Cancers

2024

Jump to: 2023, 2022

34 pages, 509 KiB

Open AccessReview

Exploring the Potential Link between PFAS Exposure and Endometrial Cancer: A Review of Environmental and Sociodemographic Factors

by Aderonke Ayodele and Emmanuel Obeng-Gyasi

Cancers 2024, 16(5), 983; https://doi.org/10.3390/cancers16050983 - 28 Feb 2024

Cited by 1 | Viewed by 3556

Abstract

This exploratory narrative review paper delves into the intricate interplay between per- and polyfluoroalkyl substances (PFAS) exposure, sociodemographic factors, and the influence of stressors in the context of endometrial cancer. PFAS, ubiquitous environmental contaminants notorious for their persistence in the ecosystem, have garnered [...] Read more.

This exploratory narrative review paper delves into the intricate interplay between per- and polyfluoroalkyl substances (PFAS) exposure, sociodemographic factors, and the influence of stressors in the context of endometrial cancer. PFAS, ubiquitous environmental contaminants notorious for their persistence in the ecosystem, have garnered attention for their potential to disrupt endocrine systems and provoke immune responses. We comprehensively examine the various sources of PFAS exposure, encompassing household items, water, air, and soil, thus shedding light on the multifaceted routes through which individuals encounter these compounds. Furthermore, we explore the influence of sociodemographic factors, such as income, education, occupation, ethnicity/race, and geographical location and their relationship to endometrial cancer risk. We also investigated the role of stress on PFAS exposure and endometrial cancer risk. The results revealed a significant impact of sociodemographic factors on both PFAS levels and endometrial cancer risk. Stress emerged as a notable contributing factor influencing PFAS exposure and the development of endometrial cancer, further emphasizing the importance of stress management practices for overall well-being. By synthesizing evidence from diverse fields, this review underscores the need for interdisciplinary research and targeted interventions to comprehensively address the complex relationship between PFAS, sociodemographic factors, stressors, and endometrial cancer. Full article

2023

Jump to: 2024, 2022

12 pages, 899 KiB

Open AccessArticle

Personalized Breast Cancer Screening: A Risk Prediction Model Based on Women Attending BreastScreen Norway

by Javier Louro, Marta Román, Nataliia Moshina, Camilla F. Olstad, Marthe Larsen, Silje Sagstad, Xavier Castells and Solveig Hofvind

Cancers 2023, 15(18), 4517; https://doi.org/10.3390/cancers15184517 - 12 Sep 2023

Cited by 2 | Viewed by 1784

Abstract

Background: We aimed to develop and validate a model predicting breast cancer risk for women targeted by breast cancer screening. Method: This retrospective cohort study included 57,411 women screened at least once in BreastScreen Norway during the period from 2007 to 2019. The [...] Read more.

Background: We aimed to develop and validate a model predicting breast cancer risk for women targeted by breast cancer screening. Method: This retrospective cohort study included 57,411 women screened at least once in BreastScreen Norway during the period from 2007 to 2019. The prediction model included information about age, mammographic density, family history of breast cancer, body mass index, age at menarche, alcohol consumption, exercise, pregnancy, hormone replacement therapy, and benign breast disease. We calculated a 4-year absolute breast cancer risk estimates for women and in risk groups by quartiles. The Bootstrap resampling method was used for internal validation of the model (E/O ratio). The area under the curve (AUC) was estimated with a 95% confidence interval (CI). Results: The 4-year predicted risk of breast cancer ranged from 0.22–7.33%, while 95% of the population had a risk of 0.55–2.31%. The thresholds for the quartiles of the risk groups, with 25% of the population in each group, were 0.82%, 1.10%, and 1.47%. Overall, the model slightly overestimated the risk with an E/O ratio of 1.10 (95% CI: 1.09–1.11) and the AUC was 62.6% (95% CI: 60.5–65.0%). Conclusions: This 4-year risk prediction model showed differences in the risk of breast cancer, supporting personalized screening for breast cancer in women aged 50–69 years. Full article

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23 pages, 4433 KiB

Open AccessArticle

A Clinical Risk Model for Personalized Screening and Prevention of Breast Cancer

by Mikael Eriksson, Kamila Czene, Celine Vachon, Emily F. Conant and Per Hall

Cancers 2023, 15(12), 3246; https://doi.org/10.3390/cancers15123246 - 19 Jun 2023

Cited by 4 | Viewed by 2290

Abstract

Background: Image-derived artificial intelligence (AI) risk models have shown promise in identifying high-risk women in the short term. The long-term performance of image-derived risk models expanded with clinical factors has not been investigated. Methods: We performed a case–cohort study of 8110 women aged [...] Read more.

