External beam radiation therapy for breast cancer does not increase mortality risks

Sep. 24, 2013 — Early-stage breast cancer patients who receive external beam therapy (XRT) are not at higher risk for serious long-term side effects in the chest area, including increase in deaths from cardiac disease and secondary malignancies, according to research presented today at the American Society for Radiation Oncology's (ASTRO's) 55th Annual Meeting.

The study utilized patient information from the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) database. It evaluated women identified as having primary Stage T1aN0 breast cancer (tumor of 5mm or less that has not spread to the lymph nodes), who received surgery, with or without post-operative radiation therapy, between 1990 and 1997. The analysis was done to determine if XRT was associated with increased mortality due to breast cancer, secondary cancer in the chest area or cardiac conditions for these patients; only patients with breast cancer (BC) identified as the first malignancy were included. The women had a median age of 55-59 and were divided into two groups: 2,397 who received XRT after surgery, and 2,988 who did not receive XRT after surgery.

Cause of death (COD) codes were used to identify cardiac mortality, breast cancer mortality, and deaths from secondary chest cancers in order to assess overall survival (OS), breast cancer survival (BCS), second-tumor specific survival and cardiac-cause specific survival (CCS), and then compared between the XRT and non-XRT groups. The incidence of mortality was compared between the XRT and non-XRT groups utilizing the Chi-Square test; and, the relative risk (RR) and associated 95 percent confidence interval (CI) were calculated. Kaplan-Meier survival analysis and log-rank test were performed to assess OS, BCS, second-tumor specific survival and CCS.

At 10 years post-treatment, OS rates were 91.6 percent for the XRT patients and 87 percent for the non-XRT group; BCS rates were 97 percent for the XRT patients and 95.7 percent for the non-XRT group; and CCS was 96.7 percent for the XRT patients and 92.7 percent for the non-XRT group.

Analysis of the data further demonstrates that, with a median follow up of 14 years, there was no statistically significant difference in deaths from subsequent non-breast cancers in the chest area, the majority of which were lung cancers. The number of deaths from cardiac causes was not significantly higher for those patients treated with XRT for left-sided breast cancer, compared to those with right-sided breast cancer among the patient sample and time period reviewed. More women from the non-XRT group died from all causes, including cardiac causes, suggesting that those patients had worse general health conditions than the women who received radiation therapy.

"Breast conserving therapy, consisting of lumpectomy and XRT, has been an excellent approach to early breast cancer treatment, offering equivalent disease control and better cosmetic results compared to mastectomy as demonstrated by multiple randomized controlled trials in the past," said Jason Ye, MD, the study's presenting author and a second-year resident in radiation oncology at Weill Cornell Medical College in New York City. "Our study's results suggest that serious long-term side effects of radiation therapy, such as increase in deaths from cardiac disease and secondary malignancies, are rare. Radiation therapy is an integral part of early stage breast cancer treatment for those who choose to have a lumpectomy instead of a mastectomy, with its benefits likely far outweighing the potential risks in majority of the cases. The field of radiation oncology is rapidly changing, with new technology constantly being introduced that may reduce these risks further. Continued long term follow up and additional studies are needed to monitor for potential long term side effects."

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Warning of three-person IVF 'risks'

19 September 2013 Last updated at 15:10 ETBy James Gallagher Health and science reporter, BBC News

Concerns about the safety of a pioneering therapy which would create babies with DNA from three people have been raised by researchers.

The advanced form of IVF could eliminate debilitating and potentially fatal mitochondrial diseases.

Writing in the journal Science, the group warned that the mix of DNA could lead to damaging side effects.

The expert panel which reviewed the safety of the technique said the risks described would be "trivial".

The UK is leading the world in the field of 'mitochondrial replacement'. Draft regulations to allow the procedure on a case-by-case basis will be produced this year and some estimate that therapies could be offered within two years.

Power source

Mitochondria are the tiny, biological "power stations" that provide nearly every cell, which make up the body, with energy. They are passed from a mother, through the egg, to her child.

But if the mother has defective mitochondria then it leaves the child starved of energy, resulting in muscle weakness, blindness and heart failure. In the most severe cases it is fatal and some families have lost multiple children to the condition.

The proposed therapy aims to replace the defective mitochondria with those from a donor egg.

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1) Two eggs are fertilised with sperm, creating an embryo from the intended parents and another from the donors 2) The pronuclei, which contain genetic information, are removed from both embryos but only the parents' is kept 3) A healthy embryo is created by adding the parents' pronuclei to the donor embryo, which is finally implanted into the womb

1) Eggs from a mother with damaged mitochondria and a donor with healthy mitochondria are collected 2) The majority of the genetic material is removed from both eggs 3) The mother's genetic material is inserted into the donor egg, which can be fertilised by sperm.

