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.

In research conducted on mice, scientists at Michigan State University found that a diet high in saturated animal fat caused excess cell growth that altered the normal structure of the breast and altered immune cells.

And the effects of the high-fat diet were found even if the mice did not gain weight.  That means that the "findings are relevant to a much broader segment of the population than just those who are overweight," according to microbiology professor and co-author researcher Richard Schwartz. "This shows the culprit is the fat itself rather than weight gain."

• 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!

Is Engrailed 1 the key to metastases in basal-like tumors?

Lab research points to an over expression of the protein Engrailed 1 in basal-like tumors, which may be why these tumors are more likely to metastasize.  Scientists have developed a chain of amino acids to fight the protein, which is not present in non-basal tumors.  The treatment will have to be tested through clinical trials.

Researchers at the UNC School of Medicine, working with cell lines in a lab, have discovered why some of the most aggressive and fatal breast cancer cells are resistant to chemotherapy, and UNC scientists are developing ways to overcome such resistance.

"Patients with basal-like breast cancer tend to initially respond well to chemotherapy, but it's common for patients to relapse even more aggressively," said Beltran, the first author of a paper published in the journal Oncogene. "We believe that relapse is caused by a small number of cancer cells that have stem cell properties that allow them to survive chemotherapy. In these cells we've identified the overexpression of Engrailed 1."

Adriana S. Beltran, PhD, a research assistant professor in the department of pharmacology, found that the protein Engrailed 1 is overexpressed in basal-like carcinomas and designed a chain of amino acids to shut down the protein and kill basal-like tumors in the lab.

Beltran and her colleagues – UNC pharmacologist Lee Graves, PhD, and former UNC pharmacologist Pilar Blancafort, PhD – discovered that Engrailed 1 is not involved in the rapid proliferation of cells that cause tumor growth. Nor is Engrailed 1 present in luminal tumors – the most common form of breast cancer. The culprit protein only appears in basal-like breast cancer.

In fact, Engrailed 1 is normally confined to the brain, where it protects neurons from cell death and helps maintain their normal activity. The absence of the protein in the brain has been linked to the onset of Parkinson's disease. But there is no known function of Engrailed 1 within breast tissue.

"We think that Engrailed 1 confers protective features to breast cancer cells, similar to the features observed in long-lived neurons," Beltran said. "This may explain why these cells survive and become resistant to chemotherapy in our experiments."

The researchers found Engrailed 1 through a series of experiments designed to find genes highly expressed in basal-like cells but not in luminal breast cancers. They discovered that Engrailed 1was most highly expressed in cell lines isolated frominflammatory breast cancer. Working with the UNC Michael Hooker Proteomics Center, Beltran and colleagues also determined that Engrailed 1 was associated with the gene EPRS, which expresses an enzyme that controls messenger RNA and protein synthesis, particularly in proteins involved with inflammation.

"Inflammation is associated with cancer development," Beltran said. "It's interesting to us that Engrailed 1, alone, is able to control inflammatory responses that may promote more aggressive forms of cancer.

Why Engrailed 1 is manifested in cancerous breast tissue remains a mystery. "Nature seems to always find a way," Beltran said. "Cancer cells are part of nature; everything in nature strives to survive."

But Beltran and her colleagues might have found a way to stop Engrailed 1. After studying how Engrailed 1 binds to DNA and other proteins, the researchers created a synthetic peptide – a chain of amino acids – that can stifle the binding power of Engrailed 1. In cell lines – not in animals or patients – Beltran and colleagues used their peptide to disrupt Engrailed 1 from binding to its protein partners and DNA.

"Cancer cells need Engrailed 1 to live," Beltran said. "The peptide abolishes all interactions of Engrailed 1, and as a consequence Engrailed 1 cannot perform its functions, causing rapid cell death of the cancer cell.

"The goal now is to validate our findings in animal models."

If Engrailed 1 turns out to be as critical to basal-like metastasis as it seems from this basic research, then a drug could be developed to fight cancer relapse in some of most deadly forms of breast cancer.

From the University of North Carolina Health Care.

• 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!

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.  

This was a phase II study at the European Institute of Oncology (IEO) in Milan, Italy on 100 patients with stage I–IIIa breast cancer who were candidates for elective surgery.

