Thursday, April 24, 2014

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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Monday, March 24, 2014

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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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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Sunday, March 9, 2014

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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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 17, 2014

One sure thing about winter:  Spring is coming next.

Sunday, February 16, 2014

Will Research on the Nuclear Protein Twist Lead to Targeted TNBC Treatment?

A nuclear protein called Twist may provide an effective approach for treating triple-negative breast cancer, according to a recent study published in Cancer Cell.  Twist is an accelerant of the epithelial-mesenchymal transition (EMT) program in human cells, which is significant because TNBC has an activated EMT program. EMT provides tumor cells with stem cell-like characteristics, making them resistant to chemotherapy and increasing their chances for early metastasis.

Researchers found that Twist interacted with a key nuclear transcription regulator, BRD4. When many DNA viruses (such as papillomaviruses) enter into human “host” cells during infection, they hijack host cell machinery to replicate and synthesize their viral DNA and proteins. BRD4 is the virus's favored molecule and is often seized by DNA papillomaviruses for gene transcription during replication and growth.

The study showed that two BRD4 inhibitors, JQ1 and MS417, can specifically disrupt the interaction of Twist with BRD4, resulting in the suppression of triple-negative breast cancer cells.

"This finding has significant clinical ramification, because drugs that can target the Twist-BRD4 interaction provide a new hope for treating life-threatening triple-negative breast cancer," said lead researcher Peter Zhou, associate professor of molecular and cellular biochemistry at the University of Kentucky Markey Cancer Center.  

—Information from a news release from the University of Kentucky

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

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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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Is Smoking Associated with TNBC? Yes. Or No. Depends on Which Study You Look At

Young women who smoke and have been smoking a pack a day for a decade or more have a significantly increased risk of developing hormone-positive  breast cancer, but smoking is not related to a woman’s risk of triple-negative breast cancer, according to a new analysis published online in Cancer, a peer-reviewed journal of the American Cancer Society.

The majority of recent studies evaluating the relationship between smoking and breast cancer risk among young women have found that smoking is linked with an increased risk; however, few studies have evaluated risks according to different subtypes of breast cancer.

To investigate, Christopher Li, MD, PhD, of the Fred Hutchinson Cancer Research Center in Seattle, and his colleagues conducted a population-based study consisting of 778 patients with estrogen receptor positive breast cancer and 182 patients with triple-negative breast cancer. 

Patients in the study were 20 to 44 years old and were diagnosed from 2004-2010 in the Seattle-Puget Sound metropolitan area. The study also included 938 cancer-free controls.
The researchers found that young women who were current or recent smokers and had been smoking a pack a day for at least 10 years had a 60 percent increased risk of estrogen receptor positive breast cancer. 

“The health hazards associated with smoking are numerous and well known. This study adds to our knowledge in suggesting that with respect to breast cancer, smoking may increase the risk of the most common molecular subtype of breast cancer but not influence risk of one of the rarer, more aggressive subtypes,” said Dr. Li.

Previous research has also shown that postmenopausal women who smoke do not face an increased risk of TNBC, according to research using data from the Women's Health Initiative. The study enrolled 148,030 women, 300 of whom had TNBC and 2,479 of whom had estrogen-positive disease. Smoking and alcohol use were both associated with ER-positive breast cancer, but not with TNBC. The research was published in Cancer Causes Control (2011).* 

BUT:  An older study showed just the opposite. A 2001 study in the International Journal of Cancer found evidence that smoking—even for those who gave up the habit—was associated with an increased risk of hormone-negative breast cancer.  In this long-term study, 10,902 women, 35 percent of whom were smokers, were followed for an average of 12.4 years. Those who smoked had an increased risk of hormone-negative breast cancer, but not of hormone-positive.  Ex-smokers specifically had an increased risk of progesterone-negative breast cancer.**

THE MORAL:  Don't smoke, because you don't want any kind of cancer.

*Kabat, Geoffrey C., Kim, Mimi, Phipps, Amanda I., Li, Christopher I., Messina, Catherine R., Wactawski-Wende, Jean, Kuller, Lewis, Simon, Michael S., Yasmeen, Shagufta, Wassertheil-Smoller, Sylvia  Rohan, Thomas E., ”Smoking and alcohol consumption in relation to risk of triple-negative breast cancer in a cohort of postmenopausal women.” Cancer Causes and Control : CCC , pp. 1-9 (2011).

** Manjer, J., Malina, J., Berglund, G., Bondeson, L., Garne, J. P.   Janzon, L., “Smokingassociated with hormone receptor negative breast cancer.” International Journal of Cancer, vol. 91, no. 4, 580-584 (2001).

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

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New Lumpectomy Margins Set by Surgical Oncologists

As many of you have observed from personal experience, doctors disagree on the definition of an adequate surgical margin in a lumpectomy. To reduce confusion, worry and unnecessary second surgeries yet maintain excellent outcomes, the Society of Surgical Oncology (SSO) has  created a "definitive guideline." 

Roughly 25 percent of breast cancer patients return to the operating room following lumpectomies to obtain more normal tissue around the cancer, and this often results in mastectomies.  In about half of these cases, the tumor has been removed and the margin is free of cancer cells, but doctors have believed that a larger amount of normal breast tissue might reduce the risk of cancer recurrence.

The new guideline: No cancerous cells should touch the edge of the lumpectomy specimen.  Beyond that, additional surgery is not effective. This is true for women of all ages and with all forms of breast cancer, including triple-negative.  