Background: Image-derived artificial intelligence (AI) risk models have shown promise in identifying high-risk women in the short term. The long-term performance of image-derived risk models expanded with clinical factors has not been investigated. Methods: We performed a case–cohort study of 8110 women aged 40–74 randomly selected from a Swedish mammography screening cohort initiated in 2010 together with 1661 incident BCs diagnosed before January 2022. The imaging-only AI risk model extracted mammographic features and age at screening. Additional lifestyle/familial risk factors were incorporated into the lifestyle/familial-expanded AI model. Absolute risks were calculated using the two models and the clinical Tyrer–Cuzick v8 model. Age-adjusted model performances were compared across the 10-year follow-up. Results: The AUCs of the lifestyle/familial-expanded AI risk model ranged from 0.75 (95%CI: 0.70–0.80) to 0.68 (95%CI: 0.66–0.69) 1–10 years after study entry. Corresponding AUCs were 0.72 (95%CI: 0.66–0.78) to 0.65 (95%CI: 0.63–0.66) for the imaging-only model and 0.62 (95%CI: 0.55–0.68) to 0.60 (95%CI: 0.58–0.61) for Tyrer–Cuzick v8. The increased performances were observed in multiple risk subgroups and cancer subtypes. Among the 5% of women at highest risk, the PPV was 5.8% using the lifestyle/familial-expanded model compared with 5.3% using the imaging-only model, p < 0.01, and 4.6% for Tyrer–Cuzick, p < 0.01. Conclusions: The lifestyle/familial-expanded AI risk model showed higher performance for both long-term and short-term risk assessment compared with imaging-only and Tyrer–Cuzick models. Full article

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12 pages, 1415 KiB

Open AccessArticle

Comparing Prognostic Factors of Cancers Identified by Artificial Intelligence (AI) and Human Readers in Breast Cancer Screening

by Cary J. G. Oberije, Nisha Sharma, Jonathan J. James, Annie Y. Ng, Jonathan Nash and Peter D. Kecskemethy

Cancers 2023, 15(12), 3069; https://doi.org/10.3390/cancers15123069 - 6 Jun 2023

Cited by 3 | Viewed by 2335

Abstract

Invasiveness status, histological grade, lymph node stage, and tumour size are important prognostic factors for breast cancer survival. This evaluation aims to compare these features for cancers detected by AI and human readers using digital mammography. Women diagnosed with breast cancer between 2009 [...] Read more.

Invasiveness status, histological grade, lymph node stage, and tumour size are important prognostic factors for breast cancer survival. This evaluation aims to compare these features for cancers detected by AI and human readers using digital mammography. Women diagnosed with breast cancer between 2009 and 2019 from three UK double-reading sites were included in this retrospective cohort evaluation. Differences in prognostic features of cancers detected by AI and the first human reader (R1) were assessed using chi-square tests, with significance at p < 0.05. From 1718 screen-detected cancers (SDCs) and 293 interval cancers (ICs), AI flagged 85.9% and 31.7%, respectively. R1 detected 90.8% of SDCs and 7.2% of ICs. Of the screen-detected cancers detected by the AI, 82.5% had an invasive component, compared to 81.1% for R1 (p-0.374). For the ICs, this was 91.5% and 93.8% for AI and R1, respectively (p = 0.829). For the invasive tumours, no differences were found for histological grade, tumour size, or lymph node stage. The AI detected more ICs. In summary, no differences in prognostic factors were found comparing SDC and ICs identified by AI or human readers. These findings support a potential role for AI in the double-reading workflow. Full article

