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Research roundup: Overcoming EGFR-targeted therapy resistance in breast cancer, and more

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Femtech World explores the latest developments in women’s health research – from overcoming EGFR-targeted therapy resistance in breast cancer to understanding obesity’s role in triple-negative breast cancer, and more.

EGFR-targeted therapy resistance in breast cancer

Researchers have reviewed current research on why Epidermal Growth Factor Receptor (EGFR)-targeted therapies often fail in breast and head and neck cancers.

The article explores how cancer cells evade these treatments by activating alternative survival pathways and offers an in-depth look at the molecular barriers to EGFR inhibition, providing insights that could inform the development of more effective and durable treatments.

EGFR is a critical protein that regulates cell growth and survival, and it is frequently overexpressed in breast and head and neck cancers. Although therapies targeting EGFR showed early promise, resistance has become a significant challenge.

In breast cancer, resistance mechanisms include the movement of EGFR from the cell surface into the nucleus, where it promotes DNA repair, as well as ligand-dependent activation that helps tumour growth despite therapy.

The review describes how tumour cells in these cancers commonly activate other receptor tyrosine kinases (RTKs), such as MET, AXL, and RON, to continue growing even when EGFR is blocked.

By analysing these resistance mechanisms, the authors highlight combination therapies from current research that target EGFR and other key molecular pathways.

Strategies such as dual inhibition of EGFR and MET or blocking inflammation-driven survival signals may enhance treatment outcomes.

Several clinical trials are evaluating these approaches in patients.

For example, in breast cancer, combinations of EGFR inhibitors with chemotherapy and immune checkpoint inhibitors are being tested to improve responses, particularly in triple-negative breast cancer.

These efforts aim to overcome resistance and provide more effective treatment options for patients with EGFR-driven tumours.

The review also emphasises the necessity of identifying biomarkers to predict which patients are most likely to benefit from EGFR-based therapies.

Screening women with diabetes for intent to conceive at every doctor visit

Adverse pregnancy outcomes such as miscarriages or birth defects are common in individuals with pre-existing diabetes and are often related to modifiable factors such as maternal high blood sugar and body mass index (BMI).

With this in mind, a new, joint guideline released by the Endocrine Society and the European Society of Endocrinology (ESE) has recommended that women with diabetes receive proper preconception care.

This includes access to emerging diabetes technology and therapeutics to manage their blood sugar before, during and after pregnancy.

Screening women of reproductive age who have diabetes for intent to conceive at every reproductive, diabetes and primary care visit helps ensure they get the appropriate preconception care and reduces health risks.

Care suggestions from the guidelines include screening by asking all women with diabetes of reproductive age about intent to conceive at every reproductive, diabetes and primary care visit; timing delivery before 39 weeks for pregnant individuals with diabetes as the risks associated with continued pregnancy may outweigh those of early delivery; discontinuing anti-obesity medications called GLP-1s prior to pregnancy; and, avoiding prescribing metformin in pregnant individuals with preexisting diabetes already on insulin.

Further suggestions include using diabetes technology, recommending hybrid closed loop systems for pregnant individuals with type 1 diabetes; and suggesting that women with diabetes use contraception until they are ready to become pregnant.

Premenstrual symptoms linked to increased risk of cardiovascular disease

A new study has revealed that women diagnosed with premenstrual symptoms have a slightly increased risk of developing cardiovascular disease later in life.

Premenstrual symptoms include premenstrual syndrome (PMS) and the more severe form, premenstrual dysphoric disorder (PMDD).

The study followed more than 99,000 women with premenstrual symptoms for up to 22 years, comparing their health with women without these symptoms – both in the general population and by comparing them with their own sisters to take into account hereditary factors and upbringing.

The results show that women with premenstrual symptoms had about a 10 per cent higher risk of developing cardiovascular disease.

