An experimental approach that looks for the DNA leaking out from dead and dying cells may provide a route to a blood test for breast cancer, U.S. researchers reported on Tuesday.

An initial study showed the test detected 70 percent of breast cancer cases, and correctly cleared 100 percent of women who did not have breast cancer, the team at Chronix Biomedical, a privately-owned company in San Jose, California, said.

The experimental test is not ready to develop into a product but provides a basis for further research, they wrote in the journal Molecular Cancer Research.

“It is based on finding the unique DNA fingerprints from dead and dying cells,” Chronix CEO Howard Urnovitz said in a telephone interview.

Technological advances in DNA sequencing made the test possible, Urnovitz said. His team sequenced the entire genomes of 26 breast cancer patients and of 67 apparently healthy women.

They were looking for extra DNA in the blood of the breast cancer patients that would come from cells dying because of the tumors.

“If a breast cell is injured, it will overexpress the genes that make it a breast cell,” Urnovitz said. In theory, if a patient has excess DNA from breast cells that are dying, there is something going on that is killing breast cells.

The search is not easy. “The entire genome can be found in the blood,” Urnovitz said. And billions of cells die every day in the human body.

But eventually the Chronix team found what they believe is tell-tale DNA from dying breast cells.

“This study supports the potential of an entirely new approach to identifying cancer at its earliest stages when therapies may be most effective,” Dr. William Mitchell of Vanderbilt University School of Medicine in Tennessee, who worked on the study, said in a statement.

SCREENING AND MONITORING

“Laboratory tests using this approach may have the potential both to screen large populations for cancer before symptoms appear and to monitor patients for the recurrence of cancer once treated,” Mitchell added.

Much more testing needs to be done, Urnovitz said. But so far the test seems to specifically home in on breast cells. Unpublished data shows, for instance, that the DNA signature is not found in men with prostate cancer.

The cost of genetic sequencing will have to come down more before the test would be practical, Urnovitz added.

His team used Roche AG’s 454 sequencer at a cost of thousands of dollars per person, but companies are working to speed up sequencing and get the costs down.

The tests might be used to screen women for breast cancer and to tailor treatments, Urnovitz said.

“Imagine we can come in and say ‘you have damage to the protein kinase gene that would preclude you from these 10 cancer drugs, but here are 20 others that should work’,” he said.

“You would be selecting drug treatment based on each person’s lesions. This would be a really good example of personalized medicine.”

Urnovitz also hopes such a test could monitor patients who have completed treatment for cancer. Instead of coming to a cancer center to undergo a PET scan to check for tumors that may have returned, patients could get a blood test at their convenience and have it sent in for analysis.

“You could have one blood test for everything that is going on,” he said.

Source: Reuters

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Scientists have developed a gene test which predicts how well chemotherapy will work in cancer patients.

Starting with 829 genes in breast cancer cells, the team whittled down the possibilities to six genes which had an impact on whether a drug worked.

They then showed that these genes could be used to predict the effectiveness of a drug called paclitaxel in patients.

It is hoped the approach, reported in The Lancet Oncology, can be replicated for other cancers and treatments.

The international project, including researchers from Cancer Research UK’s London Research Institute, opens the way for breast cancer treatment to be targeted to those who will benefit the most.

To find which genes, if missing or faulty, could prevent the drug from working, they deleted them one by one from cancer cells in the laboratory.

They eventually highlighted the six genes which if absent or not working prevent paclitaxel from properly killing breast cancer cells.

Spare treatment

More than 45,500 women are diagnosed with breast cancer in the UK each year – and it is estimated that around 15% of these women will be prescribed paclitaxel.

The researchers estimate they could potentially spare half of the patients currently receiving this drug from treatment which would not be effective.

Study leader, Dr Charles Swanton, head of translational cancer therapeutics at the Institute, said one of the great challenges in cancer medicine is determining which patients will benefit from particular cancer drugs, which are in themselves toxic and carry severe side effects.

