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 ===== ETIOLOGY ===== ===== ETIOLOGY =====
-The exact causes ​of breast cancer ​are unknown; however, what we know for sure is that the disease ​is caused by damage to a cell’s DNA (cite). In addition, ​certain risk factors make some women more likely than others to develop breast cancer. Many of these factors can be controlled, such as a person’s diet and whether or not they smoke and/or consume high levels of alcohol. ​Although higher alcohol consumption is seen to be associated with increased risk of breast cancer (Newcomb, 2013), studies have shown that an individual consuming ​moderate intake of alcohol before and/or after diagnosis experienced better survival than non-drinkers (Newcomb2013). Yetalcohol consumption and breast cancer ​observations are varied in each study; ​in some studies, the risk of breast cancer from consuming about two or more drinks per day (>24g) compared to non-drinkers is higher; a lighter alcohol intake is associated with a weaker risk of breast cancer, and moderate and heavy drinking both contribute to greater risks of developing the disease than that of non-drinkers ​(Longnecker1988). Thus, studies can show conflicting results when it comes to alcohol consumption and breast cancer risk.+The exact aetiology ​of breast cancer ​is unknown; however, what scientists ​know for sure is that it is caused by some damage to a cell’s DNA (National Breast Cancer, 2016). It is also known that there are certain risk factors ​that make some women more likely than others to develop breast cancer. Many of these factors can be controlled, such as a person’s diet and whether or not they smoke and/or consume high levels of alcohol. ​Consuming ​diet high in fats for exampleespecially trans fatscan induce ​breast cancer in some individualsas these fats promote free radicals that can damage DNA and mutate cells (Farvid et al.2016). 
  
-Furthermore,​ women that are taking hormones or using contraceptives like birth control put themselves at a higher risk of developing breast cancer (cite). Hormones that can be taken include progesterone and estrogen; where estrogen can be taken by itself or together with progesterone or progestin (a synthetic hormone that mimics effects of progesterone) (cite). Some studies have shown that women taking hormones like these had a higher chance of developing breast cancer than women that are not using this form of treatment (Chlebowski,​ 2008). 
  
-Other modifiable risk factors are associated with an individual’s ​exercise habits and weightas obesity puts an individual at a higher risk of becoming diagnosed with the disease ​(cite). +It is also essential for individuals that smoke to change their smoking habits. Smoking does not only damage ​an individual’s ​lungs but it also increases blood clot risks when taking exogenous hormones (Breast Cancer2014). As well, smoking cigarettes are seen to cause high levels ​of toxic material accumulation in the breast tissue. A study by Gaudet et al. assessed the effects of tobacco smoke in lab rodents and found that at least 20 lipophilic chemical compounds contained in cigarettes induced tumours in mammary adipose tissues, which can have similar effects in humans ​(2013).
  
-Unfortunately,​ some risk factors cannot be controlled, such as an individual’s age, including the age at which they get their first menstruation and the age they reached menopause. Genetics plays a role as well, as some abnormal genes are known to predispose an individual to breast cancer. These include BRCA1 and BRCA2 (Breast cancer gene 1 and 2 respectively),​ and they put carriers at a 65-85% chance of developing breast cancer by the age of 70 (cite). 
  
-Breast density is another contributing factoras women with denser breasts have a higher ​chance ​of developing ​breast cancer (cite). Breasts that have more duct and glandular tissue and less fatty tissue ​are considered to be more dense. When doctors look at x-rays like mammogramsdenser breasts make them harder to read and thus making it harder ​to detect any tumors ​(see Figure ) (cite). In this way, denser breasts pose a greater risk of having ​breast cancer.+In terms of alcohol consumptionalthough ​higher ​intakes are seen to be associated with increased risk of breast cancer, studies have shown that an individual consuming a moderate intake of alcohol before and/or after diagnosis experienced better survival than non-drinkers ​(Newcomb, 2013). Yet, alcohol consumption ​and breast cancer observations ​are varied in each study; in some studies, the risk of breast cancer from consuming about two or more drinks per day (>24g) compared to non-drinkers is higher; a lighter alcohol intake is associated with a weaker risk of breast cancer, and moderate and heavy drinking both contribute ​to greater risks of developing the disease than that of non-drinkers ​(Longnecker, 1988). In this way, comparing studies regarding alcohol consumption and breast cancer ​risk show inconclusive results.
  
