ScienceDaily (June 14, 2009)— Aggressive, deadly and often misdiagnosed, inflammatory breast cancer (IBC) is the most lethal form of primary breast cancer, often striking women in their prime and causing death within 18 to 24 months. Now, scientists from The Cancer Institute at NYU Langone Medical Center have identified a key gene—eIF4G1—that is overexpressed in the majority of cases of IBC, allowing cells to form highly mobile clusters that are responsible for rapid metastasis. 

The new findings, Essential Role for eIF4G1 Overexpression in Inflammatory Breast Cancer Pathogenesis, scheduled for advance online publication on Nature Cell Biology’s website (Embargoed for June 14th, 2009 at 1:00PM EST) could lead to the identification of new approaches, therapies and a new class of drugs to target and treat IBC. This would be a critical development in the fight against IBC, which respond poorly to chemotherapy, radiation or any other current treatments for breast cancer, according to the study’s lead authors Dr. Robert Schneider, associate director for translational research at The Cancer Institute, co-director of breast cancer research, and the Albert B. Sabin Professor of Molecular Pathogenesis at NYU School of Medicine, and Dr. Deborah Silvera, a postdoctoral research fellow.

“The tragedy of IBC is that it is often misdiagnosed and misclassified. Rather than presenting as a ‘typical’ lump, IBC looks like an inflammation of the breast and is frequently mistaken for an infection. Physicians often prescribe antibiotics, losing valuable time for treating this fast-moving killer,” says Dr. Schneider, noting that IBC accounts for several percent of all breast cancer cases but takes a high toll on mortality, with an incidence that is 50 percent higher in African American women. He adds that there has been little progress in treating IBC over the past two decades, and there are no drugs specifically for this form of cancer. “In fact, IBC has only recently been recognized as a unique, genetically distinct form of breast cancer.”

Dr. Schneider and his colleagues found that the overexpressionof the gene eIF4G1 reprograms how the IBC tumor cells make proteins. Other researchers have identified genes associated with IBC, but this is the first gene shown to orchestrate how IBC tumor cells form special structures—unique to this disease—known as “tumor emboli.” These small clusters of highly mobile tumor cells are responsible for the rapid metastasis of IBC. Because these cell clumps are not stationary or fixed, they can quickly travel to other areas of the body.

“The good news is that we’re beginning to understand IBC at both a molecular and genetic level,” says Dr. Schneider. “We believe this gene is a target for new drug discovery, and we also believe it is possible to silence the gene without hurting normal cells. Our next step will be to focus on the genetic basis of this disease and look at the genetic changes underlying IBC to reveal more targets at the genetic level.”

The study is co-authored by Dr. Silvia Formenti, chair of the department of radiation oncology at NYU Langone Medical Center and the Sandra and Edward H. Meyer Professor of Radiation Oncology at NYU School of Medicine, and Dr. Paul Levine of George Washington University, who contributed tissues.

Funding for the project was provided by the Department of Defense (DOD) Breast Cancer Research Program and the Breast Cancer Research Foundation (BCRF). The DOD funds a six-year, $6 million Center of Excellence grant for breast cancer to Dr. Formenti (PI) and Dr. Schneider (co-PI). The BCRF funds a four-year, $4 million grant to Dr. Formenti and Dr. Schneider as co-PIs.

A new drug for genetic breast cancer could help thousands of women with hereditary forms of the disease, the first tests on patients suggest.

A study involving 54 women with advanced genetic breast cancer found that the drug olaparib could stop the growth of tumours, and shrink them in more than 40 per cent of cases.

In one case, a woman’s tumour disappeared completely after treatment with the drug, according to results to be presented at a science conference today.

About 5 per cent of the 46,000 cases of breast cancer in Britain each year are caused by defects on the BRCA-1 and BRCA-2 genes, which put women at much higher risk of developing aggressive cancers of the breast or ovaries.

Many women who test positive for the mutations have their breasts removed as a precaution, as they have an 80 per cent risk of developing breast cancer in their lifetime.

