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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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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.
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.
The relative risk of breast cancer based on a median follow-up of 8 years, in a case control study of US registered nurses, is 3.7.
80% of cases in the United States are diagnosed by mammography screening.
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.
The exact cause of VIN is unknown. Studies are being done to determine the cause of VIN. The following factors have been associated with VIN:
- HPV (Human Papilloma Virus)
- HSV-2 (Herpes simplex Virus - Type 2)
- Smoking
- Immunosuppression
- Chronic vulvar irritation
- Conditions such as Lichen Sclerosus
In breast pathology, a radial scar of the breast, formally radial scar of the breast, is a benign breast lesion that can radiologically mimic malignancy, i.e. cancer.
Radial scar is associated with atypia and/or malignancy and may be an independent risk factor for the development of carcinoma in either breast.
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.
Vaccinating girls with HPV vaccine before their initial sexual contact has been claimed to reduce incidence of VIN.
Fibrosclerosis of the breast is most frequently used to mean sclerosing lobular adenosis of the breast. It is not well known if it is related to non-sclerosing adenosis of the breast (which is normally classified as fibrocystic breast changes) and unlike this it is believed to be correlated with an elevated risk of breast cancer.
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.
The rate at which breast cancer (ductal carcinoma in situ "or" invasive mammary carcinoma (all breast cancer except DCIS and LCIS)) is found at the time of a surgical (excisional) biopsy, following the diagnosis of ADH on a core (needle) biopsy varies considerably from hospital-to-hospital (range 4-54%). In two large studies, the conversion of an ADH on core biopsy to breast cancer on surgical excision, known as "up-grading", is approximately 30%.
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%.
Because Cowden syndrome can be difficult to diagnose, the exact prevalence is unknown; however, it probably occurs in at least 1 in 200,000 people.
A 2010 review of 211 patients (21 from one center, and the remaining 190 from the external literature) studied the risks for cancer and Lhermitte-Duclos disease in Cowden syndrome patients.
The cumulative lifetime (age 70 years) risks were 89% for any cancer diagnosis (95% confidence interval (CI) = 80%,95%), breast cancer [female] 81% (CI = 66%,90%), LDD 32% (CI = 19%,49%), thyroid cancer 21% (CI = 14%,29%), endometrial cancer 19% (CI = 10%,32%) and renal cancer 15% (CI = 6%,32%). A previously unreported increased lifetime risk for colorectal cancer was identified (16%, CI = 8%,24%). Male CS patients had fewer cancers diagnosed than female patients and often had cancers not classically associated with CS.
Risk factors can be divided into two categories:
- "modifiable" risk factors (things that people can change themselves, such as consumption of alcoholic beverages), and
- "fixed" risk factors (things that cannot be changed, such as age and biological sex).
The primary risk factors for breast cancer are being female and older age. Other potential risk factors include genetics, lack of childbearing or lack of breastfeeding, higher levels of certain hormones, certain dietary patterns, and obesity. Recent studies have indicated that exposure to light pollution is a risk factor for the development of breast cancer.
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.
Endometrial hyperplasia is a condition of excessive proliferation of the cells of the endometrium, or inner lining of the uterus.
Most cases of endometrial hyperplasia result from high levels of estrogens, combined with insufficient levels of the progesterone-like hormones which ordinarily counteract estrogen's proliferative effects on this tissue. This may occur in a number of settings, including obesity, polycystic ovary syndrome, estrogen producing tumours (e.g. granulosa cell tumour) and certain formulations of estrogen replacement therapy. Endometrial hyperplasia is a significant risk factor for the development or even co-existence of endometrial cancer, so careful monitoring and treatment of women with this disorder is essential.
Radial scars are diagnosed by a microscopic examination of excised tissue, i.e. they are diagnosed by pathologists based on their histomorphology.
Although the synergistic effect of alcohol with smoking in the development of oral cancer is beyond doubt, there is no clear evidence that alcohol is involved in the development of leukoplakia, but it does appear to have some influence. Excessive use of a high alcohol containing mouth wash (> 25%) may cause a grey plaque to form on the buccal mucosa, but these lesions are not considered true leukoplakia.
