Showing posts with label triple-negative breast cancer. Show all posts
Showing posts with label triple-negative breast cancer. Show all posts

Monday, June 4, 2018

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.

Tuesday, June 27, 2017

Studies Show Obamacare Improves Breast Cancer Prognosis, Cutting Medicaid Puts Women at Risk

Two separate analyses demonstrate that women with access to mammograms 
and other breast cancer screenings are diagnosed at earlier, more treatable, 
and less costly stages.

More women were diagnosed with early stage breast cancer after the Affordable Care Act took effect, according to a study published this month in the journal Cancer Epidemiology.  Equally important, there was a decrease in later stage, and more serious, cancers.

Late-stage breast cancer is more costly to treat and is more likely to be fatal than early-stage cancer.

Increases in early diagnoses were higher among African American and Latina breast cancer patients. 
In the past, the cost of mammograms has prevented many Latinas and African Americans to receive mammograms overall or at recommended intervals.

The Affordable Care Act eliminated copayments and other out-of-pocket costs for 45 preventive care services, including mammograms, making them more affordable and leading to the potential for earlier diagnoses, researchers say. Diagnosing breast cancer when it is still in Stage 1 could improve the prognosis for thousands of women and reduce the need for expensive and invasive treatments such as chemotherapy, wrote lead author Abigail Silva, PhD, MPH, of Loyola University Chicago Stritch School of Medicine.
 

The study included 470,465 breast cancer patients between the ages of 50 and 74 who were covered by private insurance or Medicare and were newly diagnosed with breast cancer. Researchers examined two time periods: 2007-2009 (before the Affordable Care Act took effect) and 2011-2013 (after the act took effect). They used data from the National Cancer Database, which includes approximately 70 percent of all newly diagnosed cancers in the United States from about 1,500 hospitals.
 

Overall, the number of breast cancers that were diagnosed at Stage 1 increased 3.6 percent, from 54.4 to 58.0 percent. There was a corresponding decrease in Stage 2 and Stage 3 diagnoses, while the proportion of Stage 4 cancers did not change.

The diagnosis of Stage 1 breast cancer increased by 3.2 percentage points among whites, 4.0 percentage points among African Americans and 4.1 percentage points among Latinas. 


Historically, more white women are diagnosed with Stage 1 breast cancer, while African Americans and Latinas are diagnosed at a higher stage. This disparity decreased following the Affordable Care Act, as minorities saw improvements in Stage 1 diagnoses.
 

This is especially significant for triple-negative breast cancer, which has been shown to be more prevalent and aggressive among African Americans.

Cutting Medicaid Puts Women At Risk
Tennessee women with breast cancer were more likely to be diagnosed at later, more dangerous, stages after a substantial rollback of Medicaid coverage for adults in the state, with the biggest effects being among women in low-income areas, according to an analysis published in the journal Cancer.

Researchers analyzed Tennessee Cancer Registry data from 2002 to 2008 and compared women 
diagnosed with breast cancer who lived in low-income zip codes with a similar group of women who 
lived in high-income zip codes, before and after Tennessee’s Medicaid restrictions. They found that 
women were not only diagnosed at later stages but also experienced more delays in treatment after 
the restrictions were imposed. Low-income women had a 3.3 percent increase in late-stage diagnosis 
compared to those with higher incomes.

Tennessee restricted Medicaid enrollment in 2005

The findings suggest that women did not get screenings or other essential primary care that may 
have led to an earlier diagnosis, according to team leader Wafa Tarazi, PhD, of Virginia 
Commonwealth University. The reason: lack of affordable care.


“Medicaid rollbacks may contribute to widening disparities in health outcomes between low-income women and their wealthier counterparts,” said team leaders Lindsay Sabik, PhD, of the University of Pittsburgh, another team leader.

Tuesday, November 25, 2014

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.

Monday, November 3, 2014

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

Wednesday, September 24, 2014

To Joan Lunden: Most Women Beat TNBC

Joan Lunden is being treated for triple-negative breast cancer, according to People magazine.  It's the same type of cancer Robin Roberts has battled.  And, of course, me and many of those who read this blog.

She has started chemotherapy and has agreed to go public with her treatments, which I hope takes some fear out of the disease for others facing it.   I send her virtual hugs, but more important, I send hope. Even though this disease can be aggressive, it is not necessarily so, and the great majority of women with non-metastatic TNBC beat it.  

Go, Joan. 