Olaparib, made by AstraZeneca , is the first of a new class of drugs specifically designed to treat BRCA-related cancers to be tested on patients. If further tests are successful, they could be used at an early stage to treat or prevent disease occurring within affected families, scientists say.

Pharmaceutical companies are also due to present targeted therapies for cancers of the lung, stomach and ovaries this week at the American Society of Clinical Oncology conference in Orlando, Florida, the world’s largest gathering of cancer scientists.

Andrew Tutt, director of the Breakthrough Breast Cancer Research Unit at King’s College London, who led the trial, said that the results for olaparib were “very promising”.

“We are hopeful that olaparib could provide a targeted treatment for women with BRCA-related breast cancer,” he said. “Some women also develop breast cancer before they know they are carrying the gene, or see it recur if they have been diagnosed previously.”

Charlotte Sword, 40, has had breast cancer diagnosed twice, because of the potentially deadly mutation to the BRCA-1 gene which runs in her family. Her younger sister Audrey has suffered it three times. Both women have had double mastectomies and their ovaries removed.

“Breast cancer has left a horrific mark on our family due to a mutation being passed down the paternal line”, Mrs Sword said yesterday. “I have three nieces who could benefit from this treatment, and could be spared the dreadful illness and side-effects of treatment that my sister and I had to go through.”

Olaparib works by blocking a protein that makes cancer cells which have a BRCA fault unable to repair their own DNNA. This causes the cancer cell to die and means that the tumour should either stop growing or get smaller.

Because the drug works in a targeted way, it kills cancer cells while leaving healthy cells alone in a way that chemotherapy does not, which could help to reduce the punishing side-effects of cancer treatment.

In the study carried out at hospitals in Britain, Europe, the US and Australia, 27 patients took 100mg oral doses of olaparib while another 27 took 400mg doses. More than 40 per cent of tumours in the higher dose group reduced significantly in size, while all tumours were prevented from progressing for an average of six months.

The Times reported this year that the London community of Ashkenazi Jews is being offered screening for BRCA genes that raise risks of breast, ovarian and prostate cancers. Ashkenazi have a high incidence of BRCA-related breast cancer.

The NHS currently offers BRCA testing, but only for women whose relatives have had cancer because of the mutations. But up to 50 per cent of people with the faulty genes do not have a family history of the diseases, largely because the gene can be carried by men.

Dr Tutt said that orlaparib may also have potential as an early-stage or preventative treatment. He added: “It is important to remember this drug is at a very early stage of development.” Herbie Newell, Cancer Research UK scientist at the Northern Research Institute, Newcastle University, said he was “extremely encouraged” by the study’s results.

He said: “Olaparib is one of a family of targeted therapies currently in clinical trials and Cancer Research UK expect that this new class of anti-cancer treatments will make a significant impact in the fight against cancer.”

In the family

8% Proportion of cases of breast cancer in women thought to be triggered by genetic factors, although many of the exact causes remain a mystery

2,000 Number of breast cancer cases a year (5 per cent of the total) known to be caused by changes in either the BRCA-1 or BRCA-2 genes that were the first to be associated with a much higher risk of developing breast cancer

1 in 800 Proportion of women in whom a faulty BRCA-1 gene is present. One in 500 carries a faulty copy of the BRCA-2 gene

50-80% Chances of a woman with these genes of getting breast cancer in their lifetime, up to seven times higher than those who do not carry the mutations. They also have a 60 per cent increased risk of ovarian cancer

Sources: Cancer Research UK; Times database

All proceeds from my shop go to maintaining LittleLifePreservers.com.

Currently I am offering a wide variety of glass and resin pendants and some handpicked cards. I plan on adding bottlecap pendants, magnets and whatever else suits my fancy.

Stop by and check it out ~

Pinkpromisedesigns.etsy.com

I just received some more wonderful cards from Girl Scout Troop 643 out of NY. THANK YOU!!

And

A ton of yummy paper from Shelley G. THANK YOU!

Pink hugs

L:)