In 2011 laboratory study, Metformin also showed effectiveness against hormone-negative breast cancer.

• Read more about Metformin and 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!

Family history trumps BRCA2 testing

At least 77 genetic variations are linked to breast cancer risk in women from families with the BRCA mutation. Testing negative for BRCA2 still means these women may have four times the risk of breast cancer than the general population.

PHILADELPHIA — Women who are members of families with BRCA2 mutations but who test negative for the family-specific BRCA2 mutations are still at greater risk for developing breast cancer compared with women in the general population, according to a study published in Cancer Epidemiology, Biomarkers & Prevention,a journal of the American Association for Cancer Research.

Women with certain mutations in their BRCA1 or BRCA2 genes are at increased risk for breast cancer. However, if a woman who comes from a BRCA family tests negative for her family-specific BRCA mutation, her risk for breast cancer is considered to be the same as someone in the general population, according to the National Cancer Institute. This study, however, suggests that it may not always be true.

“We found that women who test negative for family-specific BRCA2 mutations have more than four times the risk for developing breast cancer than the general population,” said Gareth R. Evans, M.B.B.S., M.D., M.R.C.P., F.R.C.P., honorary professor of medical genetics and cancer epidemiology at the Manchester Academic Health Science Center at the University of Manchester in the United Kingdom. “We also found that any increased risk for breast cancer is largely limited to BRCA2 families with strong family history and other genetic factors.

“It is likely that these women inherit genetic factors other than BRCA-related genes that increase their breast cancer risk,” he explained. “About 77 single nucleotide polymorphisms [SNPs—genetic variations that can help track the inheritance of disease genes within families] are linked to breast cancer risk. Identification of additional SNPs is necessary to understand why some of the BRCA-negative women from BRCA families are at higher risk.”

The authors note that specialists should use caution when stating that a woman’s breast cancer risk is the same as that of the general population following a negative test, because it may not be true for some women who come from BRCA2 families with a strong family history.

Evans and colleagues used data from the M6-Inherited Cancer in England study, which has screened families of individuals with breast and/or ovarian cancer for mutations in BRCA1 and 2 since 1996. Details on affected individuals, and all tested and untested relatives, were entered into a Filemaker Pro-7 database. From 807 BRCA families, the researchers identified 49 women who tested negative for the family-specific BRCA mutation, but subsequently developed breast cancer. The researchers called these women “phenocopies.”

Of the 49 phenocopies identified, 22 were among 279 women who tested negative from BRCA1 families, and 27 were among 251 women who tested negative from BRCA2 families. When the researchers stratified the phenocopies based on their age (30-39, 40-49, 50-59, and 69-80), they found that in each age range there were about twice as many cases of breast cancer as would have been expected from the general population.

Next, to conduct risk analyses, Evans and colleagues calculated the “observed versus expected ratio” (O/E), a ratio of observed risk for breast cancer in BRCA-negative women from BRCA families, versus the risk expected for any woman in the general population.

They found the O/E for phenocopies from BRCA1 families was not substantially higher than that of the general population; however, the O/E for phenocopies from BRCA2 families was 4.57, leading them to conclude that the more than fourfold increased risk for breast cancer among BRCA-negative women is largely limited to BRCA-negative women from BRCA2 families.

When the researchers considered the date of predictive testing (the date on which BRCA testing was done for an individual) instead of the date of family ascertainment (the date the first family member of the individual was referred to genetic service), O/E dropped from 4.57 to 2.01, “because there is less follow-up in the predictive test group from time of testing and we may be unaware of breast cancers that have occurred in the near past,” explained Evans.

This study was funded by the National Institute for Health Research. The authors declare no conflict of interest.

Ganetespib: on the horizon for TNBC?

Ganetespib, a selective inhibitor may be a potent drug for the treatment of triple-negative breast cancer (TNBC), based on the results of  small preclinical studies.   Specifically, ganetespib  effectively regulated several key proteins involved in tumor growth and metastasis, according to results published on-line in the Journal of Molecular Medicine and  in Clinical Cancer Research:

The results demonstrate that inhibition of a wide collection of protein targets, including HIF-1alpha, correlate with potent effects on TNBC tumor cell viability and metastasis when ganetespib is administered alone or when with routinely used chemotherapy drugs for treatment of TNBC, including doxorubicin, paclitaxel, and docetaxel.  Ganetespib is particularly effective against the protein HIF-1alpha, a major regulator of multiple tumor growth properties, including angiogenesis (tumor blood vessel development), metastasis (cancer spread), metabolism, cancer stem cell maintenance, and invasion. 