-Similarly, individuals with a history of breast cancer, higher ​estrogen ​levels, as well as more environmental exposure to carcinogens also have a higher risk of developing the disease ​(cite). Environmental carcinogen exposure may play a role in breast cancer development as breast anatomy makes them a susceptible target for chemical carcinogens (Li, 1996). A study by Li et all showed that the total aromatic DNA adduct levels are higher in adjacent tissues of breast cancer patients (individuals with 100% risk of having breast cancer) than the levels ​are in normal breast tissue of participants without the disease (Li, 1996). ​+ 
 +Furthermore,​ women that are taking hormones or using contraceptives like birth control put themselves at a higher risk of developing breast cancer than non-users (Chlebowski,​ 2009). Estrogen is shown to facilitate cell proliferation and high levels of estrogen can aid in the spreading of cancerous cells if the hormone binds to a mutated cell receptor (Kaczmarczyk,​ 2015). Exogenous hormones that can be taken include progesterone and estrogen; where estrogen can be taken by itself or together with progesterone or progestin (a synthetic hormone that mimics effects of progesterone) (Kaczmarczyk,​ 2015). These hormones are similar to, but not exact in, chemical composition to the hormones an individual produces naturally, thus different users may experience different side effects. Some studies have shown that women on certain hormone therapies like these had a higher chance of developing breast cancer than women that are not using these forms of treatment (Chlebowski,​ 2008).  
 + 
 + 
 +Other modifiable risk factors are associated with an individual’s exercise habits and weight, as obesity puts an individual at a higher risk of becoming diagnosed with the disease (National Cancer Institute, 2009). Estrogen can be produced in fat tissues, so the more fatty tissue an individual has, the more estrogen they will produce.  
 + 
 + 
 +Unfortunately,​ some risk factors cannot be controlled, such as an individual’s age. Girls that reach menarche at a young age (<12 years old), and women that reach menopause at a late age (>55 years old) are at higher risk of developing the disease as they produce more estrogen during their lifespan (National Breast Cancer, 2016). Genetics plays a role as well, as mutations in some genes are known to predispose an individual to breast cancer. These include BRCA1 and BRCA2 (Breast cancer gene 1 and 2 respectively),​ and they put carriers at a 65-85% chance of developing breast cancer by the age of 70 (da Silva, 2015).  
 + 
 + 
 +Breast density is another contributing factor, as women with denser breasts have a higher chance of developing breast cancer (American Cancer Society, 2016). Breasts that have more duct and lobular tissue and less fatty tissue are considered to be “more dense.” When doctors look at x-rays like mammograms, dense breasts make them harder to read and thus harder to locate any tumors (see Figure 4) (American Cancer Society, 2016). Thus, denser breasts pose a greater risk of having breast cancer.  
 + 
 + 
 +Similarly, individuals with a history of breast cancer, higher ​endogenous sex hormone ​levels, as well as more environmental exposure to carcinogens also have a higher risk of developing the disease. Environmental carcinogen exposure may play a role in breast cancer development as the breast anatomy makes breasts ​a susceptible target for chemical carcinogens (Li, 1996). A study by Li et al. showed that the total aromatic DNA adduct levels are higher in adjacent tissues of breast cancer patients (individuals with 100% risk of having breast cancer) than are the levels in normal breast tissue of participants without the disease (Li, 1996). ​Thus, all these risk factors contribute in increasing the likelihood of some individuals getting breast cancer over others. ​  
 + 
 + 
 +<box 45% round | > {{:​screen_shot_2017-02-02_at_11.40.17_pm.png|}} </box| Figure 4 - Breast Less Dense vs Extremely Dense 
 +Retrieved from: Breast Density and Your Mammogram Report. (n.d.). https://​www.cancer.org/​cancer/​breast-cancer/​screening-tests-and-early-detection/​mammograms/​breast-density-and-your-mammogram-report.html http://​dx.doi.org/​10.1158/​1055-9965.epi-15-0535>​
  
  
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-<box 80% round| > {{:​f1.large1.jpg|}} </box| Figure ​- PTEN Pathway and Mutations Retrieved from: http://​theoncologist.alphamedpress.org/​content/​16/​suppl_1/​12/​F1.expansion>​+<box 80% round| > {{:​f1.large1.jpg|}} </box| Figure ​- PTEN Pathway and Mutations Retrieved from: http://​theoncologist.alphamedpress.org/​content/​16/​suppl_1/​12/​F1.expansion>​
  
  
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 Figure shows the various types of abnormalities that can result from abnormal cell growth. Ductal hyperplasia contains lesions in the breast that are not cancerous but have active growth and division in the breast tissue cells. Atypical Ductal Hyperplasia and Ductal Carcinoma In Situ (DCIS) occurs when breast tissue is beginning to take an abnormal appearance, however the abnormal cells are still localized in within the tissue. In DCIS-microinvasion and Invasive ductal cancer, the excessive cell growth spreads outside of the tissue and invades other areas of the body (Hüsemann et al., 2008). Figure shows the various types of abnormalities that can result from abnormal cell growth. Ductal hyperplasia contains lesions in the breast that are not cancerous but have active growth and division in the breast tissue cells. Atypical Ductal Hyperplasia and Ductal Carcinoma In Situ (DCIS) occurs when breast tissue is beginning to take an abnormal appearance, however the abnormal cells are still localized in within the tissue. In DCIS-microinvasion and Invasive ductal cancer, the excessive cell growth spreads outside of the tissue and invades other areas of the body (Hüsemann et al., 2008).
  
