Do cancer risk and benefit–harm ratios influence women’s consideration of risk-reducing mastectomy? A scenario-based experiment in five European countries

Background Personal cancer risk assessments enable stratified care, for example, offering preventive surgical measures such as risk-reducing mastectomy (RRM) to women at high risk for breast cancer. In scenario-based experiments, we investigated whether different benefit–harm ratios of RRM influence women’s consideration of this, whether this consideration is influenced by women’s perception of and desire to know their personal cancer risk, or by their intention to take a novel cancer risk-predictive test, and whether consideration varies across different countries. Method In January 2017, 1,675 women 40 to 75 years of age from five European countries—Czech Republic, Germany, UK, Italy, and Sweden—took part in an online scenario-based experiment. Six different scenarios of hypothetical benefit–harm ratios of RRM were presented in accessible fact box formats: Baseline risk/risk reduction pairings were 20/16, 20/4, 10/8, 10/2, 5/4, and 5/1 out of 1,000 women dying from breast cancer. Results Varying the baseline risk of dying from breast cancer and the extent of risk reduction influenced the decision to consider RRM for 23% of women. Decisions varied by country, risk perception, and the intention to take a cancer risk-predictive test. Women who expressed a stronger intention to take such a test were more likely to consider having RRM. The desire to know one’s risk of developing any female cancer in general moderated women’s decisions, whereas the specific desire to know the risk of breast cancer did not. Conclusions In this hypothetical scenario-based study, only for a minority of women did the change in benefit–harm ratio inform their consideration of RRM. Because this consideration is influenced by risk perception and the intention to learn one’s cancer risks via a cancer risk-predictive test, careful disclosure of different potential preventive measures and their benefit–harm ratios is necessary before testing for individual risk. Furthermore, information on risk testing should acknowledge country-specific sensitivities for benefit–harm ratios.

What is your baseline risk of developing female cancers?
In order to better evaluate the potential value of this new test, it is helpful for you to understand an average woman's risk of developing any of these cancers. For the large majority of women, the risk of developing female cancers is fairly low. The following overview gives you an idea of how likely women at different ages will be diagnosed with each of the four female cancers.
Numbers of women who will develop cancer within the next 10 years … 1 Mammography screening may reduce the number of women who die from breast cancer but this has no effect on overall cancer deaths. Among all women taking part in screening, some women will be overdiagnosed with non-progressive cancer and unnecessarily treated.
Numbers for women aged 50 years or older who did or did not par8cipate in screening for about 10 years. What are current approaches for healthy women to reduce the threat of these four female cancers?

Benefits
Two approaches are currently used. The main approach -offered to all healthy women from a certain age on -is cancer screening such as mammography screening for breast cancer or ultrasound screening for ovarian cancer. Cancer screening is intended to detect cancer and precancerous lesions early. For the small proportion of women at very high risk another approach is preventive medication (e. g., with Tamoxifen © ) and prophylactic surgery (e. g., removal of the breasts), which aim at preventing occurrence of cancer.
Currently used cancer screenings such as mammography can have benefits AND harms. The main benefit is defined as the number of women who will be saved from dying from cancer. The harms are defined by the number of women who experience false alarms, diagnoses of harmless forms of cancer (called overdiagnosis), and, as a consequence, unnecessary treatment (called overtreatment). The following table gives you the numbers for such a benefit-harm ratio for mammography. It shows that per 1,000 women aged 50 years or older who participated in mammography for 10 or more years, 1 woman would be saved from dying from breast cancer due to screening. At the same time, about 5 per 1,000 women who undergo screening would be wrongly diagnosed with progressive breast cancer and treated unnecessarily. Also, mammography has no effect on overall mortality from cancer.
Researchers assume that the benefit-harm ratio of screening would become more favourable if cancer screenings were tailored to a woman's personal risk of getting cancer. Particularly for women at higher-than-average risk, the benefits of screening may outweigh its harms, whereas for women at average or lower-than-average risk, less screening could be more advantageous in terms of avoiding the potential harms of screening.

