less likely to have spread outside the breast. Training health workers to do clinical breast examination may have potential to detect breast cancer at an early stage. A 2013 Cochrane review found that it was unclear whether mammographic screening does more harm than good, in that a large proportion of women who test positive turn out not to have the disease. A 2009 review for the US Preventive Services Task Force found evidence of benefit in those 40 to 70 years of age, and the organization recommends screening every two years in women 50 to 74 years of age.
The medications tamoxifen or raloxifene may be used in an effort to prevent breast cancer in those who are at high risk of developing it. Surgical removal of both breasts is another preventive measure in some high risk women. In those who have been diagnosed with cancer, a number of treatments may be used, including surgery, radiation therapy, chemotherapy, hormonal therapy, and targeted therapy. Types of surgery vary from breast-conserving surgery to mastectomy. Breast reconstruction may take place at the time of surgery or at a later date. In those in whom the cancer has spread to other parts of the body, treatments are mostly aimed at improving quality of life and comfort.
Outcomes for breast cancer vary depending on the cancer type, the extent of disease, and the person's age. The five-year survival rates in United States and in the UK are over 90%. In developing countries, five-year survival rates are lower. Worldwide, breast cancer is the leading type of cancer in women, accounting for 25% of all cases. In 2018, it resulted in two million new cases and 627,000 deaths. It is more common in developed countries, and is more than 100 times more common in women than in men. For transgender individuals on gender-affirming hormone therapy, breast cancer is five times more common in cisgender women than in transgender men, and 46 times more common in transgender women than in cisgender men.
Signs and symptoms
Most people with breast cancer have no symptoms at the time of diagnosis; their tumor is detected by a breast cancer screening test. For those who do have symptoms, a new lump in the breast is most common. Most breast lumps are not cancer, though lumps that are painless, hard, and with irregular edges are more likely to be cancerous. Other symptoms include skin thickening known as peau d'orange swelling or pain in the breast; dimpling, thickening, redness, or dryness of the breast skin; and pain, or inversion of the nipple. Some may experience unusual discharge from the breasts, or swelling of the lymph nodes under the arms or along the collar bone.Some less common forms of breast cancer cause distinctive symptoms. Up to 5% of people with breast cancer have inflammatory breast cancer, where cancer cells block the lymph vessels of one breast, causing the breast to substantially swell and redden over three to six months. Up to 3% of people with breast cancer have Paget's disease of the breast, with eczema-like red, scaly irritation on the nipple and areola.
Advanced tumors can spread beyond the breast, most commonly to the bones, liver, lungs, and brain. Bone metastases can cause swelling, progressive bone pain, and weakening of the bones that leads to fractures. Liver metastases can cause abdominal pain, nausea, vomiting, and skin problems – rash, itchy skin, or yellowing of the skin. Those with lung metastases experience chest pain, shortness of breath, and regular coughing. Metastases in the brain can cause persistent headache, seizures, nausea, vomiting, and disruptions to the affected person's speech, vision, memory, and regular behavior.
Screening
Breast cancer screening refers to testing women without breast cancer symptoms in an attempt to diagnose breast tumors early when treatments are more successful. The most common screening test for breast cancer is low-dose X-ray imaging of the breast, called mammography. Each breast is pressed between two plates and imaged. Tumors can appear unusually dense within the breast, distort the shape of surrounding tissue, or cause small dense flecks called microcalcifications. Radiologists generally report mammogram results on a standardized scale – the six-point Breast Imaging-Reporting and Data System is the most common globally – where a higher number corresponds to a greater risk of a cancerous tumor.A mammogram also reveals breast density; dense breast tissue appears opaque on a mammogram and can obscure tumors. BI-RADS categorizes breast density into four categories. Mammography can detect around 90% of breast tumors in the least dense breasts, but just 60% in the most dense breasts. Women with particularly dense breasts can instead be screened by ultrasound, magnetic resonance imaging, or tomosynthesis, all of which more sensitively detect breast tumors.
Regular screening mammography reduces breast cancer deaths by at least 20%. Most medical guidelines recommend annual screening mammograms for women aged 50–70. Screening also reduces breast cancer mortality in women aged 40–49, and some guidelines recommend annual screening in this age group as well. For women at high risk for developing breast cancer, most guidelines recommend adding MRI screening to mammography, to increase the chance of detecting potentially dangerous tumors. Regularly feeling one's own breasts for lumps or other abnormalities, called breast self-examination, does not reduce a person's chance of dying from breast cancer. Clinical breast exams, where a health professional feels the breasts for abnormalities, are common; whether they reduce the risk of dying from breast cancer is not known. Regular breast cancer screening is commonplace in most wealthy nations, but remains uncommon in the world's poorer countries.
