TNBC patients with high T-cell signatures may have higher survival rates

Here’s one way triple-negative cancer works, according to researchers at the University of Michigan Rogel Cancer Center:

Tumor cells reprogram metabolic pathways to gain control over a type of immune cell that allows cancer growth.

Here’s the technical explanation: Myeloid-derived suppressor cells that live in and around a cancerous tumor encourage a stem cell-like growth that’s linked to TNBC. The more of these suppressor cells a patient has, the worse the outcome. This means the patient’s immune system isn’t strong enough to fight against the tumor.

And when there are a large number of myeloid-derived suppressor cells, immunotherapy treatments tend to be ineffective because the immune T-cells that immunotherapy targets are suppressed.

By looking at triple-negative breast cancer cells, researchers found that the metabolic process by which cells break down glucose also regulates the expression of a specific isoform that in turn causes more suppressor cells to develop. The immune system can’t mount enough of an assault on the tumor cells, which translates to poor outcomes in some TNBC patients. 

“We hope that by understanding the biology better, it may lead to new ways to help these patients,” says Weiping Zou, M.D., Ph.D., the Charles B. de Nancrede Professor of Surgery, Pathology, Immunology and Biology at the University of Michigan.

Looking at samples from 250 triple-negative breast cancer patients, researchers found that when the metabolic pathway for glycolysis was enriched, so were the immune suppressor cells — and this linked with worse overall survival. In contrast, tumors with a high T-cell signature exhibited fewer of these suppressor cells and the patients had better outcomes.

The study is published in Cell Metabolism.

TNBC Tied To Type 2 Diabetes in African-American Women

African-American women with type 2 diabetes had a higher risk of developing estrogen receptor (ER)-negative breast cancer, which includes TNBC, in research published in Cancer Research, a journal of the American Association for Cancer Research.  

Here’s what’s really interesting: The association was observed only among women with BMIs under 30, which could mean that abnormal metabolic status may play a larger role in ER-negative breast cancer than obesity.

The results showed an increased risk of ER-negative breast cancer primarily in black women who had type 2 diabetes for at least five years. Researchers found no association with ER-positive breast cancer in the same group.

African-American women who get breast cancer are more likely to get TNBC than white women, with double the incidence as compared to white women, according to the paper’s author, Julie R. Palmer, ScD, associate director of Boston University’s Slone Epidemiology Center. And type 2 diabetes is also twice as prevalent in African-American women.

“We are still trying to understand the basic biological processes that lead to ER-negative breast cancer. One way to do this is to study factors that are more common in an African-American population,” she said. Several studies suggest that diabetes is a risk factor for breast cancer and insulin resistance is a factor in TNBC.

The study was based on information provided by participants in the Black Women’s Health Study (BWHS, which uses twice-yearly questionnaires from 59,000 African- American women from across the United States.

 “Our findings may account for some of the racial disparity in breast cancer, and could partly explain why mortality from breast cancer is so much higher in black women than white women,” Palmer said. “Women could reduce their chances of getting ER-negative breast cancer if they could avoid developing type 2 diabetes. Monitoring of blood sugar levels to identify pre-diabetes may allow for early interventions to prevent diabetes.”

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Genetics Lead the Way to Targeted TNBC Treatment: 17q25.3

The q25.3 region of chromosome 17 may be another genetic marker that defines subtypes of triple-negative breast cancer and, therefore, could lead to the golden grail: targeted treatment, especially for those forms of TNBC linked to the BRCA1 mutation.  In research published in the journal Breast Cancer Research, 17q25.3 was detected in 86 percent of the mutated TNBC tumors.

This is significant because, as the researchers note, the BRCA1 mutation is closely linked to TNBC, with  as many as  90 percent of tumors with the mutation being triple negative.  This does not mean, however, that all TNBC tumors have the BRCA1 mutation.  In fact, only 10 to 20 percent of all TNBC tumors have the BRCA1 mutation.  I explain this link in my book on TNBC.

Identifying patients with the BRCA1 mutation will ultimately help select patients who could benefit from  selective treatments 17q25.3.   First, though, we need those treatments.  Baby steps, friends.  But at least they are steps.

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For more details on triple-negative breast cancer, check out my book, Surviving Triple-Negative Breast Cancer.

Protein Successfully Stops TNBC in Mice

A team at the University of Kansas School of Medicine has identified a potential target for treating triple-negative breast cancer: atypical protein kinase C signaling. In a recent paper, published in the journal Cell Death and Differentiation, Soumen Paul, Ph.D and his colleagues conclude that this finding holds "tremendous" promise for treating breast cancer.

