1. Genetic and Molecular Epidemiology
Bio364
Special Thanks to
Emily Chen, Ph.D.
Department Of Pharmacological Sciences

2. Lecture Breast Cancer Statistics
Breast Cancer Subtypes & Potential Risk Factors
Breast Cancer Susceptibility Genes
Breast Cancer Prognosis

3. 2011 ESTIMATED US CANCER DEATHS
* Cancer Statistics 2011, American Cancer Society

4. FEMALE BREAST CANCER INCIDENCE RATES
FEMALE BREAST CANCER INCIDENCE RATES* BY RACE & ETHNICITY, US,
*Rates are age-adjusted to the 2000 US standard population
Data source: Surveillance, Epidemiology, and End Results (SEER) Program, , Division of Cancer Control and Population Science, National Cancer Institute, Data for whites and blacks are from the SEER 9 registries. Data for other race/ethnicities are from the SEER13 registries.

5. Lecture Breast Cancer Statistics
Breast Cancer Subtypes & Potential Risk Factors
Breast Cancer Susceptibility Genes
Breast Cancer Prognosis

6. PROGRESSION OF BREAST CANCER
Histologic Subtypes By Percentage Of Cases
Infiltrating ductal carcinoma (IDC): the most commonly diagnosed breast tumor; metastatic (lymphatics); account for 75% of breast cancers
Ductal carcinoma in situ (DCIS): most common type of non-invasive breast cancer
Lobular carcinoma in situ (LCIS): 2.8 per 100,000 women; high incidence in women aged years
Infiltrating lobular carcinoma (ILC): <15% of invasive breast cancers
Medullary carcinoma: ~ 5% ; generally occurs in younger women
Mucinous (colloid) carcinom: <5% of invasive breast cancer cases
Papillary carcinoma: older women (>60 years); 1-2% of all breast cancers
Metaplastic breast cancer: <1% ; older women (>60 years); higher incidence in African American Women

7. INTRINSIC SUBTYPES OF BREAST CANCER
Basal-Like (Triple Negative, cytokeratin 5/6+ &/or EGFR+)
Aggressive subtype
High grade histology, and high mitotic rate
Risk at younger age (<40)
More likely preenopausal African American Women
Luminal A
(ER+ &/or PR+, HER-)
Most common subtype
Less aggressive
Lower histological grade
Good prognosis
Hormone responsive
Associated with increasing age
HER2+ (ER-)
Less common, highly aggressive subtype
High grade histology
Risk at young age (<40) greater than luminal subtypes
African American ethnicity maybe a risk factor
Outcome improved with HER2
Luminal B
(ER+ &/or PR+, HER+)
Similar to Luminal A
More frequently ER+/PR-
Worse outcome than Luminal A

8. ESTABLISHED RISK FACTORS FOR BREAST CANCER
Table Source: American Cancer Society. Breast Cancer Facts & Figures Atlanta.

9. ANATOMY OF A GENE DNA RNA PROMOTER Transcription Start site EXONS
INTRONS
PROMOTER
RNA
Translation start site
Stop codon

10. GENETIC LINKS TO BREAST CANCER
Epidemiologic studies have clearly established the role of family history as an important risk factor for both breast and ovarian cancer.
The search for genes associated with hereditary susceptibility to breast cancer has been facilitated by studies of large kindreds with multiple affected individuals, and has led to the identification of several susceptibility genes
Penetrance of Mutations - Estimates of penetrance by age 70 years for BRCA1 and BRCA2 mutations show a large range, from 40% to 87% for breast cancer

11. FOR YOUR INFORMATION ONLY, THIS WILL NOT BE ON THE EXAM SUMMARY OF SIX BREAST CANCER SUSCEPTIBILITY GENES
Gene
Pop’n carrier frequency
Risk of BC by 70 yrs (95% CI)
BRCA1
1 in 860
65% (44-78%)
BRCA2
1 in 740
45% (31-56%)
CHEK2
1 in 90
11% (9-14%)
ATM
1 in 100
23% (13-39%)
TP53
1 in 5,000
50-60% by 45 yrs
PTEN
1 in 250,000
30-50%
From Thompson & Easton J Mammary Gland Biol Neoplasia 9:221.

12. FOR YOUR INFORMATION ONLY, THIS WILL NOT BE ON THE EXAM BREAST CANCER METASTASIS – TISSUE TROPISM
Cell 127, November 17, 2006