Still, mammography has its disadvantages. Overall, screening mammograms miss about 1 in 8 breast cancers, they can also give false-positive results, causing extra anxiety and making patients overgo unnecessary additional exams, such as bioposies.
Diagnosis
Those who have a suspected tumor from a mammogram or physical exam first undergo additional imaging – typically a second "diagnostic" mammogram and ultrasound – to confirm its presence and location. A biopsy is then taken of the suspected tumor. Breast biopsy is typically done by core needle biopsy, with a hollow needle used to collect tissue from the area of interest. Suspected tumors that appear to be filled with fluid are often instead sampled by fine-needle aspiration. Around 10–20% of breast biopsies are positive for cancer. Most biopsied breast masses are instead caused by fibrocystic breast changes, a term that encompasses benign pockets of fluid, cell growth, or fibrous tissue.Classification
Breast cancers are classified by several grading systems, each of which assesses a tumor characteristic that impacts a person's prognosis. First, a tumor is classified by the tissue it arises from, or the appearance of the tumor tissue under a microscope. Most breast cancers are ductal carcinoma – derived from the lining of the mammary ducts. 10% are lobular carcinoma – derived from the mammary lobes – or mixed ductal/lobular carcinoma. Rarer types include mucinous carcinoma, tubular carcinoma, medullary carcinoma, and papillary carcinoma. Oftentimes a biopsy reveals cells that are cancerous but have not yet spread beyond their original location. This condition, called carcinoma in situ, is often considered "precancerous" rather than a dangerous cancer itself. Those with ductal carcinoma in situ are at increased risk for developing true invasive breast cancer – around a third develop breast cancer within five years. Lobular carcinoma in situ rarely causes a noticeable lump, and is often found incidentally during a biopsy for another reason. It is commonly spread throughout both breasts. Those with lobular carcinoma in situ also have an increased risk of developing breast cancer – around 1% develop breast cancer each year. However, their risk of dying of breast cancer is no higher than the rest of the population.Invasive tumor tissue is assigned a grade based on how distinct it appears from healthy breast. Breast tumors are graded on three features: the proportion of cancer cells that form tubules, the appearance of the cell nucleus, and how many cells are actively replicating. Each feature is scored on a three-point scale, with a higher score indicating less healthy looking tissue. A grade is assigned based on the sum of the three scores. Combined scores of 3, 4, or 5 represent grade 1, a slower-growing cancer. Scores of 6 or 7 represent grade 2. Scores of 8 or 9 represent grade 3, a faster-growing, more aggressive cancer.
In addition to grading, tumor biopsy samples are now tested by immunohistochemistry to determine if the tissue contains the proteins estrogen receptor, progesterone receptor, or human epidermal growth factor receptor 2. Earlier ER and PR were quantified using standardized assays developed by New England Nuclear & Wittliff. Tumors containing either ER or PR are called "hormone receptor-positive" and can be treated with hormone therapies. Around 15 to 20% of tumors contain HER2; these can be treated with HER2-targeted therapies. The remainder that do not contain ER, PR, or HER2 are called "triple-negative" tumors, and tend to grow more quickly than other breast cancer types.
After the tumor is evaluated, the breast cancer case is staged using the American Joint Committee on Cancer and Union for International Cancer Control's TNM staging system. Scores are assigned based on characteristics of the tumor, lymph nodes, and any metastases. T scores are determine by the size and extent of the tumor. Tumors less than 2 centimeters across are designated T1. Tumors 2–5 cm across are T2. A tumor greater than 5 cm across is T3. Tumors that extend to the chest wall or to the skin are designated T4. N scores are based on whether the cancer has spread to nearby lymph nodes. N0 indicates no spread to the lymph nodes. N1 is for tumors that have spread to the closest axillary lymph nodes. N2 is for spread to the intramammary lymph nodes, or for axillary lymph nodes that appear attached to each other or to the tissue around them. N3 designates tumors that have spread to the highest axillary lymph nodes, to the supraclavicular lymph nodes, or to both the axillary and intramammary lymph nodes. The M score is binary: M0 indicates no evidence metastases; M1 indicates metastases have been detected.
TNM scores are then combined with tumor grades and ER/PR/HER2 status to calculate a cancer case's "prognostic stage group". Stage groups range from I to IV, with groups I, II, and III further divided into subgroups IA, IB, IIA, IIB, IIIA, IIIB, and IIIC. In general, tumors of higher T and N scores and higher grades are assigned higher stage groups. Tumors that are ER, PR, and HER2 positive are slightly lower stage group than those that are negative. Tumors that have metastasized are stage IV, regardless of the other scored characteristics.