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Discuss the hormonal influences on breast tissue during the normal menstrual cycle. Why is this important when scheduling a breast MRI? (max 500 words)
During puberty, breast tissue is hormonally controlled. Paracrine and endocrine hormones affect normal as well as neoplastic breast tissues. The issue of whether the breast tissue experiences morphological changes in the course of menstruation has been controversial. However, the late twentieth century studies have reflected conclusively that cyclical alterations occur within the breast lobules, stroma, and ducts. Clinically, the transformations manifest through modifications in consistency and size of the breast (Ellis, 2009). Cyclic expression of ER and d PR for estrogen and progesterone receptors respectively in normal breast tissue has been noted in varying phases during the normal menstrual cycle causing fibrocystic breast changes.
From research, it is affirmed that estrogen and progesterone have a huge impact on breast epithelium. Breast cancer cells depict a higher frequency in the expression of PR and ER ads compared to normal cells. It is fascinating that postmenopausal women with breast cancer reflect an increased frequency in ER and PR expression, as compared to premenopausal women indicating a likely hormonal stimulus (Ramakrishnan, 2002). Currently, breast tissues are examined particularly in premenopausal women who are not under hormonal therapy or oral contraceptives and morphologically assessed to determine the menstrual cycle stage they are in.
Normal breast tissue is hormonally responsive and modifies in the course of the menstrual cycle, which has an impact on breast morphology, cell kinetics as well as protein expression. Therefore, morphological breast dating is crucial for women to gather information on histological changes the breast tissue undergoes as hormones fluctuate (Croyle & Botkin, 2006). This could help to formulate cycle-matched subsets when conducting epidemiological research concerning the risks of breast cancer. Besides, it would offer a prognostic advantage for surgical patients in the luteal half of the menstrual cycle.
From research, it has been indicated that scans conducted at the time of follicular phase i.e. 3rd-14th day of the usual 28-day cycle lessened tissue augmentation because of hormonal variations. Perimenopausal women having regular menstruation, her menstrual history allows timely directions to conduct appropriate MRI exams. All the same, some females, have no regular cyclical menses to offer appropriate timing for MRI such as perimenopausal women who have done hysterectomy but have usual operational ovaries, those under oral/injectable contraceptives, those with chemically induced perimenopausal status, and perimenopausal women having irregular menses (Hampel, 2009). However, some clinicians ignore these factors and go-ahead to conduct MRIs for women with abnormal menstrual cycles disregarding the proper hormonal cycle timing, forcing them to undertake several un-diagnostic exams. According to Ellis, Serum progesterone concentrations corresponding to the follicular phase of a normal menstrual cycle can aid in optimal scheduling of breast MRI examinations for premenopausal women who lack cyclical menses (2009).
Discuss the BRCA 1 and BRCA 2 genes. What are the implications for a patient who has a harmful BRCA gene mutation, and how are such patients managed clinically? (max 1000 words)
BRCA 1 and BRCA 2 are genes for cancer1 and cancer 2 respectively. BRCA1 gene is categorized under a group of genes referred to as tumor suppressor genes. In most cases, tumor suppressors in the body produce a protein that is gotten direct from the BRCA1 gene and prevent cells from developing and subdividing at a higher rate by putting some control measures. Through the work of the BRCA1 gene, some instructions for producing proteins are relied upon in repairing the denatured DNA (Garber & Offit, 2005). Normal cells have a nucleus, whereby BRCA1 protein gets an opportunity to interrelate with several other proteins, especially the proteins from RAD51 and BARD1 genes. The interaction of these types of proteins helps in repairing the damages in DNA.
The main causes of these damages are natural and medical radiation, and at times, environmental exposures. The genetic changes that can result in such damages include when chromosomes are exchanging genetic materials in getting ready for cell division. During the process of repairing DNA, the major role played by BRCA1 is to maintain the stability and structure of cells genetic components. According to most of the studies done concerning the roles of breast cancer genes, it is evident that BRCA1 protein assists in regulating the activities and works of other genes (Jensen & Thompson, 2007). These proteins are also known to take an important function in embryonic development. For these functions to be effective, the BRCA1 protein works with many other proteins such as tumor suppressors and proteins that take care of cell division.
