“A hormone that helps children grow may cause breast cancer, and women with high levels are at higher risk,” reported The Independent.
This report is based on a large review that combined the results of 17 studies on the relationship between levels of insulin-like growth factor (IGF1) and the development of breast cancer. It found that women with higher levels of IGF1 were at greater risk of developing oestrogen-dependent breast cancer. Women with the highest levels of this hormone in their blood were 28% more likely to develop breast cancer than those with the lowest levels.
The nature of the studies that were included means there is some certainty that higher hormone levels preceded the development of cancer (and not vice versa). However this is still not proof of cause and effect. Although there may be future implications for breast cancer prevention as blood levels of IGF1 can be influenced by dietary factors, this has not been examined by this research, and requires further study.
Where did the story come from?
The study was carried out by researchers from the Endogenous Hormones and Breast Cancer Collaborative Group, in the Cancer Epidemiology Unit at the University of Oxford. Contributors from institutes in Europe, the US and Australia also took part. The analysis was funded by Cancer Research UK and published in the peer-reviewed medical journal The Lancet Oncology.
The study was accurately reported in The Independent , though the headline mistakenly claimed that the “growth hormone causes breast cancer”. The study did show a positive link between the hormone and breast cancer risk, but this type of research cannot establish cause and effect.
What kind of research was this?
This was a pooled analysis of raw data from 17 individual studies from 12 countries, which looked at the possible links between blood levels of insulin-like growth factor 1 (IGF1) and breast cancer risk. IGF1 is a natural chemical in the body that is mainly secreted by the liver. It is essential for early growth and development.
Several previous studies have indicated there may be an association, but these studies were small with inconsistent results. It was unclear whether other factors were involved, such as menopausal status, the presence of other chemicals and the role of oestrogen. By pooling the data from several studies (which were largely nested case control studies), the researchers aimed to establish the risk more precisely and to find out whether other risk factors play a role.
To identify these studies, the researchers searched one electronic database and did further searches of the reference lists of the studies they identified. It is possible they may have missed some potentially eligible studies. Differences between the individual studies also need be taken into account. For example, the population that was studied, how levels of growth hormones were measured, and the length of follow-up. The researchers took this into account where appropriate.
What did the research involve?
The researchers systematically searched a research database for studies that looked for associations between breast cancer risk, IGF1, and another chemical that binds the hormone (IGF binding protein 3; IGFBP3). They say that most IGF1 in the body is bound to IGFBP3, so most previous studies have also looked at levels of this protein to see whether women with a high concentration of IGF1 relative to IGFBP3 are at an increased risk of breast cancer. Studies were only eligible if they were prospective in design, which means they had identified and followed a group of women over time to find out who went on to develop breast cancer and who did not, and what factors might be involved.
The raw data from the individual studies on blood levels of IGF1 and IGFBP3 and other factors associated with breast cancer risk, such as menopausal status was collated. Established statistical techniques were used to analyse the relationship between breast cancer, IGF1 and other possible risk factors, and to calculate the risk that might be associated with increasing concentrations of IGF1. The women were put into one of five categories according to their levels of IGF1 and IGFBP3.
What were the basic results?
In total 17 studies matched the inclusion criteria, providing data on 4,790 women who developed breast cancer and 9,428 women who did not develop the disease and who formed the control group. Average ages ranged from 35 to 72. Most women had experienced pregnancy, and most menopausal women had gone through a natural menopause. Average BMI was 23 to 28.
IGF1 concentrations were higher in certain groups, including taller women, moderately overweight women and in moderate consumers of alcohol.
The researchers found that, overall, the higher a woman’s blood level of IGF1, the higher her breast cancer risk. Women in the top fifth of cases, with the highest levels of IGF1, had a 28% higher risk of breast cancer than women in the bottom fifth, who had the lowest levels of IGF1 (odds ratio 1.28, 95% CI 1.14 to 1.44). The risk was not substantially changed by the presence of other chemicals or by menopausal status, or by the researchers' adjustments for other risk factors, but the relationship seemed to be limited to oestrogen-receptor-positive cancers.
How did the researchers interpret the results?
The researchers say their analysis confirms there is a link between levels of the hormone IGF1 and breast cancer-risk. They say it is not known if the hormone actually causes breast cancer, but there are “plausible biological mechanisms that could explain such an effect”.
If the link is causal, then this has important implications for prevention, since levels of IGF1 are influenced by nutritional factors, such as energy and protein intake. They advise that the possibility of lowering breast cancer risk by reducing IGF1 should be explored.
This is a large, well-conducted review of studies examining a link between insulin-like growth factor and breast cancer development. The researchers also adjusted for numerous other potential risk factors for breast cancer that may have confounded the relationship. It confirms a previously suspected link between IGF1 and breast-cancer risk, and tells us more about the size of the risk and whether any other factors are involved.
However, the researchers point out that:
- As with all reviews, individual study designs and methods often vary. In this case, IGF1 and IGFB3 and other risk factors were measured using various methods, which could make the results less reliable.
- Hormone concentrations varied substantially between studies. The reasons for this are unclear, and although the researchers allowed for this, it may bias the results. Also, hormone levels were measured only on one occasion, and may not necessarily represent hormone levels over a woman’s lifetime.
As the researchers say, there may be future implications for breast cancer prevention as IGF1 levels can be influenced by diet. This will need to be examined in future research. Further study is also needed to see why the relationship appeared to be specific to oestrogen receptor-positive breast cancers.