When the researchers also looked at different types of cardiovascular disease, they found that the link was particularly strong for heart rhythm disorders (arrhythmias), where the risk was 31 per cent higher, and for stroke caused by a blood clot, where the risk was 27 per cent higher.

Even after the researchers took into account other factors such as smoking, BMI and mental health, the link between premenstrual symptoms and increased disease risk remained.

Research has not yet identified the cause of this link, but the researchers behind the study suggest three possible explanations.

One is that women with premenstrual symptoms may have a disrupted regulation of the renin-angiotensin-aldosterone system (RAAS), which controls blood pressure and fluid balance in the body, among other things.

The second is that these women have increased levels of inflammation in the body, which is a known risk factor for atherosclerosis and other heart problems.

Finally, it may be because women with premenstrual symptoms may have metabolic abnormalities, which are linked to an increased risk of both stroke and heart attack.

Obesity’s role in triple-negative breast cancer

Among the various subtypes of breast cancer, triple-negative breast cancer (TNBC) stands out due to its aggressive nature and poor prognosis.

It is characterised by the absence of three critical hormone receptors: oestrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2, which are common targets for breast cancer therapies.

Consequently, TNBC lacks targeted treatment options, relying primarily on conventional cytotoxic therapies, often referred to as chemotherapy in which drugs kill or damage cancer cells.

This limitation contributes to the subtype’s high recurrence rates and significantly lower survival rates compared to other forms of breast cancer.

Researchers have now discovered that exosomes, messenger nanovesicles that carry proteins, RNA, and other molecules to other cells, that are released into the blood by different organs and tissues in obese, insulin-resistant models, carry signals that turn otherwise slow-moving TNBC cells into highly mobile, invasive cells.

This is the first time a study has shown that exosomes from an obese, diabetic environment directly cause this aggressive change in TNBC, and that Rho-proteins (molecular switches that turn “on” or turn “off” signal transduction pathways) play a key role in driving the change.

According to the researchers, by revealing how obesity-driven exosomes push aggressive breast cancer to spread, they hope to unlock new blood tests and drug targets, like Rho-protein inhibitors that stop this deadly process.

“These findings support the development of clinical tests to quantify obesity-derived exosomes in patient plasma as noninvasive biomarkers of metastatic risk, allowing earlier identification and tailored management of aggressive TNBC,” said corresponding author Gerald Denis, Shipley Prostate Cancer Research professor and professor of pharmacology, physiology and biophysics.

“Ultimately, our goal is to improve survival and quality of life for patients facing both metabolic disease and hard-to-treat cancers.”

Pregnancy

Ultrasound Direct extends Trice Imaging partnership

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Ultrasound Direct has extended its Trice Imaging partnership for three years, adding a reporting tool across its 70-clinic UK network.

The private ultrasound provider will continue using the Tricefy platform for secure image storage and patient engagement, alongside TriceIQ for efficiency and productivity analytics.

It will also introduce Trice Workspace Reporting across its network. The companies say the tool will help standardise ultrasound reporting templates and workflows and reduce variation between clinics.

Ultrasound Direct carries out an estimated 120,000 patient scans each year across services including pregnancy, fertility, women’s health, men’s health and other diagnostic pathways.

Its network uses a large pool of sonographers working across different ultrasound systems and serves referral routes including self-referring patients, GPs and commercial partners.

Mike Steward, founding director at Ultrasound Direct, said: “Having worked with Trice Imaging since 2018, we first partnered to replace manual methods of providing scan images to expectant parents with Trice’s secure electronic image-sharing platform. Today, every study performed across the Ultrasound Direct Network is recorded and stored on Tricefy, while our clinical services have expanded considerably beyond pregnancy into fertility, women’s health, men’s health and other diagnostic pathways.”

He added: “To continue futureproofing our image management strategy across a network of 70 clinics, a large team of sonographers, varying ultrasound systems and a growing number of referral partners with different needs, we decided to extend with Trice Imaging. This includes the introduction of the new Trice Workspace Reporting module to help us scale and standardise our ultrasound reporting templates and workflow, reducing variability between clinics.”