Within the body, the BRCA1 gene shares some characteristics with genes that are contained in-group RNF. BRCA1 genes belong to a gene family and that is why they share some crucial characteristics. Allocating genes to a certain family assists researchers a great deal in describing how genes are related to one another in the body. Most of the changes that are found in the BRCA1 gene are related to health conditions (Lerman, 2004). Breast cancer is diagnosed because of increased risks received from deviations of the BRCA1 gene. According to reports obtained from several researchers, it has proved that there are more than 1000 types of mutations associated with the BRCA1 gene. Most of these mutations are connected with the increased risk of cancer especially breast cancer in women. Most of the mutations found in the BRCA1 gene result in the production of an abnormally shortened type of the BRCA1 protein.
In addition, such mutation may also prevent any protein from being produced from one type of gene. Other known BRCA1 mutations distort single protein building blocks that are contained in other proteins or other words do away with big segments of DNA from the BRCA1 gene. Researchers have a notion that a damaged or a missing BRCA1 protein cannot assist in repairing the spoiled DNA (Malone & Daling, 2010). Defective BRCA1 gene cannot even solve the problems of mutations that occur in other genes. When such defects happen for a long time and accumulate, they create a chance for cells to develop and divide uncontrollably resulting in a tumor.
Different types of mutations in the BRCA1 gene are known to cause female breast cancer as well as other types of cancer such as fallopian tube cancer, male breast cancer, etc. Most of such mutations of BRCA1 distort the formation of one of the most important amino acids used in the production of BRCA1 protein leading to a type of protein that cannot perform its normal DNA repair role.
BRCA2 gene is another name for breast cancer 2 referred to as early-onset. During the normal functioning of this gene, it is found in a group of genes called tumor suppressor genes. Just like many other tumor suppressors, the protein generated from the BRCA2 gene assists in controlling cells from developing and subdividing so fast in an uncontrollable way. The BRCA2 gene gives instructions for producing a protein that directly takes place in the repair of spoiled DNA. Just like BRCA1 protein, BRCA2 works with several other proteins such as those generated in RAD51 and PALB2 genes to repair damages in DNA. These damages are caused by the same factors that are discussed above (Narod & Offit, 2005). It is suspected that BRCA2 protein has some other additional roles within one single cell. For instance, this protein may also assist a great deal in regulating cytokinesis, which is one of the steps passed through when cells are dividing, at the point when the cytoplasm is separating to form two cells.
Continuous research is ongoing to prove more potential activities of this protein. According to various studies that are done, it is evident that there are more than 800 types of mutations, which are found in the BRCA2 gene. Most of the mutations found in this gene are related to the cases of increased dangers of breast cancer. They act in the same manner just like BRCA1 in disrupting the process of generating proteins. The defective BRCA2 protein is considered ineffective just like the defective BRCA1.
The types of mutations contained in the BRCA2 gene are known to cause some other disorders like Fanconi anemia type D1, which occurs when two defective types of BRCA2 gene appear in the same cell (Narod & Offit, 2005). Such mutations are known to affect the amount of BRCA2 protein by lowering it. Insufficiency of this protein, it hard for the damages in DNA to be repaired hence resulting in the accumulation of genetic damage. People suffering from Fanconi anemia have high chances of contracting other types of cancers like blood cancer, developing solid tumors, mostly on the skin or on any other external body organs.
Still, some other complications are related to Fanconi anemia such as bone marrow suppression that reduces the level of red and white bold cells, as well as the blood platelets. When those components of blood are inadequate, there is a high probability of one suffering from anemia (Malone & Daling, 2010). The experienced variations of the BRCA2 gene in the body may also lead to serious complications like cancers in sensitive organs like ovaries, prostate, fallopian tube, skin, etc.
Such patients are handled clinically through some measures and practices like chemotherapy and radiotherapy (Ellis, 2009). Some other prescriptions are also given to such patients to handle the level of toxicities and relieve some of the serious symptoms associated with this condition.