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15 pages, 4516 KiB

Open AccessArticle

Co-Creation of Breast Cancer Risk Communication Tools and an Assessment of Risk Factor Awareness: A Qualitative Study of Patients and the Public in India

by Divya Pillai, Jyoti Narayan, Aleksandra Gentry-Maharaj, Suryanarayana Deo, Dehannathparambil Kottarathil Vijaykumar, Poulome Mukherjee, Nitya Wadhwa, Aparajita Bhasin, Ashutosh Mishra, Anupama Rajanbabu, Ravi Kannan, Zakir Husain, Avinash Kumar, Antonis C. Antoniou, Ranjit Manchanda and Usha Menon

Cancers 2023, 15(11), 2973; https://doi.org/10.3390/cancers15112973 - 30 May 2023

Cited by 3 | Viewed by 2548

Abstract

Background: Low awareness of BC and its associated risk factors causes delays in diagnosis and impacts survival. It is critical to communicate BC risk to patients in a format that they are easily able to understand. Our study aim was to develop easy-to-follow [...] Read more.

Background: Low awareness of BC and its associated risk factors causes delays in diagnosis and impacts survival. It is critical to communicate BC risk to patients in a format that they are easily able to understand. Our study aim was to develop easy-to-follow transmedia prototypes to communicate BC risk and evaluate user preferences, alongside exploring awareness of BC and its risk factors. Methods: Prototypes of transmedia tools for risk communication were developed with multidisciplinary input. A qualitative in-depth online interview study was undertaken using a pre-defined topic guide of BC patients (7), their relatives (6), the general public (6), and health professionals (6). Interviews were analyzed using a thematic approach. Findings: Most participants preferred pictographic representations (frequency format) of lifetime risk and risk factors and storytelling using short animations and comic strips (infographics) for communicating genetic risk and testing: “In a short time, they explained it very well, and I liked it”. Suggestions included minimizing technical terminology, decreasing the delivery speed, “two-way dialogue”, and using local “language for different locations”. There was low awareness of BC, with some understanding of age and hereditary risk factors but limited knowledge of reproductive factors. Interpretation: Our findings support use of multiple context-specific multimedia tools in communicating cancer risk in an easy-to-understand way. The preference for storytelling using animations and infographics is a novel finding and should be more widely explored. Full article

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24 pages, 2658 KiB

Open AccessSystematic Review

Breast Cancer Risk and Breast-Cancer-Specific Mortality following Risk-Reducing Salpingo-Oophorectomy in BRCA Carriers: A Systematic Review and Meta-Analysis

by Faiza Gaba, Oleg Blyuss, Alex Tan, Daniel Munblit, Samuel Oxley, Khalid Khan, Rosa Legood and Ranjit Manchanda

Cancers 2023, 15(5), 1625; https://doi.org/10.3390/cancers15051625 - 6 Mar 2023

Cited by 6 | Viewed by 3762

Abstract

Background: Risk-reducing salpingo-oophorectomy (RRSO) is the gold standard method of ovarian cancer risk reduction, but the data are conflicting regarding the impact on breast cancer (BC) outcomes. This study aimed to quantify BC risk/mortality in BRCA1/BRCA2 carriers after RRSO. Methods: We [...] Read more.

