Tag: breast cancer

Link Between High Cholesterol and Breast Cancer Explained

Source: National Cancer Institute

While chronically high cholesterol levels are linked to increased risks of breast cancer and worse outcomes in most cancers, the link had not been fully understood until now.

In a study published in Nature Communications, researchers identify the mechanisms at work, describing how breast cancer cells utilise cholesterol to develop stress tolerance, preventing them from dying as they migrate from the original tumour site.

“Most cancer cells die as they try to metastasise – it’s a very stressful process,” said senior author Donald P. McDonnell, Ph.D., professor in the departments of Pharmacology and Cancer Biology and Medicine at Duke University School of Medicine. “The few that don’t die have this ability to overcome the cell’s stress-induced death mechanism. We found that cholesterol was integral in fueling this ability.”

McDonnell and colleagues built on earlier research in their lab focusing on the link between high cholesterol and oestrogen-positive breast and gynaecological cancers. Those studies found that cancers fueled by the oestrogen hormone benefitted from derivatives of cholesterol that act like oestrogen, stoking cancer growth.

But a paradox emerged for estrogen-negative breast cancers. These cancers are not oestrogen dependent, but high cholesterol is still associated with worse disease, which indicates the possible effect of a different mechanism.

In the current study using cancer cell lines and mouse models, the Duke researchers found that migrating cancer cells gobble cholesterol in response to stress. Most die.

However, those that live emerge with a super-power that makes them able to withstand ferroptosis, a natural process in which cells succumb to stress. These stress-impervious cancer cells then proliferate and readily metastasise.

Other tumours beside ER-negative breast cancer cells use this process. including melanoma. And the mechanisms identified could be targeted by therapies.

“Unraveling this pathway has highlighted new approaches that may be useful for the treatment of advanced disease,” McDonnell said. “There are contemporary therapies under development that inhibit the pathway we’ve described. Importantly, these findings yet again highlight why lowering cholesterol — either using drugs or by dietary modification — is a good idea for better health.”

Source: Duke University

Many Breast Cancer Patients Don’t Discuss Cannabis Use with Docs

Photo by Crystalweed Cannabis on Unsplash

About half of US adults with breast cancer use cannabis as an adjunct to cancer treatment for symptom and side effect management. However, most don’t discuss their use of cannabis with their physicians, according to a new study.

Pain, fatigue, nausea, and other difficulties often arise from cancer and its treatment, and some patients turn to cannabis for relief of their symptoms. However, many physicians feel that they lack the necessary knowledge to discuss cannabis with their patients. Such knowledge is especially important now that cannabis use is becoming more widespread.

In a study published in CANCER, researchers reported the results of an anonymous online survey to examine cannabis use among adults who were diagnosed with breast cancer within five years and were members of the Breastcancer.org and Healthline.com online health communities.

The findings revealed that:

  • Of the 612 participants, 42% reported using cannabis for relief of symptoms, including pain, insomnia, anxiety, stress, and nausea/vomiting. Among those who used cannabis, 75% reported that it was extremely or very helpful at relieving their symptoms.
  • Nearly half (49%) of participants who used cannabis believed that medical cannabis can be used to treat cancer itself; however, its effectiveness against cancer is unclear.
  • Among those using cannabis, 79% had used it during treatment, which included systemic therapies, radiation, and surgery.
  • Participants reported using a wide range of different cannabis products known to vary in quality and purity.
  • Half of participants sought information on medical cannabis, and websites and other patients were ranked as the most helpful sources of information. Physicians ranked low on the list.
  • Among those who sought information on cannabis use for medical purposes, most were unsatisfied with the information they received.
  • Most participants believed cannabis products to be safe and were unaware that the safety of many products is untested.

“Our study highlights an important opportunity for providers to initiate informed conversations about medical cannabis with their patients, as the evidence shows that many are using medical cannabis without our knowledge or guidance,” said lead author Marisa Weiss, MD, of Breastcancer.org and Lankenau Medical Center near Philadelphia, Pennsylvania. “Not knowing whether or not our cancer patients are using cannabis is a major blind spot in our ability to provide optimal care, and as healthcare providers, we need to do a better job of initiating informed conversations about medical cannabis with our patients to make sure their symptoms and side effects are being adequately managed while minimising the risk of potential adverse effects, treatment interactions, or non-adherence to standard treatments due to misinformation about the use of medical cannabis to treat cancer.”

Dr Weiss added that patients should never use cannabis as an alternative to standard cancer treatment, and clinicians should inform patients about the safe and effective use of cannabis as an adjunct to their cancer treatment plan.