Atypical hyperplasia is a high-risk premalignant lesion of the breast. It is believed that atypical ductal hyperplasia (ADH) is a direct precursor for low-grade mammary ductal carcinoma, whereas atypical lobular hyperplasia (ALH) serves as a risk indicator.
Tobacco smoking or chewing is the most common causative factor, with more than 80% of persons with leukoplakia having a positive smoking history. Smokers are much more likely to suffer from leukoplakia than non-smokers. The size and number of leukoplakia lesions in an individual is also correlated with the level of smoking and how long the habit has lasted for. Other sources argue that there is no evidence for a direct causative link between smoking and oral leukoplakia. Cigarette smoking may produce a diffuse leukoplakia of the buccal mucosa, lips, tongue and rarely the floor of mouth. Reverse smoking, where the lit end of the cigarette is held in the mouth is also associated with mucosal changes. Tobacco chewing, e.g. betel leaf and areca nut, called paan, tends to produce a distinctive white patch in a buccal sulcus termed "tobacco pouch keratosis". In the majority of persons, cessation triggers shrinkage or disappearance of the lesion, usually within the first year after stopping.
Atypical hyperplasia is a benign (noncancerous) cellular hyperplasia in which cells show some atypia. In this condition, cells look abnormal under a microscope and are increased in number.
There are usually no adverse side effects to this condition. In almost all cases it subsides after menopause. A possible complication arises through the fact that cancerous tumors may be more difficult to detect in women with fibrocystic changes.
Some of the more commonly known clinical forms of hyperplasia, or conditions leading to hyperplasia, are:
- Benign prostatic hyperplasia, also known as prostate enlargement.
- Cushing's disease – Physiopathology of hyperplasia of adrenal cortex due to increased circulating level of ACTH (adrenocorticotropic hormone).
- Congenital adrenal hyperplasia – Inherited disorder of gland (adrenal).
- Endometrial hyperplasia – Hyperproliferation of the endometrium, usually in response to unopposed estrogen stimulation in the setting of polycystic ovary syndrome or exogenous administration of hormones. Atypical endometrial hyperplasia may represent an early neoplastic process which can lead to endometrial adenocarcinoma. The development of endometrial adenocarcinoma from endometrial hyperplasia is a typical example of how the effects of pathologic hyperplasia can lead to neoplasia, and females who exhibit hyperplasia of the endometrium are indeed more likely to develop cancer of these cells.
- Hemihyperplasia when only half (or one side) of the body is affected, sometimes generating limbs of different lengths.
- Hyperplasia of the breast – "Hyperplastic" lesions of the breast include "usual ductal hyperplasia", a focal expansion of the number of cells in a terminal breast duct, and "atypical ductal hyperplasia", in which a more abnormal pattern of growth is seen, and which is associated with an increased risk of developing breast cancer.
- Intimal hyperplasia – The thickening of the tunica intima of a blood vessel as a complication of a reconstruction procedure or endarterectomy. Intimal hyperplasia is the universal response of a vessel to injury and is an important reason of late bypass graft failure, particularly in vein and synthetic vascular grafts.
- Focal epithelial hyperplasia (also known as Heck's disease) – This is a wart-like growth in the mucous tissues of the mouth or, rarely, throat that is caused by certain sub-types of the human papillomavirus (HPV). Heck's disease has not been known to cause cancer.
- Sebaceous hyperplasia – In this condition, small yellowish growths develop on the skin, usually on the face. This condition is neither contagious nor dangerous.
- Compensatory liver hyperplasia – The liver undergoes cellular division after acute injury, resulting in new cells that restore liver function back to baseline. Approximately 75% of the liver can be acutely damaged or resected with seemingly full regeneration through hepatocyte division, i.e., hyperplasia. This is what makes living-donor liver transplants possible.
In medicine, desmoplasia is the growth of fibrous or connective tissue. It is also called desmoplastic reaction to emphasize that it is secondary to an insult. Desmoplasia may occur around a neoplasm, causing dense fibrosis around the tumor, or scar tissue (adhesions) within the abdomen after abdominal surgery.
Desmoplasia is usually only associated with malignant neoplasms, which can evoke a fibrosis response by invading healthy tissue. Invasive ductal carcinomas of the breast often have a scirrhous, stellate appearance caused by desmoplastic formations.