The prognosis for breast cancer has improved, allowing more and more women to be cured with a combination of surgery, radiotherapy and medical treatment. A new trial led by Karolinska Institutet will investigate whether combining neoadjuvant chemotherapy with exercise will improve the outcomes of breast cancer patients.
Neoadjuvant chemotherapy (NACT) is increasingly used in breast cancer. The main benefit of NACT is its ability to downstage large tumours with a view to treatment by breast-conserving surgery, although there is a non-significant increase in the local recurrence rate. The best proof of NACT efficacy is pathological complete response (pCR), ie the absence of invasive tumour on post-NACT on surgical histopathology.
“While it is known that physical exercise can help patients to better tolerate often harsh cancer treatments, it is an emerging area of research to understand if and how exercise exerts anti-tumour effects and improves oncological outcomes”, explained Jana de Boniface, principal investigator of the trial and associate professor in the Breast Surgery Group, Department of Molecular Medicine and Surgery.
The Neo-ACT trial opened for recruitment in September 2022, and it is estimated that inclusion may be completed in December 2025.
The pharmaceutical industry is facing a serious challenge as it struggles to source enough non-human primates (NHPs) such as macaques for research and testing. Alongside demand created by HIV/AIDS research, the pandemic has tightened supplies of the animals further as China, a major supplier, has clamped down on exports.
Since NHPs have great genetic and physiological similarity to humans, scientists use these animals, most commonly rhesus macaques, to study medical conditions and conduct trials which are not yet possible in humans. In 2019, US scientists used 68 257 NHPs in research, according to US government data.
As a result of this shortage, many projects may not be able to be completed, according to industry insiders, with implications for medical research. Pre-pandemic prices of $11 000 per macaque have risen to $35 000.
In July last year, Nature reported that the US government pledged to increase funding to make primates available for clinical research. However, this would not do anything to address the current shortage.
To make room for more NHPs, the US National Institutes of Health (NIH) has invested about US$29 million to refurbish housing, build outdoor enclosures and making other infrastructure improvements at the US National Primate Research Centers (NPRCs), which it funds.
“A couple of years ago, we were feeling the pinch,” Nancy Haigwood, director of the Oregon NPRC in Beaverton, which houses about 5 000 non-human primates. But because of the pandemic, “we are truly out of animals”, she told Nature. “We’re turning away everyone.”
China had been a cheap source of cynomolgus macaques (Macaca fascicularis) since 1985, but in 2013 began to prioritise local research, restricting exports. Adding to this was soaring demand was sparked by multiple NIH grants awarded in 2016 to study HIV/AIDS, according to a 2018 report. Housing and feeding NHPs is costly, and NPRCs could not expand due to budget caps. The report warned of a coming shortage of various primates in coming years.
The situation has drawn the public’s attention – and opposition. Complaints made to airlines has resulted in many no longer carrying the animals, making transportation a major challenge. Air France was one of the last holdouts, and last year said it would stop carrying NHPs for research purposes.
With the arrival of the pandemic and the need for NHP research and testing, vaccine research was naturally prioritised, while trying to supply other projects as well.
When COVID hit, China completely suspended exports of macaques, hitting pharmaceutical companies hardest, which prefer that species for drug trials. Even if the export ban were to be lifted, the Chinese demand for macaques in research is so high that there would be few available for export: of 30 000 macaques that became suitable for use in research last year, 28 000 were used.
Other restrictions constrain the supply, such as a European Union requirement that all non-human primates for research come from self-sustaining colonies by November this year. The UK also carried through this directive following its exit from the EU.
Pregnant smokers reduced their smoking by an average of one cigarette per day before becoming aware they were pregnant, according to a new study in in Addiction Biology. In the month after learning of their pregnancy, participants reduced smoking by another four cigarettes per day.
“Our findings suggest that pregnancy could curb smokers’ desire to smoke before they are even aware of having conceived,” said the study’s lead author and principal investigator, Dr Suena Huang Massey, associate professor of psychiatry and behavioural sciences and medical social sciences at Northwestern University Feinberg School of Medicine.