Background: Risk-reducing salpingo-oophorectomy (RRSO) is the gold standard method of ovarian cancer risk reduction, but the data are conflicting regarding the impact on breast cancer (BC) outcomes. This study aimed to quantify BC risk/mortality in BRCA1/BRCA2 carriers after RRSO. Methods: We conducted a systematic review (CRD42018077613) of BRCA1/BRCA2 carriers undergoing RRSO, with the outcomes including primary BC (PBC), contralateral BC (CBC) and BC-specific mortality (BCSM) using a fixed-effects meta-analysis, with subgroup analyses stratified by mutation and menopause status. Results: RRSO was not associated with a significant reduction in the PBC risk (RR = 0.84, 95%CI: 0.59–1.21) or CBC risk (RR = 0.95, 95%CI: 0.65–1.39) in BRCA1 and BRCA2 carriers combined but was associated with reduced BC-specific mortality in BC-affected BRCA1 and BRCA2 carriers combined (RR = 0.26, 95%CI: 0.18–0.39). Subgroup analyses showed that RRSO was not associated with a reduction in the PBC risk (RR = 0.89, 95%CI: 0.68–1.17) or CBC risk (RR = 0.85, 95%CI: 0.59–1.24) in BRCA1 carriers nor a reduction in the CBC risk in BRCA2 carriers (RR = 0.35, 95%CI: 0.07–1.74) but was associated with a reduction in the PBC risk in BRCA2 carriers (RR = 0.63, 95%CI: 0.41–0.97) and BCSM in BC-affected BRCA1 carriers (RR = 0.46, 95%CI: 0.30–0.70). The mean NNT = 20.6 RRSOs to prevent one PBC death in BRCA2 carriers, while 5.6 and 14.2 RRSOs may prevent one BC death in BC-affected BRCA1 and BRCA2 carriers combined and BRCA1 carriers, respectively. Conclusions: RRSO was not associated with PBC or CBC risk reduction in BRCA1 and BRCA2 carriers combined but was associated with improved BC survival in BC-affected BRCA1 and BRCA2 carriers combined and BRCA1 carriers and a reduced PBC risk in BRCA2 carriers. Full article

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14 pages, 1227 KiB

Open AccessArticle

Uptake and Effectiveness of Risk-Reducing Surgeries in Unaffected Female BRCA1 and BRCA2 Carriers: A Single Institution Experience in the Czech Republic

by Martina Zimovjanova, Zuzana Bielcikova, Michaela Miskovicova, Michal Vocka, Anna Zimovjanova, Marian Rybar, Jan Novotny and Lubos Petruzelka

Cancers 2023, 15(4), 1072; https://doi.org/10.3390/cancers15041072 - 8 Feb 2023

Viewed by 1897

Abstract

Unnafected female carriers of BRCA1 and BRCA2 pathogenic/likely pathogenic variants (P/LPVs) are at higher risk of breast cancer (BC) and ovarian cancer (OC). In the retrospective single-institution study in the Czech Republic, we analyzed the rate, longitudinal trends, and effectiveness of prophylactic risk-reducing [...] Read more.

Unnafected female carriers of BRCA1 and BRCA2 pathogenic/likely pathogenic variants (P/LPVs) are at higher risk of breast cancer (BC) and ovarian cancer (OC). In the retrospective single-institution study in the Czech Republic, we analyzed the rate, longitudinal trends, and effectiveness of prophylactic risk-reducing mastectomy (RRM) and risk-reducing salpingo-oophorectomy (RRSO) on the incidence of BC and OC in BRCA1/2 carriers diagnosed between years (y) 2000 to 2020. The study included 496 healthy female BRCA1/2 carriers. The median follow-up was 6.0 years. RRM was performed in 156 (31.5%, mean age 39.3 y, range 22–61 y) and RRSO in 234 (47.2%, mean age 43.2 y, range 28–64 y) BRCA1/2 carriers. A statistically significant increase of RRM (from 12% to 29%) and RRSO (from 31% to 42%) was observed when comparing periods 2005–2012 and 2013–2020 (p < 0.001). BC developed in 15.9% of BRCA1/2 carriers without RRM vs. 0.6% of BRCA1/2 carriers after RRM (HR 20.18, 95% CI 2.78- 146.02; p < 0.001). OC was diagnosed in 4.3% vs. 0% of BRCA1/2 carriers without vs. after RRSO (HR not defined due to 0% occurrence in the RRSO group, p < 0.001). Study results demonstrate a significant increase in the rate of prophylactic surgeries in BRCA1/2 healthy carriers after 2013 and the effectiveness of RRM and RRSO on the incidence of BC and OC in these populations. Full article

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12 pages, 1232 KiB

Open AccessArticle

Is Reflex Germline BRCA1/2 Testing Necessary in Women Diagnosed with Non-Mucinous High-Grade Epithelial Ovarian Cancer Aged 80 Years or Older?

