bims-ovdlit 2024-08-25 papers

Am J Epidemiol. 2024 Aug 21. pii: kwae293. [Epub ahead of print]

Ovarian Cancer Risk Prediction - a Clinical Epidemiology Perspective.

Nicolas Wentzensen, Kari Ring, Britt K Erickson, Brett Reid, Thomas O'Donnell, David Check, Shelley S Tworoger, Parichoy Pal Choudhury.

Ovarian cancer is a rare and highly heterogeneous disease usually detected at late stages when outcomes are poor. Population-based screening approaches have not been successful at reducing ovarian cancer mortality, but preventive bilateral salpingo-oophorectomy is highly effective at preventing ovarian cancer in high-risk populations. Ovarian cancer risk prediction models may allow identification of populations at increased risk of ovarian cancer for preventive interventions or targeted early detection. We propose a life-course approach to ovarian cancer risk prediction based on the time at which a risk model should be applied and the risk factors that are available. The discriminative ability of ovarian cancer risk prediction models published so far is limited, with areas under the curve ranging from 0.58-0.65 for different combinations of risk factors and genetic susceptibility markers. Currently proposed absolute risk thresholds for preventive surgery are around 4% lifetime risk. The absolute risk predicted by ovarian cancer risk models ranges from 0.6-2.5% lifetime risk in the general population, highlighting the need to improve ovarian cancer risk prediction models and evaluating new preventive approaches that can be offered to individuals at lower risk.

Keywords: clinical epidemiology; ovarian cancer; prevention; risk prediction

DOI: https://doi.org/10.1093/aje/kwae293

Gynecol Oncol. 2024 Aug 21. pii: S0090-8258(24)01052-7. [Epub ahead of print]189 148-155

Incidence of endometrial cancer in BRCA mutation carriers.

OBJECTIVE: Whether or not women who harbor a germline pathogenic variant ('mutation') in the BRCA1 or BRCA2 genes are at elevated risk of developing endometrial cancer is yet to be determined.
METHODS: We conducted a prospective analysis of 4959 BRCA mutation carriers with no prior history of cancer (except for breast or melanoma) and an intact uterus.
RESULTS: After a mean of 6.7 years of follow-up there were 38 incident cases of endometrial cancer diagnosed; 30 among BRCA1 carriers and eight among BRCA2 carriers. The mean age at diagnosis was 58.4 years (range 46.8-76.1). The majority were of the endometrioid subtype (n = 16), followed by mixed endometroid and serous (n = 4), serous (n = 3) or clear cell (n = 1) (missing = 13). The cumulative incidence from age 40 to age 70 was 3.4% for BRCA1 carriers and was 1.6% for BRCA2 mutation carriers. Prior tamoxifen use was associated with a significant two-fold increased risk (HR = 2.24; 95% CI 1.10-4.55). There was no significant association between exogenous hormone use, oophorectomy, smoking or BMI at age 40 and risk (P ≥ 0.32).
CONCLUSIONS: Compared to the general population, we observed higher rates of endometrial cancer among young BRCA1 mutation carriers; however, lifetime risks were similar. Women with prior tamoxifen exposure were at a significantly increased risk. These findings were based. on a small number of incident cases and require confirmation with additional follow-up of our aging cohort.

Keywords: BRCA; Endometrial cancer; Hysterectomy; Prospective; Tamoxifen

DOI: https://doi.org/10.1016/j.ygyno.2024.07.687

J Natl Cancer Inst. 2024 Aug 22. pii: djae184. [Epub ahead of print]

Probing the relevance of BRCA1 and BRCA2 germline pathogenic variants beyond breast and ovarian cancer.

William D Foulkes, Paz Polak.

DOI: https://doi.org/10.1093/jnci/djae184