New Genetic Pathway Linked to TNBC

Scientists from Houston Methodist and Weill Cornell Medical College have found that a gene previously unassociated with breast cancer plays a pivotal role in the growth and progression of triple negative breast cancer. Their research, published in the April 3 Nature (online today), suggests that targeting the gene may be a new approach to treat the disease.

"We are really beginning to understand what initiates the cancer and why cancer cells evade treatment," said coauthor and Houston Methodist Cancer Center Director Jenny Chang, M.D. "Our group learned this pathway was activated in about two-thirds of patients with this type of breast cancer, and we believe we may be able to treat the disease by manipulating elements of the pathway."

About 42,000 new cases of triple negative breast cancer (TNBC) are diagnosed in the United States each year, about 20 percent of all breast cancer diagnoses. If patients relapse, they typically do so within one to three years of being treated.

Using cells taken from patients' tumors and transplanted into mice, researchers found that the gene, XBP1, is especially active in TNBC, particularly in the progression of malignant cells and their resurgence after treatment.

"Patients with the triple negative form of breast cancer are those who most desperately need new approaches to treat their disease," said senior author Laurie H. Glimcher, M.D., professor of medicine at Weill Cornell. "This pathway was activated in about two-thirds of patients with this type of breast cancer. Now that we better understand how this gene helps tumors proliferate and then return after a patient's initial treatment, we believe we can develop more effective therapies to shrink their growth and delay relapse."

The group, which included investigators from nine institutions, examined several types of breast cancer cell lines. They found that XBP1 was particularly active in basal-like breast cancer cells cultivated in the lab and in TNBC cells from patients. When they suppressed the activity of the gene in laboratory cell cultures and animal models, however, the researchers were able to dramatically reduce the size of tumors and the likelihood of relapse, especially when these approaches were used in conjunction with the chemotherapy drugs doxorubicin or paclitaxel. The finding suggests that XBP1 controls behaviors associated with tumor-initiating cells that have been implicated as the originators of tumors in a number of cancers, including that of the breast, supporting the hypothesis that combination therapy could be an effective treatment for TNBC.

The scientists also found that interactions between XBP1 and another transcriptional regulator, HIF1-alpha, spurs the cancer-driving proteins. Silencing XBP1 in the TNBC cell lines reduced the tumor cells' growth and other behaviors typical of metastasis.

"This starts to demonstrate how cancer cells co-opt the endoplasmic reticulum stress response pathway to allow tumors to grow and survive when they are deprived of nutrients and oxygen," said lead author Xi Chen, Ph.D., a postdoctoral associate at Weill Cornell, referring to the process by which healthy cells maintain their function. "It shows the interaction between two critical pathways to make the cells better able to deal with a hostile microenvironment, and in that way offers new strategies to target triple negative breast cancer."

Scientists still need to study how those strategies would help women with the disease.

"Obviously we need to know now whether what our group saw in models is what we'll see in patients," Chang said. "We are very excited about the prospect of moving this research forward as soon as possible for the benefit of patients."

—Information from a news release from Houston Methodist and Weill Cornell Medical College

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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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How did you feel the year after treatment?

I'd like a little favor from those of you more than a year past treatment:  How did you feel in that first year, once treatment was over?  I have a question about this from a reader—how do other women feel?— and have discovered this has not been that well studied.  There are a lot of "you should feel" suggestions through various cancer organizations, but I have not found any decent actual research.


So I would like us to at least have a discussion of this.  I am lucky to be so far past that first year that my memory is not all that strong, but I do know I was extra tired and had pain in my surgical incisions, and some pain generally around my chest, which I was told was related to radiation.   That pain is gone and cancer has not returned, so whatever it was ended up not being any sort of a threat.  My energy level still is not anything to write home about, but I tend to get a lot done, and I am fairly committed to regular exercise, so I think I am doing just fine.  (Yay!)

So, how did you feel in that first year?  (Or how do you feel, if you're now in that year?)  Do you think you got more colds and other viruses/infections than normal?  Do you feel you had a weakened immune system?  For longer survivors, how long did this last?

There is a lot we can do to keep ourselves healthy, and this reader is already on that—she is eating healthy and maintaining a healthy level of physical activity.  Still, she has been getting a lot of colds and she wants to know if other women feel like she does.  And, even though she did not say it, I think she wants to know if this is going to go away soon.

I'll post this on my Facebook page so you can discuss it there, or you can comment below.

I think we will all feel better once this awful winter is past and we can get our usual doses of natural vitamin D.

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