by Robert D. Morgan, George J. Burghel, Nicola Flaum, Michael Bulman, Philip Smith, Andrew R. Clamp, Jurjees Hasan, Claire L. Mitchell, Zena Salih, Emma R. Woodward, Fiona Lalloo, Emma J. Crosbie, Richard J. Edmondson, Helene Schlecht, Gordon C. Jayson and D. Gareth R. Evans

Cancers 2023, 15(3), 730; https://doi.org/10.3390/cancers15030730 - 25 Jan 2023

Cited by 2 | Viewed by 2098

Abstract

Women diagnosed with non-mucinous high-grade epithelial ovarian cancer (EOC) in England are often reflex-tested for germline and tumour BRCA1/2 variants. The value of germline BRCA1/2 testing in women diagnosed aged ≥80 is questionable. We performed an observational study of all women [...] Read more.

Women diagnosed with non-mucinous high-grade epithelial ovarian cancer (EOC) in England are often reflex-tested for germline and tumour BRCA1/2 variants. The value of germline BRCA1/2 testing in women diagnosed aged ≥80 is questionable. We performed an observational study of all women diagnosed with non-mucinous high-grade EOC who underwent germline and tumour BRCA1/2 testing by the North West of England Genomic Laboratory Hub. A subgroup of women also underwent germline testing using a panel of homologous recombination repair (HRR) genes and/or tumour testing for homologous recombination deficiency (HRD) using Myriad’s myChoice® companion diagnostic. Seven-hundred-two patients successfully underwent both germline and tumour BRCA1/2 testing. Of these, 48 were diagnosed with non-mucinous high-grade EOC aged ≥80. In this age group, somatic BRCA1/2 pathogenic/likely pathogenic variants (PV/LPVs) were detected nine times more often than germline BRCA1/2 PV/LPVs. The only germline PV reported in a patient aged ≥80 was detected in germline and tumour DNA (BRCA2 c.4478_4481del). No patient aged ≥80 had a germline PV/LPVs in a non-BRCA1/2 HRR gene. Thirty-eight percent of patients aged ≥80 had a tumour positive for HRD. Our data suggest that tumour BRCA1/2 and HRD testing is adequate for patients diagnosed with non-mucinous high-grade EOC aged ≥80, with germline BRCA1/2 testing reserved for women with a tumour BRCA1/2 PV/LPVs. Full article

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24 pages, 346 KiB

Open AccessReview

Long-Term Non-Cancer Risks in People with BRCA Mutations following Risk-Reducing Bilateral Salpingo-Oophorectomy and the Role of Hormone Replacement Therapy: A Review

by Amanda S. Nitschke, Helena Abreu do Valle, Lesa Dawson, Janice S. Kwon and Gillian E. Hanley

Cancers 2023, 15(3), 711; https://doi.org/10.3390/cancers15030711 - 24 Jan 2023

Cited by 4 | Viewed by 3240

Abstract

Risk-reducing bilateral salpingo-oophorectomy (RRBSO) is the gold standard preventative option for BRCA mutation carriers at high risk for ovarian and breast cancer. However, when performed at the recommended ages of 35–45 years, RRBSO induces immediate premature surgical menopause, along with the accompanying adverse [...] Read more.

Risk-reducing bilateral salpingo-oophorectomy (RRBSO) is the gold standard preventative option for BRCA mutation carriers at high risk for ovarian and breast cancer. However, when performed at the recommended ages of 35–45 years, RRBSO induces immediate premature surgical menopause, along with the accompanying adverse psychosocial, cardiovascular, bone, and cognitive health consequences. While these health consequences have been thoroughly studied in the general population, little is known about the long-term health outcomes in the BRCA population. Hormone replacement therapy (HRT) until the average age of natural menopause can help mitigate these health risks, yet the initiation of HRT is a complex decision among BRCA carriers due to concern of increasing the already high risk of breast cancer in these people. This review summarizes the current research on long-term non-cancer risks in BRCA carriers following RRBSO-induced premature surgical menopause, and highlights the existing evidence in support of HRT use in this population. Full article

