"Men with high oestrogen more likely to develop breast cancer," reports the Daily Telegraph.
This headline is based on an international study looking at potential risk factors for male breast cancer. This is a much rarer cancer compared to female breast cancer – an estimated 350-400 UK cases per year for men compared to 50,000 cases in women.
It is known that the hormone oestrogen can trigger the development of some types of female breast cancer. Men as well as women produce oestrogen, but at much lower levels, so researchers wanted to see if there was a similar connection.
This study compared blood samples taken from 101 men who went on to develop breast cancer, with 217 men who didn’t.
It found that men with the highest levels of one form of the hormone oestrogen were about two-and-a-half times more likely to develop the condition than those with the lowest levels.
The study used a good design and approach, and the findings seem plausible, given what is known in women. However, it is still difficult to say whether a raised oestrogen level is directly raising the risk of breast cancer, or if both could be the result of another underlying factor.
Learning more about the causes of male breast cancer might help to find ways to prevent it or find new treatments in the long term.
Where did the story come from?
The study was carried out by researchers from the National Cancer Institute in the US, and other research centres in the US, Europe and Canada. It was part of the Male Breast Cancer Pooling Project, and was funded by various international sources, including the National Cancer Institute in the US, and Cancer Research UK and the UK Medical Research Council.
The study was published in the peer-reviewed Journal of Clinical Oncology.
The Telegraph covers this study reasonably well.
What kind of research was this?
This was a nested case-control study looking at whether levels of sex hormones are related to a man’s risk of developing breast cancer.
Breast cancer can occur in men, but is very rare. In the UK, about 350 men are reported to be diagnosed with the condition each year. This makes the condition difficult to study, and this is why researchers came together to form an international collaboration, so that they could identify more cases than they would be able to by working alone.
Men and women both produce the sex hormones oestrogen and testosterone – but at different levels. In women, breast cancer is known to be influenced by these hormones. The roles these hormones play in male breast cancer is not known.
A nested case-control study is the most feasible way of looking for possible risk factors for rare diseases. Being "nested" means that information is collected on risk factors in a prospective fashion in a larger group of people, and then people who develop the condition are identified. These people are the "cases" and a matched group of people with similar characteristics, but without the condition, are the "controls".
What did the research involve?
The researchers identified 101 men with breast cancer (cases), and 217 similar men without the condition were selected as controls. They analysed blood samples that had been collected from the men before their diagnosis, and compared hormone levels to see if there were any differences from cases and controls.
The participants were identified through seven cohort studies that recruited men without breast cancer. The men provided blood samples, and these were stored. They were then followed up to see if they developed breast cancer. When a case was identified, the researchers selected up to 40 control men from their cohort who were similar to the affected man in terms of race, year of birth, year they entered the study, and how long they had been followed up for.
The researchers then analysed the stored samples to measure the levels of various forms of the steroid sex hormones oestrogen and testosterone. They compared levels in men who later went on to develop breast cancer and controls, to see if they differed. They took into account factors that might affect results (potential confounders) such as:
- age when the blood sample was taken
- body mass index (BMI)
- date of the blood sample
What were the basic results?
The researchers found that for the male sex hormones (androgens such as testosterone) there were no differences in levels between men who went on to develop breast cancer, and those who did not.
However, men who developed breast cancer did have higher levels of the hormone oestradiol (one form of oestrogen) than controls. Men who had the highest oestradiol levels were about two-and-a-half times more likely to develop the condition than those with the lowest levels (odds ratio (OR) 2.47, 95% confidence interval (CI) 1.10 to 5.58).
How did the researchers interpret the results?
The researchers conclude that their results support a role for oestradiol (oestrogen) in the development of breast cancer in men. They report that this is similar to the level of effect seen in postmenopausal women.
This study has identified that oestrogen may play a role in the development of breast cancer in men. The study’s strengths include the prospective collection of data, and the relatively large group of cases, given how rare the disease is.
One of the main limitations of this type of study is that other factors may influence results. In this study, this risk was minimised by matching controls to cases within each country, and by adjusting for various confounders in the analyses. Despite this, some unmeasured confounders may still have an effect. For example, breast cancer in a first-degree relative (parent or sibling) was five times more common in men who developed breast cancer, and there was no information on whether any of the men carried a high risk form of the BRCA genes, which increase the risk of cancer.
In addition, only one blood sample appeared to be tested for each man, and at various times before their diagnosis. It is possible that the single sample taken may not be representative of levels over a longer period.
It is difficult to say from this type of study whether oestrogen levels are directly causing an increase in risk. The authors note that it is not clear how higher levels of oestrogen might increase breast cancer risk.
Overall, the findings of this study seem plausible, given what is known about breast cancer in women, and could increase knowledge about possible risk factors for male breast cancer.