Stopping ovarian cancer screening in BRCA1/2 mutation carriers: Effects on risk management decisions & outcome of risk-reducing salpingo-oophorectomy specimens

doi:10.1016/j.maturitas.2014.12.009

Maturitas

Volume 80, Issue 3, March 2015, Pages 318-322

https://doi.org/10.1016/j.maturitas.2014.12.009 Get rights and content

Highlights

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After stopping ovarian cancer screening we found a shorter time interval between DNA test disclosure and RRSO.
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More women underwent RRSO within the recommended age range after stopping ovarian cancer screening.
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The percentage of occult cancers in RRSO specimens remained low (1.8%) after stopping ovarian cancer screening.

Abstract

Objective

Ovarian cancer screening (OCS) for BRCA1/2 mutation carriers was stopped in our family cancer clinic in 2009 because of its ineffectiveness. The study objective was to investigate the effect of stopping OCS on the timing and uptake of risk-reducing salpingo-oophorectomy (RRSO) and on the percentage of occult cancers in the specimens.

Methods

419 BRCA1/2 mutation carriers were recruited between January 1999 and June 2013.

Uptake, timing and the outcome of the RRSO specimens before stopping OCS (period I) were compared to those after stopping OCS (period II).

Results

The percentage of women undergoing RRSO within the recommended age range increased from 81% to 95%. Receiving DNA test results in period II independently predicted a shorter time interval to RRSO (hazard ratio: 2.48, 95% confidence interval: 1.81–3.39). The incidence of detecting occult cancers in RRSO specimens before and after stopping OCS was 1.3% and 1.8%, respectively, and was not statistically significantly different.

Conclusions

The presentation of risk management options to women may influence their decision. The increased patient awareness of the ineffectiveness of OCS could have led to a higher percentage of women undergoing RRSO and doing so more often within the recommended age range.

Introduction

Women who carry a BRCA1/2 mutation have a high lifetime risk of developing ovarian cancer. A recent prospective study estimated a lifetime risk for ovarian cancer in BRCA1 and BRCA2 mutation carriers of 59% (95% confidence interval (CI) = 43–76%) and 16.5% (95% CI = 7.5–34%), respectively [1]. Since 2007, the perspective on optimal risk management for ovarian cancer in BRCA1/2 mutation carriers has changed in response to studies which reported that ovarian cancer screening (OCS) lacked effectiveness for early detection of ovarian cancer in these mutation carriers [2], [3], [4], [5]. In light of these findings and in advance of national guideline changes, our family cancer clinic stopped offering OCS in October 2009. From that time onwards, the only ovarian cancer risk management option offered to BRCA1/2 mutation carriers is risk-reducing salpingo-oophorectomy (RRSO). RRSO is recommended for patients younger than the age at which the ovarian cancer incidence rises, 35 to 40 years for BRCA1 mutation carriers and 40 to 45 years for BRCA2 mutation carriers, provided that the patients have completed their childbearing [6], [7], [8]. RRSO reduces the risk of ovarian cancer with 80–90% when performed within the recommended age range [9], [10], [11], [12], [13], [14]. Moreover, RRSO may also reduce the risk of breast cancer in premenopausal women [9], [10], [11], [12], [13], [14]. However, RRSO is also associated with adverse effects in premenopausal women due to acute surgical menopause [15], [16], [17].

Both younger age and nulliparity at the time of receiving the DNA test result were factors related to a longer interval between receiving DNA test results and RRSO [18], [19], [20], [21]. In the aforementioned studies BRCA1/2 mutation carriers could choose between OCS and RRSO. Our objective was to investigate the effect of stopping OCS on the timing and uptake of RRSO and on the percentage of occult cancers found in the RRSO specimens.

