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. 2023 Jun 26;23(1):590.
doi: 10.1186/s12885-023-10956-6.

Decision-analytic evaluation of the comparative effectiveness and cost-effectiveness of strategies to prevent breast and ovarian cancer in German women with BRCA-1/2 mutations

Lára R Hallsson  1   2   3 , Gaby Sroczynski  1 , Jutta Engel  4 , Uwe Siebert  5   6   7   8
Affiliations

Decision-analytic evaluation of the comparative effectiveness and cost-effectiveness of strategies to prevent breast and ovarian cancer in German women with BRCA-1/2 mutations

Lára R Hallsson et al. BMC Cancer. .

Abstract

Background: Women with inherited mutations in the BRCA1 or BRCA2 genes have increased lifetime risks for developing breast and/or ovarian cancer and may develop these cancers around the age of 30 years. Therefore, prevention of breast and ovarian cancer in these women may need to start relatively early in life. In this study we systematically evaluate the long-term effectiveness and cost effectiveness of different prevention strategies for breast and ovarian cancer in women with BRCA-1/2 mutation in Germany.

Methods: A decision-analytic Markov model simulating lifetime breast and ovarian cancer development in BRCA-1/2 carriers was developed. Different strategies including intensified surveillance (IS), prophylactic bilateral mastectomy (PBM), and prophylactic bilateral salpingo-oophorectomy (PBSO) alone or in combination at different ages were evaluated. German clinical, epidemiological, and economic (in 2022 Euro) data were used. Outcomes included cancer incidences, mortality, life years (LYs), quality-adjusted life years (QALYs), and discounted incremental cost-effectiveness ratios (ICER). We adopted the German health-care system perspective and discounted costs and health effects with 3% annually.

Results: All intervention strategies are more effective and less costly than IS alone. Prevention with PBM plus PBSO at age 30 maximizes life expectancy with 6.3 LYs gained, whereas PBM at age 30 with delayed PBSO at age 35 improves quality of life with 11.1 QALYs gained, when compared to IS alone. A further delay of PBSO was associated with lower effectiveness. Both strategies are cost effective with ICERs significantly below 10,000 EUR/LYG or QALY.

Conclusion: Based on our results, PBM at age 30 plus PBSO between age 30 and 40 prolongs life and is cost effective in women with BRCA-1/2 mutations in Germany. Serial preventive surgeries with delayed PBSO potentially improve quality of life for women. However, delaying PBM and/or PBSO further may lead to increased mortality and reduced QALYs.

Keywords: Breast cancer; Cancer risk; Gynecological cancer; Ovarian cancer; Prevention; Screening.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Illustration of the decision-analytic model. Health states representing the natural history of breast and ovarian cancer represented in the Markov model are shown as bubbles: No breast and ovarian cancer (well), undetected invasive breast cancer stage I to stage IV, diagnosed invasive breast cancer stage I to stage IV (pT1- pT4), breast cancer survivors 10 years after initial breast cancer diagnosis and treatment (breast cancer survivor), death from breast cancer (breast cancer death), undetected invasive ovarian cancer stage I to stage IV, diagnosed invasive ovarian cancer stage I to stage IV (FIGO states I–IV), ovarian cancer survivors 10 years after ovarian cancer diagnosis and treatment (ovarian cancer survivor), death from ovarian cancer (ovarian cancer death), and death from other causes (death other causes). Progression from one health state to the other is indicated with solid arrows and remaining in the same health state with curved arrows
Fig. 2
Fig. 2
Clinical effectiveness in undiscounted incremental life years (LYs) and undiscounted incremental quality-adjusted life years (QALYs) compared to standard care (intensified surveillance for breast cancer). incr.: incremental; LYs: Life years; PBM: Prophylactic bilateral mastectomy; PBSO: Prophylactic bilateral salpingo-oophorectomy; QALYs: quality-adjusted life years; y: years of age
Fig. 3
Fig. 3
Cost-effectiveness plane of different preventive strategies:(A) discounted total life-time costs (in €) versus effectiveness expressed in discounted total life years (LYs) and (B) discounted total life-time costs (in €) versus discounted total quality-adjusted life years (QALYs). The respective stepwise ICER (in €/LY) and ICUR (in €/QALY) on the efficiency frontier (blue line) are shown in boxes. Reference strategy: PBM at age 30 and PBSO at age 40 (S12) PBM: Prophylactic bilateral mastectomy; PBSO: Prophylactic bilateral salpingo-oophorectomy; y: years of age
See this image and copyright information in PMC

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