  

Saturday, May 24, 2014

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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Thursday, March 20, 2014

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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Saturday, February 22, 2014

Osteoporosis Drug Evista May Treat TNBC

The osteoporosis drug raloxifene, primarily prescribed for post-menopausal women, may also be able to treat triple-negative breast cancer,  according to research published in Cell Death and Disease.
In lab tests, researchers found that the drug, marketed under the brand name Evista, killed human TNBC cells as well as liver .   Raloxifene binds with a protein called the aryl hydrocarbon receptor (AhR) and kills cancer cells that do not have receptors for estrogen.  Included in the study was an analysis of data on women who had estrogen-negative breast cancers, in which researchers found increased survival rates in the women whose breast cancers had higher levels of the AhR protein.
Raloxifene would have to go through clinical trials, showing its effects on women rather than just on cells in the lab, before it can become an approved therapy, but, under the Affordable Care Act, most health insurance plans are now required to offer raloxifene at no cost to women who have an increased risk of developing breast cancer.
Raloxifene belongs to a class of drugs called  selective estrogen receptor modulators (SERMs). Research presented at the San Antonio Breast Cancer Symposium in December 2013 demonstrated that a different class of osteoporosis drugs, bisphosphonates, can reduce the risk of breast cancer recurrence in all types of breast cancer. 





Monday, February 10, 2014

High BMI Linked to TNBC

Significant increases in body mass index are associated with an increased risk of triple-negative breast cancer, according to research published in the journal Cancer, produced by the American Cancer Society.  In the study, women who went up ten points or more—from, for example, a BMI of 22 to one of 32—between the ages of 18 and 44 doubled their risk of TNBC.   There was no increased risk of estrogen-positive breast cancer.

The sampling included women ages 20 to 44 years who were diagnosed from 2004 to 2010 in the Seattle-Puget Sound metropolitan area:
• 779 with estrogen receptor-positive breast cancer
•182 triple-negative breast cancer
• 60 with ER-negative/HER2-overexpressing, invasive breast cancer
• 939 cancer-free controls.  

This supports a fairly large body of research that has associated weight gain with TNBC risk.


Read more about BMI and TNBC, plus a roadmap for a healthy lifestyle, in my book, Surviving Triple-Negative Breast Cancer.
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Monday, January 6, 2014

Top Triple-Negative Breast Cancer Research: 2013

Last year was a lively one for research on triple-negative breast cancer.  Below is my list of the year's top studies—all pointing toward understanding what makes TNBC tick, which will ultimately lead to treatment and a reduction in the risk of recurrence.  Remember, though, that the road from research to clinical practice can be long and rocky, so most of these treatments  won't be immediately available.  Still, this list points to a rich reservoir of inquiry and information—which is good news for those of us on the TNBC Road and for those who follow us.


Bisphosphonates such as Zometa and Reclast reduced the risk of bone metastases following breast cancer in post-menopausal women by 34 percent in research presented at the 2013 San Antonio Breast Cancer Symposium. And they reduced the risk of death in that same group by 17 percent, regardless of receptor status, node involvement or previous chemotherapy.   More.

Genetic Details of Triple-Negative Breast Cancer
Beyond its most basic definition—negative for receptors for estrogen, progesterone and Her2/neu—triple-negative breast cancer has unique genetic characteristics.  Research published in the journal Cancer Research has outlined some of TNBC’s genetic associations.   Once they know what it is rather than what it isn't, they can target it.  Put a big red bull’s eye on its nasty old back.  More.

New Drug Regimens Can Lead to Improved Outcomes for Women with Stages II and III TNBC Adding the chemotherapy drug carboplatin to standard treatment improved outcomes for women with triple-negative breast cancer in two studies presented at the 2013 San Antonio Breast Cancer Symposium.  Both measured pathological complete response (pCR), which is recognized as a positive marker for overall survival.  The second study also showed improved outcomes using bevacizumab (Avastin). More.

Tumor-infiltrating lymphocytes may become an additional factor in determining which types of triple-negative breast cancer respond best to chemotherapy.  Seventy-five percent of tumors with the highest levels of lymphocytes—researchers call this lymphocyte predominate breast cancer (LPBC)—had a pathological complete response to doxorubicin and taxane plus carboplatin when compared to non-LPBC tumors. The results came from the GeparSixto trial (GBG 66) in Germany.  More.

High Fat Diet in Puberty Linked to Basal-Like Breast Cancer
Young women who eat excess amounts of saturated fats during their teenage years increase their risk of basal-like breast cancer, according to a study published in Breast Cancer Research. Many basal-like tumors are also triple-negative. More

Metformin: New Agent Against TNBC?
The diabetes drug Metformin can effectively reduce breast cancer risk that is associated with insulin resistance and was directly correlated with Ki67 status, according to research in the British Journal of Cancer.  TNBC has shown links to insulin resistance in previous studies, and many TNBC tumors are positive for Ki67, so this could be additional support for considering metformin as a treatment for TNBC.  More.

Restorative Yoga Can Help Trim Fat
Yoga’s health benefits may go beyond stress reduction – a study funded by the National Institutes of Health (NIH) found that for overweight women, restorative yoga may offer a way to actually trim subcutaneous fat.  Obesity is a risk factor for breast cancer, including TNBC. The benefits of restorative yoga – a form of the practice that emphasizes relaxation over flowing movements or challenging balance poses – compared favorably with simple stretching when tested among a group of women who were clinically obese.  More.

