Breast Cancer

.. tive risk of breast cancer. Those who have more than nine drinks a week have an increase of two and a half times the rate of breast cancer for a non-drinking person. In 1987, the National Cancer Institute published a report comparing 1524 women with breast cancer against a control group of 1896 without the disease. Again, alcohol appeared to promote breast cancer (Risk Factors for Breast Cancer).

Several medical procedures or side effects of them have been thought to promote breast cancer. It was hypothesized that self-induced abortions could greatly increase the chances of getting cancer, as during pregnancy the cells in the breast quickly divide and reproduce. By having an abortion and thus suddenly halting cell division, a number of cells would become greatly unprotected by there not being any differentiation, and thus would be vulnerable to cancer (Risk Factors for Breast Cancer). Radiation has also been thought of, and for all thorough purposes has been proven to be a cause of breast cancer. There have been three major studies that have been done concerning radiation. The first was performed around the bombings of Hiroshima and Nagasaki.

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It was quickly ascertained that within a ten mile radius of the bombing there was a definite cancer zone. More importantly, younger people got much more cancer, especially with regards to breast cancer, than did older ones. This forces more weight on the theory that the changing years of the breasts in women are their most vulnerable and possibly cancer causing ones (Risk Factors for Breast Cancer). Prevention is one point of the attempt to cure breast cancer, but it is extremely important to get breast examinations often to make sure of no lumps or early tumors. The simplest forms of breast exam are a self-exam, one with a doctor, or a mammography. A mammogram is simply an X-ray of the breast.

Mammography can pick up small lesions of under one half a centimeter, whereas one can not feel a lump until it is a full centimeter in diameter. But, if breasts are small or dense, a mammogram might not be able to detect a cancerous lump. Another procedure could be a wire localization. A thin wire is used to show where the lesion is after the wire is inserted, and local anesthetic is administered. Thermography is based on the idea that cancer gives off more heat than regular cells.

Transillumination is founded in the concept that light shines through breast tissue, but is blocked by lumps. An ultrasound is the use of high frequency sound waves, which are sent off in a radar fashion, and reflect off objects that they hit. A CAT scan is the process of visually cutting the body into cross-sections (Guidelines for the Early Detection of Breast Cancer, 1999). Another controversy runs deep in the issue of using CAT scans to find cancer tissue. The radiation required to examine a five milliliter lump is often considered simply too high for safety, and has a possibility of just simply spreading the cancer to other body parts.

A MRI takes advantage of the electromagnetic qualities of the hydrogen nucleus to produce an electric chart or visual. While the most common form of breast exam is mammography, there are many critics of that procedure. Cancer patients have said that the mammogram is often uncomfortable and takes too much time. Younger women are at increased risk for biologically more aggressive carcinoma, meaning that the future battle for curing cancer is not getting any easier. Cancer growths are dependant upon the growth of blood vessels to nurture the cancer cells.

New drugs are being developed to stop the growth of cancer cells by preventing nourishment of the cancers by new blood vessels. By cutting off the blood supply to the cells, they die, and thus are eliminated from the system (Guidelines for the Early Detection of Breast Cancer, 1999). Chemotherapy involving tamoxifen has proved useful in delaying breast cancer recurrence, but the majority of patients treated with Tamoxifen eventually go into relapse. Traditionally, there are three types of cancer treatments: radiation, mastectomy, and cytotoxic chemotherapy. The type of surgery really has its basis on the size of the tumor. A lumpectomy removes the tumor and surrounding tissues.

A simple mastectomy removes the breast, nearby lymph nodes, and portions of the chest and arms (Treatment). Doctors can also perform preventative mastectomies. Some surgeons feel that if the breast is fairly lumpy, and the patient appears to be at very high risk of breast cancer, the surgery may be beneficial. The whole surgery is highly controversial. Both doctors and patients generally prefer a total bilateral mastectomy and reconstruction.

This removal takes out the entire breast including the nipple and duct system so that there can be little chance of relapse (Treatment). There are various treatments aimed at killing the cancerous cells- from surgically removing that area of the body to killing them off by use of chemicals. A very common procedure is chemotherapy. Chemotherapy is an antibiotic designed to kill rapidly dividing cells. Monoclonal antibodies are antibodies that can be engineered to carry drugs or radiation directly to the tumor, and is an efficient way of delivering chemotherapy to the body. Another adaptation that has been added to chemotherapy is the use of genes that are chemo-resistant.

