Cancer
New treatment avenue emerges from work on breast cancer diagnostic test
New findings have provided further evidence that anti-fibrosis drugs could improve outcomes from breast cancer.
They come out of the progress of a new diagnostic test that could better predict breast cancer outcomes; building on a recent research breakthrough in identifying a connection between fibrosis and advanced stages of the disease.
The link between breast cancer progression and fibrosis – the development of fibrous connective tissue as a reparative response to injury or damage – was first described in a 2021 study from the University of Arizona.
Researchers at the same institution later developed the MeCo Score diagnostic to potentially predict the likelihood of relapse or recurrence among patients with early-stage breast cancer.
And now a new study from the Spanish National Cancer Research Center has tested the invention, providing further evidence that tissue stiffening in the most common types of breast cancer, HER2-negative, can directly cause disease progression and metastasis, leading to detrimental outcomes for patients.
When standard chemotherapy alone was prescribed, high MeCo Scores were associated with much worse survival compared with low MeCo Scores; however, this difference in survival was minimised in patients who received antifibrotic therapy in addition to chemotherapy.
Among high MeCo Score patients, antifibrotic therapy reduced the risk of recurrence by 62 per cent, with an average follow-up period of 9.7 years after therapy.
The link between breast cancer progression to bone metastasis and fibrosis was first described in a 2021 study published in Cell Reports and authored by Ghassan Mouneimne, an associate professor of cellular and molecular medicine at the University of Arizona’s College of Medicine.
On this latest development, Mouneimne says: “We’re hopeful that additional clinical confirmation of this discovery will firmly establish a new way to determine which patients may benefit from this fundamentally new therapeutic modality.
“As a generic-emergent drug, [fibrosis drug] nintedanib is set for a substantial drop in price in the next couple of years, which may help mitigate the rising cost of treating breast cancer. It’s all about seeking new ways to personalise care and find more cost-effective treatments.
“We are in the initial stages of planning a prospective, multi-centre trial using the MeCo Score to guide nintedanib treatment in patients with luminal, ER-positive breast cancer.”
Mouneimne’s previous work identifying the link between fibrosis and advanced stages of breast cancer provided the mechanistic basis for developing the MeCo Score and led to the launch of MeCo Diagnostics LLC, a startup working to advance the technology so it can be used in the clinic.
A combination of THC and CBD derived from cannabis was shown to kill ovarian cancer cells without harming healthy cells in laboratory studies.
The findings suggest that drugs made from these compounds could be developed to fight ovarian cancer in future, though researchers caution that much more work is needed before results can be translated into patient treatments.
The research was led by Dr Siyao Tong of Khon Kaen University.
The researcher said: “Ovarian cancer remains one of the deadliest gynaecological malignancies, characterised by late diagnosis, high recurrence rates, and limited effective treatment options.
“Our goal is to find alternative drugs that can improve efficacy and potentially reduce toxicity, ultimately bringing new hope to patients facing this challenging disease.”
Scientists tested the effects of CBD (cannabidiol, which is not psychoactive) and THC (delta-9-tetrahydrocannabinol, which is) on two ovarian cancer cell lines.
One line was sensitive to platinum-derived drugs and one was resistant.
The team found that cells from both cancer lines treated with CBD or THC formed fewer and smaller colonies.
While both compounds limited cancer cell growth, combining them produced particularly strong results.
A combination of the two was very successful at killing cancer cells.
“Notably, the inhibitory effect was most pronounced when CBD and THC were used in a 1:1 ratio,” said Tong.
Additional tests showed the compounds prevented cells from migrating, suggesting they might be able to stop ovarian cancer spreading to other parts of the body.
Both cell lines were similarly affected, indicating the compounds could work equally well for different types of ovarian cancer. The compounds also had minimal effects on healthy cells.
To explore how this worked, scientists examined cell signalling pathways. The PI3K/AKT/mTOR pathway, which regulates cell growth and survival, is overactive in ovarian cancer cells and contributes to tumour development and treatment resistance.
The CBD and THC combination appeared to restore normal regulation of the pathway.
Tong said: “Although our study is still preliminary, it lays an important foundation for future research into the potential applications of CBD and THC in ovarian cancer treatment.
“By confirming their anti-cancer activity and identifying key molecular mechanisms, our findings are expected to drive further preclinical research.
