Breast cancer is not a single disease but a collection of at least five separate conditions that differ in prognosis and response to treatment, a detailed genetic study has revealed.

A comparison of the genomes of 24 breast tumours has found several distinct patterns of DNA damage, each of which appeared to be characteristic of a peculiar sub-type of cancer.

The findings, from a British team that unveiled last week the first comprehensive genetic maps of two tumours, offer insights into the biology of breast cancer that promise improvements to diagnosis and treatment.

As more is understood of the genetic architecture of different kinds of breast cancer, scientists expect to be able to classify patients’ tumours according to their DNA signatures.

This information could then be used by doctors to establish how aggressive the tumour will be, and which therapy is most likely to work.

Mike Stratton, of the Cancer Genome Project at the Wellcome Trust Sanger Institute, said: “There is massive diversity between individual breast cancers and it is quite clear that these 24 tumours are not all examples of the same disease.

“As time goes on, we are becoming increasingly aware that breast cancer is very biologically diverse. Our work supports the view that breast cancer is not one but several diseases.

“If this diversity is associated with a different prognosis, or sensitivity to drugs, it will become very useful on a clinical level.”

Oncologists already recognise that there are three to four broad groups of breast cancers, which differ in their responses to particular drugs.

Herceptin (trastuzumab), for example, works only against tumours that are positive for a receptor called HER-2, while tamoxifen is effective only when cancer cells have a receptor for the female hormone oestrogen.

There are also “triple-negative” cancers that lack receptors for HER-2, oestrogen and progesterone, which are often particularly aggressive and difficult to treat.

Professor Stratton’s study, which is published in the journal Nature, has identified genetic profiles characteristic of each of these groups, along with several others that suggest that these classes can be subdivided still further.

“It’s already understood that breast cancer is at least three to four different animals,” Professor Stratton said.

“The genetic architecture suggests that we’re probably going to be dealing with at least five to ten different animals. It’s clear that the triple-negative cancers, for example, are clearly going to subdivide into multiple different categories.”

In the study, the scientists examined 24 tumours for evidence of rearrangements — a type of genetic damage in which large chunks of chromosomes break off and reattach themselves in unusual ways.

It revealed great differences between one tumour and another: while some tumours were relatively undisturbed, others were chaotic with more than 200 rearrangements.

“We were, frankly, astounded at the number and complexity of rearrangements in some cancers,” Professor Stratton said.

The research comes a week after his team published the first comprehensive catalogues of all the mutations present in two cancer genomes, of a lung tumour and a melanoma.

The breast cancer study has not yet investigated the disease in this exhaustive detail, but a project is under way to do this for 1,500 breast tumours, under the £600 million International Cancer Genome Consortium.

“When we are a fair way into this, we will have a clearer idea of how many well-defined sub-types of breast cancer there are,” Professor Stratton said.

“Once we have pinned that down, we will need to look at this in the context of clinical progression, to see what is useful to look at in patients.

“The aim is to identify cancer-causing genes that are produced by these rearrangements, and to develop therapies that target them,” Professor Stratton said.

Jorge Reis-Filho, of the Breakthrough Breast Cancer Research Centre at the Institute of Cancer Research in London, another member of the research team, said that the study suggested that faulty DNA repair mechanisms underlay rearrangements in breast cancer.

“It appears that in different sub-types of breast cancers, distinct mechanisms of DNA repair are impaired, leading to different types of genomic disorganisation,” he said.

“If we damage further an already faulty DNA repair system using tailored therapies, one can kill tumour cells selectively, without harming normal cells.

“There are already some highly interesting results suggesting that breast cancers with defects in DNA repair are more sensitive to drugs that cause additional DNA damage.”

New drug offers hope against Ewing’s sarcoma

A new drug may halt the growth of a rare form of cancer that mainly affects teenage boys, scientists say (David Rose writes).

An early study of the drug figitumumab has found that it can be an effective treatment for Ewing’s sarcoma, which forms in the bones of about 30 young people in Britain each year.

The promising results, published online in the Lancet Oncology journal, come from a study on 29 patients which aimed to check whether figitumumab was safe for sarcoma patients.

The trial covered a range of relatively uncommon cancers that form in the bones or soft tissues of the body.