One treatment involves stem cell transplantation. Stem cells are often referred to as master cells, and they seem to carry antibodies that rapidly reproduce which fight malignancies, and may be able to fight cancer. One solution to cancer may be hormone therapy (Treatment). The hormone, usually tamoxifen, slows growth of cancer cells by blocking some growth enhancing properties of estrogen. The controversy over Tamoxifen is that it might cause other types of cancer.

In 1989, the National Cancer Institute ran a test in which women took a placebo or Tamoxifen. Women with the drug were less likely to develop cancer of the breast, but they were more likely to develop blood clots, ovarian cancer, or breast cancer (Tamoxifen). One complication that can result in cancer is Ductal Carcinoma Insitu. The ductal area houses the lobules and ducts and is the area in which milk is produced. Similar to rust clogging up pipes, often extra cells or cancerous cells will clog up the tubes providing for some discomfort and other risks.

Studies show that 20-25% of women with untreated DCIS will get invasive cancer within 10 years (American Cancer Society, 1999: 7). As the twentieth century comes to an end, breast cancer continues to be a devastating killer in the new millennium. Breast cancer takes the lives of our mothers, our sisters, our daughters, and our friends. Although progress is being made through research, early detection is all we can do to possibly prevent breast cancer. Women should learn to do a self-examination at a young age, and should continue throughout their lives.

If a lump is found a professional should be contacted. If people work together, maybe sometime soon a cure will be found (Breast Cancer, 1991). Bibliography Breast Cancer. The World Book Encyclopedia. Volume 2; 601.

1991. Breast Cancer Key Statistics. http://www3.cancer.org/cancerinfo/main cont.asp?st=wi&ct=5#stats. September 20, 1999. Case Studies. http://www.cancergenetics.org/bc.htm. April 12, 1999. Detection. http://www3.cancer.org/cancerinfo/main cont.asp?st=ds&ct=5#early.

September 20, 1999. Exercise Reduces Breast Cancer. http://www.oncolink.com/cancer news/1994/exercise bc.html. August 26, 1999. Fitzgerald et al. The New England Journal of Medicine. Vol.

334, No. 3. January 18, 1996. Guidelines for the Early Detection of Breast Cancer. The American Breast Cancer Guide (1999): 6. Newly Synthesized Compound Can Inhibit Development of Precancerous Cells. http://www.ag.uiuc.edu/~ffh/vitamind.htm. Perceptions of Breast Cancer Risk and Screening Effectiveness in Women Younger Than 50 Years of Age. http://cancernet.nci.nih.gov/jnci/issue10/87-720.h tml.

Risk Factors for Breast Cancer. http://www3.cancer.org/cancerinfo/main cont.asp?st=pr&ct=5#risk. September 20, 1999. Tamoxifen. http://www.infomed.org/100drugs/tamofram.html. 1996. Treatment. http://www3.cancer.org/cancerinfo/main cont.asp?st=tr&ct=5. September 20, 1999. Types of Breast Cancer, Breast Cancer Stages.

Breast Cancer Treatment Guidelines for Patients, Version II (June 1999): 7, 10. Human Sexuality.

Breast Cancer

Breast Cancer Hereditary breast cancer is a disease caused by mutations on breast cancer suppresser genes (ACCV Pg.17). Mutations allow normal cells to divide abnormally (ACCV Pg.13). Resulting cells divide faster as they do not specialize and form useless lumps of cells called malignant tumours (ACCV Pg.13). Genetic Screening is the process where Deoxyribonucleic Acid (DNA) fragments are analyzed for a specific gene. The purpose is to identify individuals carrying disease causing genes so they can change their life style and also help invent a cure (ACCV Pg.20). This is done by amplifying DNA withdrawn from an individual, then specific gene mutations are targeted using the Electrophoresis process. The two genes, BRCA1 and BRCA2 isolated in 1994 and 1995 respectively are breast cancer suppresser genes (Internet 1).

BRCA1 is located on chromosome 17q21 and BRCA2 on 13q(Internet 2). A person that possesses certain mutations to these genes has an increased risk of up to 80-90% in developing breast cancer (Internet 3). The cost of genetic screening ranges among several hundred to several thousand dollars depending on the tests performed and can take several weeks to many months from the initial blood sample (Internet 4). Public acceptance of genetic screening for severe disease causing genes in early childhood is high (New Scientist Pg. 14).