Section snippets

Study design and patients

A prospective cohort design was used to investigate the effect of stopping OCS on the timing and uptake of RRSO and on the percentage of occult cancers found in the RRSO specimens. This study was performed in BRCA1/2 mutation carriers who visited the family cancer clinic at least once between 1999 and June 2013. All the women who visited the family cancer clinic in this time period were asked for informed consent before entering their data into the prospectively maintained, password protected

Population

Between January 1999 and June 2013, 541 BRCA1/2 mutation carriers visited the family cancer clinic at least once. Of these, 24 (4.4%) women had already undergone bilateral salpingo-oophorectomy (for any reason) and 12 (2.2%) women had developed ovarian cancer before the date of receiving DNA test results. In total, 84 (15.5%) patient files were either unavailable (n = 38, 7.0%) or incomplete (n = 46, 8.5%). Two (0.4%) women were unable to make their own decisions due to a mental incapacity and were

Discussion

The objective of this study was to investigate the effect of stopping OCS on the timing and uptake of RRSO and on the percentage of occult cancers found in the RRSO specimens. We found that after stopping OCS the percentage of women who underwent RRSO within the recommended age range increased from 81 to 95%. Only one woman did not perform RRSO within the recommended age range in period II. This concerned a BRCA1 mutation carrier who received her DNA test results at the age of 39 years and

Contributors

The main writing was done by Catheleine M.G. van Driel, Geertruida H. De Bock, Jan C. Oosterwijk and Marian J.E. Mourits. The other authors contributed from their field of expertise.

Competing interests

None.

Conflict of interest statement

The authors declare that they have no conflict of interest.

Funding

None.

Ethics

Protection of the patients’ identity was guaranteed by assigning study-specific, unique patient numbers. According to Dutch law no further Institutional Review Board approval was needed for this study.