MRI can be used to assess breast implant integrity. Discuss intracapsular and extracapsular rupture and their MRI appearances (max 500 words)
Magnetic resonance imaging is a scientific system of determining a medical condition and finding its treatment (Narod & Offit, 2005). Using magnetic and radio frequencies, parts of the body can be examined and a detailed copy is obtained using a computerized printout. Magnetic resonance imaging is the best technique for resolving many breast conditions compared to other systems such as ultrasound.
Currently, MRI application is widely used but its limited by hormonal fluctuations in perimenopausal women particularly during their normal menstrual cycle due to its sensitivity to the hormones progesterone and estrogen that cause symptomatic breast modifications called fibrocystic change that could affect both breasts particularly during the forties but absent after menopause since they lack hormonal stimulations (Finkelstein, 2007). This is attributed to the acceptance of gadolinium in ordinary breast tissue, which impedes the outcomes of MRI examination since it offers false-positive outcomes.
Intracapsular rupture is a situation whereby, the gel trickles beyond the silicone shell of the implant, which stays inside the fibrous capture surrounding it. Extracapsular rupture occurs when free silicone gel escapes past the capsule to the breast cells; alternatively, the gel may move to the lymph nodes (Narod & Offit, 2005). During intracapsular rapture, the implants look depressed with a different feeling portraying a likely leakage. By use of magnetic resonance imaging, the leakage could be examined.
If the problem is confirmed, collective implant surgery is done by removing the leaking silicone and ruptured shell or by placing a fresh pair of implants.
Implants are usually placed in two parts of the body namely sub-glandular implants around the pectoralis muscle with minimal possibilities of rupturing in the cause of treatment. For the second type known as a subpectoral implant, the implant is fixed posterior to the pectoralis muscle (Ellis, 2009). This type of implant is more difficult to carry out and is likely to rupture during treatment. However, it is associated with various advantages, which include a few instances of capsular contracture and non-visible marks. In most cases, the fibrous capture appears after surgery.
For extracapsular rupture, the fibrous capsule forms near the implant and does not allow silicone gel to get into the breast. Different findings have shown that intracapsular implants can develop into extracapsular, which results in big scars and granuloma formation associated with painful masses. An instance where fibromyalgia appears on breasts is also common in extracapsular implants. Although silicone is found in the breast, it can also extend to such areas as the bronchial plexus, arms, abdominal wall, and the groin subtle intracapsular (Finkelstein, 2007). The existence of any foreign object in the body may result in serious scarring to happen, hence making breasts turn tender and hard. Such foreign objects include silicone that is contained in an implant, and this can only happen due to some reasons such as trauma, internal implant, or mishandling. The implant may be removed through painless procedures, due to some reasons like implant leakage, capsular contracture, or variations in size and shapes.
References
Croyle, R., & Botkin, J. (2006). Psychological responses to BRCA1 mutation testing: preliminary findings. Health Psychology , 63-72.
Ellis, R. (2009). Optimal Timing of Breast MRI Examinations for Premenopausal women who do not have a normal menstrual cycle. American Journal of Roentgenol , 1738-1740.
Finkelstein, D. (2007). Germ-line BRCA1 mutations in Jewish and non-jewish women with early-onset breast cancer. N Engl J Med , 143-149.
Garber, J., & Offit, K. (2005). Hereditary cancer predisposition syndromes. J Clin Oncol , 276-92.
Hampel, R. (2009). Sequence analysis of BRCA1 and BRCA2: correlation of mutations with family history and ovarian cancer risk. J Clin Oncol , 2417-25.
Jensen, R., & Thompson, M. (2007). BRCA1 is secreted and exhibits properties of a granin. Nat Genet , 303-8.
Lerman, C. (2004). BRCA1 testing in families with hereditary breast-ovarian cancer. A prospective study of patient decision making and outcomes. JAMA , 1885-92.
Malone, K., & Daling, J. (2010). Family history and survival of young women with invasive breast carcinoma. Cancer , 1417-25.
Narod, S., & Offit, K. (2005). Prevention and management of hereditary breast cancer. J Clin Oncol , 1656-63.
Ramakrishnan, R. (2002). Morphological Changes in Breast Tissue with Menstrual Cycle. Modern Pathology , 1348-1356.
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