The partnership began in 2018, initially focusing on replacing manual methods of sharing pregnancy scan images with expectant parents.

Johanna Wollert Melin, founder and chief executive of Trice Imaging Europe, said: “Ultrasound Direct has been a valued partner in the UK for 8 years.”

She added: “At the heart of the relationship is a willingness to explore new ideas, test new tools and the spirit to solve real challenges across a large and complex clinical network.”

Mark A. Samii, chief revenue officer at Trice Imaging, said: “We are delighted to retain and extend our relationship with Ultrasound Direct.”

He added: “The addition of Trice Workspace Reporting addresses a challenge we hear from multi-site providers globally – keeping reporting quality consistent across many users, systems, referral or payer relationships.”

Steward said Ultrasound Direct continues to see growing demand for private diagnostics alongside NHS care from self-referring patients and an increasingly diverse range of professional and commercial referral partners.

He added: “As that development continues, scalable digital infrastructure becomes increasingly important. Our focus is on ensuring that a growing national network can support consistent clinical workflows, different referral pathways and the technology requirements of the future, while continuing to provide patients with accessible diagnostic services.”

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Paracetamol use may impact future fertility, studies suggest

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Paracetamol use in pregnancy was not linked to autism or ADHD, while separate research found reproductive differences in girls exposed before birth.

One study analysed health records from more than 120,000 children and found no increased risk of autism following prenatal paracetamol exposure.

A separate analysis of nearly 100,000 children also found no increased risk of ADHD among those born to mothers who used the painkiller during pregnancy.

Researchers from the Hong Kong Hospital Authority examined electronic health records covering pregnancies between January 2001 and December 2023.

The autism analysis included 124,333 children, who were nine years old on average and split almost evenly between males and females. There were 3,445 autism diagnoses, representing 2.8 per cent of the group.

The ADHD analysis involved 97,285 children, who were seven years old on average and also split evenly between males and females. There were 5,168 ADHD diagnoses, representing 5.3 per cent.

Women prescribed paracetamol during pregnancy were more likely to be older and have pre-existing conditions including psychiatric disorders, as well as reasons for taking the drug such as infection, fever or chronic pain.

No association was found between prenatal paracetamol exposure and either autism or ADHD.

The findings did not differ according to the trimester in which paracetamol was taken or whether use was intermittent or daily. Advanced maternal age, defined as pregnancy in women over 35, did not alter the findings.

The researchers wrote: “Paracetamol remains a safe and essential analgesic [pain reliever] and antipyretic [fever reducer] during pregnancy, whereas alternatives, such as NSAIDs and opioids carry well-documented risks.

“Unwarranted reluctance to use paracetamol could lead to undertreatment of pain and fever, or the use of more harmful alternatives, both posing risks to the pregnancy and developing fetus.”

The authors said women should assess paracetamol use with guidance from their doctor.

A separate study involving 685 pregnant women without pre-existing conditions and 302 infant daughters found associations between prenatal paracetamol exposure and differences in reproductive organs and hormone levels.

Researchers from Copenhagen University Hospital enrolled the women during their first trimester and assessed them during the first trimester, third trimester and again when their babies were three months old.

At around three months, infants experience a temporary rise in reproductive hormones sometimes called mini-puberty.

Pregnant participants completed questionnaires every two weeks about their use of pain medicines including paracetamol. Infant girls underwent ultrasound scans of their reproductive organs and blood tests to measure hormone levels.

Researchers also examined a separate group of 1,210 girls followed from infancy to adolescence whose mothers reported paracetamol use during the third trimester.

Three-month-old girls exposed to paracetamol before birth had an average 40 per cent smaller ovarian volume, 13 per cent smaller uterine volume and 23 per cent fewer ovarian follicles.