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Ovarian cancer surveillance in the clinical follow up of women with known BRCA1 or BRCA2 pathogenic variants in a large health care system
2021, Gynecologic Oncology
Citation Excerpt :
The National Comprehensive Cancer Network (NCCN) [2] and American College of Obstetricians and Gynecologists (ACOG) [3] have established guidelines for the management of women with BRCA1 or BRCA2 PV, which state that the most effective ovarian cancer risk-reduction strategy for these women is bilateral salpingo-oophorectomy, recommended at age 35–40 years for BRCA1 PV carriers and age 40–45 for BRCA2 PV carriers. [4] While reported uptake of risk-reducing salpingo-oophorectomy (RRSO) is high in women with BRCA1 or BRCA2 PV (range 70–84% [5–7]), the majority of those who do have RRSO are older than the recommended age for surgery and many still choose to never undergo oophorectomy. Thus, there is large group of women with intact ovaries for whom the NCCN suggests the option of surveillance with pelvic ultrasound and CA 125 every 6–12 months be “considered.” [2]
To assess CA 125 and transvaginal ultrasound surveillance in women with BRCA1 or BRCA2 pathogenic variants in a pragmatic clinical setting with>1 year follow up.
Retrospective cohort study in a large integrated health care system of women identified from 1/1/2003 to 12/31/2017 with a BRCA1 or BRCA2 pathogenic variant with at least one intact ovary. Demographic and clinical data were collected from date of genetic testing until oophorectomy, an ovarian cancer diagnosis, or 7/1/2019. Primary outcome was frequency and findings of CA 125 tests and ultrasounds performed; secondary outcome was epithelial ovarian cancers diagnosed.
There were 1418 women, age ≥ 30 years with a BRCA1 or BRCA2 pathogenic variant with at least one intact ovary. Of the total of 1683 ultrasounds and 2437 CA 125 tests done, 1022 ultrasounds and 1709 CA 125 tests were performed for surveillance in 771 women followed >1 year. Of these women 241 (31%) women had no surveillance, and 530 (69%) women underwent any surveillance. Only 108 (20%) underwent regular surveillance. The number who underwent regular surveillance declined each year. Twenty-one women underwent surveillance indicated surgery with only 2 ovarian cancers found by surveillance.
Many women with BRCA1 or BRCA2 pathogenic variants undergo ultrasound and CA 125 surveillance testing but abnormal surveillance testing led to diagnosis of ovarian cancer in only two cases. These findings question the use of CA 125 and ultrasound surveillance in the clinical setting for ovarian cancer detection in women with BRCA1 or BRCA2 pathogenic variants.
Feasibility, patient compliance and acceptability of ovarian cancer surveillance using two serum biomarkers and Risk of Ovarian Cancer Algorithm compared to standard ultrasound and CA 125 among women with BRCA mutations
2020, Gynecologic Oncology
Citation Excerpt :
For those who decline RRSO, the NCCN guidelines state that surveillance comprised of biannual or annual transvaginal ultrasounds and serum cancer antigen 125 (CA125) testing be initiated “at the clinician's discretion” between age 30–35 years [1]. Much controversy exists as to whether pelvic ultrasounds or serum biomarkers, particularly CA125, can serve as acceptable surveillance measures for ovarian cancer given their high false-positive rate, and many suggest that these tests are not effective [2–7]. Compounding this, women generally show low compliance with these ovarian cancer surveillance strategies [8,9].
We assessed the feasibility, patient acceptability of and compliance of a new surveillance strategy for ovarian cancer surveillance in women with BRCA mutations, based on assessments of serum CA125 and HE4 every 4 months (Risk of Ovarian Cancer Algorithm (ROCA) arm), compared to Standard of Care (SOC) surveillance with CA125 blood tests and pelvic ultrasounds every 6 months.
Women were recruited 6/13/16–9/11/17 from an integrated health care system in California for this non-randomized prospective cohort study. Women were invited to participate in a novel serum biomarker surveillance strategy using ROCA or they could opt to be in the standard of care control arm with ultrasound and CA 125 every 6 months. Outcomes assessed included compliance, self-reported distress using the Impact of Event Scale (IES) and cancer anxiety using the Cancer Worry Scale.
There were 159 women in the ROCA arm and 43 in the SOC arm. Overall, compliance was higher in the ROCA arm (83.2%) than in SOC (51.9%), p < 0.0001. Based on the IES, ROCA arm women reported less feelings about intrusion and avoidance at 12 months compared to baseline; the difference approached significance for intrusion (7.6% vs 4.1% severe, p = 0.057) and was statistically significant for avoidance (20.8% vs 9.9% severe, p = 0.034).
This pilot demonstrated that compliance was high with blood tests performed every four months for ovarian cancer surveillance. Moreover, ROCA women had lower stress scores over time than SOC women. Given the lack of clinical utility and poor compliance shown with traditional ultrasound and CA125 tests, further investigation is warranted of longitudinal biomarker surveillance for early detection of ovarian cancer.
Very high uptake of risk-reducing salpingo-oophorectomy in BRCA1/2 mutation carriers: A single-center experience
2016, Gynecologic Oncology
Citation Excerpt :
Specifically, the possibility of less invasive ovarian cancer screening might reduce the uptake of RRSO, although proven ineffective. This is supported by a Dutch study [19]: overall uptake of RRSO within one year after genetic test disclosure increased from 53% to 85% after stopping ovarian cancer screening, and from 77% to 91% among women who reached the recommended age for RRSO. Offering screening as part of a clinical trial was mentioned as a possible explanation for the low uptake of RRSO observed in women at risk of familial EOC in the United Kingdom (both BRCA mutation carriers and women with unknown BRCA status) [18].
Risk-reducing salpingo-oophorectomy (RRSO) is the only effective surgical strategy to reduce the increased risk of epithelial ovarian cancer in BRCA1/2 mutation carriers. Given the long-term health consequences of premature surgical menopause, we need insight in uptake and timing of RRSO to guide us in improving healthcare.
A single-center retrospective cohort study of BRCA1/2 mutation carriers diagnosed and counseled at the multidisciplinary Family Cancer Clinic of the Radboud university medical center in Nijmegen, The Netherlands, between 1999 and 2014. Descriptive statistics were used to analyze uptake and timing of RRSO.
Data of 580 BRCA1/2 were analyzed. The uptake of RRSO among mutation carriers who are currently above the upper limit of the recommended age for RRSO, is 98.5% and 97.5% for BRCA1 and BRCA2 mutation carriers, respectively. The vast majority undergoes RRSO ≤ 40 (BRCA1) or ≤ 45 (BRCA2) years of age, provided that mutation status is known by that age: 90.8% and 97.3% of BRCA1 and BRCA2 mutation carriers, respectively.
The uptake of RRSO among BRCA1/2 mutation carriers who were counseled at our Family Cancer Clinic is extremely high. High uptake might be largely attributed to the directive and uniform way of counseling by professionals at our Family Cancer Clinic. Given the fact that RRSO is often undergone at premenopausal age in our population, future research should focus on minimizing long-term health consequences of premature surgical menopause either by optimization of hormone replacement therapy or by investigating alternative strategies to RRSO.
Cardiovascular risk of BRCA1/2 mutation carriers: A review
2016, Maturitas
BRCA1/2 mutation carriers are at high risk of breast and ovarian cancer. The number of studies on non-cancer endpoints in BRCA1/2 mutation carriers is still limited. BRCA1/2 mutation carriers may be at higher cardiovascular risk due to early menopause after risk-reducing salpingo-oophorectomy and/or due to the potential cardiotoxic effects of breast cancer treatment (radiotherapy and chemotherapy). Moreover, BRCA genes have a role as a gatekeeper in cardiac function and structure, which may affect susceptibility to cardiac damage. Our goal is to review current knowledge of cardiovascular risk among BRCA1/2 mutation carriers.
Application of wavelet techniques for cancer diagnosis using ultrasound images: A Review
2016, Computers in Biology and Medicine
Citation Excerpt :
The lynch syndrome, and BRCA1 and BRCA2 gene mutations are high risk inherited genetic conditions. Moreover, genetic studies show stong familial predisposition responsitble for 5–10% of prostate cancer [46]. Generally, it is diagnosed using prostate specific antigen and digital rectal examination.
Ultrasound is an important and low cost imaging modality used to study the internal organs of human body and blood flow through blood vessels. It uses high frequency sound waves to acquire images of internal organs. It is used to screen normal, benign and malignant tissues of various organs. Healthy and malignant tissues generate different echoes for ultrasound. Hence, it provides useful information about the potential tumor tissues that can be analyzed for diagnostic purposes before therapeutic procedures. Ultrasound images are affected with speckle noise due to an air gap between the transducer probe and the body. The challenge is to design and develop robust image preprocessing, segmentation and feature extraction algorithms to locate the tumor region and to extract subtle information from isolated tumor region for diagnosis. This information can be revealed using a scale space technique such as the Discrete Wavelet Transform (DWT). It decomposes an image into images at different scales using low pass and high pass filters. These filters help to identify the detail or sudden changes in intensity in the image. These changes are reflected in the wavelet coefficients. Various texture, statistical and image based features can be extracted from these coefficients. The extracted features are subjected to statistical analysis to identify the significant features to discriminate normal and malignant ultrasound images using supervised classifiers. This paper presents a review of wavelet techniques used for preprocessing, segmentation and feature extraction of breast, thyroid, ovarian and prostate cancer using ultrasound images.
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Stopping ovarian cancer screening in BRCA1/2 mutation carriers: Effects on risk management decisions & outcome of risk-reducing salpingo-oophorectomy specimens