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But mitochondria have their own DNA, albeit a tiny fraction of the total. It means a baby would have genetic information from mum, dad and a second woman's mitochondria.

The concerns raised - by scientists at the University of Sheffield, the University of Sussex and Monash University in Australia - are about a poor match between the mitochondrial DNA and that from the parents.

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The woman who lost all her children

Every time Sharon Bernardi became pregnant, she hoped for a healthy child.

But all seven of her children died from a rare genetic disease that affects the central nervous system - three of them just hours after birth.

When her fourth child, Edward, was born, doctors discovered the disease was caused by a defect in Sharon's mitochondria.

Edward was given drugs and blood transfusions to prevent the lactic acidosis (a kind of blood poisoning) that had killed his siblings.

Five weeks later Sharon and her husband, Neil, were allowed to take Edward to their home in Sunderland for Christmas - but his health slowly began to deteriorate.

Edward survived into adulthood, dying in 2011 at the age of 21.

Now Sharon is supporting medical research that would allow defective mitochondria to be replaced by DNA from another woman.

• Sharon's full story
• Three-person IVF: Your stories

They said there was an interaction between the DNA in the mitochondria and the rest which is packaged in a cell's nucleus.

Their studies on fruit flies suggested that a poor match of genetic information between the nucleus and mitochondria could affect fertility, learning and behaviour.

"Describing it as like changing the batteries in a camera is too simplistic," Dr Klaus Reinhardt from the University of Sheffield told the BBC.

He added : "It is not at all our intention to be a roadblock, we think it is fantastic that for women affected there could be a cure.

"We have pointed out one or two points which need to be looked at."

'Trivial'

The Human Fertilisation and Embryology Authority, which regulates fertility treatment in the UK, commissioned a review into the safety of the technique.

Prof Robin Lovell-Badge, who was on the review panel, disagreed. He said humans had diverse mitochondrial and nuclear DNA, so any consequences of poor matches would have already become apparent.

He told the BBC news website: "Humans are breeding between races and producing healthy children all the time. If there is an effect then it must be very trivial as it's not been noticed."

He has called for further safety testing, such as research into the risks posed by any defective mitochondria which might still be passed onto a child.

Prof Doug Turnbull, who is developing the mitochondrial replacement therapy at Newcastle University, insisted: "One of our prime interests is about the safety of these techniques.

"It's perfectly reasonable to draw some of these concerns, I just don't share the same concerns.

"Mismatch between the mitochondrial and nuclear genome is a potential risk, but I don't think it's personally as big a risk as they're saying."

Hundreds of mitochondria in every cell provide energy

In a statement, the Human Fertilisation and Embryology Authority said: "The panel of experts convened by the HFEA to examine the safety and efficacy of mitochondria replacement carefully considered the interaction between nuclear and mitochondrial DNA and concluded that the evidence did not show cause for concern.

"As in every area of medicine, moving from research into clinical practice always involves a degree of uncertainty. Experts should be satisfied that the results of further safety checks are reassuring and long term follow-up studies are crucial.

"Even then patients will need to carefully weigh up the risk and benefits for them."

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Childbirth risks not the same for all obese women

Sep. 10, 2013 — Obesity raises the chances of complications and medical interventions in childbirth. But a new study by Oxford University shows the risks are not the same for all obese women.

For otherwise healthy women, the increase in risk with obesity may not be as great as previously suspected.

'The increased risk was fairly modest for obese women who did not have conditions such as high blood pressure, diabetes or a previous caesarean section, and the risks were quite low if the woman had given birth previously,' says lead researcher Dr Jennifer Hollowell of the National Perinatal Epidemiology Unit at Oxford University.

'It is important to appreciate that we are not saying that obesity isn't important or that obesity doesn't increase a woman's risks during pregnancy,' she adds. 'We found that around half of very obese women giving birth in obstetric units have medical problems or pregnancy complications when admitted. But our study focused on women who were obese but otherwise healthy when they went into labour, and some of them had much lower risks than might have been expected.'

The Oxford University researchers point out that, among healthy women with a straightforward pregnancy, childbirth risks are influenced more by whether someone is a first-time mum than whether they are obese.

They found that the chances of first-time mums of normal weight having medical interventions or complications during childbirth are greater than for 'very obese' but otherwise healthy women having a second or subsequent child. The findings are published in the British Journal of Obstetrics and Gynaecology.