DIET
What is the rationale behind the currently developed WID test and what would it potentially change?
The rationale of the new WID test -currently under development -is to provide a woman with such a personalized risk prediction about getting certain female cancers within the next 10 years. The female cancers it targets are: breast cancer, ovarian cancer, cervical cancer, and womb cancer. In contrast to cancer screenings, the WID test is meant to predict the risk of these four female cancers before cancer is present. By using this test in the future, women may learn whether their personal risk is lower-thanaverage, at average, or higher-than-average.
To achieve this goal, the WID test will be based on the technology of epigenomics.
Because each human being's epigenome records the life-time exposure to environmental cancer-triggering factors such as infections, diet, or smoking on an individual level, changes in our epigenome seem to be a promising target for predicting cancer risk. Not only may this technology assist in better predicting women's personal cancer risk in the future, but it may also make more information available on the relation between a woman's personal lifestyle and her cancer risk. The following figure illustrates the influence of some environmental factors on our epigenome.
If the WID test became available, it would be for women aged 50 years onwards. As the technology would use the epigenome of cervix cells, samples for the test would be obtained from cervical cells by a smear test. The test would be carried out by gynaecologists, general practitioners, and nurses who are qualified to perform smear tests. The test would take less than a minute and should not involve any pain. The cells taken from the smear test sample would be sent to a laboratory in order to test for your risk. When your results are made available, they would be discussed with your doctor at a follow-up meeting. Currently, the WID test is under clinical investigation in order to identify appropriate risk groups and interventions that work best for each risk group. If these risk groups and interventions are eventually identified, the WID risk test may help women and their doctors in the future adjust a woman's health care to her personal risks, with the following advantages: • Women who are predicted to have a higher-than-average risk of developing any of the female cancers could take preventive actions (e. g., adopting a healthier lifestyle if risk is slightly elevated, preventive medication or prophylactic surgery if risk is high) in order to control or to lower their risk. Also, they could do more frequent screening to detect a cancer as early as possible. • Women who are predicted to have an average or lower-than-average risk may decide to maintain their current lifestyle and have less screenings that entail potential harms. • Because the WID test will be able to record changes in the epigenome that are caused by environmental and life-style factors, the test may also allow for monitoring how effective preventive actions such as changes in life-style are on reducing the personal cancer risk over time.
What are potential harms of taking the test?
No test is perfect. The WID test may lead to an inaccurate prediction of your risk of developing cancer and could therefore lead to unnecessary anxiety, diagnostic procedures, or medical interventions, or to the illusion of being at low risk when one is actually at higher risk. Even if the prediction is accurate, it does not mean that a woman with a higher-than-average risk will get cancer for certain and a woman with a lower-thanaverage risk will not get cancer.
Because numerical information about the quality of the test is not available at the current developmental stage, the likelihood of its making inaccurate predictions is not yet known. Furthermore, whether the WID test will eventually help in further reducing the number of women dying from any of the four female cancers or in reducing the number of women experiencing wrong diagnoses needs to be demonstrated in a larger clinical study in the future.
Who will be able to access my test data if I have the WID test in the future?
If you did not consent to the permanent storage of your test sample and results, your sample would be destroyed after risk estimation. As with other diagnostic and predictive tests, your risk information falls under medical confidentiality, meaning that access would be restricted to you, the laboratory, and your doctor.
Are there any other considerations?
The technology of the test makes information available on the relation between a woman's personal lifestyle and her cancer risk. Receiving the result of a higher-thanaverage risk may make you feel personally responsible for this result. In addition, many people often take predictive tests to reassure themselves that everything is fine, which is not always the case. Before having the test you should therefore also think about how you would cope with receiving a higher-than-average result. It is recommended that you talk to your doctor and your family members about your thoughts and concerns before having such a test.
Women's cancer risk identification (WID) test A test under development to identify a woman's risk of developing breast cancer, ovarian cancer, cervical cancer, and womb cancer