Mammograms 'boost breast cancer risk' in women with 'faulty genes'

Behind the Headlines

Monday September 10 2012

Mammograms reduce the risk of dying from breast cancer

“Mammograms may boost breast cancer risk in women with faulty gene,” the Daily Mail reports.

This story appears to suggest that mammograms increase women's risk of developing breast cancer. In fact, the research looked at whether exposure to radiation in general (including X-rays and CT scans) increased the risk of breast cancer in women who had a genetic mutation known to increase breast cancer risk. It found that exposure to radiation before the age of 30 increased risk of disease in these already high-risk women.

Despite the media headlines, when exposure to mammograms alone was studied, the increase in risk was not significant, suggesting this finding could be the result of chance.

The researchers speculate that women with specific mutations may be more sensitive to the effects of radiation. They suggest that alternative techniques that do not use radiation (such as MRI or ultrasound) should be used with women known to have genetic risk factors for breast cancer. Reassuringly, MRI is already used for breast cancer screening in young, high-risk women. 

It is important that the findings don’t deter women from attending breast cancer screening. Mammography has been demonstrated to reduce the risk of dying from breast cancer. Any small increased risk from radiation exposure is likely to be outweighed by the benefit of detecting breast cancers early.

 

Breast cancer screening

The NHS Breast Screening Programme currently invites women aged between 50 and 70 to attend for breast screening every three years. The programme is gradually being extended to include women aged 47 to 73.

Women who are considered to be at higher risk of breast cancer are offered screening more frequently.

Where did the story come from?

The study was conducted by researchers from the Netherlands Cancer Institute and various other institutions in Europe and the US. Funding was provided by the Euratom Programme, Fondation de France and Ligue National Contre le Cancer, Cancer Research UK and the Dutch Cancer Society.

The study was published in the peer-reviewed British Medical Journal.

The Daily Mail’s headline is misleading, suggesting to women that mammography may be dangerous and increase cancer risk. This is not the case. The research looked at all forms of diagnostic radiation and did not focus only on mammography.

In fact the link between mammography screening and higher cancer risk in women with these genetic mutations who had received a mammogram before the age of 30 was not statistically significant.

The newspaper does not make clear that the use of screening methods not involving radiation for high-risk women is recommended ‘best practice’ in England (the same is not true in other European countries). However, access to MRI scanners can be limited so the waiting time for an MRI scan is often longer than for a mammogram.

 

What kind of research was this?

This was a retrospective observational cohort study looking at whether increased exposure to radiation, such as X-rays and CT scans, was associated with increased risk of breast cancer in women with a mutation in BRCA1 or BRCA2, which puts them at higher risk of breast cancer.

The researchers say that previous observational studies have noticed a link between exposure to radiation for diagnostic purposes, and increased risk of breast cancer in women with BRCA1/2 mutations. However, they say that these studies have given inconclusive results and have limitations such as small sample numbers, a lack of information on radiation dose and look at only a single type of diagnostic procedure.

This study aimed to explore this association further, looking at different types of diagnostic radiation procedures and doses of radiation used, and analysing whether the age at which the women were exposed to radiation had any effect. A cohort is an appropriate study design to look at whether a particular exposure (in this case radiation) increases the risk of a particular outcome (in this case breast cancer).

 

What did the research involve?

This study included 1,993 women (aged over 18) who were identified to be carriers of the BRCA1 or BRCA2 mutation. The women were recruited to this study between 2006 and 2009, and were all participating in three larger nationwide cohort studies of mutation carriers in France, the UK and the Netherlands.

They asked the women to complete detailed questionnaires containing questions on lifetime exposure to the following radiological diagnostic procedures, including the reasons they had them done:

  • fluoroscopy – a type of ‘real time’ X-ray showing continuous images (for example, a barium examination to help diagnose digestive conditions)
  • conventional radiography (X-ray) of the chest or shoulders
  • mammography
  • computed tomography (CT scan) of the chest or shoulders
  • other diagnostic procedures involving the chest or shoulders that use ionising radiation (such as bone scans)

For fluoroscopy, radiography and mammography, they were asked about:

  • ever/never exposure
  • age at first exposure
  • number of exposures before the age of 20 years
  • exposures at ages 20-29 and 30-39 years
  • age at last exposure

For the other types of radiological examination they were just asked about their age at exposure and number of exposures. The researchers also estimated the cumulative radiation dose to the breast.

Diagnoses of breast cancer were recorded through national registries or medical records. The main outcome of interest was risk of breast cancer according to cumulative radiation dose to the breast, and according to age at exposure.