-<box 40% round| > {{:​untitled_copy.jpg|}} </box| Figure ​- Type of Abnormalities. (Da Silva, R. (2015) Module 3 Lecture 2: Breast Cancer[PowerPoint Slides]. ​ Retrieved from McMaster University Health and Disease)>​+<box 40% round| > {{:​untitled_copy.jpg|}} </box| Figure ​- Type of Abnormalities. (Da Silva, R. (2015) Module 3 Lecture 2: Breast Cancer[PowerPoint Slides]. ​ Retrieved from McMaster University Health and Disease)>​
  
  
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 Future treatments are underway. These specific treatments are called target therapies and are a group of drugs which target specific changes in genes of cancer cells, a preventative measure in cancer cell proliferation. Some of these target therapies include PARP inhibitors. PARP inhibitors target the BRCA mutations (American Cancer Society, 2016). These target drugs have shown success in some types of breast cancers and are further being studies to determine exactly when these drugs have their highest potential to be helpful in treatment. Another target therapy in current research is anti-angiogenesis drugs, which refers to the blocking process of angiogenesis. Fast growing cancer cells require blood cells to nourish their cell bodies. Therefore preventing the proliferation and rapid growth of the cancer cells, blocking angiogenesis may be helpful in slowing down the disease (American Cancer Society, 2016). Future treatments are underway. These specific treatments are called target therapies and are a group of drugs which target specific changes in genes of cancer cells, a preventative measure in cancer cell proliferation. Some of these target therapies include PARP inhibitors. PARP inhibitors target the BRCA mutations (American Cancer Society, 2016). These target drugs have shown success in some types of breast cancers and are further being studies to determine exactly when these drugs have their highest potential to be helpful in treatment. Another target therapy in current research is anti-angiogenesis drugs, which refers to the blocking process of angiogenesis. Fast growing cancer cells require blood cells to nourish their cell bodies. Therefore preventing the proliferation and rapid growth of the cancer cells, blocking angiogenesis may be helpful in slowing down the disease (American Cancer Society, 2016).
-<box 75% round| > {{:​3qtgdv.jpg|}} </box| Figure ​-  (Zetter, 2008)>+<box 75% round| > {{:​3qtgdv.jpg|}} </box| Figure ​-  (Zetter, 2008)>
  
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 Berns, K., Horlings, H. M., Hennessy, B. T., Madiredjo, M., Hijmans, E. M., Beelen, K., ... & Beijersbergen,​ R. L. (2007). A functional genetic approach identifies the PI3K pathway as a major determinant of trastuzumab resistance in breast cancer. Cancer cell, 12(4), 395-402. Berns, K., Horlings, H. M., Hennessy, B. T., Madiredjo, M., Hijmans, E. M., Beelen, K., ... & Beijersbergen,​ R. L. (2007). A functional genetic approach identifies the PI3K pathway as a major determinant of trastuzumab resistance in breast cancer. Cancer cell, 12(4), 395-402.
 +
 +Breast Density and Your Mammogram Report. (n.d.). Retrieved January 25, 2017, from https://​www.cancer.org/​cancer/​breast-cancer/​screening-tests-and-early-detection/​mammograms/​breast-density-and-your-mammogram-report.html
  
 Canadian Cancer Society. (2017). Retrieved January 26, 2017, from http://​www.cancer.ca/​ Canadian Cancer Society. (2017). Retrieved January 26, 2017, from http://​www.cancer.ca/​
 +
 +Causes of Breast Cancer :: The National Breast Cancer Foundation. Retrieved January 24, 2017, from http://​www.nationalbreastcancer.org/​causes-of-breast-cancer
 +
 +Chlebowski RT, Kuller LH, Prentice RL, et al. Breast cancer after use of estrogen plus progestin in postmenopausal women. New England Journal of Medicine 2009; 360(6):​573–587
  
 Da Silva, R. (2015) Module 3 Lecture 2: Breast Cancer[PowerPoint Slides]. ​ Retrieved from McMaster University Health and Disease. ​ Da Silva, R. (2015) Module 3 Lecture 2: Breast Cancer[PowerPoint Slides]. ​ Retrieved from McMaster University Health and Disease. ​
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 DeSantis, C., Bray, F., Ferlay, J., Lortet-Tieulent,​ J., Anderson, B., & Jemal, A. (2015). International Variation in Female Breast Cancer Incidence and Mortality Rates. Cancer Epidemiology Biomarkers & Prevention, 24(10), 1495-1506. http://​dx.doi.org/​10.1158/​1055-9965.epi-15-0535 DeSantis, C., Bray, F., Ferlay, J., Lortet-Tieulent,​ J., Anderson, B., & Jemal, A. (2015). International Variation in Female Breast Cancer Incidence and Mortality Rates. Cancer Epidemiology Biomarkers & Prevention, 24(10), 1495-1506. http://​dx.doi.org/​10.1158/​1055-9965.epi-15-0535
 +
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 +
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