“While recognition of pregnancy is a common motivation to reduce or quit smoking, if biological processes in early pregnancy are also involved as suggested by this study, identifying precisely what these processes are can lead to the development of new smoking-cessation medications.”
The vast majority of research in this field focuses on the impact of a person’s smoking on the pregnancy and the baby. This study examines, instead, the impact of pregnancy on a person’s smoking behaviour.
Though it is well known that smoking is reduced in pregnancy, it was not known when it started and whether the smokers knew they were pregnant.
“Before this paper, it was largely assumed that the only thing causing pregnant smokers to cut down was a desire to protect the baby,” Dr Massey said. “While our study does support the discovery of pregnancy as a salient event, levels of pregnancy smoking began to decline before smokers suspected they were pregnant.”
These findings support a new line of research into what happens biologically during pregnancy that might be interrupting addictive behaviours, Massey said. Her hope is that the answer to this question will lead to the discovery of new and improved ways to treat addiction.
Pregnancy hormones a contributing factor?
Human chorionic gonadotropin (hCG) is a hormone produced by the placenta in early pregnancy that is linked to morning sickness (nausea and vomiting during pregnancy).
“Strikingly, we observed the steepest declines in smoking precisely when hCG levels typically peak – between five and 10 weeks of pregnancy,” Massey said. “What’s more, pregnant smokers who do not quit during the first trimester (when hCG levels are elevated) are unlikely to quit before delivery, even with assistance from medications or financial incentives.”
Study methodology
Scientists estimated changes in cigarettes per day smoked, reported retrospectively, by 416 participants from two independent cohorts (145 from 2000 to 2005 and 271 from 2006 to 2009). Every participant was a smoker prior to becoming pregnant. Women in the study were interviewed about their smoking habits at 16 weeks of pregnancy and provided urine samples, so researchers could verify their reports.
On average, participants smoked about 10 cigarettes per day before conception. Between conception and the date they realised they were pregnant (highly variable and reported by each participant), smoking fell by an average of one cigarette per day. In the month after recognising the pregnancy, smoking dropped from an average of 9 cigarettes per day to five. Importantly, these declines were seen whether pregnancies were planned or unplanned, and whether smokers quit or did not quit.
The emerging Omicron variant BA.2.75.2 largely evades neutralising antibodies in the blood and resists several monoclonal antibody antiviral treatments, according to a study published in the journal The Lancet Infectious Diseases. The findings suggest a risk of increased COVID infections in the northern hemisphere’s winter, unless the new updated bivalent vaccines help to boost immunity in the population.
“While antibody immunity is not completely gone, BA.2.75.2 exhibited far more dramatic resistance than variants we’ve previously studied, largely driven by two mutations in the receptor binding domain of the spike protein,” said the study’s corresponding author Ben Murrell, assistant professor at the Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet.
The study shows that antibodies in random serum samples from 75 blood donors in Stockholm were approximately only one-sixth as effective at neutralising BA.2.75.2 compared with the now-dominant variant BA.5. The serum samples were collected at three time points: in November 2021 before the emergence of Omicron, in April 2022 after a large wave of infections in the country, and at the end of August to early September after the BA.5 variant became dominant.
The researchers found that only one of the clinically available monoclonal antibody treatments that were tested, bebtelovimab, managed to effectively neutralise the new variant.
BA.2.75.2 is a mutated version of another Omicron variant, BA.2.75. Since it was first discovered earlier this fall, it has spread to several countries but so far represents only a minority of registered cases.
A possible increase in infections
“We now know that this is just one of a constellation of emerging variants with similar mutations that will likely come to dominate in the near future,” Ben Murrell says, adding “we should expect infections to increase this winter.”
Some questions remain. It is unclear whether these new variants will drive an increase in hospitalisation rates. Also, while current vaccines have, in general, had a protective effect against severe disease for Omicron infections, there is not yet data showing the degree to which the updated COVID vaccines provide protection from these new variants. “We expect them to be beneficial, but we don’t yet know by how much,” Ben Murrell says.
