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:• 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: Mary-Claire 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)

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

Death Rates by Race ("Seer stat fact," 2012)

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• 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/compete-info-of-mammogram/• Mandal, A. (2013). History of breast cancer. Retrieved from http://

www.news-medical.net/health/History-of-Breast-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