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