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Molecular profiling can safely reduce radiation for women with endometrial cancer, shows study

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A major international study, PORTEC-4a, provides the strongest evidence yet that molecular profiling can safely reduce radiotherapy for women with early stage endometrial cancer while identifying those who would benefit from more intensive treatment.

Endometrial cancer is the most common gynaecological cancer in high-developed countries, most often affecting women after menopause. The majority of women are diagnosed at an early stage, when treatment outcomes are generally favourable.

For women with high-intermediate risk disease, adjuvant radiotherapy – particularly vaginal brachytherapy (a form of internal radiotherapy delivered directly to the vaginal area) – is commonly used after surgery to reduce the risk of recurrence.

However, patients don’t need it equally, and some may receive more treatment than necessary, exposing them to potential side effects without added benefit. Furthermore a small subgroup of patients seem to be under-treatment when only treated with vaginal brachytherapy.

 

 

This has sparked growing interest in tailoring treatment using molecular profiling, a method that examines the genetic and biological features of a tumour to guide clinical decisions. It helps identify which patients are most likely to benefit from radiotherapy, and which can safely avoid it.

The results from this new study, presented at ESTRO 2025, the annual congress of the European Society for Radiotherapy and Oncology (ESTRO), mark a significant step forward in personalised cancer treatment.

Endometrial cancer is the most common gynaecological cancer, and its incidence is rising globally. The PORTEC trials have played a key role in refining treatment strategies, ensuring that radiotherapy is used effectively while minimising side effects.

The findings from PORTEC-4a highlight that molecular profiling helps tailor radiotherapy decisions based on individual tumour characteristics, nearly half of patients in the trial safely avoided radiation without compromising cancer control, and  suggests that patients with unfavourable tumour profiles benefit from a more intensive radiation approach.

The randomised PORTEC-4a trial enrolled 592 women across eight European countries with (high-)intermediate risk endometrial cancer. Molecular testing classified tumours into risk categories, allowing treatment to be adapted accordingly.

A total of 46 per cent of patients in the molecular-profile arm safely avoided radiotherapy, patients with an unfavourable molecular profile received a more intensive radiation approach, pelvic radiotherapy instead of vaginal brachytherapy and the results suggest better locoregional control, with a recurrence rate of 8.4 per cent compared to 30.5 per cent in those who received standard treatment without molecular profiling.

“By using molecular profiling, we can tailor treatment to each patient’s individual risk,” said Dr Anne Sophie van den Heerik, lead investigator of the PORTEC-4a trial, from The Leiden University Medical Centre, The Netherlands.

“This approach allows us to safely reduce radiotherapy for many women while ensuring that those who need it receive the most effective therapy. It’s a major step towards more personalised and less invasive cancer treatment.”

The findings demonstrate that nearly half of patients can be safely spared radiotherapy while maintaining excellent survival rates. Additionally, exploratory analyses suggest that patients with an unfavourable molecular profile may benefit from a more intensive radiation approach to reduce recurrence risks.

“The PORTEC-4a trial is a game-changer,” said Prof Matthias Guckenberger, President of ESTRO, Chairman of the Department of Radiation Oncology and full Professor at the University Hospital Zurich and University of Zurich.

“This research proves that precision medicine is transforming cancer treatment. By identifying patients who have the largest benefit from radiotherapy, we can maximise its impact, improve quality of life for thousands of women worldwide, and maintain excellent cancer control.”

These findings pave the way for a more personalised approach to treating endometrial cancer, ensuring that each patient receives the most effective and least invasive treatment based on their tumour biology and risk profile.

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Black women want more accessible breast cancer screening info, study finds

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Black women in the UK want clearer, more accessible breast cancer screening information, research has found.

The study looked at why Black African and Black Caribbean women are less likely than white women to attend breast screening.

Researchers at the University of Surrey held focus groups and interviews with 47 Black African and Black Caribbean women aged 50 to 71.

Women in this age group are routinely invited for NHS breast screening.

The researchers said only 45 per cent of Black women attend screening, compared with 63 per cent of white women.

Anietie Aliu, lead author, postgraduate researcher at the University of Surrey and registered nurse, said: “Diagnosing breast cancer early can dramatically improve a person’s chance of survival.

“Breast cancer screening plays an important role in this by identifying the cancer and ensuring a person receives speedy treatment.

“Despite the importance of screening, Black women are less likely to attend appointments than white females.

