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Deep Learning Technology: Sebastian Arnold, Betty van Aken, Paul Grundmann, Felix A. Gers and Alexander Löser. Learning Contextualized Document Representations for Healthcare Answer Retrieval. The Web Conference 2020 (WWW'20)
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Smoking tobacco appears to increase the risk of breast cancer, with the greater the amount smoked and the earlier in life that smoking began, the higher the risk. In those who are long-term smokers, the risk is increased 35% to 50%. A lack of physical activity has been linked to about 10% of cases. Sitting regularly for prolonged periods is associated with higher mortality from breast cancer. The risk is not negated by regular exercise, though it is lowered.
There is an association between use of hormonal birth control and the development of premenopausal breast cancer, but whether oral contraceptives use may actually cause premenopausal breast cancer is a matter of debate. If there is indeed a link, the absolute effect is small. Additionally, it is not clear if the association exists with newer hormonal birth controls. In those with mutations in the breast cancer susceptibility genes "BRCA1" or "BRCA2", or who have a family history of breast cancer, use of modern oral contraceptives does not appear to affect the risk of breast cancer.
The association between breast feeding and breast cancer has not been clearly determined; some studies have found support for an association while others have not. In the 1980s, the abortion–breast cancer hypothesis posited that induced abortion increased the risk of developing breast cancer. This hypothesis was the subject of extensive scientific inquiry, which concluded that neither miscarriages nor abortions are associated with a heightened risk for breast cancer.
A number of dietary factors have been linked to the risk for breast cancer. Dietary factors which may increase risk include a high fat diet, high alcohol intake, and obesity-related high cholesterol levels. Dietary iodine deficiency may also play a role. Evidence for fiber is unclear. A 2015 review found that studies trying to link fiber intake with breast cancer produced mixed results. In 2016 a tentative association between low fiber intake during adolescence and breast cancer was observed.
Other risk factors include radiation and shift-work. A number of chemicals have also been linked, including polychlorinated biphenyls, polycyclic aromatic hydrocarbons, and organic solvents Although the radiation from mammography is a low dose, it is estimated that yearly screening from 40 to 80 years of age will cause approximately 225 cases of fatal breast cancer per million women screened.
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. Evidence is not strong enough to support this procedure in anyone but those at the highest risk. BRCA testing is recommended in those with a high family risk after genetic counseling. It is not recommended routinely. This is because there are many forms of changes in "BRCA" genes, ranging from harmless polymorphisms to obviously dangerous frameshift mutations. The effect of most of the 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.
In some population studies moderate alcohol consumption is associated with increase the breast cancer risk.
In contrast, research by the Danish National Institute for Public Health, comprising 13,074 women aged 20 to 91 years, found that moderate drinking had virtually no effect on breast cancer risk.
Studies that control for screening incidence show no association with moderate drinking and breast cancer, e.g.. Moderate drinkers tend to screen more which results in more diagnoses of breast cancer, including mis-diagnoses. A recent study of 23 years of breast cancer screening in the Netherlands concluded that 50% of diagnoses were over-diagnoses.
Studies suggest that drinking alcohol during pregnancy may affect the likelihood of breast cancer in daughters. "For women who are pregnant, ingestion of alcohol, even in moderation, may lead to elevated circulating oestradiol levels, either through a reduction of melatonin or some other mechanism. This may then affect the developing mammary tissue such that the lifetime risk of breast cancer is raised in their daughters."
It occurs in all adult age groups. While the majority of patients are between 40 and 59 years old, age predilection is much less pronounced than in noninflammatory breast cancer. The overall rate is 1.3 cases per 100000, black women (1.6) have the highest rate, Asian and Pacific Islander women the lowest (0.7) rates.
Most known breast cancer risk predictors do not apply for inflammatory breast cancer. It may be slightly associated with cumulative breast-feeding duration.
Cancer affects approximately 1 in 1,000 pregnant women. The most common cancers found during pregnancy are the same as the most common cancers found in non-pregnant women during childbearing ages: breast cancer, cervical cancer, leukemia, lymphoma, melanoma, ovarian cancer and colorectal cancer.
Diagnosing a new cancer in a pregnant woman is difficult, in part because any symptoms are commonly assumed to be a normal discomfort associated with pregnancy. As a result, cancer is typically discovered at a somewhat later stage than average. Some imaging procedures, such as MRIs (magnetic resonance imaging), CT scans, ultrasounds and mammograms with fetal shielding are considered safe during pregnancy; some others, such as PET scans, are not.