DCIS Study Does NOT Mean TNBC Recurrence Is More Likely

I am very careful about what I put on this page.  If I think a research report is weak and could cause unnecessary worrying without adding to our knowledge in any meaningful way, I do not share it.    The internet, however, is a wild and wooly place, without gatekeepers and perspective.  So I often hear from readers about a study that "proves" things that are counter to what the broader body of research has told us about triple-negative breast cancer.

One recent study, published in BMC Cancer,  has caused readers to believe that the recurrence of TNBC after five years is greater than that of other forms of breast cancer.  This runs counter to several other studies that have shown the opposite--that TNBC tends to recur within three years if it is going to recur, and that the incidence after five years is significantly lower than for other forms of breast cancer.

Here's the deal.  This new research studied DCIS and found that those cases of DCIS that were TNBC tended to recur after five years at a higher rate than other types of breast cancer.  The researchers, though, warned that only 27 women in the study had TNBC, far too small a sample for any generalization.  In addition,  it does not appear, from the report, that any of the women with DCIS had chemotherapy—the treatments mentioned were surgery and radiation. This is not unusual, as few docs give chemo for DCIS.  So the small group of TNBC women studied did not have the insurance most women now have against TNBC—chemo.  And most research on long-term survival of invasive breast cancer deals with women who have had chemo.  And it shows that chemo often works better for estrogen-negative breast cancer than for estrogen-positive.

A few things this might tell us  (although, again, with such a small sample it is difficult to generalize):  Chemo works.  And DCIS perhaps should be treated more aggressively if it is TNBC.

It does NOT tell us that those of us with TNBC have more cause to worry about long-term recurrence.

• 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!

Test Determines Who Is at Risk of Lymphedema

Bioelectrical Impedance Analysis (BIA) ratios can effectively assess a woman's risk of lymphedema after breast cancer surgery that includes lymph node removal, according to a study published in the journal Lymphology.  BIAs operate on low frequency electronic current, which cannot travel through cell membranes, therefore providing a direct measure of lymph fluid outside the cells. 

“To lessen breast cancer survivors’ worry about lymphedema development, the BIA may have a role in clinical practice by adding confidence in the detection of arm lymphedema among breast cancer survivors,” says  Mei R. Fu, PhD, RN, ACNS-BC, associate professor of Chronic Disease Management at the New York University College of Nursing and lead researcher in the study.  

The objective of the study was to examine the reliability, sensitivity, and specificity of cross-sectional assessment of BIA in detecting lymphedema in a large metropolitan clinical setting.
Measuring lymphedema is challenging because most methods cannot distinguish bone and soft tissues from extracellular fluid. BIA is time-efficient, easy to operate and easy to interpret, making it ideal for clinical practice. 

Researchers collected data from 250 women, including healthy female adults, breast cancer survivors with lymphedema, and those at risk for lymphedema.

The American Cancer society estimates that in 2013 approximately 232,340 new cases of breast cancer are detected, adding to the already 2.9 million breast cancer survivors, all with a at a lifetime risk of Lymphedema. 

“Giving that all the women who are treated for breast cancer are at a life-time risk for lymphedema, using assessment methods that can accurately identify true lymphedema cases among at-risk breast cancer survivors is of the ultimate importance for clinical practice,” Fu says.   

Lapatinib May Fight TNBC

Lapatinib, which has been approved for use on Her2-positive tumors,  is also effective against triple-negative breast cancer in lab tests on mice, according to research published in Breast Cancer Research November 12, 2013.  Lapatinib  targets EGFR and  and  p65, which are present in both HER2-positive and triple-negative breast cancer cells.  Specifically, it is effective against the NF-κB pathway that scientists believe may be a key regulator of TNBC.  Researchers suggest it should be used in combination with a proteasome inhibitor.  The study also demonstrated that lapatinib worked better than gefitinib and erlotinib, which are  specific EGFR inhibitors. 
  
