Prediction of Cancer Prevention: From Mammogram Screening to Identification of BRCA1/2 Mutation Carriers in Underserved Populations

Abstract

Background: The US Preventative Service Task Force recommends that physicians perform a genetic risk assessment to identify women at risk for BRCA1/2 mutations associated with hereditary breast and ovarian cancer (HBOC) syndrome. However, outcomes data after a diagnosis of HBOC syndrome especially in diverse populations, are minimal. Here we asked if genetic screening of high-risk underserved women identified in the mammogram population reduces cancer incidence.

Methods: We evaluated 61,924 underserved women at screening mammography for family histories suggestive of HBOC syndrome over the course of 21 months. Data were collected retrospectively from patients at two safety net hospitals through chart review. A computer model was used to calculate the long-term effect of this screening on cancer incidence by assessing both the mutation detection rate and the completion of prophylactic surgeries in BRCA1/2 mutation carriers.

Findings: We identified 20 of the 85 (23.5%) expected BRCA1/2 mutation carriers in the underserved population. The frequencies of prophylactic mastectomies and oophorectomies in the mutation carriers were 25% and 40%, respectively. Using these data, our model predicted only an 8.8% reduction in both breast and ovarian cancer in the underserved patients. This contrasts with a 57% reduction in breast cancer and 51% reduction in ovarian cancer in an insured reference population. Our data indicate that underserved patients with HBOC syndrome are difficult to identify and when identified are limited in their ability to adhere to NCCN guidelines for cancer prevention.

Interpretation: Screening for women at risk for HBOC syndrome in mammogram populations will only prevent cancers if we can increase compliance with management guidelines. This study provides prototypic baseline data for step-wise analysis of the efficacy of the use of family history analysis in the mammography setting for detection and management of HBOC syndrome.

Keywords: BRCA1/2; Genetic testing; Hereditary breast and ovarian cancer syndrome; Population screening; Underserved.

Fig. 1

Mutation detection rates from the mammogram screening program. Mammogram patients who completed the RST questionnaire and were positive for family history suggestive of HBOC were then ushered through to genetics for further evaluation. A) Insured population and B) underserved population. This population completed navigation, defined as contacting the patient at least twice for a genetic referral.

Fig. 2

Rates of prophylactic surgeries in HBOC patients. Mutation carriers in the insured population (n = 37) and in the underserved population (n = 20) were evaluated for history of A) prophylactic mastectomy or B) prophylactic oophorectomies. The one male insured patient was excluded from the calculations of prophylactic mastectomy rates and NCCN compliance since guidelines do not exist.

Fig. 3

Modeling risk reduction for HBOC. Simulation models for cancer prevention in the different populations. Solid line represents no intervention as a result of genetic testing, dotted line represents the underserved population and dashed line represents the insured population. A) HBOC patients were reviewed for whether or not they underwent prophylactic mastectomy and then this frequency was used to model breast cancer risk reduction over 30 or 40 years. B) HBOC patients were reviewed for whether or not they underwent prophylactic oophorectomies and then this frequency was used to model ovarian cancer risk reduction over 30 or 40 years.