Transcript BRCA1 - Regis University: Academic Web Server for Faculty

BRCA1(Breast Cancer
1) and its relevance
to familial breast
cancer
Skyler Newhouse and Katherine Varley
(Camazine, 2011)
Introduction
• Gene: BRCA1
– Mutation of BRCA1 increases chances of cancer by 35-85%
• Breast cancer is both genetic and non-genetic:
– Genetic risk factors:
• Presence of gene mutation of BRCA1
• Activation of proto-oncogenes (a normal gene that can become an oncogene
due to mutations or increased expression)
• Inactivation of tumor-suppressor genes
• Race
• Gender
– Non-genetic risk factors:
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Advancing age
Weight gain
More than two alcoholic beverages per day
Radiation therapy at a young age
(Dow, 2002)
Introduction-BRCA1
• “When BRCA1 mutations occur, the DNA repair
function is not regulated and there is an inherited
correlation between the BRCA1 gene and the
pathogenesis of breast cancer” (Miao et al., 2012)
– Protein coded is Breast Cancer Type 1 Susceptibility
Protein
• Breast cancer gene that shows a clear inherited pattern
(autosomal dominant) (Bird, 2003)
• Tumor-suppressor gene (Bird, 2003)
• More than 100 different types of mutations on BRCA1
(Bird, 2003)
History
• Discovered by: MaryClaire King
• Discovered in 1990,
located on chromosome
17q21
• Studied at the University
of Washington in Seattle
where she also
discovered BCRA1
("Mary-claire king bio," 2012)
History-Diagnosis
• Mammography
– Most widely used imaging tool
– Screens for abnormalities by
imaging the breast’s soft tissue
• Ultrasonography
– Is used as a confirmatory tool after
a mammogram to see whether a
lump is cystic or solid
• CT scans
– Not nearly as effective as
mammograms
• MRI scanning
– In early stages as a tool for
diagnosing breast cancer; not likely
to be very useful because it cannot
detect small calcifications in the
breast
(Engel, 1996)
("Mammogram," 2011)
History-Diagnosis
•
Biopsies (Engel, 1996)
• The ultimate method for diagnosing
cancers
• Breast Biopsy options: Fine-needle
aspiration biopsy, Large-core needle
biopsy, and Open (Surgical) biopsy
Large-core needle biopsy ("Stereotactic breast
biopsy," 2013)
Fine-needle aspiration biopsy ("Fine-needle
aspiration," 2013)
Incidence and Mortality Rates
 Most common cancer in
American women
 Second leading cause of cancer
death of American women after
lung cancer
 Incidence and mortality rates vary
by race and ethnicity
 White women have the highest
incidence rate
 Black women have this highest
mortality rate
 Survival decreases with advanced
stages of the disease
 90% of people survive after 5 years
(Dow, 2002)
Death Rates by Race
("Seer stat fact," 2012)
Race/Ethnicity
Female
All Races
23.0 per 100,000 women
White
22.4 per 100,000 women
Black
31.6 per 100,000 women
Asian/Pacific Islander
11.9 per 100,000 women
American Indian/Alaska Native a
16.6 per 100,000 women
Hispanic b
14.9 per 100,000 women
Treatment
• Removal of the tumor if is non-invasive
• Removal of the tumor with radiation, or radiation (chemotherapy) if
tumor is invasive.
– Looking at partial-breast radiation, rather than whole-breast radiation
• Drugs
• “Platinum is a common second-line antitumor drug in breast cancer
chemotherapy. It has been suggested that platinum may be an
effective drug treatment for breast cancer with genetic mutations in
the BRCA1 gene.” (Miao et al., 2012)
• Possibility of cure: Currently there are treatments for breast cancer,
and scientists are working towards a cure
(Shockney, 2008)
Treatment
• Consequences if left untreated:
– Cancer could spread to other tissues and become
different types of cancer (if invasive).
– Could lead to death by causing susceptibility to
disease
– Tumor could outgrow itself and develop necrosis
(death of tissue)
(Shockney, 2008)
Recent Research
• Use of platinum-based drugs as chemotherapy
drugs on Triple-negative breast cancer
• Triple-negative breast cancers can be caused by
BRCA1
• Found that TNBC patients had better progression
free survival up to 6 months after treatment with
platinum-based drugs
• There was little difference after one to two years,
however
(Miao et al., 2012)
Sources
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Bird, C. (2003). Introduction to breast care. London, England: Whurr Publishers Ltd.
Camazine, S. (Photographer). (2011). Women with a defective copy of the brca1 gene are more likely to develop
breast cancer.. [Web Photo]. Retrieved from http://www.nature.com/news/2011/110907/full/news.2011.524.html
Dow, K. (2002). Pocket guide to breast cancer. (2nd ed.). Boston, Massachussets: Jones and Bartlett Publishers.
Engel, J. (1996). The complete breast book. Toronto, Onterio: Key Porter Books Limited.
(2013). Fine-needle aspiration. (2013). [Web Graphic]. Retrieved from
http://www.mayoclinic.com/health/medical/IM00808
(2011). Mammogram. (2011). [Web Graphic]. Retrieved from http://www.motherhealth.info/radiology/competeinfo-of-mammogram/
Mandal, A. (2013). History of breast cancer. Retrieved from http://www.news-medical.net/health/History-ofBreast-Cancer.aspx
Mary-claire king bio. (2012). Retrieved from http://www.ashg.org/press/mcking_bio.shtml
Miao, L., Qin-Guo, M., Chang-Yuan, W., Quin-Hong, Q., Zhen, H., Jie, H., & Jie, H. (2012). Platinum-based
chemotherapy in triple-negative breast cancer: A meta-analysis. Oncology Letters, 5(3), 983-991. doi:
10.3892/ol.2012.1093
Sherman, J. (2000). Life's delicate balance causes and prevention of breast cancer. New York, New York: Taylor &
Francis.
Shockney, L. (2008). The johns hopkins breast cancer handbook for health care professionals. Sudbury,
Massachusetts: Jones and Bartlett Publishers.
U.S. National Institutes of Health, (2012). Seer stat fact sheets: Breast. Retrieved from website:
http://seer.cancer.gov/statfacts/html/breast.html
(2013). Stereotactic breast biopsy. (2013). [Web Graphic]. Retrieved from
http://www.mayoclinic.com/health/medical/IM04058