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Transcript
Breast Cancer
Jordan Liz
Donte Bland
Mentor: Dr. Thomas Brennan
Co-Mentor: Mrs. Joan McMahon
Bronx Community College
Hartwick College
Murry Bergtraum High School
Anatomy Of A Breast
• Breast profile:
A Ducts
B Lobules
C Dilated section of
duct to hold milk
D Nipple
E Fat
F Pectoralis major
muscle
G Chest wall/rib cage
• Enlargement
A Normal duct cells
B Basement
membrane
C Lumen (center of
duct)
What Is Breast Cancer?
• Cancer is caused when the body’s natural
regulators do not work properly; this causes cells
to live longer than normal. Eventually, this results
in cell growth exceeding cell death. Those cells
continue to divide without normal control and
make a mass of extra tissue, or a tumor. If the
tumor is benign, then it is not cancerous;
however, if it becomes malignant then the person
has cancer. When this occurs within the breast, it
causes breast cancer.
Symptoms
• Presence of lump or area that feels significantly
different from the surrounding tissue
• Change in size of breast
• Change in skin over breast, such as dimpling
• Redness of the skin over the breast
• Liquid discharging from nipple (usually blood), but
not milk
• Breast pain or discomfort
• Swelling of arm(s)
• Weight loss
Risk Factors
• Age (People over 50 years old are more likely to
develop breast cancers)
• Gender (Women are much more likely to develop
breast cancer)
• Family History (Higher risk of breast cancer if a
close relative had it)
• Genetics (Certain gene defects can increase
chance of acquiring breast cancer up to 80%)
• Menstrual Cycle (Women who get their periods
early, before age of 12, or went through
menopause late, after age of 55, are at a greater
risk)
Statistics
Statistics (Cont’d)
• For women in the US,
breast cancer is the
second deadliest type
of cancer (after lung
cancer)
• There are about 2.5
million women in the
US who have survived
breast cancer
• 90% of cancers are
due to genetic
defects, not heredity
factors
Bioinformatics
• Bioinformatics is a field of
science that combines
elements of biology,
computer science and
information technology into
one discipline.
• It involves analyzing and
interpreting biological data
to create molecular
modeling, discover genes,
assign function(s) to genes,
and establish relationship
between genes and
proteins.
Breast Cancer Encoding Genes and
Proteins
• The two genes
responsible for breast
cancer are BRCA1
and BRCA2 if a
mutation occurs in
both of them.
• Two proteins that
interact with breast
cancer, such as
HER2 and HER4.
BRCA1
• Stands for Breast Cancer 1, early
onset
Chromosome 17
Location: 17q21
• Its purpose is to suppress cell
growth, aid in DNA repair, cell cycle
regulation and control and overall
stability to genetic information.
• Mutations in this gene can lead to
breast, ovarian, prostate and other
types of cancer.
• Mutations to the gene can be
caused by natural or medical
radiations, environmental exposures,
or while interacting with other
chromosomes.
BRCA2
• Stands for Breast Cancer 2, early
onset
• Its serves the same function as
BRCA1 and a mutation in this gene
increases one’s risk at acquiring
certain types of cancers.
• It is important to note that breast
cancer occurs when a mutation in
both genes occurs, however, if one
gene mutates the other has a
greater chance of mutating as well.
Chromosome 13
Location: 13q12.3
Breast Cancer (BRCA) Gene Test
• Uses a blood sample to identify whether BRCA1
and/or BRCA2 has been mutated.
• Administered only to women who at a very high
risk of attaining breast cancer.
• Determines whether or not the patient is a carrier
for the mutation and their own estimated risk level
for getting breast cancer, or if they are safe.
HER2
• Stands for Human Epidermal Growth Factor
Receptor-2
• Helps control cell growth, divide and reparation
• If the protein is over-expressed, then a patient
can acquire a type of breast cancer known as
HER-2 Positive Breast Cancer
• The over-expression causes cancer cells to grow
and spread more quickly.
• Patients with HER-2 Positive Breast Cancer have
a more aggressive disease and has a greater rate
of recurrence than a HER-2 Negative Breast
Cancer
HER4
• Stands for Human Epidermal Growth Factor
Receptor-4
• It serves the same function as HER2
• HER4 has been linked with positive and negative
effects on breast cancer
• Some research claims that HER4 has been able
to suppress the mutation caused by BRCA1 and
BRCA2
• Other studies claim that HER4 makes the breast
cancer more severe, but not as aggressive as
HER2 makes it.
Procedure for BLAST
• Go to the National Center for Biotechnology Information
website, www.ncbi.nlm.nih.gov
• Search for the gene that you wish to BLAST (Basic
Local Alignment Search Tool)
• Afterwards, go to “Nucleotide,” there you will the
nucleotide sequenced
• Copy the sequence (you will need it shortly)
• Go the NCBI homepage and click on BLAST on the top
of the screen
• Select Nucleotide BLAST
• Paste the sequence that you copied earlier and perform
the BLAST
• The process could take anywhere from a few seconds to
a couple of minutes, depending on the sequence.
Reasons for BLAST
• BLAST, or Basic Local Alignment Search Tool,
enables researchers to compare gene sequences
of one animal against those of a different
organism to determine their similarity.