“Our research shows it is now possible to rapidly pinpoint genes which prevent cancer cells from being destroyed by anti-cancer drugs and use these same genes to predict which patients will benefit from specific types of treatment.”

Further studies will now be done to see if the technique can be developed into a simple diagnostic test to be given to patients to help inform doctors about whether or not to prescribe paclitaxel.

He said the challenge will be to apply these methods to other drugs in cancer medicine.

“These could include treatments that are currently deemed too expensive to fund on the NHS – however, in the future, treating only the patients that will benefit from certain treatments will save the NHS money in the long term.”

Dr Lesley Walker, Cancer Research UK’s director of cancer information, said: “New techniques such as these can enable drugs to be tailored to individual patients, and this could potentially improve cancer survival in the long term.

“Health professionals may in the future be able to use this information to direct treatment to patients most likely to benefit, and avoid giving treatment that is less likely to be effective to patients with drug resistant cancers.”

Source: BBC NEWS

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UK scientists say they have discovered why some women fail respond to breast cancer treatment, and it is a gene error they believe they can fix.

Tamoxifen is given to most women diagnosed with breast cancer to prevent the cancer returning.

But not all women respond to the drug – experts estimate a third get no benefit.

The work in the journal Cancer Research suggests the problem is too much of a gene called FGFR1.

This discovery could lead to new treatments for these women as scientists “switch off” the action of FGFR1, enabling Tamoxifen to work.

The team of scientists in the Breakthrough Breast Cancer Research Centre at The Institute of Cancer Research have already shown this is possible in the lab.

They introduced a drug which “switched off” the action of FGFR1.

Once FGFR1 was stopped, hormone-based treatments like Tamoxifen could get back to work in destroying cancer cells, they found.

The researchers believe this could ultimately help thousands of women each year.

They say one in 10 breast cancer patients has too much of the FGFR1 gene.

Dr Nick Turner, who led the research, said: “Understanding how this gene can cause Tamoxifen resistance reveals a new drug target for treating breast cancers in patients who would otherwise have a poor outcome.

“There are a number of drugs in development that stop FGFR1 working, and clinical studies are investigating whether these drugs work against cancers with too many copies of this gene.

“The next step is to set up a clinical trial to see whether a drug that blocks the action of this gene can counteract hormone therapy resistance in breast cancer patients.

“If these trials confirm our lab work we could be on the verge of a potentially exciting new treatment for breast cancer.”

Dr Lesley Walker of Cancer Research UK, the charity which helped fund the work, said: “Cracking the problem of resistance to treatments such as Tamoxifen would be a major advance in treating breast cancer.”

Breast cancer is the most common cancer in the UK affecting more than 45,500 women each year.

Tamoxifen blocks the female sex hormone oestrogen that fuels the growth of some breast tumours.

Source: BBC NEWS

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Breast cancer survivors who take aspirin regularly may be less likely to die or have their cancer return, U.S. researchers reported Tuesday.

The study of more than 4,000 nurses showed that those who took aspirin — usually to prevent heart disease — had a 50 percent lower risk of dying from breast cancer and a 50 percent lower risk that the cancer would spread.

“This is the first study to find that aspirin can significantly reduce the risk of cancer spread and death for women who have been treated for early stage breast cancer, ” said Dr. Michelle Holmes of Harvard Medical School, who led the study published in the Journal of Clinical Oncology.

“If these findings are confirmed in other clinical trials, taking aspirin may become another simple, low-cost and relatively safe tool to help women with breast cancer live longer, healthier lives,” Holmes added in a statement.

Holmes and her team studied 4,164 female registered nurses taking part in the Nurses’ Health Study, an ongoing analysis of a wide range of health issues.

They started in 1976, looking at who took aspirin, watching for breast cancer and all causes of death until 2006.

Over this time, 341 of the nurses died of breast cancer.

Women who took aspirin two to five days a week had a 60 percent reduced risk of their cancer spreading and a 71 percent lower risk of breast cancer death. Six to seven aspirins a week lowered the risk of spread by 43 percent and the risk of breast cancer death by 64 percent.