Dr Hollowell comments: 'This finding does highlight a possible anomaly in the guidance given to women on where to give birth.'

First-time mothers with low-risk pregnancies can plan to have their child in hospital, at home, in a free-standing midwife-led unit or an alongside midwifery unit connected to a hospital -- according to what is available where they are.

However, current guidelines suggest all women with a body mass index (BMI) over 35 should be advised to have the birth in an obstetric unit to reduce risk.

Guidelines on assessing risks for women in planning births take no account of whether a woman is having their first child or has already had children.

'We think that the guidelines might need to be reviewed to take account of this more nuanced understanding of the effect of obesity,' says Dr Hollowell. 'We think it's worth considering whether it might be safe to allow some healthy obese women having a second baby the option of a birth in an alongside midwifery unit where obstetric and neonatal care is available on site if needed.'

The researchers investigated the influence of BMI on the chances of healthy women having any type of complication during labour and childbirth that would need hospital care -- either in an obstetric unit for the mother or a neonatal unit for the baby.

This included a range of medical interventions and complications that varied in urgency and severity, ranging from being given drugs to help with labour progressing slowly, through to having a caesarean section or assisted delivery by forceps or ventouse, significant loss of blood resulting in a blood transfusion, and the baby being admitted to a neonatal unit.

The researchers included data for 17,230 women who'd had straightforward pregnancies and had no medical conditions that might influence risks at labour and birth.

Around half of obese women planning a normal birth after a straightforward pregnancy have no medical or obstetric risk factors such as diabetes or high blood pressure, so this is an important group to study.

The risks of complications during childbirth did go up with increasing body mass index among these healthy women. But the researchers found the increase was modest. Overweight, obese or very obese women showed a relative increase in risk of 6-12% compared to women with a normal BMI.

Most of the additional risk of needing treatment was accounted for by giving drugs for slow labour among those with a high body mass index, though risks of serious outcomes for mother and baby were also increased.

However, whether a woman has had a previous baby plays a larger role in influencing the chances of needing hospital care. 53% of women of normal weight having their first baby had an intervention or a complication at birth. The figure was 21% for very obese but otherwise healthy women having a second or subsequent baby.

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Sanofi's Lantus shows no cancer, heart risks: study

AppId is over the quota
AppId is over the quota

PARIS (Reuters) - Sanofi's insulin Lantus does not put people at risk of cancer, heart attacks or strokes when taken over long periods, according to a major study in which the drug failed to prove it can prevent heart disease in early-stage diabetics.

Although a positive result on heart disease could have widened Lantus's use, the findings of the longest and largest study of its kind should help shake off safety concerns about the French group's top-selling drug after a 2009 cancer scare.

A number of studies at the time suggested a possible link between Lantus and a heightened risk of cancer, with conflicting results.

"We know what the risks are of taking insulin on a long-term basis, and they are low," said the principal investigator of the trial, Hertzel Gerstein of McMaster University in Ontario, Canada, in a telephone interview with Reuters.

The closely watched study also found that people with pre-diabetes who received daily Lantus injections had a 28 percent lower chance of developing diabetes, even after the injections stopped.

The study tested more than 12,500 people at risk or in the early stages of diabetes with either a daily injection of Lantus or standard therapy for an average of six years.

The results confirmed two known side effects of insulin - low blood sugar levels and modest weight gain. Researchers said these were minor reactions.

The study also discovered that daily doses of Lovaza, a prescription pill based on fish oil and sold by Pronova Biopharma and GlaxoSmithKline, did not prevent heart-related deaths in diabetics.

The findings were presented on Monday at the American Diabetes Association congress in Philadelphia, U.S., and published online in the New England Journal of Medicine.

STUDY EXTENDED

Paris-based Sanofi said it would extend the study by two years to gather further data on Lantus.

Worldwide, Lantus has 80 percent of the market for long-acting, or basal, insulin used to treat diabetes, generating sales of around 3.9 billion euros ($4.9 billion) last year, representing 12 percent of Sanofi's total sales.

Sanofi is particularly reliant on Lantus because it faces a wave of patent expirations on other blockbuster medicines.

Fresh competition is emerging as rival drugmakers, such as U.S. group Eli Lilly and Danish company Novo Nordisk, prepare to launch newer long-acting insulin, in addition to the threat of biosimilars.

The insulin market is also vulnerable to the growth of GLP-1 therapies, including Sanofi's own Lyxumia, which is in late stage development.

(Reporting by Elena Berton; Editing by Dan Lalor)