Results of breast cancer risk assessment and hereditary cancer genetic testing in community obstetrics and gynaecology practice following a prospective quality Improvement initiative.

BACKGROUND

Clinical guidelines recommend hereditary cancer risk assessment (HCRA) to identify candidates for genetic counselling and testing based on personal and family history. Incorporating genetic testing into HCRA improves risk stratification and management. We previously showed that process improvements increase genetic testing completion rates. This study describes outcomes of routine genetic testing in a community obstetrics and gynaecology (OB/GYN) setting.

METHODS

A prospective, single-arm quality improvement initiative was conducted at five U.S. OB/GYN practices (July 2021-November 2022). A guideline-based online screening tool and virtual patient education were implemented. Genetic testing used a 48-gene hereditary pan-cancer panel (MyRisk®). The remaining lifetime breast cancer risk was estimated using Tyrer-Cuzick 7.0.2 alone or a combined risk score (CRS).

RESULTS

Of 1,285 patients meeting guideline criteria, 439 (34.2%) completed testing. Among 367 (88.0%) without a clinically significant mutation and with valid risk estimates, 233 (63.5%) had lifetime breast cancer risk <20% and 66 (18.0%) had risk ≥20% by both Tyrer-Cuzick and CRS. Discordance between Tyrer-Cuzick and CRS occurred in 68 (18.5%) patients: 49 (13.4%) were <20% by CRS but ≥20% by Tyrer-Cuzick; 19 (5.2%) were ≥20% by CRS but <20% by Tyrer-Cuzick. Overall, 134 (36.5%) had lifetime risk ≥20% by either model. Fifteen pathogenic variants were identified in 14 (3.2%) patients, including CHEK2 (n = 4), HOXB13, MITF, PALB2 (n = 2 each), and BRCA2, PMS2, MSH6, RAD51C, BRIP1 (n = 1 each).

CONCLUSION

Most patients undergoing genetic testing did not carry an inherited mutation; however, over one-third of those without a mutation had lifetime breast cancer risk ≥20% based on Tyrer-Cuzick and/or CRS. These findings underscore the importance of routine HCRA and individualised management based on comprehensive risk assessment.