Background:
Clinical management options have expanded for patients harboring pathogenic variants (PVs) in cancer predisposition genes. Historically, testing costs and clinical implementation challenges led to restrictive testing guidelines in many countries. Increasing evidence demonstrates that broader testing is a cost-effective way to identify patients with PVs. We assessed the efficacy of multiple international testing guidelines in identifying breast cancer (BC) patients with clinically actionable PVs.
Methods:
We reanalyzed a prospective cohort of U.S.-based, primarily of Northern European, BC patients, referred for germline genetic testing (PMID: 30526229). We applied testing guidelines from Australia, U.K. and 2 Canadian provinces (Ontario, British Columbia) to this cohort to determine their sensitivity for selecting patients with PVs in high risk (>4x risk compared to general population) breast/ovarian cancer genes. These populations were chosen because of similar healthcare systems and ancestral distribution.
Results:
Table 1 displays the distribution of in criteria (IC) vs. out of criteria (OOC) patients by testing criteria. Over 75% of patients in each country/province analyzed were OOC. Rates of PVs were similar between IC and OOC patients across countries. Existing Canadian, Australian and U.K. criteria missed up to 30% of patients with high risk PVs. The majority (>80%) of PVs in OOC patients were in genes with published management guidelines.
Conclusions:
In our cohort, select international testing criteria identified <30% of patients with PVs. These data suggest expanding certain international guidelines would allow better identification and improved management for BC patients across the globe.
|
Overall |
In criteria |
Out of criteria |
||||||
|
Country/providence |
Guideline |
Total n of cohort |
IC (% of total cohort) |
OOC (% of total cohort) |
Total PV IC (% of IC cohort) |
Total PV OOC (% of OOC cohort) |
High risk^ PVs (% of total PVs) |
High risk^ PVs (% of total PVs) |
|
U.S. |
NCCN |
953 |
473 (49.6) |
480 (50.4) |
43 (9.1) |
40 (8.3) |
22 (26.5) |
8 (9.6) |
|
Ontario |
MOHLTC |
953 |
210 (22.0) |
743 (78.0) |
18 (8.6) |
65 (8.7) |
5 (6.0) |
25 (30.1) |
|
B.C. |
BCHCP |
953 |
203 (21.3) |
750 (78.7) |
24 (11.8) |
59 (7.9) |
9 (10.8) |
19 (22.9) |
|
Australia |
eviQ |
953 |
180 (18.9) |
773 (81.1) |
19 (10.6) |
64 (8.3) |
12 (14.5) |
18 (21.7) |
|
U.K. |
NICE* |
826** |
127 (14.7) |
736 (85.3) |
11 (8.7) |
64 (8.7) |
6 (7.2) |
22 (26.5) |
Findings in IC vs. OOC patients
US, United States; B.C., British Columbia; UK, United Kingdom
NCCN, National Comprehensive Cancer Network v. 2017
MOHLTC, Ministry of Health and Long Term Care
BCHCP, BC Provincial Health Services Authority Hereditary Cancer Program
NICE, National Institute for Health Care Excellence
*testing eligibility requires >10% BRCA mutation detection rate, typically assessed by BOADICEA model in the UK but for this cohort risk estimates were only available via BRCAPro
** BRCAPro scores were not available for the full cohort
^Includes BRCA1, BRCA2, PALB2, TP53, RAD51C, RAD51D, MSH6