In previous research, lapatinib, in combination with Herceptin, was effective against TNBC.

• 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!

Off to SABCS Again

I'll be heading to the San Antonio Breast Cancer Symposium (SABCS) again this year, specifically to keep my eye on triple-negative breast cancer research.  I will once more do a recap of TNBC research, and I hope I have lots of information and positive news, as I did in 2012.   I am looking forward to a few specific sessions and events:

• A general session on JAK 2 amplifications in TNBC.  I wrote about previous research last year.
• Incidence and survival rates for different subgroups of breast cancer.
• Updates on new chemo drugs, especially platinum agents that have shown mixed success with metastatic TNBC.
• Connecting with other groups, including After Breast Cancer Diagnosis; I wrote a brief about them in 2012.   And the Metastatic Breast Cancer Network.  Last year I wrote about Ginny Knackmuh, who was diagnosed with metastatic TNBC in 2009.  I hope to meet her again this year.
• Meeting new and old friends.  I will again visit with Carol, a blog reader from Texas and now TNBC buddy.  I wrote about her last year.  Sadly, the other friend I wrote about in that essay was Lori Redmer, former executive director of the Triple Negative Breast Cancer Foundation, who died in August, leaving behind a beautiful family and an impressive legacy.  I met her in person only once, but we talked on the phone and emailed regularly.  I have not yet moved her emails from my inbox.  This year, I will finally meet the wonderful woman who mentored me through the final edits of my book and wrote my foreword, Carol Scott-Conner.  Oddly, she and I live in the same state but have never met.  Carol was diagnosed with breast cancer last year herself and has used her experience to help serve women even better.
• Hobnobbing with the docs again.

Thanks, as always, for your support.  I do this all on my own dime and time, so your donations really do help. Just click the donate button on the top right hand side of the blog, and you'll get to a secure Paypal site.  Hugs.

Test May Determine Which Cases of TNBC are Likely to Metastasize

As many as two-thirds of those who get adjuvant chemotherapy (after surgery) for triple-negative breast cancer probably do not need it, according to researchers writing in Breast Cancer Research, published online October 31, 2013.  Yet, chemo remains the most effective way to keep the disease from metastasizing, so it becomes a pricey (in our pocketbooks and our bodies) insurance against recurrence.  And it is insurance we pay because the alternative is terrifying.

Wouldn't it be great to have a test that determines which cases of TNBC are likely to metastasize and which have a pretty rosy prognosis even without chemo?  There could be.  Scientists suggest an Integrated Cytokine Score (ICS), containing three IR-7 genes (TNFRSF17, HLA-F, XCL2) and two Buck-4 genes (CXCL13, CLIC5).  The presence of these genes suggest cases that are likely to spread.  Read the entire research article here.

• 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!

Researcher to focus on Numb and Set8 proteins in search of targeted TNBC therapy

From a New Release from Western University in Ontario, Canada

They represent less than 15 per cent of women diagnosed with breast cancer. But for Dr. Shawn Li, continuing a search for solutions in this rarely diagnosed area of breast cancer has become his main mission.

Thanks to a $200,000 (over two years) Innovation Grant from the Canadian Cancer Society, the Western Biochemistry professor hopes to find ways to overcome chemotherapy resistance in women with triple-negative breast cancer.

Li was one of 37 researchers across Canada to share in $7 million in Innovation Grants, supporting creative problem-solving in cancer research.

With this continued support of the Canadian Cancer Society, who has given Li’s research $2.4 million since 2001, Li will be studying the biochemical reaction that plays a critical role in the death of triple-negative breast cancer cells, and is also involved in chemotherapy resistance.

His new project will study how two proteins – Numb and Set8 – interact in this reaction and look for compounds that could serve as the first targeted treatments for triple-negative breast cancer.

Li’s previous work showed the Numb protein plays an important role in cancer cell death. However, the Set8 protein interferes with this process and leads to chemotherapy resistance. Li and his team will study the Set8 protein and how it interferes with cancer cell death and, more important, screen thousands of drugs to look for those that prevent Set8 from interfering with cancer cell death, which could lead to better outcomes for women with triple-negative breast cancer.

• 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!