Most of the women were taking low-dose aspirin to prevent heart attacks and stroke.

Other drugs in the same class as aspirin also apparently lowered the risks, too. These drugs, called non-steroidal inflammatory drugs or NSAIDs, include ibuprofen and naproxen but not acetaminophen, also known as paracetamol.

But there was not enough data on these drugs to give a clear answer.

The researchers said they are not sure how aspirin and other NSAIDS may affect tumors but it could be by lowering inflammation. Other studies have shown that aspirin and ibuprofen can lower colon cancer risk, for instance.

“Aspirin has relatively benign adverse effects compared with cancer chemotherapeutic drugs and may also prevent colon cancer, cardiovascular disease, and stroke,” the researchers wrote. It affected both estrogen-positive tumors and those not fueled by the hormone.

Holmes’ team stressed that patients should not take aspirin while undergoing radiation or chemotherapy because of the risk of side effects.

And aspirin can cause stomach bleeding so it should not be taken without a doctor’s supervision.

Source: Reuters

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The gene SRC-3 (steroid receptor co-activator 3) is not only involved in breast cancer growth but also in metastases, according to Baylor College of Medicine (BCM) researchers and collaborators. They were able to determine how the gene sends a signal to the cell membrane to promote cell motility. The research appears in the current issue of Molecular Cell.

SRC-3 is reportedly overexpressed in two-thirds of breast cancers. It is also known that SRC-3 enhances estrogen-dependent growth of cancer cells by activating and encouraging the transcription of a genetic message into a protein. However, how the message to invade other cells gets from the epidermal growth factor receptor (EGFR) to the activating enzyme called FAK (focal adhesion kinase) found on the cell’s membrane had not been determined, notes Bert O’Malley, M.D., chair of molecular and cellular biology at BCM and the report’s senior author.

Dr. O’Malley’s current research uncovered new activity for SRC-3 at the cell’s periphery. They found that the gene can produce a shorter form of its co-activator protein that is missing the part that keeps it in the nucleus. With this exon gone, it is free to travel into the cytoplasm and to the membrane, Dr. O’Malley explains. “At the membrane, the enzyme PAK1 phosphorylates SRC-3, allowing it to function at the membrane.”

The finding explains how the epidermal growth factor receptor at the membrane gets a signal to the enzyme that tells the cell to move and ultimately grow, allowing the cancer to invade surrounding tissue, Dr. O’Malley adds.

“Now we have a final picture as to why epidermal growth factor receptor and the estrogen receptor are the most dangerous combination of molecules overproduced in breast cancer. When they are both overfunctioning, people die quickly and are resistant to therapy,” Dr. O’Malley points out.

Source: GEN News

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Expensive extra scans using MRI on breast cancer patients make no difference to the number of patients who have a repeat operation, scientists said on Friday, raising questions about whether the scans are worth it.

A study of 1,623 women with breast cancer found that those who have a conventional triple assessment of their cancer are no more likely to be told they need a repeat operation than those assessed using magnetic resonance imaging (MRI) as well.

“Our results have important implications in routine clinical practice for the appropriate use of health-service resources and patient burden on health services,” said Lindsay Turnbull of Britain’s Hull University and Hull Royal Infirmary, who led the study. “MRI is an expensive procedure.”

Turnbull said that since the use of MRI scans in breast cancer patients is similar in many countries worldwide, her findings should be taken into account by all health authorities.

“We believe that our findings are generalisable to all healthcare providers, and show that MRI might not be necessary in this population of patients in terms of reduction of reoperation rates,” she wrote in the Lancet medical journal.

Siemens, General Electric and Philips Electronics are among the major makers scanning technology like magnetic resonance imaging, computed tomography (CT) and positron emission tomography (PET).

The industry has drawn some criticism in the United States where use of expensive scans has risen sharply in recent years.

Critics say many scans are unnecessary and often don’t improve results.