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Many people argue for less debilitating diseases that discrimination will occur against individuals carrying those genes (New Scientist Pg. 14). In human cells there are 22 pairs of autonomic chromosomes and two sex chromosomes. These chromosomes contain information for protein synthesis. DNA stores this information by a sequence of nucleotides.

There are four different nucleotides that construct DNA. They all contain a 5 ring carbon sugar (Deoxyribose), a phosphate molecule and one of four nitrogenous bases. The base names are Adenine (A), Thymine (T), Guanine (G), and Cytosine (C). Adenine is complementary to Thymine and Guanine to Cytosine. The arrangements of a series of nucleotides are genes. Hereditary Breast Cancer is an autosomal dominant disease (Internet 3), meaning only one parent needs to carry the trait expression in the parents offspring.

The disease is cause by mutations found on the BRCA1 or 2 tumour suppresser genes (Internet 3). BRCA1 has 24 exons distributed over a genomic region of 81 kilobases long and located on chromosome17q21 (Internet 3) Exon 11 being the largest that codes for 61% of a protein, 1863 amino acids and 5592 nucleotides long (ACCV Pg. 17). The irrelevant information known as introns found on BRCA1 range in size from 403 base pairs to 9.2 kilobases (Internet 3). Over 100 disease-associated mutations have be identified to this gene (Internet 3) 21 of these found in exon 11 (ACCV Pg.

17). These mutations code for a stop signal causing protein truncation (ACCV Pg. 17). BRCA2 has mutations that function the same as BRCA1 (ACCV Pg. 18).

BRCA2 has been linked to hereditary breast cancer and increases the risk for male breast cancer. (ACCV Pg. 18). BRCA2 is located on chromosome 13q12(Internet 2). Little additional detail about this gene is available. Testing for BRCA2 is not widely available except within the research laboratory. There are two distinctive stages in protein synthesis of BRCA1, transcription and translation. Transcription is the synthesis of messenger Ribonucleic Acid (mRNA). The enzyme RNA polymerase initiates transcription by separation of DNA strands.

RNA nucleotides then bind to their complementary DNA nucleotides of the BRCA1 gene to form a mRNA strand. The mRNA is different to the DNA strand of the BRCA1 gene as Uracil (U) replaces Thymine and is complementary to Adenine. The resulting mRNA strand detaches from the BRCA1 gene before the DNA Ligase enzyme joins the DNA strands together. Splicing of the mRNA occurs to remove introns (Raven 440). The mRNA now only contains exons, that are primary transcripts of the gene. The mRNA strands leave the nucleus through nuclear pores to undergo Translation the second stage of protein synthesis.

Translation occurs at the ribosome found in the cytoplasm, where production of the tomour suppresser protein from mRNA occurs. A ribosomal RNA molecule with in the ribosome binds to the “start” sequence of the mRNA strand. The ribosome then moves the mRNA strand through 3 nucleotides adding an amino acid. This process continues until the ribosome encounters a “stop” signal at this point it disengages from the mRNA and releases the completed suppresser protein. Genetic screening can allow testing DNA to determine if an individual carries mutated forms of the BRCA1 gene. DNA collection is the first stage to screen for the BRCA1gene.

White blood cells withdrawn from a blood sample contain the needed DNA. The DNA needs amplification so that a large volume of DNA is available for analysis. Polymerase Chain Reaction (PCR) is a process that amplifies DNA (ACCV Pg. 20). Endonuclease restriction enzyme shortens the DNA for amplification.

This enzyme recognises the BRCA1 gene and cuts it from the DNA fragment (ACCV Pg. 20). PCR is sensitive and requires a gene that is between known two sequences such as BRCA1(ACCV Pg. 21). Short complementary sequences to the BRCA1 gene, oligonucleotides, known as a primer is added to the solution along with a DNA polymerase enzyme(ACCV Pg.

21). The DNA polymerase enzyme, taq polymerase from the bacterium Thermus auquaticus is able to endure high temperatures (ACCV Pg. 21). High magnification occurs if the oligonucleotides are preferably 20-24 nucleotides long (ACCV Pg. 21).