BLAST Results for BRCA1(Homo
Sapiens)
• Equus Caballus (horse)
• Pan troglodytes (common chimpanzee)
BLAST Results for BRCA1 Cont’d
• Bos taurus (cattle)
• Sus scrofa (pig)
Scientific Implications
• Studying these genes can lead to the discovery of
the cause of their mutation and hopefully a means
to reverse or diminish the mutation.
• Also, further research may result in conclusive
data concerning HER4’s effect to breast cancer.
• In the past, scientists have studied breast
cancers in mice and were able to cure it,
however, the same techniques had no effect on
human breast cancer.
Treatment
• There is no cure for breast cancer.
• Breast cancer treatment include:
–
–
–
–
Chemotherapy (w/ stem cell transplant)
Radiation therapy
Hormone therapy
Medication
• Tykerb
• Herceptin
• Avastin
– Surgery
• Total mastectomy
• Modified radical mastectomy
• Radical mastectomy
Conclusion
• Breast cancer is an incurable cancer that affects
thousands of Americans each year.
• It has no cure, but scientist have been able to
cure it in other animals.
• New bioinformatics tools can lead to discovery of
cure or more effective treatment.
References
•
•
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•
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•
•
•
•
•
American Cancer Society (2005). "Breast Cancer Facts & Figures 2005-2006" (PDF).
http://www.cancer.org/downloads/STT/CAFF2005BrFacspdf2005.pdf. Retrieved on 2007-04-26.
WHO international Agency for Research on Cancer Press Release No. 180, December 2007.
Madigan MP, Ziegler RG, Benichou J, Byrne C, Hoover RN (November 1995). "Proportion of breast cancer cases in the
United States explained by well-established risk factors". Journal of the National Cancer Institute 87 (22): 1681–5.
doi:10.1093/jnci/87.22.1681. PMID 7473816.
Venkitaraman AR (January 2002). "Cancer susceptibility and the functions of BRCA1 and BRCA2". Cell 108 (2): 171–82.
doi:10.1016/S0092-8674(02)00615-3. PMID 11832208.
Cavalieri E, Chakravarti D, Guttenplan J, et al. (August 2006). "Catechol estrogen quinones as initiators of breast and other
human cancers: implications for biomarkers of susceptibility and cancer prevention". Biochimica et Biophysica Acta 1766 (1):
63–78. doi:10.1016/j.bbcan.2006.03.001. PMID 16675129.
Foray, Nicolas; Marot Didier, Randrianarison Voahangy, Venezia Nicole Dalla, Picard Didier, Perricaudet Michel, Favaudon
Vincent, Jeggo Penny (Jun. 2002). "Constitutive association of BRCA1 and c-Abl and its ATM-dependent disruption after
irradiation". Mol. Cell. Biol. (United States) 22 (12): 4020-32. ISSN 0270-7306. PMID 12024016.
Cable, P LouAnn; Wilson Cindy A, Calzone Frank J, Rauscher Frank J, Scully Ralph, Livingston David M, Li Leping,
Blackwell Courtney B, Futreal P Andrew, Afshari Cynthia A (Oct. 2003). "Novel consensus DNA-binding sequence for BRCA1
protein complexes". Mol. Carcinog. (United States) 38 (2): 85-96. doi:10.1002/mc.10148. ISSN 0899-1987. PMID 14502648.
Yan, Jinghua; Zhu Jianhua, Zhong Hongjun, Lu Qiujun, Huang Cuifen, Ye Qinong (Oct. 2003). "BRCA1 interacts with FHL2
and enhances FHL2 transactivation function". FEBS Lett. (Netherlands) 553 (1-2): 183-9. ISSN 0014-5793. PMID 14550570.
Yan, Jing-Hua; Ye Qi-Nong, Zhu Jian-Hua, Zhong Hong-Jun, Zheng Hui-Yong, Huang Cui-Fen (Dec. 2003). "[Isolation and
characterization of a BRCA1-interacting protein]". Yi Chuan Xue Bao (China) 30 (12): 1161-6. ISSN 0379-4172. PMID
14986435.
Zou JP, Hirose Y, Siddique H, Rao VN, Reddy ES (1999). "Structure and expression of variant BRCA2a lacking the
transactivation domain". Oncology reports 6 (2): 437–40. PMID 10023017.
Venkitaraman AR (2001). "Chromosome stability, DNA recombination and the BRCA2 tumour suppressor". Curr. Opin. Cell
Biol. 13 (3): 338–43. doi:10.1016/S0955-0674(00)00217-9. PMID 11343905.
Orelli BJ, Bishop DK (2001). "BRCA2 and homologous recombination". Breast Cancer Res. 3 (5): 294–8. doi:10.1186/bcr310.
PMID 11597317.
Daniel DC (2002). "Highlight: BRCA1 and BRCA2 proteins in breast cancer". Microsc. Res. Tech. 59 (1): 68–83.
doi:10.1002/jemt.10178. PMID 12242698.
Tutt A, Ashworth A (2003). "The relationship between the roles of BRCA genes in DNA repair and cancer predisposition".
Trends in molecular medicine 8 (12): 571–6. doi:10.1016/S1471-4914(02)02434-6. PMID 12470990.
Acknowledgments
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Mentor: Thomas Brennan
Co-Mentor: Joan McMahon
Eric Konadu
Bronx Community College
National Science Foundation
Harlem Children Society
Dr. Sat Bhattacharya
HCS Staff
Rockefeller University
All of you for listening
Any Questions?