Breast Cancer Risk Assessment
The Following information was referenced from the article: Assessing Women at High Risk of Breast Cancer: A Review of Risk Assessment Models; JNCI; May 2010 – Arir et al.
The full article can be viewed at http://jnci.oxfordjournals.org/content/102/10/680.full.pdf+html
Assessing Breast Cancer Risk
Breast cancer risk assessment provides women at high risk the opportunity for more intensive surveillance or preventative options such as surgery or chemoprevention.
Breast cancer risk assessment must be individualized. An appropriate disease management strategy includes the knowledge of the risk of breast cancer along with the risks and benefits associated with increased surveillance and preventative options.
Though genetic and familial factors can substantially increase the likelihood of developing breast cancer, less than 5% of new breast cancer diagnoses are due to known mutations in high risk genes. Other than age, the presence of a substantial family history of breast cancer is probably the most important risk factor for the development of the disease.
Individualized Risk Assessment Should be Performed With a Two Pronged Approach
First, Radiology Ltd. will soon be providing lifetime estimates for breast cancer risk using the Tyrer-Cuzick model on all our mammographic screening patients. In accordance with the American Cancer Society guidelines, if the lifetime breast cancer risk is greater than or equal to 20%, an annual breast MRI will be recommended in addition to mammographic screening.
Second, patients identified to be at high-risk for breast cancer should be considered for referral to a genetic counselor.
The following USPSTF guidelines can help identify high risk patients suitable for referral to genetic counselors:
- 2 first-degree relatives (mother, daughter or sister) diagnosed with breast cancer, one of whom was younger than 50 years
- 3 or more first- or second-degree relatives (aunt, grandmother) diagnosed with breast cancer regardless of age
- Combination of first- and second-degree relatives diagnosed with breast and ovarian cancer regardless of age
- First-degree relative with bilateral breast cancer
- Breast cancer in a male relative
- Combination of 2 or more first- or second-degree relatives with ovarian cancer
- For women of Ashkenazi Jewish descent: any first-degree of 2 second-degree relatives on the same side of the family diagnosed with breast or ovarian cancer
A genetic counselor creates a full pedigree and may use statistical models to calculate if the patient is at sufficient risk to justify genetic testing.
Risks Associated With BRCA Mutations
- BRCA1, 2 mutations are associated with an increased risk of breast, ovarian and pancreatic cancer (triple -ve breast cancer is associated with BRCA1).
- BRCA1 mutations are also associated with cervical, uterine, colon, testicular and prostate cancer.
- BRCA2 mutations are also associated with stomach, gallbladder and bile duct cancer and melanoma.
Comparison of Model Accuracy
Only one small study has compared multiple cancer risk models (GAIL, BRCAPRO and the Tyrer-Cuzick) in a prospective fashion.
Two versions of the BRCAPRO model were used which were calibrated to the mutation prevalence estimates described by Claus and Ford.
The study included 1,933 women, in which 52 cancers were identified over 5.27 years of follow up.
Ratios of Expected to Observed Cancers Were:
- 0.48 Gail
- 0.56 BRCAPRO (Claus)
- 0.49 BRCAPRO (Ford)
- 0.81 Tyrer-Cuzick
The Accuracy Models for Individual Patients Were Assessed Using ROC Curves With the Following AUC’s:
- 0.735 Gail
- 0.716 BRCAPRO (Claus)
- 0.737BRCAPRO (Ford)
- 0.762 Tyrer-Cuzick
The study revealed that the Tyrer-Cuzick model was the most consistently accurate model for predicting the risk of breast cancer. Further analysis showed the other models consistently underestimated the risk of breast cancer, particularly in women with a single first-degree relative affected with breast cancer.