Treatment is generally the same as for non-pregnant women. However, radiation and radioactive drugs are normally avoided during pregnancy, especially if the fetal dose might exceed 100 cGy. In some cases, some or all treatments are postponed until after birth if the cancer is diagnosed late in the pregnancy. Early deliveries are often used to advance the start of treatment. Surgery is generally safe, but pelvic surgeries during the first trimester may cause miscarriage. Some treatments, especially certain chemotherapy drugs given during the first trimester, increase the risk of birth defects and pregnancy loss (spontaneous abortions and stillbirths).
Elective abortions are not required and, for the most common forms and stages of cancer, do not improve the mother's survival. In a few instances, such as advanced uterine cancer, the pregnancy cannot be continued and in others, the patient may end the pregnancy so that she can begin aggressive chemotherapy.
Some treatments can interfere with the mother's ability to give birth vaginally or to breastfeed. Cervical cancer may require birth by Caesarean section. Radiation to the breast reduces the ability of that breast to produce milk and increases the risk of mastitis. Also, when chemotherapy is given after birth, many of the drugs appear in breast milk, which could harm the baby.
Some therapies for other forms of cancer increase the lifetime risk of endometrial cancer, which is a baseline 2–3%. Tamoxifen, a drug used to treat estrogen-positive breast cancers, has been associated with endometrial cancer in approximately 0.1% of users, particularly older women, but the benefits for survival from tamoxifen generally outweigh the risk of endometrial cancer. A one to two-year course of tamoxifen approximately doubles the risk of endometrial cancer, and a five-year course of therapy quadruples that risk. Raloxifene, a similar drug, did not raise the risk of endometrial cancer. Previously having ovarian cancer is a risk factor for endometrial cancer, as is having had previous radiotherapy to the pelvis. Specifically, ovarian granulosa cell tumors and thecomas are tumors associated with endometrial cancer.
Low immune function has also been implicated in endometrial cancer. High blood pressure is also a risk factor, but this may be because of its association with obesity. Sitting regularly for prolonged periods is associated with higher mortality from endometrial cancer. The risk is not negated by regular exercise, though it is lowered.
Smoking and the use of progestin are both protective against endometrial cancer. Smoking provides protection by altering the metabolism of estrogen and promoting weight loss and early menopause. This protective effect lasts long after smoking is stopped. Progestin is present in the combined oral contraceptive pill and the hormonal intrauterine device (IUD). Combined oral contraceptives reduce risk more the longer they are taken: by 56% after four years, 67% after eight years, and 72% after twelve years. This risk reduction continues for at least fifteen years after contraceptive use has been stopped. Obese women may need higher doses of progestin to be protected. Having had more than five infants (grand multiparity) is also a protective factor, and having at least one child reduces the risk by 35%. Breastfeeding for more than 18 months reduces risk by 23%. Increased physical activity reduces an individual's risk by 38–46%. There is preliminary evidence that consumption of soy is protective.
About one percent of breast cancer develops in males. It is estimated that about 2,140 new cases are diagnosed annually in the United States (US) and about 300 in the United Kingdom (UK). The number of annual deaths in the US is about 440 (for 2016 "but fairly stable over the last 30 years"). In a study from India, eight out of 1,200 (0.7%) male cancer diagnoses in a pathology review represented breast cancer. Incidence of male breast cancer has been increasing which raises the probability of other family members developing the disease. The relative risk of breast cancer for a female with an affected brother is approximately 30% higher than for a female with an affected sister. The tumor can occur over a wide age range, but typically appears in males in their sixties and seventies.
Known risk factors include radiation exposure, exposure to female hormones (estrogen), and genetic factors. High estrogen exposure may occur by medications, obesity, or liver disease, and genetic links include a high prevalence of female breast cancer in close relatives. Chronic alcoholism has been linked to male breast cancer. The highest risk for male breast cancer is carried by males with Klinefelter syndrome. Male BRCA mutation carriers are thought to be at higher risk for breast cancer as well, with roughly 10% of male breast cancer cases carrying BRCA2 mutations, and BRCA1 mutation being in the minority.
Cancer prevention is defined as active measures to decrease cancer risk. The vast majority of cancer cases are due to environmental risk factors. Many of these environmental factors are controllable lifestyle choices. Thus, cancer is generally preventable. Between 70% and 90% of common cancers are due to environmental factors and therefore potentially preventable.
Greater than 30% of cancer deaths could be prevented by avoiding risk factors including: tobacco, excess weight/obesity, poor diet, physical inactivity, alcohol, sexually transmitted infections and air pollution. Not all environmental causes are controllable, such as naturally occurring background radiation and cancers caused through hereditary genetic disorders and thus are not preventable via personal behavior.
