Scientists have identified the first genetic variant
specifically associated with the risk of a difficult-to-diagnose
cancer sub-type accounting for around 10-15 per cent of all breast
cancer cases.
The largest ever study of the breast cancer sub-type, called
invasive lobular carcinoma, gives researchers important clues to
the genetic causes of this particular kind of breast cancer, which
can be missed through screening.
The study used gene chip technology and complex statistical
analysis to compare the DNA of more than 6,500 women with invasive
lobular cancer with the DNA of more than 35,000 women without the
disease.
A woman with the genetic variant, called rs11977670, was found
to have a 13 per cent higher chance of developing invasive lobular
cancer than a woman without it. The variant is close to two genes
on chromosome 7: BRAF, a known cancer-causing gene, and JHDM1D,
which is involved in the activation and deactivation of other
genes.
The discovery of the genetic variant, in conjunction with other
markers, could help in the development of future genetic screening
tools to assess women's risk of developing invasive lobular cancer,
and also gives researchers important new clues about the genetic
causes of the disease and a related precursor to cancer called
lobular carcinoma in situ.
Invasive lobular carcinoma develops in the lobes of the breast
that produce milk and can be particularly difficult to diagnose,
because the cancer often does not form a definite lump and may not
show up on mammograms. As a result, women with this type of cancer
tend to be diagnosed when the cancer is more advanced and more
difficult to treat.
As well as looking for new genetic risk factors, the researchers
also evaluated 75 variants previously linked with breast cancer
overall. They found that most of these were associated with risk of
invasive lobular cancer specifically, as well as overall breast
cancer risk. The study also showed for the first time that genetic
factors for invasive breast cancer can also predispose to lobular
carcinoma in situ.
Professor Montserrat Garcia-Closas of the Institute of Cancer
Research, London, said: "Our study is the first to link a genetic
variant specifically with a higher risk of invasive lobular
carcinoma, which accounts for around 10 to 15 per cent of all
cases. It also finds that more than 50 previously discovered
variants specifically increase the risk of lobular tumours, as well
as making breast cancer overall more likely.
"Understanding the genetic factors at work in lobular cancers
could be particularly important, because they are often missed by
mammography because of their unusual growth patterns. In the
future, we hope that improving our knowledge of the genes involved
in lobular carcinoma could improve our ability to prevent and treat
it.'
Dr Elinor Sawyer of King's College London and Guys and St
Thomas' NHS Foundation Trust, said: "A diagnosis of breast cancer
can be devastating, particularly if it is not picked up early and
the cancer is at a stage when it may be more difficult to treat.
This can be the case for lobular breast cancers as they are
difficult to see on mammograms. By identifying genetic factors that
result in an increased risk of lobular cancer we hope in the future
to be able to find better ways of assessing the risk of developing
these cancers, so different screening tests can be offered to those
at high risk, as well as finding new treatments for lobular
cancer."
Dr Rebecca Roylance of Queen Mary University of London said: "We
know invasive lobular breast cancers can behave differently to
other breast cancer types, as well as be more difficult to diagnose
- both of which led us to believe there may be different genetic
factors in their development. It is really exciting that our
theories based on clinical observations have been confirmed by the
identification of specific genetic changes in patients with
invasive lobular breast cancer. The big challenge now is for these
changes to be confirmed and for this information to be used for the
benefit of patients."
Baroness Delyth Morgan, Chief Executive, Breast Cancer Campaign
said: "These results demonstrate just how vital it is to bring
researchers together to collaborate in order to unlock the answers
around genetics and risk for all sub-types of breast cancer. This
could be the first step in assessing who is at risk of developing
this type of breast cancer that is so hard to diagnose.
"Breast Cancer Campaign is now funding the study's co-author Dr
Elinor Sawyer for a further three years to understand what the new
genetic variant found in this study could be doing within cells to
increase breast cancer risk. Ultimately Dr Sawyer's work could
improve the diagnosis and survival for women with this subtype of
breast cancer."
The paper, Genetic Predisposition to In Situ and Invasive Lobular Carcinoma of
the Breast, is published in PLOS Genetics.