Study uncovers patterns suggesting breast cancer may behave differently in younger women

A research study presented in a talk at MLS Future Forum has uncovered some intriguing patterns that suggest our current understanding of breast cancer may not apply to pre-menopausal women.

It poses the question that breast cancer may behave differently in younger women and that current strategies for detecting and treating the disease may not be appropritate.

Molly Crow, of the University of the West of England in Bristol, won an award for best talk after presenting her research, ‘A Comparison of Clinicopathological Features and Gene Expression in Pre- and Post-Menopausal Women with Breast Cancer: Insights from a UK-Canada Cohort’.

“Pre-menopausal women are more likely to be diagnosed more aggressive, genetically distinct and harder to treat forms of breast cancer. This study provides novel insights, drawing on data from a new geographic population and being the first to comprehensively examine molecular features, survival, and gene expression within the same cohort,” she explained.

Pre-menopausal women

“79% of breast cancer cases occur post-menopausal women but previous research has indicated that breast cancer in younger women may behave differently, have different disease mechanisms and different survival outcomes. For me that raised the question, is our current understanding of breast cancer actually applicable to pre-menopausal women? 

“Discovering the differences between these two hormonally distinct groups could have important implications for prevention, diagnosis, the development of accurate prognostic indicators, and treatment decisions.”

The project used the data from METABRIC database that is available on cBioPortal. This dataset is an invaluable resource that contains a wealth of information from fresh-frozen breast cancer biopsies from women based in the UK and Canada, Molly says.

Clinical information

“What is so valuable about this data set though is that it also contained a lot of clinical information, such as the age at diagnosis, hormone receptor status, survival months, cause of death (if known), and relapse free months. It isn’t common for datasets to have that much information on a single cohort,” she says.  

Analysis was primarily performed in R, whilst Over Expression Analysis was performed in WebGestalt. Menopause status was defined using an age-based definition.  

Molly found that pre-menopausal women were more likely to be diagnosed with characteristics associated with a worse prognosis, such as oestrogen receptor negative, HER2-positive and triple negative BC, and these findings were reflected in the worse overall survival and disease-free survival observed in this study. 

Menopause status

Differential expression analysis identified 1,920 genes associated with menopause status. Over-representation analysis revealed their primary involvement in the biological processes of cell cycle regulation and division, epithelial development, cell adhesion, RNA and ribonucleoprotein processes, ciliary structure and function, and microtubule-based transport. 

“There aren’t many studies looking at this topic, and among what exists no one can agree with each other! I think there is something happening here but that our current methods, using retrospective definitions of menopause, ignoring perimenopause, and not having information on exposure to risk factors, make it impossible to pull apart what’s just noise from the data and what could provide a useful lead,” Molly says.

“Unfortunately, I, like many others, had to rely on a retrospective age-based definition of menopause to conduct this research. This is something I have great concerns about as to what impact it could have on the quality of results produced. 

Age-based definition

“One estimate suggests that such an age-based definition will lead to 21.5% of women age 40-54 having their menopause status miscategorised. This has a particular deleterious effect in breast cancer studies when you are often studying a much narrower age-range. 

“Having less accurate methods of definition makes it even more difficult to pull apart if the differences in results between studies are due to miss-categorisation or factors like race.”

Molly points out that perimenopause is difficult to define, particularly for research purposes, and this often leads to it being left out as a reproductive category. 

“It's such an important and potentially influential part of a women’s life. I'll be honest, this is what really excites me,” she says. 

Survival rates

“While reading for this project I came across several studies that talk about observing that women age 45-50 have a better survival rate than both their older and younger counterparts (Adami et al., 1986; Boffetta et al., 1993; Sant et al., 1998; Tai et al., 2005). 

“There needs to be more work looking at the patterns of hormonal changes through perimenopause and the impact that this has, not just on breast cancer risk and development but also on progression and responses to treatment. “

 Molly describes her research as an independent, much loved, passion project. 

“Whilst I did the work myself, I am lucky enough to have received the generous support, encouragement and advice from various academics at my university including Dr David Qualtrough, Dr Lili Ordonez, Dr Dann Turner and the Adukwu Research Group. I was also fortunate to receive Summer Studentship funding in 2024 though Student Ventures to cover part of my time,” she says. 

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