“If future studies confirm these effects, CBD-THC combination therapy may ultimately contribute to the development of new treatment strategies.”
HRT (hormone replacement therapy) may not increase breast cancer risk in women with BRCA mutations, new research suggests.
Women who inherit harmful mutations in the BRCA1 or BRCA2 genes, which help repair DNA, face elevated risks of ovarian and breast cancer.
They are often advised to have their ovaries and fallopian tubes surgically removed (bilateral salpingo-oophorectomy, removal of the ovaries and fallopian tubes) at relatively young ages to reduce ovarian cancer risk, but this brings on early menopause.
The study was led by Joanne Kotsopoulos, a scientist at the Women’s College Hospital Research and Innovation Institute and a professor at the Dalla Lana School of Public Health at the University of Toronto in Canada.
She said: “We cannot simply recommend a drastic surgery like oophorectomy for young women without offering a way for them to manage the well-established short- and long-term outcomes of surgical menopause.
“I believe we should educate patients and their health care providers on how we can safely balance the risks and benefits of MHT use to ensure longevity and improve quality of life.”
She noted there has been reluctance and misinformation regarding HRT, largely due to studies in the general population showing an association between HRT use and increased breast cancer risk.
The researchers conducted a matched prospective analysis, an observational design that pairs similar participants to mirror clinical trial conditions.
They created 676 matched pairs of women who did and did not use HRT after menopause.
Participants were matched by BRCA1 or BRCA2 status, birth year and age at menopause. The women ranged in age from 22 to 76, with an average age of 43.8.
Patients with a history of cancer, those who had received a bilateral mastectomy (removal of both breasts), and non-menopausal patients were excluded from the study.
After an average follow-up of 5.6 years, breast cancer cases were significantly lower in women who used HRT, with 87 cases in the HRT group compared with 128 cases in the non-HRT group.
Analysis by formulation showed most types of HRT were not associated with breast cancer risk.
However, two formulations were linked to decreased risk. Women who received oestrogen-only HRT were 63 per cent less likely to develop breast cancer than those who did not use HRT.
Of the 43 women who received conjugated oestrogen and bazedoxifene (a selective oestrogen receptor modulator), none developed breast cancer.
“Although based on smaller numbers, this is definitely an exciting and interesting area for future research,” Kotsopoulos said.
“Hypothetically, conjugated oestrogen and bazedoxifene could be used to mitigate breast cancer risk by avoiding progesterone, which is thought to be the breast cancer risk-associated component of MHT. Future trials will be necessary to test this hypothesis.”
There were no significant differences in results between BRCA1 and BRCA2 carriers.
“Our findings suggest that clinicians should take a personalised approach to menopause management for women with BRCA mutations who are suffering from the impact of surgical (or natural) menopause, if there are no contraindications for them,” said Kotsopoulos.
Routine mammograms could help assess cardiovascular disease risk in women, new research suggests.
The study found that both the severity of calcium in breast arteries and how it progressed on mammograms predicted future cardiovascular disease.
Researchers at Penn State College of Medicine analysed data from 10,348 women who had repeat mammograms, with an average of 4.1 years between scans.
The X-ray images can detect calcium in the breast’s arteries, a sign that blood vessels are stiffening.
As people age, calcium can build up in arteries, raising heart attack and stroke risk.
In the study, AI software assessed whether calcification was present and how severe it was.
Women with more severe calcification, and those whose calcification progressed over time, had up to two times higher risk of major events such as heart attack, stroke, heart failure and death.
Matthew Nudy is assistant professor of medicine and public health sciences at Penn State College of Medicine.
He said: “We know that women are more likely to be diagnosed at later stages of cardiovascular disease and have worse outcomes following a heart attack compared to men.
“That may be in part because the current cardiovascular risk assessment tools underestimate risk in women. We need better tools.
“In the future, assessment of breast arterial calcification may help improve our ability to predict risk and prevent cardiovascular disease.”
Vascular calcification was present in 19.4 per cent of participants at baseline.
Those who initially had no calcium but developed it on follow-up had a 41 per cent higher risk of an adverse cardiovascular event and death.
Nudy said: “This could be a way to use data that may already be available for different reason and to potentially use it to risk stratify an individual for the development of cardiovascular disease.”
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