Cancer
Researchers identify key protein in breast cancer brain metastasis

US researchers have identified a key protein whose increased presence helps promote breast cancer brain metastasis, opening a new area of research into the condition.
In their recent findings, the research team found the MUC5AC protein is upregulated in patients whose cancer has spread to the brain.
The finding provides a rationale for developing a new predictive biomarker for brain metastasis in high-risk breast cancer patients.
In addition, the researchers noted that the study offers a route to develop therapeutic targets for those cases.
Wasim Nasser, PhD, an associate professor in the UNMC Department of Biochemistry and Molecular Biology, said that the research also provides a potential platform to detect brain metastasis early in breast cancer patients.
Brain metastasis is an ominous complication that occurs in around 20-4 per cent of patients with solid tumors diagnosed with breast cancer, lung cancer or melanoma, said Dr. Nasser, who served as lead researcher and corresponding author on the study.
But with few therapies available for the affected patients with breast cancer brain metastasis, the patients typically live only for about five to 10 months, Dr. Nasser said.
According to the publication, mucin proteins previously have been implicated in cancer progression, and the researchers sought to answer whether and how they might be involved in breast cancer brain metastasis.
The study established that the secretory protein MUC5AC, through its interaction with cMET and CD44v6 receptors, is critical for breast cancer brain metastasis.
Dr. Nasser said: “It is imperative to characterise the factors responsible for brain metastasis and develop targeted therapies to challenge this complication,”
Dr. Nasser, whose research specialises in understanding the complexities that are involved in the brain metastasis pathogenesis, said the research team was intrigued to find the drivers that were potential threats to causing brain metastasis.
After analysing multiple datasets of patients with brain metastasis, Dr. Nasser said, the team found that mucins were dysregulated and MUC5AC specifically was among the top upregulated genes.
The connection was particularly strong in breast cancer patients with the HER2-positive cancer subtype, he said, and led to lower survival rates.
Having established that connection, the researchers then worked with animal models.
The researchers found that silencing MUC5AC in breast cancer brain metastatic cells for the experiment reduced brain metastasis in vivo.
In the study experiments, a cancer therapeutic already available for other uses – a cMET inhibitor known as Bozitinib, or PLB1001 – showed promise in inhibiting MUC5AC expression.
The study concluded that blocking MUC5AC and its axis with the cMET and CD44v6 proteins using a cMET inhibitor will be a novel therapeutic approach for breast cancer brain metastasis.
Dr. Nasser said the research team now is extending the study to other cancers that can metastasize to the brain, including lung cancer and melanoma.
Researchers also are hoping to push the Bozitinib therapy for clinical trials, he said.
Insight
Breast cancer rising rapidly in Asian American women, study finds

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

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.”
Wellness
Alcohol and smoking linked to breast cancer and irregular heartbeat in women, study finds

Smoking and alcohol were linked to breast cancer and irregular heartbeat in women aged 55 and over, a global analysis suggests.
Breast cancer and atrial fibrillation or flutter represent a growing global health burden, but the reasons for similar rates in some regions are not well understood.
Atrial fibrillation, also known as AFib, is an irregular heartbeat.
Study co-author Dr Shu Wang, director of the Breast Disease Center at Peking University People’s Hospital, said: “Identifying shared risk factors is important for developing interventions that support optimal health, such as smoking cessation and alcohol restriction, which could potentially reduce the global incidence of breast cancer and atrial fibrillation/flutter substantially.”
Researchers examined rates of breast cancer and atrial fibrillation or flutter among women aged 55 and over in 204 countries and territories.
They assessed exposure to 58 shared and distinct health, behavioural and lifestyle risk factors, including smoking, alcohol use, body mass index and physical activity.
The analysis found that 80 of 202 countries and territories, around 39 per cent, had similar rates of both conditions.
Breast cancer was the dominant condition in 65 countries, while atrial fibrillation or flutter was dominant in 57.
After accounting for multiple variables, smoking and alcohol use were linked to higher rates of both breast cancer and atrial fibrillation or flutter.
A further analysis estimated that reducing alcohol intake and smoking could potentially cut breast cancer risk by around 15 per cent and atrial fibrillation or flutter risk by about 12 per cent worldwide.
Alcohol use was estimated to contribute to 9.27 per cent of breast cancer cases and 7.57 per cent of atrial fibrillation or flutter cases.
High-income and developed countries, including the US, Canada, Australia, New Zealand and much of Europe, had elevated rates of both conditions.
The findings were consistent with previous research linking Western diets and sedentary lifestyles to greater risks of cardiovascular and metabolic conditions and cancer.
Wang said: “One of the most surprising aspects of our findings was how common both breast cancer and atrial fibrillation/flutter diagnoses were among women ages 55 and older in high-income regions, which highlights the influence of lifestyle.
“This is the first study combining global data with machine learning to show the relationship between the conditions, their location across the world and the shared risk factors of these two conditions.”
The highest-risk areas were mostly in Western countries, where exposure to smoking and alcohol was greater than in Eastern regions.
Researchers said the pattern could reflect lifestyle, social and community differences. Western countries were also more likely to have higher body mass index, sedentary lifestyles and greater exposure to Western diets.
Study co-authors Dr Zeye Liu and Dr Yi Shi said: “Nowadays, more and more people are paying attention to the link between cancer and cardiovascular health.
“Breast cancer and atrial fibrillation/flutter rise together across many regions of the world and share the same modifiable risk factors.
“From a cardiovascular perspective, this means that reducing smoking and alcohol use could help lower the risk of both conditions at the same time.”
Dr Laxmi Mehta, chair of the American Heart Association’s Council on Clinical Cardiology, was not involved in the research.
She said: “Many of the same modifiable factors, including smoking, alcohol use, poor diet, physical inactivity and obesity, contribute to both breast cancer and cardiovascular disease including atrial fibrillation/flutter, as confirmed by this study’s findings.
“This overlap underscores the importance of integrated lifestyle strategies to reduce risk of cardiovascular disease and cancer. The American Heart Association’s Life’s Essential 8 highlights key behaviours and health factors essential for prevention and reducing risk.”
The researchers created global risk maps that could help healthcare professionals and policymakers develop prevention strategies tailored to different regions.
They plan to add long-term research and genetic, metabolic and socioeconomic data to future analyses.
The study used information from the Global Burden of Disease 2021 database.
Machine learning was used to examine global patterns, links between the two conditions and risk factors specific to different regions. Machine learning uses computer systems to identify patterns in large amounts of data.
The research was based on national-level information and did not include data about individual patients, meaning it cannot prove cause and effect.
Differences in screening, healthcare resources, data collection and definitions between countries may also have affected the results.
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