Screening for breast cancer genes could be leading women to undergo needless mastectomies, experts have warned, recommending that detailed family histories be taken into account before any drastic decisions are made.
The advice follows a University of Exeter study, which found that the risk of developing cancer by 60, if carrying the BRCA1 or BRCA2 gene, is as low as 18%, but women are being led to believe it is as much as 80%, and opting for breast surgery as a preventative measure.
The researchers warn that the risk has been calculated based on women who were screened for BRCA because they had already had breast cancer symptoms or a family history of the disease.
To find out the true underlying risks, reports The Guardian, the team analysed more than 454 000 participants of the UK Biobank study, aged between 40 and 69.
They found that even if a woman has BRCA mutations, her risk is relatively low unless she also had a close relative with breast cancer.
Simply carrying a disease-causing BRCA variant was linked to a breast cancer risk of 18% for BRCA2 and 23% for BRCA1 by 60.
Having a close relative who has had the condition elevated the risk to 24% for BRCA2 and 45% for BRCA1.
Dr Leigh Jackson of the University of Exeter Medical School, said: “Being told you are at high-genetic risk of disease can really influence levels of fear of a particular condition and the resulting action you may take.
“Up to 80% risk of developing breast cancer is very different from 20%. That difference could well influence the decision you make around whether you have invasive breast surgery.
“Some women may decide to go ahead with that procedure knowing the risk is 20%, but we want them to make an informed decision. We’d urge that anyone communicating cancer risk does so based on a detailed family history, not just genetics alone.
Experts warned that women could be opting to have unnecessary surgery after being told they are at high risk from genetic test results which do not take family history into account.
Findings do not apply to just breast cancer
The research team found a similar result when looking at genetic risk of Lynch syndrome, which increases the risk of colon cancer and some other cancers.
The authors concluded that genetic screening in the general population could result in large numbers of people being exposed to needless scans or further procedures.
The study’s co-author, Professor Caroline Wright, of the University of Exeter Medical School, said: “Our findings will not just apply to breast and colorectal cancer.
“All risk-estimates of genetic disease have so far largely been based on relatively high-risk groups who attend specialist clinics, so they will not necessarily translate to the general population.
“This finding has important ramifications for population screening using genome sequencing.
“We need to ensure we are carrying out research to find the true risk level, and also to be responsible in how we communicate risk, to avoid unnecessary fear and distress which may lead to avoidable procedures.”
The warning has emerged in a paper published in The Lancet journal eClinical Medicine.
Study details
Influence of family history on penetrance of hereditary cancers in a population setting
Leigh Jackson, Michael Weedon, Harry Green, Bethan Mallabar-Rimmer, Jamie Harrison, Andy Wood, et al.
Published in The Lancet eClinical Medicine on 14 September 2023
Summary
Background
We sought to investigate how penetrance of familial cancer syndromes varies with family history using a population-based cohort.
Methods
We analysed 454,712 UK Biobank participants with exome sequence and clinical data (data collected between March 2006 and June 2021). We identified participants with a self-reported family history of breast or colorectal cancer and a pathogenic/likely pathogenic variant in the major genes responsible for hereditary breast cancer or Lynch syndrome. We calculated survival to cancer diagnosis (controlled for sex, death, recruitment centre, screening and prophylactic surgery).
Findings
Women with a pathogenic BRCA1 or BRCA2 variant had an increased risk of breast cancer that was higher in those with a first-degree family history (relative hazard 10.3 and 7.8, respectively) than those without (7.2 and 4.7). Penetrance to age 60 was also higher in those with a family history (44.7%, CI 32.2–59.3 and 24.1%, CI 17.5–32.6) versus those without (22.8%, CI 15.9–32.0 and 17.9%, CI 13.8–23.0). A similar pattern was seen in Lynch syndrome: individuals with a pathogenic MLH1, MSH2 or MSH6 variant had an increased risk of colorectal cancer that was significantly higher in those with a family history (relative hazard 35.6, 48.0 and 9.9) than those without (13.0, 15.4 and 7.2). Penetrance to age 60 was also higher for carriers of a pathogenic MLH1 or MSH2 variant in those with a family history (30.9%, CI 18.1–49.3 and 38.3%, CI 21.5–61.8) versus those without (20.5% CI 9.6–40.5 and 8.3% CI 2.1–30.4), but not for MSH6 (6.5% CI 2.7–15.1 with family history versus 8.3%, CI 5.1–13.2). Relative risk increases were also observed both within and across conditions.
Interpretation
Individuals with pathogenic cancer syndrome variants may be at a less elevated risk of cancer in the absence of a first-degree family history, so in the context of results return, family history should be considered when counselling patients on the risks and benefits of potential follow-up care.
The Telegraph article – Angelina Jolie breast cancer gene screening could be ‘leading women to have needless mastectomies’ (Restricted access)
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