“This puts them at risk of a potential cancer being diagnosed late and spreading to other areas of the body. We need to understand what is preventing Black women from attending these appointments and help identify ways to remove such barriers.”

The study found a need to increase awareness of breast cancer screening, especially among women less familiar with the service.

Some women, particularly those born outside the UK, knew little about breast screening before receiving their first invitation.

Others questioned why they needed screening when they had no symptoms.

The importance of trusted conversations was also identified.

Researchers found that some Black women expected their GPs to speak to them about breast screening, particularly before they reached screening age.

Although NHS breast screening is organised through national screening services, researchers said GPs often have established relationships with patients and may be well placed to offer brief advice on preventive care, including breast screening.

Participants called for stronger links between GP practices, breast screening services and Black community champions.

They said this could help women receive trusted information, ask questions and feel reassured.

Faith and religious beliefs also shaped decisions for some women.

Some Black African Christian women said illness, including cancer, was not permitted by God in their bodies, while others saw screening as a personal choice that did not conflict with Christian faith.

Muslim women highlighted the importance of being able to state their religion on medical appointment forms to help ensure they were seen by a female mammographer.

A mammographer is a healthcare professional trained to carry out breast screening scans.

Aliu added: “Breast screening can save lives, but our findings show that attendance is shaped by multiple factors, not just awareness, although awareness remains important.

“Women need relatable screening information, reassurance, flexible appointments and services that are accessible within their communities.

“Many felt that invitation letters were too formal, and that leaflets and media imagery did not reflect them, making it harder to relate to screening.”

Dr Afrodita Marcu, senior research fellow at the University of Surrey and member of the research team, said: “We need a more collaborative approach, where primary care, screening services and community voices work together to support women before, during and after the invitation.”

The researchers said future breast screening interventions should be designed with Black women, rather than for them.

They said user-friendly and culturally relevant resources, developed with communities, healthcare professionals and screening services, could improve understanding, reduce fear and make breast screening feel more accessible and reassuring.

Dr Robert Kerrison, associate professor of cancer care at the University of Surrey, said: “There is no question that breast screening can be lifesaving, but we need to make it easier for women to understand, access and feel reassured by the programme.

“This means improving communication, addressing practical barriers and making sure healthcare professionals and community partners are supported to provide clear and trusted information.”

The team has also explored healthcare professionals’ perspectives and worked with stakeholders to develop user-friendly materials with Black women.

Researchers said this co-designed approach could help ensure breast screening messages are culturally relevant, practical and shaped by the people they are intended to support.

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Breast cancer rising rapidly in Asian American women, study finds

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Breast cancer rates have risen rapidly among Asian American women over the past two decades, with some of the steepest increases among women under 50, new research has revealed.

Rates rose by more than three per cent a year in nearly every Asian American ethnic group studied, much faster than in any other US ethnic group.

The increase was particularly marked among women under 50 and in cases involving advanced-stage disease or certain aggressive subtypes of the cancer.

The study found even larger increases among Chinese and Vietnamese women.

Breast cancer rates among Native Hawaiian women were already among the highest recorded among US women, but rose by about one per cent a year, less than the increases seen in Asian American groups.

The researchers said increased screening was unlikely to explain the trend because screening would be expected to identify more cancers at an earlier stage.

Instead, cancers that had already spread increased at the fastest rate.

Triple-negative breast cancer, considered the most aggressive subtype, rose by more than six per cent a year among Chinese American women between 2017 and 2022.

Scarlett Lin Gomez, senior author and professor of epidemiology and biostatistics at the University of California, San Francisco, said: “These patterns are highly concerning from a disparities standpoint.

“They underscore why it is so important to move beyond treating Asian Americans, Native Hawaiians, and Pacific Islanders as a single population.”

Researchers analysed about 150,000 cases of invasive breast cancer diagnosed between 2000 and 2022 using data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results Programme.

The analysis covered nine Asian American, Native Hawaiian and Pacific Islander populations across 14 states. Together, these states account for about two-thirds of the US population within these groups.

Except for Native Hawaiian women, Asian American women have historically had lower breast cancer rates than non-Hispanic white women.

However, the gap has narrowed rapidly. By 2022, incidence among Asian American women under 50 was comparable with that recorded among white women.

The reasons for the increase among women under 50 remain unclear.

Changes in reproductive patterns, diet and other lifestyle factors may play a part, but researchers said they did not fully explain the findings.