Highlights

Abstract

Objective

Methods

Results

Conclusions

Introduction

Section snippets

Study design and patients

Population

Discussion

Contributors

Competing interests

Conflict of interest statement

Funding

Ethics

Am J Obstet Gynecol

Genet Med

Maturitas

Maturitas

Gynecol Oncol

Prev Med (Baltim)

Eur J Cancer

Gynecol Oncol

Cancer risks for BRCA1 and BRCA2 mutation carriers: results from prospective analysis of EMBRACE

J Natl Cancer Inst

Annual surveillance by CA125 and transvaginal ultrasound for ovarian cancer in both high-risk and population risk women is ineffective

BJOG

No efficacy of annual gynaecological screening in BRCA1/2 mutation carriers; an observational follow-up study

Br J Cancer

Time to stop ovarian cancer screening in BRCA1/2 mutation carriers?

Int J Cancer

Screening for familial ovarian cancer: poor survival of BRCA1/2 related cancers

J Med Genet

Aanbevelingen voor het beleid bij vrouwen met een erfelijk bepaalde hoge kans op gynaecologische kanker

Ned Tijdschr Geneeskd

Gynaecologic challenging issues in the management of BRCA mutation carriers: oral contraceptives, prophylactic salpingo-oophorectomy and hormone replacement therapy

Gynecol Endocrinol