Triple-negative breast cancer accounts for approximately 15%-25% of all breast cancer cases. The overall proportion of TNBC is very similar in all age groups. Younger women have a higher rate of basal or BRCA related TNBC while older women have a higher proportion of apocrine, normal-like and rare subtypes including neuroendocrine TNBC.
Among younger women, African American and Hispanic women have a higher risk of TNBC, with African Americans facing worse prognosis than other ethnic groups.
In 2009, a case-control study of 187 triple-negative breast cancer patients described a 2.5 increased risk for triple-negative breast cancer in women who used oral contraceptives (OCs) for more than one year compared to women who used OCs for less than one year or never. The increased risk for triple-negative breast cancer was 4.2 among women 40 years of age or younger who used OCs for more than one year, while there was no increased risk for women between the ages of 41 and 45. Also, as duration of OC use increased, triple-negative breast cancer risk increased.
Adjusted for age and stage the prognosis for breast cancer in males is similar to that in females. Prognostically favorable are smaller tumor size and absence or paucity of local lymph node involvement. Hormonal treatment may be associated with hot flashes and impotence.
The specific causes of DCIS are still unknown. The risk factors for developing this condition are similar to those for invasive breast cancer.
Some women are however more prone than others to developing DCIS. Women considered at higher risks are those who have a family history of breast cancer, those who have had their periods at an early age or who have had a late menopause. Also, women who have never had children or had them late in life are also more likely to get this condition.
Long-term use of estrogen-progestin hormone replacement therapy (HRT) for more than five years after menopause, genetic mutations (BRCA1 or BRCA2 genes), atypical hyperplasia, as well as radiation exposure or exposure to certain chemicals may also contribute in the development of the condition. Nonetheless, the risk of developing noninvasive cancer increases with age and it is higher in women older than 45 years.
Age distribution and relation to breastfeeding duration is suggestive of some sort of involvement of hormones in the aetiology, however significant differences exist compared to normal breast cancer.
Typically IBC shows low levels of estrogen and progesterone receptor sensitivity, corresponding with poor outcome. In cases with positive estrogen receptor status antihormonal treatment is believed to improve outcome.
Paradoxically some findings suggest that especially aggressive phenotypes of IBC are characterised by high level of NF kappaB target gene expression which can be - under laboratory conditions - successfully modulated by estrogen, but not by tamoxifen.
Breast cancer risk is elevated for defined fraction of lesions. Except for patients with a strong family history of breast cancer, where the risk is two-fold, nonproliferative lesions have no increased risk. Proliferative lesions also have approximately a 2-fold risk. In particular, atypical hyperplasia is associated with an increased risk of developing breast cancer. Atypical lobular hyperplasia is associated with the greatest risk, approximately 5-fold and especially high relative risk of developing premenopausal breast cancer. Atypical ductal hyperplasia is associated with 2.4-fold risk. In contrast, a New England Journal of Medicine article states that for women with a strong familial history of breast cancer, the risk of future breast cancer is roughly doubled, independent of histological status. The article further states "The relative risk of breast cancer for the cohort was 1.56 (95 percent confidence interval, 1.45 to 1.68), and this increased risk persisted for at least 25 years after biopsy. The relative risk associated with atypia was 4.24 (95 percent confidence interval, 3.26 to 5.41), as compared with a relative risk of 1.88 (95 percent confidence interval, 1.66 to 2.12) for proliferative changes without atypia and of 1.27 (95 percent confidence interval, 1.15 to 1.41) for nonproliferative lesions. The strength of the family history of breast cancer, available for 4808 women, was a risk factor that was independent of histologic findings. No increased risk was found among women with no family history and nonproliferative findings. In the first 10 years after the initial biopsy, an excess of cancers occurred in the same breast, especially in women with atypia."
It is not well understood whether the lesions are precursors of breast cancer or only indication of increased risk, for most types of lesions the chance of developing breast cancer is nearly the same in the affected and unaffected breast (side) indicating only coincidence of risk factors. For atypical lobular hyperplasia there is high incidence of ipsilateral breast cancers indicating a possible direct carcinogenetic link.
Most patients diagnosed with Paget's disease of the nipple are over age 50, but rare cases have been diagnosed in patients in their 20s. The average age at diagnosis is 62 for women and 69 for men. The disease is rare among both women and men.
One known cause of triple negative breast cancer is germline mutations. These are alterations within the heritable lineage that is being passed down to the offspring. 15% of TNBC can be traced back to germline mutations that are within the BRCA1 and BRCA2 genes (Song 2014). These genes were identified as high risk for triple negative due to their high predisposition for cancers of the breasts, ovaries, pancreas, and prostate (Pruss 2014). Changes or mutations in 19p13.1 and MDM4 loci have also been associated with triple negative breast cancer, but not other forms of breast cancer, thus triple negative tumors may be distinguished from other breast cancer subtypes by a unique pattern of common and rare germline alterations (Kristen 2013).