They said previously unidentified risk factors may also be contributing to the rises in some Asian American communities.

Researchers hope two UCSF-based studies, the CRANE breast cancer study and the ASPIRE cohort study, will provide insights into these factors.

Gomez said: “Understanding why breast cancer is increasing so rapidly in these communities is critical.

“At the same time, we need to ensure that women across all Asian American, Native Hawaiian, and Pacific Islander communities have access to culturally appropriate education, screening, and timely follow-up care.”

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Postpartum breast cancers may be biologically more aggressive, new study finds

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Breast cancer diagnosed within three years of childbirth, especially the first year, may be biologically more aggressive, a study suggests.

The findings add to evidence that postpartum breast cancer may be a distinct form of the disease.

They also suggest the period of greatest biological risk may occur earlier than previously thought.

The study was led by investigators at the UCLA Health Jonsson Comprehensive Cancer Center.

Dr Nimmi Kapoor, associate professor of surgery at the David Geffen School of Medicine at UCLA and senior author of the study, said: “We’ve long recognised that breast cancers diagnosed after pregnancy can behave differently, but we haven’t known when that increased risk is biologically strongest.

“Our findings suggest that the first one to three years after childbirth represent an important window when some tumours may have more aggressive characteristics.”

Breast cancer rates among younger women have been rising, and scientists have been investigating whether women having their first child later may help explain some of the trend.

Pregnancy causes major changes in breast tissue. Previous studies have found that cancers diagnosed soon after childbirth are more likely to have aggressive features and worse outcomes.

Researchers have not agreed on how long the period of increased risk lasts. Some studies define postpartum breast cancer as occurring within one or two years of delivery, while others extend the period to five or even 10 years.

To better define the period of risk, the team studied whether tumour biology varied according to the time since a woman’s most recent childbirth.

The study involved 385 women aged 45 or younger with early-stage, hormone receptor-positive and HER2-negative breast cancer who were treated at UCLA between 2011 and 2024.

Hormone receptor-positive cancers grow in response to hormones such as oestrogen or progesterone. HER2-negative cancers do not have unusually high levels of a protein that can promote tumour growth.

Each tumour had been assessed using the Oncotype DX Breast Recurrence Score, a genomic test that measures the activity of 21 genes linked to the risk of cancer returning and the potential benefit of chemotherapy.

Researchers grouped the women according to the time between their last childbirth and breast cancer diagnosis.

They compared women who had never given birth with those diagnosed at different intervals after childbirth.

The team then examined whether recurrence scores and other tumour features differed between the groups and whether any patterns remained after accounting for factors including age and lymph node status.

Women diagnosed within the first year after childbirth had significantly higher recurrence scores than those who had never given birth.

This suggested biological features associated with a higher risk of the cancer returning.

Scores were also higher, but to a lesser extent, among women diagnosed during the second and third years after delivery.

Women diagnosed within three years of childbirth were nearly three times more likely to fall into a higher recurrence score category than women who had never given birth.

They were also more likely to have higher-grade tumours, meaning their cancer cells appeared more abnormal and potentially more aggressive under a microscope.

Women diagnosed more than three years after childbirth did not show the same consistent increase in recurrence scores.

The findings also suggest that standard clinical measures, including tumour size and whether the cancer has reached the lymph nodes, may not fully capture the differences in this group.

Gene expression testing appeared to identify biological risk that was not always reflected in routine examination of tumour tissue.

The researchers said reproductive history could therefore provide additional context when genomic test results are interpreted in younger patients.

Despite the more aggressive genetic features, women diagnosed within three years of childbirth did not have significantly worse short-term outcomes.

After about four years of follow-up, recurrence and survival rates were similar to those among other patients in the study.

Researchers said one possible explanation was that women with higher-risk tumours received more intensive treatment, including chemotherapy, ovarian function suppression and newer targeted therapies.

The findings also suggest that aggressive tumour biology does not necessarily lead to worse short-term outcomes when patients receive effective treatment.

The researchers said larger studies involving several institutions and longer follow-up periods are needed to confirm the findings.

They added that postpartum status may need greater consideration when breast cancer is assessed and treated in younger women.

Kapoor said: “Our findings suggest that the years immediately following childbirth represent a unique biological window for some breast cancers.

“Understanding why these tumours behave differently may help us better identify patients who need closer monitoring or more tailored treatment approaches.”

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