Turnbull’s study took place in 45 centers across Britain where the 1,623 women were all given a standard triple assessment — a clinical examination, an x-ray or ultrasound image of the breast, and lab tests to assess the tumor’s pathology — and then received either MRI or no further scans.

The researchers found 19 percent in the MRI group needed reoperation versus 19 percent of those who had no MRI.

Yet while the outcomes for patients were virtually the same, the costs — both in terms of hospital resources and patient time — were higher for those who had MRI scans, they said.

Breast cancer is the most common cancer in women worldwide, accounted for around 16 percent of all female cancers.

It kills around 519,000 people globally each year, but the World Health Organization says survival rates vary widely from more than 80 percent in the United States, Sweden and Japan to under 40 percent in low-income countries.

The researchers said their findings should benefit Britain taxpayer-funded National Health Service (NHS) since they show MRI might be unnecessary in some scenarios and “could assist in improved use of NHS services.”

Source: Reuters

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The popular antidepressant drug Paxil may interfere with breast cancer treatments, making patients more likely to relapse and die, researchers in Canada reported on Monday.

Women who took GlaxoSmithKline’s Paxil while taking tamoxifen at the same time were more likely to die of their breast cancer, the researchers found. The longer the overlap between Paxil and tamoxifen, the more likely the patients were to die, they reported in the British Medical Journal.

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It is likely because Paxil, sold generically as paroxetine, interferes with the compound the body uses to process tamoxifen, the researchers said.

“There is probably a better choice of antidepressants for women taking tamoxifen but (any change) should be done gradually with a doctor,” said Dr. David Juurlink of the Institute for Clinical Evaluative Sciences and Sunnybrook Health Sciences Center in Toronto.

“It is easy for women on tamoxifen to become alarmed by the results of this study,” Juurlink added in a telephone interview.

“People shouldn’t be stopping their tamoxifen. It is an extremely important medication.” And he said no-one should immediately stop taking paroxetine either without first consulting a doctor because suddenly stopping an anti-depressant can be dangerous.

Juurlink and colleagues looked at the healthcare records of 2,430 breast cancer patients 66 or older who took tamoxifen between 1993 and 2005. About 30 percent of the patients also took an antidepressant at some time during their treatment with tamoxifen, and paroxetine was the most common one.

Fifteen percent of the patients died of breast cancer during the study.

After other factors were taken into the account, the researchers found that women who took Paxil and tamoxifen together for a quarter of the treatment time were 25 percent more likely to die of breast cancer.

This rose to a 91 percent risk for the women who took tamoxifen and Paxil together for 75 percent of the time.

“In contrast, no such risk was seen with other antidepressants,” the researchers wrote.

Tamoxifen can reduce the risk of breast cancer returning by 50 percent if women take it for five years, although the drug is often being replaced with a newer class of drugs called aromatase inhibitors.

For the body to use it, tamoxifen must be broken down by an enzyme called CYP2D6.

A class of antidepressants called selective serotonin reuptake inhibitors or SSRIs can interfere with CYP2D6.

“Paxil is a fairly potent inhibitor of that enzyme,” Juurlink said. So is fluoxetine, the first SSRI antidepressant.

His team did not find that fluoxetine, sold under the brand name Prozac, had the same effect, but it could be because so few women took that particular antidepressant, he said.

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“These results highlight a drug interaction that is extremely common, widely underappreciated and potentially life-threatening, yet uniformly avoidable,” Juurlink said.

Source: Reuters

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Boston-area researchers have discovered the reason why some breast cancer patients respond to normal chemotherapy but others do not.

Led by Andrea Richardson and Zhigang Charles Wang, investigators at the Dana-Farber Women’s Cancers Program have identified two genes that, when abnormally active, enabled cancer cells to resist the effects of drugs called anthracyclines, a class that includes doxorubicin, daunorubicin, and epirubicin.

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Despite their resistance to drugs of the anthracycline class, the breast cancers bearing this gene signature will probably still be vulnerable to other types of chemotherapy agents, the scientists note in a letter published online in Nature Medicine.

