Published evidence on treatment costs of breast cancer varies widely in methodology and a global systematic review is lacking. This study aimed to conduct a systematic review to compare treatment costs of breast cancer by stage at diagnosis across countries at different levels of socio-economic development, and to identify key methodological differences in costing approaches. MEDLINE, EMBASE, and NHS Economic Evaluation Database (NHS EED) before April 2018. Studies were eligible if they reported treatment costs of breast cancer by stage at diagnosis using patient level data, in any language. Study characteristics and treatment costs by stage were summarised. Study quality was assessed using the Drummond Checklist, and detailed methodological differences were further compared. Twenty studies were included, 15 from high-income countries and five from low- and middle-income countries. Eleven studies used the FIGO staging system, and the mean treatment costs of breast cancer at Stage II, III and IV were 32%, 95%, and 109% higher than Stage I. Five studies categorised stage as in situ, local, regional and distant. The mean treatment costs of regional and distant breast cancer were 41% and 165% higher than local breast cancer. Overall, the quality of studies ranged from 50% (lowest quality) to 84% (highest). Most studies used regression frameworks but the choice of regression model was rarely justified. Few studies described key methodological issues including skewness, zero values, censored data, missing data, and the inclusion of control groups to estimate disease-attributable costs. Treatment costs of breast cancer generally increased with the advancement of the disease stage at diagnosis. Methodological issues should be better handled and properly described in future costing studies.

Clinical criteria/Family history-based BRCA testing misses a large proportion of BRCA carriers who can benefit from screening/prevention. We estimate the cost-effectiveness of population-based BRCA testing in general population women across different countries/health systems. A Markov model comparing the lifetime costs and effects of BRCA1/BRCA2 testing all general population women ≥30 years compared with clinical criteria/FH-based testing. Separate analyses are undertaken for the UK/USA/Netherlands (high-income countries/HIC), China/Brazil (upper–middle income countries/UMIC) and India (low–middle income countries/LMIC) using both health system/payer and societal perspectives. BRCA carriers undergo appropriate screening/prevention interventions to reduce breast cancer (BC) and ovarian cancer (OC) risk. Outcomes include OC, BC, and additional heart disease deaths and incremental cost-effectiveness ratio (ICER)/quality-adjusted life year (QALY). Probabilistic/one-way sensitivity analyses evaluate model uncertainty. For the base case, from a societal perspective, we found that population-based BRCA testing is cost-saving in HIC (UK-ICER = $−5639/QALY; USA-ICER = $−4018/QALY; Netherlands-ICER = $−11,433/QALY), and it appears cost-effective in UMIC (China-ICER = $18,066/QALY; Brazil-ICER = $13,579/QALY), but it is not cost-effective in LMIC (India-ICER = $23,031/QALY). From a payer perspective, population-based BRCA testing is highly cost-effective in HIC (UK-ICER = $21,191/QALY, USA-ICER = $16,552/QALY, Netherlands-ICER = $25,215/QALY), and it is cost-effective in UMIC (China-ICER = $23,485/QALY, Brazil−ICER = $20,995/QALY), but it is not cost-effective in LMIC (India-ICER = $32,217/QALY). BRCA testing costs below $172/test (ICER = $19,685/QALY), which makes it cost-effective (from a societal perspective) for LMIC/India. Population-based BRCA testing can prevent an additional 2319 to 2666 BC and 327 to 449 OC cases per million women than the current clinical strategy. Findings suggest that population-based BRCA testing for countries evaluated is extremely cost-effective across HIC/UMIC health systems, is cost-saving for HIC health systems from a societal perspective, and can prevent tens of thousands more BC/OC cases.

We present findings of a cancer multidisciplinary-team (MDT) coordinated mainstreaming pathway of unselected 5-panel germline BRCA1/BRCA2/RAD51C/RAD51D/BRIP1 and parallel somatic BRCA1/BRCA2 testing in all women with epithelial-OC and highlight the discordance between germline and somatic testing strategies across two cancer centres. Patients were counselled and consented by a cancer MDT member. The uptake of parallel multi-gene germline and somatic testing was 97.7%. Counselling by clinical-nurse-specialist more frequently needed >1 consultation (53.6% (30/56)) compared to a medical (15.0% (21/137)) or surgical oncologist (15.3% (17/110)) (p < 0.001). The median age was 54 (IQR = 51–62) years in germline pathogenic-variant (PV) versus 61 (IQR = 51–71) in BRCA wild-type (p = 0.001). There was no significant difference in distribution of PVs by ethnicity, stage, surgery timing or resection status. A total of 15.5% germline and 7.8% somatic BRCA1/BRCA2 PVs were identified. A total of 2.3% patients had RAD51C/RAD51D/BRIP1 PVs. A total of 11% germline PVs were large-genomic-rearrangements and missed by somatic testing. A total of 20% germline PVs are missed by somatic first BRCA-testing approach and 55.6% germline PVs missed by family history ascertainment. The somatic testing failure rate is higher (23%) for patients undergoing diagnostic biopsies. Our findings favour a prospective parallel somatic and germline panel testing approach as a clinically efficient strategy to maximise variant identification. UK Genomics test-directory criteria should be expanded to include a panel of OC genes.

Unselected multigene testing for all women with breast cancer (BC) identifies more cancer susceptibility gene (CSG) carriers who can benefit from precision prevention compared with family history (FH)/clinical-criteria-based guidelines. Very little CSG testing is undertaken in middle-income countries such as China, and its cost-effectiveness remains unaddressed. We aimed to estimate cost-effectiveness and population impact of multigene testing for all Chinese BC patients. Data from 8085 unselected BC patients recruited to a Peking University Cancer Hospital study were used for microsimulation modeling, comparing three strategies in the Chinese setting: all BC women undergo BRCA1/BRCA2/PALB2 genetic testing, only BC women fulfilling FH/clinical criteria undergo BRCA testing, and no genetic testing. Prophylactic mastectomy and salpingo-oophorectomy would be adopted where appropriate. Societal and payer perspectives with a lifetime horizon along with sensitivity analyses were presented. Incremental cost-effectiveness ratio (ICER): incremental cost per quality-adjusted life-year (QALY) gained is compared to the USD 10,260/QALY (one-times GDP per capita) willingness-to-pay threshold. BC incidence, ovarian cancer (OC) incidence, and related deaths were also estimated. FH/clinical-criteria-based BRCA testing was ruled out on the principle of extensive dominance. Compared with no genetic testing, multigene testing for all BC patients had an ICER = USD 4506/QALY (societal perspective) and USD 7266/QALY (payer perspective), well below our threshold. Probabilistic sensitivity analysis showed unselected multigene testing remained cost-effective for 94.2%/86.6% of simulations from the societal and payer perspectives. One year’s unselected multigene testing could prevent 7868 BC/OC cases and 5164 BC/OC deaths in China. Therefore, unselected multigene testing is extremely cost-effective and should be offered to all Chinese women with BC.