To develop the guideline, an expert methodologist conducted a comprehensive review of the available scientific evidence.  Leaders in surgical oncology, radiation oncology, medical oncology, pathology and patient advocacy then met to review the findings and develop a consensus. 

"Our hope is that this guideline will ultimately lead to significant reductions in the high re-excision rate for women with early-stage breast cancer undergoing breast conserving surgery.  Based on the consensus panel's extensive review of the literature, the vast majority of re-excisions are unnecessary because disease control in the breast is excellent for women with early-stage disease when radiation and hormonal therapy and/or chemotherapy are added to a woman's treatment plan," said Meena S. Moran, MD, Associate Professor of Therapeutic Radiology at Yale School of Medicine and Yale Cancer Center and co-chair of the Margin Consensus Panel.

You can download the guidelines and accompanying research on the SSO's website.

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!

Saturday, February 8, 2014

Androgen and Vitamin D therapy could make TNBC chemo better and less toxic.

Targeting androgen and vitamin D receptors could be an effective treatment for triple-negative breast cancer, according to a new study  published online in the Journal of Clinical Investigation.  

Researchers studied more than 15,000 normal breast cells and discovered eleven previously undefined cell subtypes, which they then categorized into four new hormonal groups characterized by vitamin D, androgen and estrogen hormone receptor expression.

The study results suggest that two-thirds of triple-negative patients may be candidates for androgen and vitamin D-targeted hormone therapy. Perhaps equally important, researchers found that some breast tumor subtypes, such as basal-like, have been classified erroneously due to inaccurate definition of normal cell types.

"[E]arly data suggest that targeting androgen and vitamin D receptors in addition to standard chemotherapy may increase effectiveness, and may allow for lower doses of chemotherapy with the same effect." according to the study's first study author, Sandro Santagata, MD, PhD, Brigham and Women's Hospital (BWH) Department of Pathology, and senior study author Tan A. Ince MD, PhD, University of Miami Miller School of Medicine. "We have much more to learn about why normal breast cells are so diverse and how that information can help us better improve the diagnosis, prognosis and treatment of breast cancer patients."

A good deal of previous research has linked androgen to TNBC.  One study, presented at the San Antonio Breast Cancer Symposium in 2012, suggested that androgen might be included in the definition of TNBC. Another study, also presented at SABCS, successfully tested a prostrate drug, which targets androgens, on TNBC.  And a host of studies have shown that vitamin D deficiencies are linked to all types of breast cancer, including TNBC.

Read more about androgens, vitamin D, 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!

Monday, February 3, 2014

Mammograms Every Two Years Recommended for Most Women

If you have a family history or any other risk factors, such as the BRCA mutation,  yearly mammograms are still recommended.  And, always do good self exams.

Adoption of new guidelines recommending screening mammography every two years for women ages 50 to 74 would result in breast cancer screening that is equally effective, while saving the United States $4.3 billion a year in health care costs, according to a study led by UC San Francisco.

The study compares three possible mammography screening strategies with a model of current U.S. screening practices.

The article appears on February 4, 2014 in Annals of Internal Medicine.

The authors call for the adoption of guidelines developed in 2009 by the U.S. Preventive Services Task Force (USPSTF). Under those guidelines, in addition to biennial screening for women age 50 to 74, women age 40 to 49 would be screened according to other risk factors, and women 75 and older would be screened depending on the presence or absence of other diseases.

The study was led by Laura J. Esserman, MD, MBA, professor of surgery and radiology at UCSF and an internationally known leader in the field of breast cancer.

 “The USPSTF guidelines are based on the best scientific evidence to date,” said Esserman, director of the Carol Franc Buck Breast Care Center at the UCSF Helen Diller Family Comprehensive Cancer Care Center. “What we need now is a better way to assess breast cancer risk and implement a more risk-based approach to screening. We have demonstrated that the resources for doing this are already in the system. We should redirect them to learning, enabling change, and improving outcomes.”

According to the authors’ estimate, approximately 70 percent of women in the U.S. were screened for breast cancer in 2010, at a cost of $7.8 billion. Some women are screened annually, some biennially, and some are screened on an irregular basis.

The scientists compared this current picture of breast cancer screening with three simulated models: annual screening of 85 percent of women age 40 to 84, in accordance with recommendations from the American Cancer Society and many other policymaking organizations, at an annual estimated cost of $10.1 billion; biennial screening of 85 percent of women age 50 to 70, in line with guidelines used in many European countries, at an annual estimated cost of $2.6 billion; and screening in accordance with USPSTF recommendations, which the authors estimate would cost $3.5 billion per year at a screening rate of 85 percent.

“Over the last decade, in study after study, it has become very clear that – apart from limited, specific high risk groups – biennial screening is as effective as annual screening mammography,” said Esserman. “At the same time, annual screening is associated with a greater likelihood of false positive results, which have an adverse impact on women’s well-being and quality of life. From the viewpoint of women’s health, the USPSTF screening recommendations make sense.

“We can go one step further and learn who is at risk for what kind of breast cancer, and over time, further tailor screening by adjusting the age to start and frequency as well as include recommendations for prevention,” Esserman said.

Lead author Cristina O’Donoghue, MD, currently at the University of Illinois at Chicago but with UCSF at the time of the study, noted that the billions of dollars saved from avoiding less-effective mammography screening could be used to improve women’s health.

“We could increase women’s participation in screening, improve routine assessment of breast cancer risk and referral services for women at high risk, offer better genetic counseling for women with a family history of breast cancer and work on improving the quality of screening, with an emphasis on higher-quality mammography read by specialized mammographers,” said O’Donoghue. “These would be only some of the potential benefits of using our health care resources more intelligently.”