New Imaging Technique Can Determine Cancer Subtype and Response to Treatment
An optical imaging technique that measures metabolic activity in cancer cells can accurately differentiate breast cancer subtypes, and it can detect responses to treatment as early as two days after therapy administration, according to a study published in Cancer Research, a journal of the American Association for Cancer Research.  More.

Existing Drugs Kill TNBC Drugs By Targeting Their Own Waste
Triple-negative breast cancers may be vulnerable to drugs that attack the proteasome, a cellular structure that acts as the cell's waste disposal, breaking down damaged or unneeded proteins, according to a new paper in Cancer Cell.  In lab tests, researchers selectively "turned off" genes in triple-negative tumor cells. When turned off, the cells die. These data suggest that triple-negative breast cancers may respond to treatment with drugs similar to bortezomib (Velcade), which is used in multiple myeloma.  More.

Protein May Be Path to Targeted TNBC Treatment
A protein called Numb (seriously) may  promote the death of cancer cells by binding to and stabilizing the tumor suppressor protein p53, which is implicated in many cases of triple-negative breast cancer, according to research published in the May 23rd issue of Molecular Cell.   When Numb is reduced by the Set8 enzyme , it will no longer protect p53.  More.

HMGA1 Turns TNBC Cells Back to More Normal and Slows Their Growth
Researchers at Johns Hopkins have identified a gene that, when repressed in tumor cells, puts a halt to cell growth and a range of processes needed for tumors to enlarge and spread to distant sites. The researchers hope that this so-called “master regulator” gene may be the key to developing a new treatment for tumors resistant to current drugs.  More.

Diamonds May Be A TNBC Girl's Best Friend
UCLA researchers  have developed a potential new treatment for triple-negative breast cancer that uses nanoscale, diamond-like particles called nanodiamonds.  Nanodiamonds are between 4 and 6 nanometers in diameter and are shaped like tiny soccer balls. Byproducts of conventional mining and refining operations, the particles can form clusters following drug binding and have the ability to precisely deliver cancer drugs to tumors, significantly improving the drugs' desired effect. In the UCLA study, the nanodiamond delivery system has been able to home in on tumor masses in mice with TNBC.  More.

Omega 3 Fatty Acids in Fish Oil May Slow Triple-Negative
Researchers from Fox Chase Cancer Center have found that omega-3 fatty acids and their metabolite products slow or stop the proliferation, or growth in the number of cells, of triple-negative breast cancer cells more effectively than cells from luminal types of the disease. The omega-3s worked against all types of cancerous cells, but the effect was observed to be stronger in triple-negative cell lines, reducing proliferation by as much as 90 percent. More.

SOX11 and p53 May Spell Unique Development of Triple-Negative Breast Cancer
Could you create a breast cancer tumor in mature mice by reactivating how embryonic breast cancer cells develop?  And, if you could, what would you learn?  In a study published in the journal Breast Cancer Research, scientists discovered that basal-like  breast cancers with the BRCA1 mutation—many of them triple-negative breast cancers—grow differently than other cancers.  In fact, the way they grow predicts the prognosis of the tumor. More.

Could Copper Depletion Be a Cure for Metastatic TNBC?
An anti-copper drug compound that disables the ability of bone marrow cells from setting up a "home" in organs to receive and nurture migrating cancer tumor cells has shown surprising benefit for metastatic triple-negative breast cancer. Results of a phase II clinical trial conducted by researchers at Weill Cornell Medical College and reported in the Annals of Oncology shows that patients who are copper depleted show a significantly reduced risk of relapse.  In fact, only two of 11 study participants with a history of advanced triple-negative breast cancer relapsed within 10 months after using the anti-copper drug, tetrathiomolybdate (TM). More.

Scientists Map TNBC's Metastatic Path
Cancer Scientists at Weill Cornell Medical College have discovered the molecular switch that allows triple negative breast cancer cells to grow the amoeba-like protrusions they need to crawl away from a primary tumor and metastasize throughout the body. Their findings, published in Cancer Cell, suggest a novel approach for developing agents to treat cancer once it has spread. More.

Protease May Help Define New Subset of TNBC—and Lead to Treatment.
Researchers at St, Louis University have  found a molecular signature that may define a particular subset of triple-negative breast cancer,  which can ultimate lead to target therapy for that group of patients.  In specific, they have uncovered a pathway responsible for the loss of 53BP1 in TNBC tumors related to the  BRCA1 mutation. Loss of BRCA1, they discovered, increases the expression of the protease cathepsin L (CTSL), which causes the degradation of 53BP1. Cells that have lost both BRCA1 and 53BP1 have the ability to repair DNA and proliferate. That means the protease helps cancer cells with faulty BRCA1 survive—it is a defined bad guy in TNBC growth.  And, when we know who the bad guy is, we can stop looking at ways to stop him in his mean old tracks. More


Read more about TNBC in my book, Surviving Triple-Negative Breast Cancer.

Please consider a donation to Positives About Negative to keep this site going.  This work is entirely supported by readers.  Just click on the Donate button in the right of the page.  Thank you!