A PCR waterbath then incubates the DNA samples at different temperatures (ACCV Pg. 21). The first bath, denaturing, occurs at 940C(ACCV Pg. 22). The high temperature removes the hydrogen bonds between the nucleotides thus separating the BRCA1 sense and non-sense strands (ACCV Pg.

21). Annealing occurs at 500C (ACCV Pg. 22), in this stage the primer bonds to its target sequence (ACCV Pg. 21). The final bath is the polymerisation stage that occurs at 720C(ACCV Pg. 22). In this stage the DNA polymerase uses the primers as a starting point to replicate the DNA (ACCV Pg.

21). (refer to Fig 2 (ACCV Pg. 21)). The waterbath cycles repeat 30 cycles resulting in over a billion copies of the desired sequence (ACCV Pg. 21).

The next technique separates the cloned BRCA1 by electrophoresis on an agarose gel (Raven Pgs. 439-441). DNA is a negatively charged molecule due to the phosphate molecules in its makeup. For this reason it is possible to separate the fragments of DNA using an electric potential across the gel (Raven Pg. 439).

Fragments migrate down the gel by size — smaller fragments move faster (and therefore go further) than larger ones (Raven 439-441). Blotting of the agarose gel removes the nucleic acid onto a nitrocellulose sheet (Raven 440). This is done by placing a nitrocellulose sheet over the gel and then paper towel. The paper towel draws a buffer solution through the agarose gel transposing the nucleic acid on to the nitrocellulose sheet (Raven Pg. 440). A solution is added to the nitrocellulose sheet containing radioactive probes.

The single strand probe hybridises with the BRCA 1 gene allowing the gene to expose an x-ray film (Raven 440) (Refer to Fig 3 (Raven 439-441)). Analysis of the film determines if BRCA1 is carried by the individual. Genetic screening indicates if an individual with a family history carries a susceptibility gene to breast cancer. This information has large benefits to these high risk individuals. People carrying the susceptibility genes have an increased risk of up to 80-90% in developing breast cancer (Internet 3).

This information will enable the individual to change their life style as a consequence. The individual carrying the faulty gene is able to have children that may never develop the cancer, but any children this individual has will also fall into the high risk category. Individuals who choose not to have children will not pass the mutated gene to there offspring and then from generation to generation. In doing so this will reduce the amount of people carrying a mutated gene from inheritance. A person with no family history can carry a mutation to these susceptibility genes. This is possible because mutations occur regularly during cell division.

Individuals in the high risk category deciding to live their live without having children both increase the survival of the species while altering the gene pool and as a result altering genetic diversity. This concept will not alter the gene pool dramatically as only 5-10% of breast cancer occurrences are due to genetic factors (ACCV Pg. 13). Increased developments in genetic screening have enabled scientists to take a single cell from an eight celled embryo and screen for mutations on BRCA1 or 2(New Scientist Pg. 14).

The genetically abnormal embryos face abortion. Issues arise on what we should screen for in embryos, as some diseases occur later in life like hereditary breast cancer while others such as Downs Syndrome causes severe suffering in early life. Many professionals believe that this technique should not be conducted on diseases that increase risk of developing that disease later in life such as breast cancer (New Scientist Pg. 14). A study result from the general public shows that less than half of the people surveyed where against genetic screening of genes that predispose for cancer in their early thirties (New Scientist Pg. 14).

If genetic screening of embryos is available the amount of inherited disease will reduce and perhaps eliminated occurrences altogether. The information also allows scientists to develop possible cures for diseases such as breast cancer (Internet 5). Bibliography www.ndsu.nodak.edu/instruct/mcclean/plsc431/studen ts/mickelson.html Internet 2, Gene Watch: The New Genetics-Consequences for Clinical Practice. Author Dr. Eric Sidebottom, Oxford. Copyright Bandolier-Last Update: 10-July-98 Internet Address: www.

Internet 3, www3.ncbi.nlm.nih.gov:80 Internet 4, National Action Plan on Breast Cancer. NAPBC Fact Sheet: “Genetic Testing For Breast Cancer Risk: Its Your Choice” Internet Address: www.napbc.org Internet 5, Breast Cancer Gene May be Useful in Treating the Disease Its Protein Slows Formation, Growth of Tomours in Lab, Author David Brown.