The average age of patients in the trial was 30, but all had advanced cancers that were responding poorly to existing treatments such as chemotherapy and radiotherapy.

But figitumumab was shown to be effective for at least 16 patients with Ewing’s sarcoma, which is typically diagnosed between the ages of 10 and 20, and more commonly affects boys than girls.

DNAWellnessinfo.com Resource:  http://www.timesonline.co.uk/tol/news/uk/article6966927.ece

A team of Canadian researchers has decoded the genetic structure of metastatic lobular breast cancer – a major breakthough that could lead to the development of new treatments and therapies for that type of breast cancer.

Scientists with the BC Cancer Agency in British Columbia unlocked all 3 billion letters in the cancer’s DNA sequence and identified all of the mutations that caused the cancer to spread. Metastatic lobular breast cancer accounts for about 10 percent of all breast cancer.

“One in nine women is expected to develop breast cancer, and breast cancer accounts for 29 percent of all cancer diagnoses for B.C. women,” said Health Services Minister Kevin Falcon. “As a result of the efforts of the scientists behind the study, this breakthrough finding gives further hope to the thousands of women with this terrible disease.”

The researchers used the latest DNA sequencing technology to compare a single patient’s lobular breast cancer tumor at two different times – when the cancer first presented itself and when it came back nine years later. They found 32 mutations in the tumor and compared that to the original tumor’s DNA. Only five were present in all of the cells from the original tumor, indicating that those mutations likely caused the disease.

Marco Marra, director of the BC Cancer Agency’s Genome Sciences Centre, said the project largely was made possible by advances in DNA sequencing technology. The project that first decoded the human genome took years, while this study was conducted in a matter of weeks.

Katie Hoadley, a research associate at the University of North Carolina at Chapel Hill’s Lineberger Comprehensive Cancer Center, said the Canadian research represents the new wave of cancer genetic research. The Canadian researchers examined the complete genetic structure from every possible angle, something that had not been done before. In past genetic studies, researchers would look at portions of the genetic code.

And this study was particularly interesting because the researchers were able to examine the genetic structure of a tumor at two different points in its evolution, providing some insight into what was going on within the tumor to cause the cancer and to cause its to return, said Hoadley.

But, she said, the research is not a definitive answer to curing breast cancer. Rather, the study provides a guide for researchers to follow to better understand the causes and possible treatments for lobular breast cancer. Other breast cancers still need to be studied.

The study will be published in the Thursday issue of the journal Nature.

UNC, DUKE ALSO STUDYING CANCER GENETICS

Similar research is being conducted at the University of North Carolina at Chapel Hill and Duke University.

Researchers at Duke University Medical Center and the National Cancer Institute have discovered a genetic alteration – in this case, a second copy of an entire gene – that is a cause of familial chrodoma, an uncommon form of bone cancer.

“This alteration is unlike anything we have ever seen before in families that tend to develop the same kind of cancers,” says Michael Kelley, an associate professor at Duke University Medical Center. “We are not talking about a mutation in a single gene, but the duplication of an entire gene. This discovery is a classic example of where science answers one question but raises many, many more.”

Chrodoma is a rare, but severe disease, affecting only one in every million people. The disease causes tumors at the base of the skull, pelvis or along the spinal column. There is no cure and few treatments, and Chrodoma usually causes death within 10 years.

Researchers at UNC, including Hoadley, were selected to participate in the Cancer Genome Atlas project, an initiative created by the National Cancer Institute and the National Human Genome Research Institute to characterize genomic changes that occur in cancer. UNC is one of 12 centers nationally working on the project.

“This project represents one of the most ambitious and challenging human genetics efforts to date, only rivaled by its predecessor, the Human Genome Project,” said Dr. Charles Perou, associate professor of genetics and pathology and laboratory medicine. “The TCGA project takes a comprehensive approach to the study of human cancers and applies multiple cutting-edge technologies to the same large set of tumors. The real power of this project is in the integration of these different genetic data types into a common framework that should provide a much more complete picture of why a tumor is a tumor.”

DNAWellnessinfo.com Resource:  http://triangle.bizjournals.com/triangle/stories/2009/10/05/daily42.html