These findings could lead to a genetic test of breast cancers to help physicians choose the best initial treatment for an individual, thus avoiding the trial-and-error approach that in some cases exposes patients to the toxic side effects of a cancer drug that is destined to be ineffective. However that such a tool should not be difficult to develop, she said, and could be available for clinical testing within a year or two, Richardson says in a statement.

Source: FierceBiotech

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The more scientists look, the more complex cancer seems to become.

British scientists said on Wednesday they had found a batch of new gene mutations linked to kidney cancer, suggesting even this apparently “straightforward” cancer type can be divided into subtypes requiring tailored treatment.

Clear cell renal cell carcinoma (ccRCC), the most common type of kidney cancer, stands out from other cancers because it is remarkably consistent and the majority of cases are known to be driven by mutations in a single gene, called VHL.

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Yet when researchers conducted a large DNA sequencing study of more than 3,500 genes from around 100 tumor samples, they found evidence that additional mutations in other genes were also driving cells to become cancerous.

Three of the genes were involved in modifying proteins called histones, which help package DNA into chromosomes and are critical to the functioning of cells, they reported in the journal Nature.

“Even in this clearest of cases, we see evidence for substantial genetic heterogeneity,” said Andy Futreal, co-leader of the Cancer Genome Project at the Wellcome Trust Sanger Institute in Cambridge.

While none of the new mutations accounted for more than 5 percent of cancer cases, the discovery should ultimately help in diagnosis and better selection of treatments for patients.

The latest findings underline the case for personalized medicine, or tailoring drugs to the genetic make-up of individual patients.

Scientists at the Sanger Institute last month also produced genetic “maps” identifying thousands of genetic mutations behind melanoma skin cancer and lung cancer.

Several personalized drugs are already used in cancer, including Roche’s Herceptin for breast cancer and AstraZeneca’s Iressa for lung cancer.

For drugmakers, tailored medicine is both an opportunity and a challenge as sub-dividing tumors by their molecular type shrinks the market for individual therapies.

Kidney cancer kills more than 100,000 people worldwide each year. Recent new drugs against the disease include Pfizer’s Sutent and Bayer’s Nexavar, which block cell proliferation and starve tumors of blood supply.

Source: Reuters

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As usual when oncologists get together to talk shop, lots of pharma news hit the streets over the weekend during the annual Breast Cancer Symposium in San Antonio. Here’s a sampling of developments for already approved therapies:

• Nexavar, the Bayer/Onyx Pharmaceuticals drug, may trounce some cancers’ resistance to treatments, helping hormone-blocking therapies work longer. Hormone-receptor positive breast cancers are wily things that eventually figure out how to circumvent hormonal therapies, but the kidney-and-liver cancer drug Nexavar seemed to “put the brakes” on treatment resistance. That could open up a whole new world for Nexavar, but the companies first would have to mount a late-stage study.

• Doctors shouldn’t wait to use Genentech’s Herceptin until after chemotherapy, according to a Mayo Clinic study. When women were given chemo and Herceptin at the same time, the five-year survival rate increased to 84 percent from 80 percent among those taking chemo then Herceptin, and from 72 percent in those using chemo alone. “Concurrent use is the best way” to decrease the risk of cancer recurrence,” Dr. Edith Perez told the Los Angeles Times.

• An older class of chemo meds carries greater risk of side effects than newer versions when used with Herceptin, a study found. Both anthracyclines and non-anthracyclines were effective in combination with the drug, but patients on the former had more heart damage. Some doctors suggest that the standard of care be updated to privilege the non-anthracyclines, but others say more data is needed.

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Plus, there was news of studies-to-come: Concurrent with the symposium, Roche announced that FDA had cleared it to go ahead with a study of Avastin in early breast cancer. Enrollment was suspended back in September because of six cases of heart failure, but the study’s safety board has since concluded that the risk-benefit analysis of Avastin in combo with three difference drugs was “unchanged.”

Source: FiercePharma

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