2022

Jump to: 2024, 2023

20 pages, 1277 KiB

Open AccessSystematic Review

Cost-Effectiveness of Risk-Reducing Surgery for Breast and Ovarian Cancer Prevention: A Systematic Review

by Xia Wei, Samuel Oxley, Michail Sideris, Ashwin Kalra, Li Sun, Li Yang, Rosa Legood and Ranjit Manchanda

Cancers 2022, 14(24), 6117; https://doi.org/10.3390/cancers14246117 - 12 Dec 2022

Cited by 5 | Viewed by 5025

Abstract

Policymakers require robust cost-effectiveness evidence of risk-reducing-surgery (RRS) for decision making on resource allocation for breast cancer (BC)/ovarian cancer (OC)/endometrial cancer (EC) prevention. We aimed to summarise published data on the cost-effectiveness of risk-reducing mastectomy (RRM)/risk-reducing salpingo-oophorectomy (RRSO)/risk-reducing early salpingectomy and delayed oophorectomy [...] Read more.

Policymakers require robust cost-effectiveness evidence of risk-reducing-surgery (RRS) for decision making on resource allocation for breast cancer (BC)/ovarian cancer (OC)/endometrial cancer (EC) prevention. We aimed to summarise published data on the cost-effectiveness of risk-reducing mastectomy (RRM)/risk-reducing salpingo-oophorectomy (RRSO)/risk-reducing early salpingectomy and delayed oophorectomy (RRESDO) for BC/OC prevention in intermediate/high-risk populations; hysterectomy and bilateral salpingo-oophorectomy (BSO) in Lynch syndrome women; and opportunistic bilateral salpingectomy (OBS) for OC prevention in baseline-risk populations. Major databases were searched until December 2021 following a prospective protocol (PROSPERO-CRD42022338008). Data were qualitatively synthesised following a PICO framework. Twenty two studies were included, with a reporting quality varying from 53.6% to 82.1% of the items scored in the CHEERS checklist. The incremental cost-effectiveness ratio/incremental cost-utility ratio and cost thresholds were inflated and converted to US$2020, using the original currency consumer price index (CPI) and purchasing power parities (PPP), for comparison. Eight studies concluded that RRM and/or RRSO were cost-effective compared to surveillance/no surgery for BRCA1/2, while RRESDO was cost-effective compared to RRSO in one study. Three studies found that hysterectomy with BSO was cost-effective compared to surveillance in Lynch syndrome women. Two studies showed that RRSO was also cost-effective at ≥4%/≥5% lifetime OC risk for pre-/post-menopausal women, respectively. Seven studies demonstrated the cost-effectiveness of OBS at hysterectomy (n = 4), laparoscopic sterilisation (n = 4) or caesarean section (n = 2). This systematic review confirms that RRS is cost-effective, while the results are context-specific, given the diversity in the target populations, health systems and model assumptions, and sensitive to the disutility, age and uptake rates associated with RRS. Additionally, RRESDO/OBS were sensitive to the uncertainty concerning the effect sizes in terms of the OC-risk reduction and long-term health impact. Our findings are relevant for policymakers/service providers and the design of future research studies. Full article

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16 pages, 1115 KiB

Open AccessArticle

Real World Cost-Effectiveness Analysis of Population Screening for BRCA Variants among Ashkenazi Jews Compared with Family History-Based Strategies

by Rachel Michaelson-Cohen, Matan J. Cohen, Carmit Cohen, Dan Greenberg, Amir Shmueli, Sari Lieberman, Ariela Tomer, Ephrat Levy-Lahad and Amnon Lahad

Cancers 2022, 14(24), 6113; https://doi.org/10.3390/cancers14246113 - 12 Dec 2022

Cited by 4 | Viewed by 2722

Abstract

Identifying carriers of pathogenic BRCA1/BRCA2 variants reduces cancer morbidity and mortality through surveillance and prevention. We analyzed the cost-effectiveness of BRCA1/BRCA2 population screening (PS) in Ashkenazi Jews (AJ), for whom carrier rate is 2.5%, compared with two existing strategies: cascade testing (CT) in [...] Read more.