The researchers analyzed tissue samples of breast cancer that had spread to the liver, lung and other organs and found that atypical protein kinase c lambda/iota, which is known to influence cell growth, was highly expressed and phosphorylated in metastatic breast cancers.

In tests conducted on mice, the researchers depleted the protein in a line of triple-negative breast cancer and found that this significantly slowed the breast tumor growth.

Previous studies have implicated the atypical protein kinase c lambda/iota in the other cancers, they say, but no prior study had indicated any role in breast cancer metastasis. 

"We have been able to show that this protein is highly expressed in metastatic triple-negative breast cancer, and when we are depleting it from triple-negative breast cancer cells, we found that the cancer cells are not metastasizing," Dr. Paul said. "The tumor growth is slowing down. This is giving us an opportunity for a targeted therapy."

The next step would be to begin clinical trials on humans, but that could be years away.

Source: The University of Kansas

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Today's treat: healthy watermelon juice

Watermelons may be, duh, mostly water, but they are also high in dietary fiber, thiamin and folate.  Fiber and folate are both especially good cancer-fighters.   And when you juice it with the rind, you add the antioxidant citrulline plus vitamin C and B-6 to strengthen your immune system.

You’ll need a juicer if you include the rind—make sure you wash it thoroughly.  Organic is best.   If you don't have a juicer, cut the rind off and use a blender, then try some other uses of the leftover rind.  Livestrong has several great suggestions.

One cup of watermelon juice has only 71 calories, but it has 15 grams of sugar, so don’t go over a cup a day.

Also, you can easily freeze this summer's watermelons for use later in the year.  Just cube, put in a freezer bag, squeeze out the excess air, and freeze.  You'll want to use them right out of the freezer, though, as they turn to mush pretty fast.

For more information on a cancer-fighting diet, check out my book, Surviving Triple-Negative Breast Cancer.  You can get a free signed copy just by donating $25 to this site.  Click the Donate button on the right to donate through PayPal.   You'll then get an email from me asking how you want your book signed and where you want it sent.  Thanks!  And hugs.

Cantaloupe Juice: Healthy and Delicious

Today's treat: cantaloupe juice.   High in anti-oxidants and anti-inflammatory nutrients, especially vitamins A and C and potassium.   We juice it rind and all, but cut out the seeds.  Some folks suggest juicing the seeds and adding pineapple juice for a nut drink and I might try that next time.

The anti-inflammatory issue is especially important, given recent research that shows that anti-inflammatory drugs could treat triple-negative breast cancer.

You'll need a good juicer and nicely ripe fruit.  Clean the rind well—we soak it in vegetable wash and then scrub it with a brush.   I'd go organic here because I never feel I get all the dirt off the rind.

Drink a small glass a day—the serving I show here is about half a cup, which is about 1/8th of a cantaloupe.  All juices are high in sugar,  so don't overdo.

Enjoy.

For more information on a cancer-fighting diet, check out my book, Surviving Triple-Negative Breast Cancer.  You can get a free signed copy just by donating $25 to this site.  Click the Donate button on the right to donate through PayPal.   You'll then get an email from me asking how you want your book signed and where you want it sent.  Thanks!  And hugs.

Study Finds Clues to How TNBC Spreads

Researchers have identified chemical signals that triple-negative breast cancer cells use to recruit two types of normal cells needed for the cancer’s spread. The study, which was done on mice, appears in the online early May edition of the Proceedings of the National Academy of Sciences.

The research focused on a chemical signal called hypoxia-inducible factor 1 (HIF-1), which cells release to help them cope with low-oxygen conditions. Earlier, the group determined that HIF-1 helps breast tumor cells survive the low-oxygen conditions in which they often live, and spread to other parts of the body such as the lungs. "In breast cancer, it's not the original tumor that kills patients, but the metastases," says Gregg Semenza, M.D., Ph.D., a professor and director of the Vascular Biology Program in the Johns Hopkins University School of Medicine's Institute for Cell Engineering.

All of the breast cancer cells used in the study were triple-negative, which have been shown in previous research to contain more HIF-1 than other types of breast cancers.

"This study adds to the evidence that a HIF-1 inhibitor drug could be an effective addition to chemotherapy regimens, especially for triple-negative breast cancers," Semenza says. Several potential drugs of this kind are now in the early stages of development, he notes.

