Women at genetic risk of breast cancer are more influenced by the potential protection offered by different types of preventive surgery than the potential for menopausal symptoms afterwards, although these do play a role in their decisions.
The findings, reported in JAMA Network Open, shed light on the complex decisions involved in choosing risk-reducing strategies for those with a family history of cancer and should help guide counseling.
They are particularly pertinent given the introduction of clinical genetic testing for hereditary risk, particularly for those cancers without effective screening options.
Through a series of “choice experiments,” U.S. researchers showed that the degree of risk reduction was the main driver affecting which type of preventive surgery to choose.
Surgical menopausal symptoms triggered by ovary removal and the hormones they produce affected preferences, but these factors were less important than the risk reduction offered by the different types of surgery.
“Counseling models that recognize the complexity of ovarian cancer risk reduction and provide personalized guidance tailored to each woman’s unique needs are likely to improve the decision-making process and enhance patient outcomes,” predicted lead researcher Mary Daly, PhD, from Fox Chase Cancer Center in Philadelphia, and co-workers.
Women carrying a BRCA1/2 genetic variant have a 10% to 45% risk of getting ovarian cancer within their lifetime, which is up to 30 times higher than the general population.
These women and others carrying high-risk genetic variants must weigh the pros and cons of cancer surveillance or risk reducing strategies.
Surgery to remove both the ovaries and both ovarian tubes—known as bilateral salpingo-oophorectomy—offers the best protection and is associated with an 80% reduction in the risk of ovarian, fallopian tube, and peritoneal cancer. However, this induces premature or early menopause in many women.
More recently, a two-stage process has been proposed that involves salpingectomy, in which the fallopian tubes—where most serous ovarian carcinomas originate—are removed early on, followed by ovary removal later after the menopause.
To find out how women came to the choices they made, Daly and team presented a series of hypothetical options to 355 premenopausal college graduates who sought genetic testing and had a personal history of breast cancer or had a familial or hereditary risk of ovarian cancer.
This allowed them to understand how the women’s health preferences reflected the inherent trade-offs between risk reduction and adverse effects.
The women, who had a median age of 37 years, were given basic education on treatment options to reduce the risk of ovarian cancer and associated adverse effects. Participants chose between paired hypothetical scenarios that reflected different states of health and the value they attached to these attributes, including mitigating cancer risk.
They completed the survey twice, before and two months after genetic test results were revealed.
The researchers found that the particular surgical strategy did not play a substantial role. More important was the degree to which a surgery reduced cancer risk or impacted menopausal symptom severity.
The dominant driver was how much a particular choice reduced the risk of ovarian cancer, although this was slightly lessened with age.
Women preferred risk-reducing salpingo-oophorectomy to risk-reducing salpingectomy, with an odds ratio of 1.24. These choices were neither influenced by the timing of genetic test result disclosure, nor by the presence or absence of a cancer-related pathogenic variant.
Overall, 47 study participants (13%) had pathogenic variants in ovarian cancer–related genes. Risk-reducing salpingectomy was the least preferred treatment, although the difference between surveillance and risk-reducing salpingectomy was not statistically significant.
Scenarios with menopause-associated risks such as osteoporosis, heart disease, and more severe menopause symptoms reduced these preferences but impacted less than the reduced risk of cancer obtained from salpingo-oophorectomy.
“While our data support the central role of the magnitude of ovarian cancer risk as a motive for choice of treatment, they also suggest that women at increased risk of ovarian cancer consider a range of additional factors when assessing preventive strategies for ovarian cancer,” the researchers noted.
“The preference for a natural age of menopause was less pronounced than the desire to avoid severe menopausal symptoms, suggesting that symptoms are a greater concern than age at menopause.
“Additionally, family history of cancer and long-term conditions linked to premature menopause, such as cardiovascular disease and osteoporosis, were factors in women’s decisions.”
In an accompanying Commentary article, Ilana Cass, MD, from Dartmouth Health in New Hampshire added: “The findings of Daly et al. are essential to our understanding of our patients’ priorities and preferences as we counsel them regarding available and evolving surgical options to reduce ovarian cancer.”