Source: Wiley

Radiation after Breast-conserving Surgery Reduces Cancer Recurrence

Source: National Cancer Institute

A long-term follow up analysis of a trial has shown that breast radiation following lumpectomy significantly reduces incidence of ipsilateral breast recurrence (IBR) for “low risk” DCIS.

NRG-RTOG 9804 is a clinical study conducted by the National Cancer Institute National Clinical Trials Network group NRG Oncology. These results were recently published in JCO.

IBR occurs at a rate of 5-10% after breast-conserving surgery. The NRG-RTOG 9804 study enrolled 636 women with a median age of 58 between December 1999 and July 2006. Patients were randomised to breast radiation (RT) or observation (OBS) treatment groups. All patients who participated in the trial underwent annual mammography and specified clinical exam intervals. For this analysis, the median follow up time was 13.9 years.

Analysis focused on the long-term cumulative incidence of IBR, the primary endpoint in the study. The study hypothesised that radiation would significantly reduce IBR from 6% to 3.5% at 5 years, assuming that the reduction in IBR from RT would be less than previous trials that included higher grades and larger sizes of DCIS. With long-term follow-up, cumulative incidence of IBR remained statistically significantly lower with RT, as compared to OBS. At 10 and 15 years, the cumulative incidence of IBR with OBS was 9.2% and 15.1%, respectively, and was 1.5% and 7.1%, respectively, with RT. The 10 and 15 year invasive IBR incidence, respectively, was 0.4% and 5.4%  with RT; 4.3%  and 9.5% with OBS. A total of 52 IBRs were observed; 14 in the RT arm and 38 in the OBS arm.

No statistically significant differences in mastectomy, distant metastasis, overall or disease-free survival were seen between the two treatment arms.

“Since IBR risk continues to increase through at least 15 years, with radiation conferring both a delay and decrease in this risk, the data presented support the decision to treat patients who wish to minimise their IBR and particularly the invasive cancer risk long term. Factors such as age, life expectancy, and willingness (if oestrogen receptor–positive) to take antioestrogen therapy should be taken into consideration in this patient-doctor shared decision,” stated lead author Beryl McCormick, MD, of the Memorial Sloan Kettering Cancer Center.

Source: NRG Oncology

Mastectomies Significantly Impact Quality of Life in Young Women

Photo by Victoria Strukovskaya on Unsplash

Many young women with breast cancer choose mastectomies but afterwards experience a persistent decline in their sexual and psychosocial well-being, according to new research reported in JAMA Surgery.

In surveys conducted after patients underwent breast cancer surgery, significant quality of life (QoL) impacts were seen with mastectomies, with a greater extent of surgery worsening the QoL outcomes. The findings are important in light of recent trends towards younger women with breast cancer opting for bilateral mastectomies for unilateral breast cancer when breast conserving surgery was also an option.

“Historically, it was felt that 75 percent of breast cancer patients should be eligible for breast conserving surgery. Over time, however, more women, particularly young women, are electing to have a mastectomy,” said study lead author Laura Dominici, MD, a surgeon at Dana-Farber Brigham Cancer Center. “They frequently offer peace of mind as the reason for their decision – even though research shows that unless a woman has a genetic predisposition to breast cancer, she has a very low risk of developing cancer in the healthy breast.”

In this study, 560 participants, 40 and younger with breast cancer, filled in a patient reported outcomes survey known as BREAST-Q, an average 5.8 years after diagnosis.

Compared to those who had breast-sparing surgery, patients who had a mastectomy scored significantly lower in three QoL measures – satisfaction with the appearance of their breasts, psychosocial well-being, and sexual well-being. The results were consistent regardless of whether one or both breasts were removed, and that most had breast reconstruction surgery.

  • For breast satisfaction, patients who had breast-conserving surgery had an average BREAST-Q score of 65.5, compared with 54.6 in the bilateral mastectomy group.
  • For psychosocial well-being,  patients who had breast-conserving surgery had an average BREAST-Q score of 75.9, compared with 65.1 in the bilateral mastectomy group.
  • For sexual well-being, patients who had breast-conserving surgery had an average BREAST-Q score of 57.4, compared with 53.4 for the unilateral mastectomy group and 46.2 for the bilateral mastectomy group.

A fourth area examined by the survey, physical function, showed no difference between the groups. Women with financial challenges tended to have lower scores in all four categories.

