Treatments for Hormone Sensitive Breast Cancer

Treatments for internal secretion Sensitive Breast CancerRae BrozOestrogen inhibiting Tamoxifen Citrate an Antineoplastic Agent used to Treat Hormone Sensitive Breast CancerThe Hormone Oestrogen (E) fuels female breast growth production at puberty. Within the breast of mature women, in that respect atomic number 18 milk ducts called lobes which branch out to form lobules or acinus. Together, these be called the margeinal lobular unit (TDLU) (Bullock, 2013, pp. 917-918).Due to the various hormonal cycles that happen during a charrs lifetime including, but not limited to child birth, Oestrogen and Progesterone levels are continuously fluctuating causing constant remodelling of the breast tissue. For example, full stop causes the breast tissue to become increasingly vascular and encourages acinar tissue and ductal growth. Ancinar tissue converts to secretory glands through the release of progesterone at the luteal order of the menstrual cycle. At this stage the terminal ducts a re also dilated. (Craft. J, 2011, p. 951)Mitotic stem cell division is increased within the TDLU during these stages lead-in to the development and renewal of the epithelial lining, increasing the chance of cell mutations in the TDLU an area where the majority of breast cancer (BC) occur (Craft. J, 2011, p. 983). Studies show a positive sign of hormone cutting BC is the increased amount of Oestrogen receptors (ER). The more Ers in the affected cells, the greater affinity with E, therefore cell reproduction rises, leading to faster BC cell replication (Patani, 2014).A benign tumor within the breast will remain localized and closely resembles normal epithelial tissue cells within the tissue. Growth is at a slow rate within the TDLU, unlike a malignant (cancerous) tumor. The malignant tumor grows rapidly differentiating from the normal epithelial cell. It invades other tissue space and nearby blood and lymph vessels explaining why BCs easily spread into the lymphatic system and oth er areas of the reproductive system.Risk factors affecting hormone sensitive breast cancer development in women are Post-menopausal obesity and the womans age at the birth of her first child, as connections in the midst of older mothers and obese post-menopausal women to ER positive BC have been discovered (Yager Davidson, 2006).Tamoxifen Citrate (Trans-1-4- (2-dimethylaminoethoxy) phenyl 1, 2 -diphenyl-1 butene) is a non-steroidal drug and an antineoplastic agent called a selective estrogen receptor modulator (SERM) (Marrero-Alonso et al., 2013). It is recommended as part of the treatment of hormone sensitive breast cancer due to its affinity with ER acting as an antagonist to E, slowing cell division within the breast consequently stopping the progression of the BC (Bryant, 2011, p. 822).Tamoxifen is given orally, absorbed in the gastro enteral tract and metabolized in the liver by the enzymes CYP-450, 2D6 and 2C9. (Mandlekar, 2000 20) Metabolites, produced are the ER receptor binding 4-hydroxytamoxifen (OHT) and N-desmethyltamoxifen (DMT). Both have anti Oestrogen affects very close to their farm drug and cause apoptosis of BC cells. After dosing, various serum levels of Tamoxifen and metabolites were found within the lungs, liver ovaries and the endometrium and corpes luteum of the uterus, also in metastases within the promontory and pancreas ( health Communication, 2004). Levels peak in about 3-6hours post a 10mg dose and reach a steady state around 4 weeks of therapy. They bind to albumin and are excreted mainly in the faeces so have a long half-life 5-7 days for Tamoxifen and 10-14 days for DMT (Health Communication, 2004).Due to the metabolism of Tamoxifen and its metabolites, there is a risk of serum accumulation in prolonged treatment and or patients with poor hepatic function dosing regimens major need intermittent appointment according to serum level findings. (Health Communication, 2004). Phenytoin lowers Tamoxifen metabolism and should ther efore not be used concurrently with Tamoxifen for extended periods of time unless a therapeutic drug (Endoxifen) monitoring strategy