Alcohol use is associated with an increased risk of salivary gland cancer.
Alcohol is a risk factor for breast cancer in women.
A woman drinking an average of two units of alcohol per day has an 8% higher risk of developing breast cancer than a woman who drinks an average of one unit of alcohol per day. A study concluded that for every additional drink regularly consumed per day, the incidence of breast cancer increases by 11 per 1000. 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). Moderate to heavy consumption of alcoholic beverages (at least three to four drinks per week) is associated with a 1.3-fold increased risk of the recurrence of breast cancer. Further, consumption of alcohol at any quantity is associated with significantly increased risk of relapse in breast cancer survivors.
The presence of three factors for the prognosis has been suggested, whether there is a palpable mass of the disease, whether lymph nodes are positive and whether there is an underlying malignant cancer.
If there is none of these, the five- and 10-year survival is 85% and 80% respectively, with adjuvant chemotherapy even 95% and 90%. If there is a palpable mass, it is 32% and 31% respectively, with adjuvant chemotherapy (40% and 35%).
Positive lymph-nodes have been positively associated with a palpable mass and affect the prognosis to be now just 28% survival after 10 years (vs 79% without palpable mass and without affected lymph-nodes). Involvement of the lymph nodes does not directly cause any harm, but is merely an indicator of systemic spread.
Furthermore, patients with an identifiable associated underlying breast tumor have a survival rate of 38-40% at five years and a survival rate of 22-33% at 10 years. The death rate of metastatic breast carcinoma in patients with mammary Paget's disease and underlying cancer is 61.3%, with a 10-year cumulative survival rate of 33%.
Among women worldwide, breast cancer is the most common cause of cancer death. Breast self-examination (BSE) is an easy but unreliable method for finding possible breast cancer. Factors that appear to be implicated in decreasing the risk of, early diagnosis of. or recurrence of breast cancer are regular breast examinations by health care professionals, regular mammograms, self-examination of breasts, healthy diet, and exercise to decrease excess body fat.
80% of cases in the United States are diagnosed by mammography screening.
Most people with cancer of unknown primary origin have widely disseminated and incurable disease, although a few can be cured through treatment. With treatment, typical survival with CUP ranges from 6 to 16 months. Survival rates are lower in cases with visceral metastatic disease, ranging from 6 to 9 months. Survival rates are higher when the cancer is more limited to lymph nodes, pleura, or peritoneal metastasis, which ranges from 14 to 16 months. Long-term prognosis is somewhat better if a particular source of cancer is strongly suggested by clinical evidence.
Metastatic breast cancer, also referred to as metastases, advanced breast cancer, secondary tumours, secondaries or stage 4 breast cancer, is a stage of breast cancer where the disease has spread to distant sites beyond the axillary lymph nodes. There is no cure for metastatic breast cancer. There is no stage after IV.
It usually occurs several years after the primary breast cancer, although it is sometimes diagnosed at the same time as the primary breast cancer or, rarely, before the primary breast cancer has been diagnosed.
Metastatic breast cancer cells frequently differ from the preceding primary breast cancer in properties such as receptor status. The cells have often developed resistance to several lines of previous treatment and have acquired special properties that permit them to metastasize to distant sites. Metastatic breast cancer can be treated, sometimes for many years, but it cannot be cured. Distant metastases are the cause of about 90% of deaths due to breast cancer.
Breast cancer can metastasize anywhere in body but primarily metastasizes to the bone, lungs, regional lymph nodes, liver and brain, with the most common site being the bone. Treatment of metastatic breast cancer depends on location of the metastatic tumours and includes surgery, radiation, chemotherapy, biological, and hormonal therapy.
Typical environmental barriers in a metastatic event include physical (a basement membrane), chemical (reactive oxygen species or ROS, hypoxia and low pH) and biological (immune surveillance, inhibitory cytokines and regulatory extra-cellular matrix (ECM) peptides) components. Organ-specific anatomic considerations also influence metastasis; these include blood-flow patterns from the primary tumor and the homing ability of cancer cells to certain tissues. The targeting by cancer cells of specific organs is probably regulated by chemo-attractant factors and adhesion molecules produced by the target organ, along with cell-surface receptors expressed by the tumor cells.
Roughly 70% of all patients living with advanced breast cancer have bone metastases. Very often bone metastases can be successfully managed for a long time.