“The decision of whether to have a mastectomy or breast-conserving surgery should be a shared decision between patients and their doctors,” Dr Dominici added. “Particularly when talking to young women, who are likely to have a long period of survivorship, it’s important that we as clinicians discuss the potential impacts of mastectomy on their quality of life. As our study indicates, those impacts are not insignificant and persist years into the future.”

The study’s main limitation is that it was not randomised, and quality of life was only evaluated at a single time point. Dr Dominici added there was no information about women’s quality of life prior to the study, which could have infuenced their decision making and their quality of life after surgery.

Source: Dana-Farber Cancer Institute

Common Chemical in Medical Products Linked to Breast Cancer

Photo by Bill Oxford on Unsplash

Researchers in Japan have found that widely used chemicals called photoinitiators cause breast tumours to accelerate in mice. 

Photoinitiators, which release reactive molecules in response to UV radiation,  are used in a wide range of products, including plastics, paints, inks, and adhesives. Photoinitiators are present in common objects as well as in medical products and instruments such as dental fillers and containers.

Recent studies have demonstrated several health hazards associated with photoinitiators, raising safety concerns. In particular, the presence of these compounds in clinical instruments, routinely used for treating high-risk individuals such as cancer patients, has become a major cause for concern. Previous research has shown that three photoinitiators commonly found in plastics and paints 1-HCHPK, MBB, and MTMP show oestrogen-like effects on cultured breast cancer cells, increasing their proliferation. Found in marketed injection solutions, the clear link between oestrogen activity and breast cancer made determining their effect a priority.

In a study published in Current Research in Toxicology, lead researcher Dr Yoichi Kawasaki and Prof Toshiaki Sendo from Okayama University examined how exposure to 1-HCHPK, MBB, and MTMP affected the growth of transplanted breast cancer tumours in mice. They found that all three compounds caused a faster increase in the growth of breast tumors, within 13 weeks of treatment. “This study extends our previous findings and shows that in addition to promoting the proliferation of breast cancer cells in culture, these photoinitiators also increase the growth of breast tumours in live animals. This implies that they could also potentially hasten disease progression in breast cancer patients,” explained Dr Kawasaki.    

The study results show that 1-HCHPK, MBB, and MTMP have oestrogen-like activity and could thus act as hormonal disruptions. Given oestrogen’s role in regulating reproductive function in both men and women, such disruptions could affect not only patients with breast cancer, but also healthy individuals. While the researchers intend to explore the effects of photoinitiators on reproduction in future research, the present study informs breast cancer management, as well as making urgent call-to-action to eliminate toxic materials from medical equipment.

“Photoinitiators have helped us improve the quality of several commonly used products. But it is time we reconsider whether their benefits outweigh their risks, and our findings are an important milestone in encouraging this conversation. We hope that it will prompt more intensive research and stricter regulations on what materials can be adopted for commonly used products, especially those with medical applications,” said Dr Kawasaki.

Source: EurekAlert!

Humans Still Beat AI in Breast Cancer Screening

Source: National Cancer Institute

A review in The BMJ finds that humans still seem to beat AI when it comes to the accuracy of spotting possible cases of breast cancer during screening.

At this point, there is a lack of good quality evidence to support a policy of replacing human radiologists with artificial intelligence (AI) technology when screening for breast cancer, the researchers concluded.

A leading cause of death for among women the world over, mammography screening is a high volume, repetitive task for radiologists, and some cancers are not picked up.

Previous research has suggested that AI systems outperform humans and might soon be used instead of experienced radiologists. However, a recent review of 23 studies highlighted evidence gaps and concerns about the methods used.

To address this uncertainty, researchers reviewed 12 studies carried out since 2010. They found that, overall, the methods used in the studies were of poor quality, with low applicability to European or UK breast cancer screening programmes.

Three large studies involving nearly 80 000 women compared AI systems with the clinical decisions of the original radiologist. Of these, 1878 had screen detected cancer or interval cancer (cancer diagnosed in-between routine screening appointments) within 12 months of screening.

The majority (34 out of 36 or 94%) of AI systems in these three studies were less accurate than a single radiologist, and all were less accurate than the consensus of two or more radiologists, which is the standard practice in Europe.

In contrast, five smaller studies involving 1086 women reported that all of the AI systems evaluated were more accurate than a single radiologist. However, these were at high risk of bias and not replicated in larger studies.

In three studies, AI used as a pre-screen to triage which mammograms need to be examined by a radiologist and which do not screened out 53%, 45%, and 50% of women at low risk but also 10%, 4%, and 0% of cancers detected by radiologists.

The authors point to some study limitations such as excluding non-English studies, as well as the fast pace of AI development. Nevertheless, stringent study inclusion criteria along with rigorous and systematic evaluation of study quality suggests their conclusions are robust.

