When worry drives behavior

From M. Robyn Andersen, Public Health Sciences Division

Epithelial ovarian cancer (EOC) begins in the cells that cover the ovaries or line the fallopian tubes and includes serous ovarian, fallopian tube, and primary peritoneal carcinoma subtypes. EOC is the most common and deadly type of ovarian cancer in the United States. Women at an elevated risk for EOC include those who harbor a mutation in the BRCA1/2 genes, in which an estimated 39% of BRCA1 carriers and 22% of BRCA2 carriers will develop it. Current guidelines recommend that BRCA1/2 carriers undergo prophylactic bilateral salpingo-oophorectomy (pBSO; surgical removal of the ovaries and fallopian tubes). Some women with a high-risk pedigree for EOC choose to undergo genetic testing and this surgery but others decide against it. These women may instead opt for other screening which may include testing for serum markers (such as CA125 or HE4) or ultrasound and may include appointments every 6 months. However, whether participation in these screening programs may influence the decision to subsequently undergo pBSO had not been studied in detail until now. Dr. Robyn Andersen and colleagues in the Public Health Sciences Division recently published results from a study in the journal Health Psychology that reveal the effects of worry and false-positive screening events (FPSE) on treatment decisions in high-risk women.

With any screening or testing procedure, there is a likely risk for a result to incorrectly indicate that the result is positive. Previous work has shown that such FPSE lead to increased worry about breast cancer risk among women with BRCA1/2 mutations, but that study was limited in its ability to specifically assess effects on ovarian cancer screening and surgery use. Dr. Andersen described the importance of their new study within this context, “For many of these women with BRCA mutations deciding to get surgery is probably a good thing, that is what the guidelines recommend. The questions arise for women who might have a mutation but haven’t tested, and for those who are younger and might see substantial health benefits associated with keeping their ovaries or keeping their ovaries for a few more years. We want these women to make the best decisions for themselves based on their values and an understanding of the risks they face.” Finding that FPSE and worry drive these decisions to undergo surgery for some women “really brings up bigger questions about health care decision-making, these false-positive events don’t generally mean these women are at higher risk for cancer but appear to be changing women’s decisions about what to do about their elevated risk,” added Dr. Andersen.

Graphical representation of Kaplan-Meier curves for rates of prophylactic surgery for removal of ovaries and fallopian tubes in women with a high-risk pedigree for ovarian cancer, stratified by the occurrence of a false-positive screening event.
Kaplan-Meier curves for rates of prophylactic surgery for removal of ovaries and fallopian tubes in women with a high-risk pedigree for ovarian cancer, stratified by the occurrence of a false-positive screening event. Image from the publication

To determine whether worry or FPSE are predictors in the decision to have pBSO, the authors analyzed data from 1,100 high-risk women enrolled in an ovarian cancer screening trial. The participants were categorized into one of two EOC risk groups: (1) having a known germ line mutation in either BRCA1 or BRCA2 or (2) a personal or family history of cancer suggestive of increased genetic risk. The women were screened semiannually with a primary screening of CA125 alone or CA125 and HE4. If the primary screen was positive, women were asked to return for a confirmatory test in which both biomarkers were measured. If either biomarker was positive in the confirmatory test, the participant was asked to undergo a pelvic ultrasound. Women who received two out of three positive test results (among ultrasound, CA125, and HE4) were recommended to undergo a follow-up surgery consult. In addition to the screening tests, all women completed questionnaires at every screening appointment to assess their level of worry about risk for cancer.

The authors analyzed data from 4,700 screening visits. The overall pBSO rate was significantly lower for women with a high-risk pedigree than for those who were known mutation carriers at the time of enrollment. At baseline, 55% of women with a known BRCA1/2 mutation reported moderate/severe worry about cancer risk while approximately 24% of women in the high-risk pedigree group reported that level of worry. The level of moderate/severe worry among women who had never received a FPSE fell from 30% at enrollment to less than 15% by the time of their fifth screening appointment. The authors discovered that the level of worry was indeed a significant predictor of the decision to undergo pBSO. Among women experiencing moderate to severe levels of worry, the rate of pBSO surgery was 1.74 times that in BRCA1/2 carriers and 3.4 times that in women with a high-risk pedigree as compared to women with none to mild worry. When the study looked specifically at women with a FPSE, the authors found similar results. The rate to pBSO was most pronounced in women with a high-risk pedigree, in which the rate to time of surgery in women with at least one FPSE was 2.3 that of those who did not experience FPSE (see figure).

These results clearly reveal the impact that worry and FPSE have on women’s decision to undergo prophylactic surgery. However, these analyses could not determine whether the decision to have pBSO following a FPSE is a direct cause of the FPSE itself or indirectly due to elevated levels of worry. The overall finding from the study was summarized by Dr. Andersen, “the important point about this study for other health psychologists is that this is the first study to find that false-positive screening events, events that can be as small as just being asked to come back and repeat a blood test appear to contribute to women’s decisions to get surgeries.” These new results clearly fill a knowledge gap in the field, “Past studies have shown these events increase levels of worry about cancer risk and may contribute to decisions about screening (e.g. mammography use) but until now we haven’t had data to show they affect bigger decisions like ovarian surgery,” added Dr. Andersen.

The interdisciplinary nature of the study team facilitated the ability to address these questions in greater detail than had previously been possible, a feature that Dr. Andersen emphasized, “I could look at these issues of cancer worry and quality of life in a larger population than prior studies could because I was included as a health psychologist in the big initial developmental work looking for a better screening strategy and people didn’t treat how these women felt about screening and their elevated risk as an afterthought to be dealt with after a team found some screening strategy they thought would work and then started to wonder why there were all these women who don’t participate in screening and get surgeries that aren’t based on the screening programs’ findings or recommendations.”

Fred Hutch/UW Cancer Consortium members Robyn Andersen and Charles Drescher contributed to this research.

This research was supported by the Canary Foundation, Marsha Rivkin Center for EOC Research, and the National Institutes of Health.

Andersen MR, Karlan BY, Drescher CW, Paley P, Hawley S, Palomares M, Daly MB, Urban N. 2018. False-positive screening events and worry influence decisions about surgery among high-risk women. Health Psychology. doi: 10.1037/hea0000647