The main analyses focused on a smaller subset of women who were diagnosed with cancer more recently (1,122 women). If the researchers looked at women who were diagnosed prior to study recruitment, then there may have been other women who were diagnosed at the same time, and who would also have been eligible for the study, but who had died so were not able to take part. If radiation exposure was linked to poorer cancer outcomes (women with higher radiation exposure were more likely to die), then the study could be over-representative of people with less radiation exposure. This problem is called survivor bias. Therefore, by looking only at women with more recent diagnoses they hoped to include a representative sample of women from all levels of radiation exposure. 

What were the basic results?

Radiography was the most common diagnostic procedure, with 48% of the cohort (919) reporting having had an X-ray. A third of women in the cohort had had a mammogram, and the average age at first mammogram was 29.5 years old. The average number of procedures performed before the age of 40 was 2.5 X-rays and 2.4 mammograms. The average estimated cumulative radiation dose was 0.0140 Grays (Gy), ranging from 0.0005 to 0.6130Gy. Of the entire cohort, 848 of 1,993 (43%) went on to develop breast cancer.

Any exposure to diagnostic radiation before the age of 30 was associated with an increased risk of breast cancer (hazard ratio 1.90, 95% confidence interval [CI] 1.20 to 3.00). There was evidence of a dose-response pattern with a trend for increasing risk with each increasing estimated cumulative radiation dose.

There was a suggestion that mammography before the age of 30 was also associated with an increased risk of breast cancer, but the link was not statistically significant. While the researchers estimated the hazard ratio at 1.43 it could have been as low as 0.85 (the CI was calculated at 0.85 to 2.40) meaning that mammograms may actually reduce cancer risk.

 

How did the researchers interpret the results?

The researchers conclude that in their large European cohort study, carriers of BRCA1/2 mutations had increased risk of breast cancer if exposed to diagnostic radiation before the age of 30. They say that their results “support the use of non-ionising radiation imaging techniques (such as magnetic resonance imaging) as the main tool for surveillance in young women with BRCA1/2 mutations”.

 

Conclusion

This study suggests that women who carry the genetic mutation BRCA1/2 may have increased risk of breast cancer if they are exposed to diagnostic radiation before the age of 30. The cohort has looked at a range of diagnostic procedures and radiation doses, finding that risk was increased even at low radiation doses. The researchers call for diagnostic imaging techniques that do not involve radiation (such as MRI) to be considered in higher risk women with BRCA1/2 mutations, and this seems an appropriate suggestion which will need further consideration.

The study benefits from the fact that it involved a large number of women with BRCA1/2 mutations. However, as radiation was assessed through self-report there is the possibility that responses were inaccurate, and that estimations of the number of diagnostic examinations, age at examination and, therefore, the researchers’ estimates of cumulative radiation dose were inaccurate. A review of procedures recorded in medical records, for example, may have given a more accurate indication of radiation exposure. 

The media has focused upon the finding of an increased risk specifically with mammography prior to the age of 30. This link was not in fact statistically significant. However, as mammography does involve radiation, a link is plausible. All screening programmes involve a balance of weighing up the risks of screening against the benefits, but the benefits of screening, which include earlier diagnosis of breast cancer and improved chance of successful treatment and survival, are likely to outweigh the risks.

The results do support the use of MRI for surveillance of young women with BRCA1/2 mutations, and MRI is in fact already used in the NHS Breast Cancer Screening Programme for the screening of younger, higher risk women, though it does depend on resources and availability. The NHS advises that mammography is more reliable for detecting breast cancers in older breast tissue. The Department of Health’s Advisory Committee on Breast Cancer Screening is currently developing a practical guideline for the NHS on the surveillance of women considered to be at a higher risk of breast cancer.

Overall, it is important that the findings do not deter women from attending for breast cancer screening. The Department of Health reports that around a third of breast cancers are currently diagnosed through screening and breast cancer screening is estimated to save 1,400 lives a year. For most women the benefits of mammography screening are likely to outweigh any small increased risk from radiation exposure. For higher risk women, guidelines are likely to consider the risk of increased radiation exposure and the need for using techniques such as MRI, which do not involve radiation. 

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on twitter.

Analysis by Bazian

Edited by NHS Choices

Links to the headlines

Mammograms may boost breast cancer risk in women with faulty gene. Daily Mail, September 7 2012

Links to the science

Pijpe A, Andrieu N, Easton DF, et al. Exposure to diagnostic radiation and risk of breast cancer among carriers of BRCA1/2 mutations: retrospective cohort study (GENE-RAD-RISK). BMJ. Published online September 6 2012

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