is utilized as Tamoxifen will lose effectiveness. (Gryn, Teft, Kim, 2014).It has been found that Tamoxifen treatment in postmenopausal women is near in reducing calcium loss by reducing apoptosis of osteoclasts thus sustaining bone density (Nakamura et al., 2007). This unfortunately is not the case in premenopausal women in these cases osteoporosis is often increased with the use of Tamoxifen, dependent on whether chemotherapy had caused amenorrhea or not (Vehmanen, Elomaa, Blomqvist, Saarto, 2006).Tamoxifen use has been linked to increased episodes of deep nervure thrombosis (VTE) in women using the drug in breast cancer prevention treatment (Decensi et al., 2005). Finally patients receiving Tamoxifen treatment for breast cancer long term ( five years) are at greater risk of mortality from endometrial cancer than those who did not receive Tamoxif en (Jones et al., 2012). say count 687ReflectionI hope I have created a better assignment this time round. I found the tutorial held on the 29/4/2014 very stabilizing as was the typed feedback sheet. I printed the latter out and sat it beside me while I typed out my assignment, along with the rubric and learning outcomes from the subject outline, referring to them often. The handwritten feedback was a diminished harder to decipher but I managed ok. My suggestion would be to type in an alternate colour e.g. Red for the feedback remarks on the actual assignment. I have learnt a lot from this assignment both about the subject and myself. I have incorporated more information into this assignment and have not included any quotes or paraphrasing from any of the texts I have used. The only similarities shown in turnitin were from my previous assignment. I have to say even with the setback I have enjoyed it.Word count 151ReferencesBryant, B. a. K., K. (2011). Pharmacology for health prof essionals. Chatswood, NSW, Australia Elsevier.Bullock, S. a. H., Majella. (2013). Principles of Pathophysiology. Frechs Forest, NSW, Australia Pearson.Craft. J, G. C. a. t. A. (2011). Understanding Pathophysiology. Chatswood, NSW, Australia Elsevier.Decensi, A., Maisonneuve, P., Rotmensz, N., Bettega, D., Costa, A., Sacchini, V., . . . Veronesi, U. (2005). Effect of tamoxifen on venous thromboembolic events in a breast cancer prevention trial. Circulation, 111(5), 650-656. inside 10.1161/01.cir.0000154545.84124.acGryn, S. E., Teft, W. A., Kim, R. B. (2014). overweight reduction in the tamoxifen active metabolite endoxifen in a patient on phenytoin for epilepsy compared with a CYP2D6 genotype matched cohort. Pharmacogenetics and Genomics, Publish Ahead of Print, 10.1097/FPC.0000000000000051.Health Communication, N. (2004). MIMS Online. from Health Communication NetworkJones, M., van Leeuwen, F., Hoogendoorn, W., Mourits, M., Hollema, H., van Boven, H., . . . Swerdlow, A. (2012). En dometrial cancer survival after breast cancer in relation to tamoxifen treatment Pooled results from trey countries. Breast Cancer Research, 14(3), R91.Marrero-Alonso, J., Morales, A., Garca Marrero, B., Boto, A., Marn, R., Cury, D., . . . Daz, M. (2013). Unique SERM-like properties of the novel fluorescent tamoxifen derivative FLTX1. European Journal of Pharmaceutics and Biopharmaceutics, 85(3, Part B), 898-910. doi http//dx.doi.org/10.1016/j.ejpb.2013.04.024Nakamura, T., Imai, Y., Matsumoto, T., Sato, S., Takeuchi, K., Igarashi, K., . . . Kato, S. (2007). Estrogen prevents bone loss via estrogen receptor alpha and induction of Fas ligand in osteoclasts. Cell, 130(5), 811-823. doi 10.1016/j.cell.2007.07.025Patani, N. a. M. L. A. (2014). Understanding response and resistance to oestrogen deprivation. Molecular and cellular Endocrinology, Volume 382(1), 683-894.Vehmanen, L., Elomaa, I., Blomqvist, C., Saarto, T. (2006). Tamoxifen treatment after adjuvant chemotherapy has opposite e ffects on bone mineral density in premenopausal patients depending on menstrual status. J Clin Oncol, 24(4), 675-680. doi 10.1200/jco.2005.02.3515Yager, J. D., Davidson, N. E. (2006). Estrogen Carcinogenesis in Breast Cancer. New England Journal of Medicine, 354(3), 270-282. doi doi10.1056/NEJMra050776