As such, the authors said: “Current evidence on the use of AI systems in breast cancer screening is a long way from having the quality and quantity required for its implementation into clinical practice.”

They added: “Well designed comparative test accuracy studies, randomized controlled trials, and cohort studies in large screening populations are needed which evaluate commercially available AI systems in combination with radiologists in clinical practice.”

Source: Medical Xpress

Fewer Side Effects in New Breast Cancer Therapy

Breast cancer cells. Image source: National Cancer Institute on Unsplash

Researchers have shown that a new treatment for breast cancer using an antibody linked to a cytotoxic drug is as effective as the previous combination, but with less side effects. The study was published in JAMA Oncology.

The development of treatment with antibodies directed towards HER2 positive breast cancer trastuzumab and pertuzumab, has proven the possibility of improved treatment and cure of this cancer type if these antibodies are combined with chemotherapy, often taxaner. Preoperative (neoadjuvant) treatment with this combination confers complete response in a high proportion of cases. Trastuzumab emtansine (T-DM1) consists of trastuzumab (T) and the cytotoxic substance emtansine (DM1) which clinical trials have shown have good efficacy and low toxicity.

The randomised phase II study PREDIX HER2 was conducted at 9 Swedish clinics to investigate the effect (the proportion of complete response after neoadjuvant treatment) of this treatment in relation to frequency and degree of side effects. The standard treatment was a combination of docetaxel, trastuzumab and pertuzumab which was compared with T-DM1 as experimental treatment, and patients received 6 treatments every 3rd week. The treatment effect was monitored with mammography and PET-CT with 18- fluorodeoxyglucose (18F-FDG). Tissue and blood samples were regularly taken from the patients for later analysis.

The study showed that the effect measured as pathologic complete response was similar in both treatment groups. With T-DM1 treatment, the frequency and degree of side effects was significantly lower and quality of life was higher during treatment. After a median follow up time of 40,4 months no difference was observed between the treatment groups.

In conclusion, the study showed that both treatments were equally efficient, but with fewer side effects in patients treated with T-DM1. A phase III study will allow definitive conclusions to be drawn regarding the efficiency. Meanwhile, the collected samples are being analysed to investigate factors which can explain the response in individuals.

Source: Karolinska Institute

Olaparib Excels in Breast Cancer Trial

A clinical trial of olaparib has been shown to help keep certain early-stage, hard-to-treat breast cancers at bay after initial treatment in promising early findings.

The results were so promising they were published early, ahead of the American Society of Clinical Oncology’s annual meeting and published in the New England Journal of Medicine

Olaparib, sold under the name Lynparza, was found to help breast cancer patients with harmful mutations have a longer disease-free survival after their cancers had been treated with standard surgery and chemotherapy.

It was studied in patients with BRCA1 and BRCA2 gene mutations, which can not only predispose people to breast cancer if they don’t work properly, but who did not have a gene flaw that can be targeted by the drug Herceptin.

Most patients in the study also had tumours not fuelled by oestrogen or progesterone. Triple negative breast cancers are not fuelled by these two hormones nor by the gene Herceptin targets.

The new study tested Lynparza in 1836 women and men with early-stage disease who were given the drug or placebo pills for one year after surgery and chemotherapy. About 82% of participants had triple-negative breast cancer.

Independent monitors advised releasing the results after observing clear benefit from Lynparza. After three years, 86% of patients on it were alive without cancer recurrence compared to 77% in the placebo group.

The results suggest more patients should get their tumours tested for BRCA mutations to help guide treatment decisions, said ASCO president Dr Lori Pierce, a cancer radiation specialist at the University of Michigan.

Serious side effects were rare, and other less serious side effects included anaemia, fatigue and blood cell count abnormalities.

Lynparza, which is marketed by AstraZeneca and Merck, is already sold in the United States and elsewhere for treating metastatic breast cancers and for treating certain cancers of the ovaries, prostate and pancreas. It costs roughly US$14 000 per month, though what patients pay out of pocket varies depending on income, insurance and other factors.

Source: Medical Xpress

Diet Affects both Breast Microbiome and Breast Cancer Tumours

Breast cancer cells. Image source: National Cancer Institute on Unsplash

The breast has its own microbiome of bacteria, and new research has shown it can be influenced by diet, as can breast cancer tumours.

In 2018, scientists at Wake Forest School of Medicine, part of Wake Forest Baptist Health, showed that diet, just like the gut microbiome, can influence the breast microbiome.