Identifying carriers of pathogenic BRCA1/BRCA2 variants reduces cancer morbidity and mortality through surveillance and prevention. We analyzed the cost-effectiveness of BRCA1/BRCA2 population screening (PS) in Ashkenazi Jews (AJ), for whom carrier rate is 2.5%, compared with two existing strategies: cascade testing (CT) in carrier’s relatives (≥25% carrier probability) and international family history (IFH)-based guidelines (>10% probability). We used a decision analytic-model to estimate quality-adjusted life-years (QALY) gained, and incremental cost-effectiveness ratio for PS vs. alternative strategies. Analysis was conducted from payer-perspective, based on actual costs. Per 1000 women, the model predicted 21.6 QALYs gained, a lifetime decrease of three breast cancer (BC) and four ovarian cancer (OC) cases for PS vs. CT, and 6.3 QALYs gained, a lifetime decrease of 1 BC and 1 OC cases comparing PS vs. IFH. PS was less costly compared with CT (−3097 USD/QALY), and more costly than IFH (+42,261 USD/QALY), yet still cost-effective, from a public health policy perspective. Our results are robust to sensitivity analysis; PS was the most effective strategy in all analyses. PS is highly cost-effective, and the most effective screening strategy for breast and ovarian cancer prevention. BRCA testing should be available to all AJ women, irrespective of family history. Full article

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23 pages, 1012 KiB

Open AccessSystematic Review

Quality of Life after Risk-Reducing Hysterectomy for Endometrial Cancer Prevention: A Systematic Review

by Samuel Oxley, Ran Xiong, Xia Wei, Ashwin Kalra, Michail Sideris, Rosa Legood and Ranjit Manchanda

Cancers 2022, 14(23), 5832; https://doi.org/10.3390/cancers14235832 - 26 Nov 2022

Viewed by 3844

Abstract

Background: Risk-reducing hysterectomy (RRH) is the gold-standard prevention for endometrial cancer (EC). Knowledge of the impact on quality-of-life (QoL) is crucial for decision-making. This systematic review aims to summarise the evidence. Methods: We searched major databases until July 2022 (CRD42022347631). Given the paucity [...] Read more.

Background: Risk-reducing hysterectomy (RRH) is the gold-standard prevention for endometrial cancer (EC). Knowledge of the impact on quality-of-life (QoL) is crucial for decision-making. This systematic review aims to summarise the evidence. Methods: We searched major databases until July 2022 (CRD42022347631). Given the paucity of data on RRH, we also included hysterectomy as treatment for benign disease. We used validated quality-assessment tools, and performed qualitative synthesis of QoL outcomes. Results: Four studies (64 patients) reported on RRH, 25 studies (1268 patients) on hysterectomy as treatment for uterine bleeding. There was moderate risk-of-bias in many studies. Following RRH, three qualitative studies found substantially lowered cancer-worry, with no decision-regret. Oophorectomy (for ovarian cancer prevention) severely impaired menopause-specific QoL and sexual-function, particularly without hormone-replacement. Quantitative studies supported these results, finding low distress and generally high satisfaction. Hysterectomy as treatment of bleeding improved QoL, resulted in high satisfaction, and no change or improvements in sexual and urinary function, although small numbers reported worsening. Conclusions: There is very limited evidence on QoL after RRH. Whilst there are benefits, most adverse consequences arise from oophorectomy. Benign hysterectomy allows for some limited comparison; however, more research is needed for outcomes in the population of women at increased EC-risk. Full article

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14 pages, 1012 KiB

Open AccessArticle

Cost-Effectiveness of Genetic Testing for All Women Diagnosed with Breast Cancer in China

by Li Sun, Bin Cui, Xia Wei, Zia Sadique, Li Yang, Ranjit Manchanda and Rosa Legood

Cancers 2022, 14(7), 1839; https://doi.org/10.3390/cancers14071839 - 6 Apr 2022

Cited by 12 | Viewed by 4042

Abstract

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 [...] Read more.

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. Full article

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