"Blocking one of these cell-recruiting signals in a mouse's tumor made it much less likely to metastasize or spread," Semenza says. "If a drug can be found that safely blocks the same signal in humans, it could be a very useful addition to current treatment—particularly for patients with chemotherapy-resistant tumors."

Also in a previous study, Semenza's group found that HIF-1 induced adult mesenchymal stem cells to release a signal to nearby breast cancer cells, which made them more likely to spread. The researchers suspected this communication might run both ways and that the stem cells' presence might also help the cancer to recruit the host animal's white blood cells. Breast cancers need the support of several types of host cells in order to metastasize, including mesenchymal stem cells and one type of white blood cell, Semenza notes.

Studying tumor cells grown in a dish, Semenza's team used chemicals that blocked the functions of various proteins to map a web of signals between breast cancer cells, menenchymal stem cells and white blood cells. One positive feedback loop brought mesenchymal stem cells close in to the breast cancer cells. A separate loop of signals between the stem cells and cancer cells caused the cancer cells to release a chemical "beacon" that drew in white blood cells.

The concentrations of all the signals in the web were increased by the presence of HIF-1—and ultimately, by low-oxygen conditions.

The team then used genetic engineering to reduce the levels of the cell-recruiting signals in breast cancer cells and implanted those cells into female mice. Compared with unaltered breast cancer cells, those with reduced recruiting power grew into similar-sized tumors, Semenza says, but were much less likely to spread.

From a news release from the Johns Hopkins University School of Medicine.

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Vegetables and Fruits Show Benefits for ER-negative Breast Cancer

Eating fruits and vegetables reduced the risk of estrogen-negative breast cancer, even though it had no effect on other kinds of breast cancer, according to a study that analyzed research from 20 previous studies and published in the Journal of the National Cancer Institute. Vegetables were slightly better than fruits.

Because researchers were looking at studies that had already been done, they could not control the types and amounts of vegetables and fruits that were studied.  Some of the studies, though, have shown that five servings a day are beneficial, with no added benefit for more than that.  This includes broccoli, cabbage and other cruciferous vegetables, plus apples, pears, peaches, nectarines, apricots, strawberries, carrots, and lettuce.

Researchers noted that, because of their "high protein or starch content," mature beans and potatoes were excluded. Pickled fruit and vegetables were also excluded "because they contain potentially carcinogenic nitrates and preservatives."

Data were analyzed on 24, 673 breast cancer survivors; 4821 of these were estrogen-negative.  Because not all studies included Her2 status, researchers did not specifically consider cases of TNBC, although other research shows that results from ER-negative studies often translate to TNBC cases.

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RIP2: A new target for a potential TNBC drug?

The receptor-interacting protein kinase 2 (RIP2),  known to be involved in  inflammatory processes, also has roles in triple-negative breast cancer metastasis, according to a study in the journal Breast Cancer Research.

The research analyzed data from six breast cancer databases, including The Cancer Genome Atlas and determined that RIP2 was significantly overexpressed in TNBC and correlated with worse progression-free survival.

The results suggest that targeting RIP2 may improve outcomes in advanced breast
cancer patients, in which it is over expressed.

It's another target, folks.  And another target might mean a targeted drug.

I do think RIP is an ominous name, but I guess they weren't looking at that.

You can read the entire study here.

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MRI Data Can Spot TNBC Earlier, Speed Treatment

Patterns in magnetic resonance images may predict if a patient has triple-negative breast cancer, slower-moving cancers or non-cancerous lesions with 95 percent accuracy, according to research published online in the journal Radiology.

The technique could enable doctors to use an MRI scan to diagnose more aggressive cancers earlier and fast track these patients for therapy.  

"Literally, what we're trying to do is squeeze out the information we're not able to see just by looking at an image," said senior author Anant Madabhushi, a professor of biomedical engineering at Case School of Engineering and director of the Center for Computational Imaging and Personalized Diagnostics.

Researchers analyzed images from 65 women and discovered that tumors from triple-negative cancer reflect different textures when images are enhanced with contrasting agents.

"Today, if a woman or her doctor finds a lump, she gets a mammogram and then a biopsy for molecular analysis, which can take two weeks or up to a month," Madabhushi said. "If we can predict the cancer is triple-negative, we can fast track the patient for biopsy and treatment. Especially in cases with triple-negative cancer, two to four weeks saved can be crucial."

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