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Underlying risk factors for breast cancer development and risk modeling
University of CoimbraFaculty of Science and Technology
Master’s Degree in Celular and Molecular Biology
Daniela Pereira
Coimbra, March 5th 2011
Breast Cancer
• The most frequently diagnosed in women• 4500 new cases/year
Globocan 2008 (IARC)
Breast
World incidence Portugal incidence
Risk factors for breast cancer development
Risk factors
Reproductive
Lifestyle
Genetic
Age/Gender
Prado, A. et al (2010) J Plast Reconstr Aesthet Surg 63, 1581-1587
Risk modeling
Amir. E et al (2010) J Natl Cancer Inst;102:680–691
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
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
Edwards, et al (2008) The Journal for Nurse Practitioners 4, 361-369Amir. E et al (2010) J Natl Cancer Inst;102:680–691
Risk modeling
Limitations
PatientPhysician
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 N0, M0 N2, M1
Molecular markers ER+, PR-, HER2+ 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 -
Clinical cases
?
• Gail Model – Breast Cancer Risk
Assessment Tool
Clinical cases - risk modeling
National Cancer Institute (www.cancer.gov)
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 N0, M0 N2, M1
Molecular markers ER+, PR-, HER2+ 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 -
Lifetime risk
17,6%12,6% (average woman)
1,4%
Lifetime risk
8,6%10,6% (average woman)
0,8%
• 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
Conclusion
Risk factors and risk modeling in breast cancer development
University of CoimbraFaculty of Science and Technology
Master’s Degree in Molecular and Celular Biology
Ana Farinha; Daniela Pereira; Nuno Machado
Coimbra, March 5th 2011
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
Risk factors
• Lifestyle– Physical inactivity– Alcohol consumption– Diet– Obesity
Porter, P.L. (2009) Salud Publica Mex 51 suppl 2, S141-146
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