Medication Use for the Risk Reduction of Primary Breast Cancer in Women

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.

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“…P8: The uptake of RRSO in unaffected BRCA1/BRCA2 carriers is taken from a study among high-risk UK women [7].…”

Section: Appendix a Probability Values And Explanationmentioning

confidence: 99%

“…In BRCA women, RRSO reduces OC risk by 79-96% [4][5][6]. Additionally, they can opt for MRI/mammography screening, chemoprevention with selective estrogen-receptor modulators (SERM) or aromatase inhibitors [7]; or risk-reducing mastectomy (RRM) [8,9] to reduce their BC risk [10]. RRM reduces BC risk by 90-95% [8,9].…”

Section: Introductionmentioning

confidence: 99%

Economic Evaluation of Population-Based BRCA1/BRCA2 Mutation Testing across Multiple Countries and Health Systems

Manchanda

Sun

Patel

et al. 2020

Cancers

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“…Breast cancer is the most common cancer in women. [ 41–43 ] Patients with TNBC show poorest prognosis among the three breast cancer subtypes. TNBC are highly heterogeneity, and a study claimed that TNBC can be further divided into 16 subtypes.…”

Section: Discussionmentioning

confidence: 99%

Inhibition Lysosomal Degradation of Clusterin by Protein Kinase D3 Promotes Triple‐Negative Breast Cancer Tumor Growth

Liu

Zhou

et al. 2021

Advanced Science

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Triple negative breast cancer (TNBC), with its lack of targeted therapies, shows the worst mortality rate among all breast cancer subtypes. Clusterin (CLU) is implicated to play important oncogenic roles in cancer via promoting various downstream oncogenic pathways. Here, protein kinase D3 (PRKD3) is defined to be a key regulator of CLU in promoting TNBC tumor growth. Mechanically, PRKD3 with kinase activity binding to CLU is critical for CLU protein stability via inhibiting CLU's lysosomal distribution and degradation. CLU and PRKD3 protein level are significantly elevated and positively correlated in collected TNBC tumor samples. CLU silencer (OGX‐011) and PRKDs inhibitor (CRT0066101) can both result in impressive tumor growth suppression in vitro and in vivo, suggesting targeting CLU and its key regulator‐PRKD3 are promisingly efficient against TNBC. Finally, secreted CLU (sCLU) is found to be elevated in serums from TNBC patients and reduced in serum from TNBC murine models post OGX‐011 and/or CRT0066101 treatment, suggesting serum sCLU is a promising blood‐based biomarker for clinical management of TNBC. Taken together, this study provides a thorough molecular basis as well as preclinical evidences for targeting CLU pathway as a new promising strategy against TNBC via revealing PRKD3 as the key regulator of CLU in TNBC.

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“…The systematic review on “Medication use for the risk reduction of primary breast cancer in women” by the U.S. Preventive Services Task Force found a RR of 2.25 (1.17–4.41) for EC in women taking tamoxifen versus placebo or 4 (1–8) more/1000 women, vs. a placebo rate of 0.62/1000 [ 18 ]. The risks of developing EC were higher in older than in younger women and returned to normal after the end of tamoxifen medication [ 19 ].…”

Section: Incidence Of Endometrial Cancer In Tamoxifen Usersmentioning

confidence: 99%

Tamoxifen and Endometrial Cancer: A Janus-Headed Drug

Emons

Mustea

Tempfer³

2020

Cancers

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Tamoxifen is a selective estrogen receptor modulator used for the treatment and prevention of estrogen receptor (ER)—positive breast cancer. However, tamoxifen increases the risk of endometrial cancer (EC) by about 2–7 fold, and more aggressive types of EC with poor prognoses are observed in tamoxifen users. On the other hand, tamoxifen is an efficacious treatment for advanced or recurrent EC with low toxicity. The differential agonistic or antagonistic effects of tamoxifen on ERα are explained by the tissue-specific expression profiles of co-activators and co-repressors of the receptor. The estrogen-agonistic effect of tamoxifen in endometrial cancers can also be explained by the expression of G-protein coupled estrogen receptor 1 (GPER-1), a membrane-bound estrogen receptor for which tamoxifen and other “antiestrogens” are pure agonists.

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Medication Use for the Risk Reduction of Primary Breast Cancer in Women

Cited by 90 publications

References 110 publications

Economic Evaluation of Population-Based BRCA1/BRCA2 Mutation Testing across Multiple Countries and Health Systems

Economic Evaluation of Population-Based BRCA1/BRCA2 Mutation Testing across Multiple Countries and Health Systems

Inhibition Lysosomal Degradation of Clusterin by Protein Kinase D3 Promotes Triple‐Negative Breast Cancer Tumor Growth

Tamoxifen and Endometrial Cancer: A Janus-Headed Drug

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