Now, new research shows that diet, including fish oil supplements, can alter not only the breast microbiome, but also breast cancer tumours. The findings were published online in Cancer Research.

To untangle the relationship between microbiome, diet and cancer risk, researchers undertook a multi-pronged approach to study both animal models and breast cancer patients.

“Obesity, typically associated with a high-fat diet consumption, is a well-known risk factor in postmenopausal breast cancer,” said Katherine L. Cook, PhD, assistant professor in the surgery – hypertension and cancer biology departments at Wake Forest School of Medicine. “But there’s still a lot we don’t know about the obesity link to microbiomes and the impact on breast cancer and patient outcomes.”

In the first part of the study, mice susceptible to breast cancer were fed either a high-fat or a low-fat diet. Mice consuming the high-fat diet had more tumours, which were also larger and more aggressive than the tumours in the low-fat diet group.

Next, to study the microbiome, researchers performed faecal transplants. Mice consuming the low-fat diet received the high-fat diet microbiome transplant, and mice consuming the high-fat diet received the low-fat diet microbiome transplant. Unexpectedly, mice that consumed the low-fat diet and received a high-fat diet microbiome had just as many breast tumours as mice on the high-fat diet.

“Simply replacing the low-fat diet gut microbiome to the microbiome of high-fat diet consuming animals was enough to increase breast cancer risk in our models,” Cook said. “These results highlight the link between the microbiome and breast health.”

Researchers also conducted a double-blind placebo-controlled clinical trial with breast cancer patients, with patients either receiving placebo or fish oil supplements for two to four weeks before lumpectomy or mastectomy.

Results showed that fish oil supplementation significantly modified the breast microbiome in both non-cancerous and malignant breast tissue. For example, scientists found longer-term administration of fish oil supplements (four weeks) increased the proportional abundance of Lactobacillus in the breast tissue near the tumour. Lactobacillus is a genus of bacteria shown to decrease breast cancer tumour growth, suggesting potential anti-cancer properties of this intervention. Researchers also found decreased proportional abundance of Bacteroidales and Ruminococcus microbes in the breast tumours of patients taking the supplements, though the significance of this is not understood.

“This study provides additional evidence that diet plays a critical role in shaping the gut and breast microbiomes,” concluded Dr Cook. “Ultimately, our study highlights that potential dietary interventions might reduce breast cancer risk.”

Dr Cook’s team is also conducting further studies to see if probiotic supplements can affect microbiome populations in mammary glands and in breast tumours.

Source: Wake Forest Baptist Medical Center

Electromagnetic Fields Could Inhibit Breast Cancer Cell Spread

A new study has shown that electrical fields can slow, and in some cases halt, the spread of breast cancer cells through the body.

The research also found how electromagnetic fields (EMFs) have the ability to hinder the number of cancer cells that can spread. Pulsed EMFs have also been shown to have some effectiveness in pain management, and low level EMFs were shown also to reduce blood glucose in animal models, a possible first step to treating diabetes.

“We think we can hinder metastasis by applying these fields, but we also think it may be possible to even destroy tumours using this approach,” said senior author Vish Subramaniam, former professor of mechanical and aerospace engineering at The Ohio State University. Subramaniam retired from Ohio State in December.

“That is unclear at this stage, but we are working on understanding that – how big should the electromagnetic field be, how close should it be to the tumour? Those are the next questions we hope to answer,” he said.
Subramaniam said that this had the effect of the EMF is to slow down some of the cancer cells. “It makes some of them stop for a little while before they start to move, slowly, again. As a group, they appear to have split up. So how quickly the whole group is moving and for how long they are moving becomes affected.”

The effect was applied to human cancer cells in vitro and has not been applied in humans.

The EMFs seem to selectively slow down the cancer cells’ metabolism by affecting the electrical fields inside the individual cells—completely noninvasively and without side effects like ionising radiation, which would mean a revolutionary form of cancer treatment if it could be made to work in practice. This ability to access a cell’s internal workings is new to the study of how cancer metastasises, said Prof  Subramaniam.

“Now that we know this, we can start to answer other questions, too,” Subramaniam said. “How do we affect the metabolism to the point that we not only make it not move but we choke it, we completely starve it. Or can we slow it down to the point where it will always remain weak?”

Source: News-Medical.Net

Journal information: Jones, T.H., et al. (2021) Directional Migration of Breast Cancer Cells Hindered by Induced Electric Fields May Be Due to Accompanying Alteration of Metabolic Activity. Bioelectricity. doi.org/10.1089/bioe.2020.0048.