Girls exposed during the first trimester also had lower levels of Anti-Müllerian hormone, a marker of ovarian function.

Among the older girls, those exposed before birth were more likely to have smaller uteruses at puberty and smaller ovaries during their teenage years.

Dr Margit Bistrup Fischer, lead study author and postdoctoral researcher in the Department of Growth and Reproduction at Rigshospitalet hospital in Denmark, said: “Animal studies have demonstrated that impaired formation of ovarian follicles can lead to reduced fertility and earlier reproductive aging.

“Whether the differences observed in our study have implications for fertility and age at menopause in humans remains unknown and will require long-term follow-up of the girls in our cohort.”

She cautioned that women who had used paracetamol during pregnancy “should not be alarmed by our findings”, as the study found associations rather than direct causation and outcomes for individual women and children are unclear.

“Importantly, our study does not evaluate whether [acetaminophen] causes reproductive problems, nor does it provide evidence that prenatal exposure affects future fertility or age at menopause,” she said.

“Although we observed similar associations in an independent cohort, long-term follow-up is needed to determine whether these early-life differences have any clinical significance later in life.”

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Pregnant women prioritised as NHS rolls out flu vaccine

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Pregnant women are among the first groups offered the NHS flu vaccine this winter, which has been updated to better match the subclade K strain.

Schoolchildren are also being prioritised and, like pregnant women, can receive the vaccine from September because they can catch and spread flu easily.

Protecting them also helps others, including younger siblings and grandparents.

Other eligible groups, including people aged 65 and over, will be able to receive a free NHS flu vaccine from October and should receive an invitation by phone or post.

Dr Amanda Doyle from NHS England said: “Last year’s flu season came early and was made worse by a new variant, which had a major impact for patients and put enormous pressure on urgent and emergency care services across the country.

“With the NHS experiencing its busiest summer on record, staff have started preparing for this winter earlier than ever – and with services already under significant pressure, it is vital that everyone offered the vaccine comes forward.”

Last winter’s flu season began more than a month earlier than usual as a new mutated strain circulated.

The strain was sometimes referred to as “Super flu”, although this is not a medical term and does not mean the virus is harder to treat. The name reflected that people had yet to build up immunity against it.

Flu vaccines are updated each year to better match the influenza viruses expected to circulate. These viruses continually mutate, so experts must predict how they are likely to change.

This winter’s vaccine includes changes intended to provide a better match for subclade K.

It remains unclear when flu will begin circulating widely this winter or how severe the season will be. Experts often look at flu activity in southern hemisphere countries such as Australia and New Zealand for indications of how the UK season could develop.

Their flu season peaks in July or August. Australia has recorded fewer cases than last year, while New Zealand has experienced high numbers.

Everyone is at risk of catching flu, regardless of age or how fit and healthy they are.

Doyle said: “Flu can really knock you for six, and for some children and pregnant women it can mean becoming seriously ill or ending up in hospital.”

The flu vaccine cannot give you flu. Instead, it helps the body know how to fight the virus.

Children aged two and over receive a nasal spray version, while adults receive an injection. One dose is needed ahead of winter.

Free NHS flu vaccines are available through pharmacies, GPs and schools. People who are not eligible for a free vaccination can pay around £10 to £20.

Schoolchildren and pregnant women can receive a free NHS flu vaccine from September onwards.

From October, free vaccination will also be available to children aged two or older who have not yet started school, people aged 65 and over, those with certain long-term health conditions, care home residents and carers of older or disabled people, including those receiving a carer’s allowance.

It will also be available to people living with someone who has a weakened immune system and those experiencing homelessness or staying in a homeless hostel or night shelter.

More adults will also be offered vaccination against respiratory syncytial virus (RSV), a virus that attacks the lungs, this winter.

From September, adults with certain pre-existing health conditions, such as chronic lung disease, will be invited for the RSV vaccine when they turn 65 rather than waiting until 75.

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