Animal Research Leads to New Breakthroughs in Breast Cancer
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October is Breast Cancer Awareness month, and while the overall death rate from breast cancer has gone down 1% every year from 2013 to 2018, breast cancer is still the most commonly diagnosed cancer among American women and has the second-highest death rates, after lung cancer. In the United States, 13% of women (about 1 in 8) will develop breast cancer at some point in their lives.
Fortunately, several new mouse studies have yielded important new information in breast cancer causes, treatments, and potential cures.
New Drug Shrinks Breast Cancer Tumors
Scientists at the University of Illinois at Urbana-Champaign have developed a new drug, called ErSO, that kills 95-100% of cancer cells in mouse models of breast cancer, including secondary tumors that have metastasized in the bone, brain, liver, and lungs.
The study specifically targeted the most common type of breast cancer—estrogen receptor positive (ER-positive) breast cancer—which accounts for 80% of all breast cancer cases and is incurable if it spreads. In ER-positive breast cancer, the cancer cells have receptors that enable them to use the hormone estrogen to fuel tumor growth.
The new drug works by stimulating a cellular stress response that usually protects cancer cells from harm. When the mechanism is overactivated, it kills the cancer cells while leaving healthy cells untouched. Best of all, even if a few cancer cells survive, they remain sensitive to ErSO treatment rather that becoming resistant, as is the case with current drug treatments such as tamoxifen.
This approach has been tried before, but the drug candidate caused undesirable side effects in mice. ErSO kills cancer cells more quickly that previous drug candidates—often shrinking tumors more than 99% within three days of treatment—and is well-tolerated in mice, rats, and dogs.
Pharmaceutical company Bayer AG has licensed ErSO and will undertake clinical trials to explore its potential for treatment in humans.
A Link Between Antibiotics and Breast Cancer Growth
Antibiotics are often used during chemotherapy treatment for breast cancer because chemotherapy weakens the immune system and makes people more vulnerable to infection. Scientists from two institutions in the U.K.—the University of East Anglia and the Quadram Institute—have uncovered a link between antibiotics and tumor growth that could change that standard practice.
The researchers found that treating mice with antibiotics increased the growth rate of breast cancer tumors in their bodies and caused larger secondary tumors to grow in other organs.
The scientists tested a mixture of five antibiotics as well as the broad-spectrum antibiotic cefalexin and found that the use of antibiotics led to the loss of a beneficial bacterial species in the gut, which caused tumor growth to increase. The effect was similar in mice models for several different types of breast cancer.
When they looked into possible methods of mitigating this effect, researchers found that the breast cancer tumors in the antibiotics-treated mice had a high number of mast cells, which are a type of immune cell. Blocking the mast cells reversed the effects of the antibiotics and slowed down the tumor growth.
The research team hopes the discovery could lead to new guidelines for using antibiotics in people with breast cancer, and a way of counteracting the negative effects of antibiotic use.
A Connection Between a Protein and Tumor Growth
MYO10, also known as Myosin X, is a protein that has been shown to occur at high levels in aggressive skin and breast cancers, and to correlate with lower survival rates.
Now, researchers at Case Comprehensive Cancer Center have discovered that levels of MYO10 could indicate which breast cancers are likely to respond to immune checkpoint inhibitor therapy, also known as immune checkpoint blockade (ICB) therapy.
In studies with mouse models of breast cancer—including the most malignant triple-negative breast cancers—the team found that breast tumors with high levels of MYO10 responded favorably to the use of ICBs, but tumors with low MYO10 had the reverse reaction, actually growing larger after ICB therapy.
The study also showed that high levels of MYO10 caused inflammation in tumors, which made T cells less able to slow tumor growth. When researchers treated the mice with aspirin to reduce inflammation, it significantly reduced the growth high-MYO10 breast tumors, which is consistent with studies showing that long-term use of aspirin significantly reduces tumor risk in several cancers, including esophageal, colorectal, breast, lung, and prostate.
Eating Patterns Can Affect Breast Cancer Risk
A new study by researchers at UC San Diego found that time-restricted feeding reduced the risk of breast cancer and improved insulin levels in mice.
Mouse models of obesity-driven post-menopausal breast cancer that were allowed to eat only within an eight-hour window showed improved overall metabolic health and a reduced risk of breast cancer development, growth, and metastasis.
The researchers tested three groups of mouse models: one with free, 24-7 access to food, one that was allowed to eat only during a nighttime eight-hour period, and one that had an unrestricted low-fat diet. In the eight-hour mice, insulin levels were lowered and tumor growth was reduced.
The finding could offer an easy, inexpensive, drug-free method of preventing breast cancer, especially for women who are overweight and have been through menopause.
Connection Between Gut Microbiome and Breast Cancer
New research by scientists at Wake Forest School of Medicine has shed light on the relationship between the microbiome, diet, and cancer risk, and shows that diet can not only alter the breast microbiome, but also breast cancer tumors.
Numerous studies have demonstrated the link between the gut microbiome and disease, as well as the connection between a poor diet and inflammation-related health problems.
To further explore these connections, researchers fed mouse models of breast cancer either a high-fat or low-fat diet. The high-fat mice developed more tumors, which were also larger and faster-growing, than in the low-fat mice.
The researchers then performed fecal transplants between the groups to study the diets’ effect on the microbiome—mice on the low-fat diet received the high-fat diet microbiome transplant, and mice on the high-fat diet received the low-fat diet microbiome transplant.
The result was a surprise: Mice on the low-fat diet with the high-fat microbiome had about the same amount of breast tumors as the high-fat mice, which signals the importance of the microbiome in breast cancer risk.
The researchers are conducting additional studies on whether probiotic supplements or other dietary interventions can reduce breast cancer risk.
High Cholesterol Fuels Breast Cancer Metastasis
High cholesterol levels are known to increase the risk of developing breast cancer, and new research with mice by a team of researchers at Duke University has identified the reason.
When cancer cells try to metastasize, many die due to ferroptosis, a type of programmed cell death related to stress. The cells that survive ferroptosis use cholesterol to develop tolerance to stress, enabling them to spread to other sites in the body.
The Duke team identified this mechanism and found that chronic exposure to the cholesterol metabolite 27-hydroxycholesterol (27HC) supported the growth and encouraged the spread of breast cancer cells. The team also found that survivor cells require the enzyme Glutathione Peroxidase 4PX4 (GPX4).
Reducing 27HC production and inhibiting GPX4, therefore, could weaken breast cancer cells, and may also be effective for other types of tumors, including melanoma.
It’s unclear of these discoveries will lead to therapies for breast cancer patients, but it does emphasize the importance of lowering cholesterol, both for breast cancer risk and general health.
In 2021, more than 330,000 new cases of breast cancer are expected to be diagnosed in women. As scientists continue learning more about how breast cancer works and developing new methods to prevent, treat, and even reverse it, a growing percentage of those cases could have a more positive outcome.