1. University of Coimbra
Faculty of Science and Technology
Master’s Degree in Celular and Molecular Biology
Underlying risk factors for breast cancer
development and risk modeling
Daniela Pereira
Coimbra, March 5th 2011

2. Breast Cancer
• The most frequently diagnosed in women
• 4500 new cases/year
World incidence Portugal incidence
Breast
Globocan 2008 (IARC)

3. Risk factors for breast cancer development
Reproductive
Age/Gender
Risk Lifestyle
factors
Genetic
Prado, A. et al (2010) J Plast Reconstr Aesthet Surg 63, 1581-1587

4. Risk modeling
Amir. E et al (2010) J Natl Cancer Inst;102:680–691

5. Risk modeling
• Gail Model - Limitations
 Does not incorporate second-degree relatives with breast cancer, age at
diagnosis, or presence of ovarian cancer
 May overestimate risk in women with nonproliferative breast lesions
 Has lower accuracy for individual risk prediction
 Uses older population prevalence data associated with lower baseline
incidence rates
Rockhill, B., et al (2001) J Natl Cancer Inst 93, 358-366
Edwards, et al (2008) The Journal for Nurse Practitioners 4, 361-369

6. Risk modeling
• Claus Model - Limitations
 May underestimate risk in hereditary families
 May not be applicable to all combinations of affected relatives members
 Does not incorporate non-familial risk factors
Amir. E et al (2010) J Natl Cancer Inst;102:680–691
Edwards, et al (2008) The Journal for Nurse Practitioners 4, 361-369

7. Risk modeling
Limitations
Physician Patient

8. Clinical cases
Case 1 Case 2
Name Julia Smith Cassandra Jones
Age 53 33
Parity 20 and 25 year old child Nulliparous
Breast biopsy Invasive ductal carcinoma Invasive ductal carcinoma
Grade T1 T2
Stage
Molecular markers
N0, M0
ER+, PR-, HER2+
N2, M1
ER-, PR-, HER2-
?
Family history Cousin Mother and aunt
Menarche 14 years old 14 years old
Hormone therapy Int. for 15 years 12 years
Menopause No menses for ≈ 3 years -
Breast feeding ≥ 6 months each son -

9. Clinical cases - risk modeling
• Gail Model
– Breast Cancer Risk
Assessment Tool
National Cancer Institute (www.cancer.gov)

10. Clinical cases
Case 1 Case 2
Name Julia Smith Cassandra Jones
Age 53 33
Parity 20 and 25 year old child Nulliparous
Breast biopsy Invasive ductal carcinoma Invasive ductal carcinoma
Lifetime risk Lifetime risk
Grade T1 T2
Stage N0, M0
8,6% N2, M1
17,6%
Molecular markers 10,6% (average woman)
ER+, PR-, HER2+ 12,6% PR-, HER2-
ER-, (average woman)
Family history Cousin Mother and aunt
Menarche 0,8%
14 years old 1,4%
14 years old
Hormone therapy Int. for 15 years 12 years
Menopause No menses for ≈ 3 years -
Breast feeding ≥ 6 months each son -

11. Conclusion
• Risk factors
– ≠ importance
– Modifiable (prevention), non-modifiable
– Risk ≠ inevitable disease
• Risk models
– ≠ models -> ≠ risk factors
– Carefull interpretation
– Helps the decision on the prevention options for breast
cancer

12. University of Coimbra
Faculty of Science and Technology
Master’s Degree in Molecular and Celular Biology
Risk factors and risk modeling in
breast cancer development
Ana Farinha; Daniela Pereira; Nuno Machado
Coimbra, March 5th 2011

13. Risk factors
• Reproductive risk factors
– Menstrual history
– Child bearing
– Breastfeeding
– Hormone replacement therapy
Porter, P.L. (2009) Salud Publica Mex 51 suppl 2, S141-146

14. Risk factors
• Lifestyle
– Physical inactivity
– Alcohol consumption
– Diet
– Obesity
Porter, P.L. (2009) Salud Publica Mex 51 suppl 2, S141-146

15. Risk factors
• Genetic factors
– Family history (first-degree relatives)
– BRCA1/2 mutations
– Ethnicity
Virnig, B. et al (2010) J Natl Cancer Inst 102, 170-178