Breast Cancer Spread: A New Test to Predict Metastases

What You Need to Know: A new test (MetaSite Breast) may be commercially available in late 2015. It relies on the tumor microenvironment of metastasis (TMEM) score, something found to be linked to the potential for breast cancer spread (metastasis).

Background: Historically, the most powerful prognosticators for breast cancer included the number of underarm (axillary) nodes involved, size of the primary tumor, and measures of proliferation such as grade. More recent tests for prognosis are based on gene signatures found within the tumors.

Seed and Soil Story: The story of how TMEM fits into the mechanism of tumor metastasis is not a simple one. In their editorial, Dr Jain and colleagues discuss the “seed and soil” theory of metastasis originally proposed by Paget more than 100 years ago, in which the “seed” is a tumor cell, and its ability to thrive depends on the “soil” of the tumor microenvironment. According to the editorial, when the tumor travels to its metastatic site (congenial soil), it carries along with it some of the the original “soil” in which it grew.

Although TMEM is focussed on a trio of cells — tumor cells, macrophages, and endothelial cells lining blood vessels — that are present at the extravasation site, Dr Jain’s editorial indicates that preclinical models of metastasis provide evidence that heterotypic clumps of cells that travel to other sites may additionally contain other cells from the original soil in which it grew — fibroblasts, myeloid cells, and stromal cells.

These observations from animal models suggest that tumor metastasis does not conform to the standard view that “single cancer cells crawl into the blood vessels, adhere downstream to the endothelium, and then transmigrate in a manner similar to leukocytes.”

  • The MetaSite Breast test could be available commercially late next year. It relies on determining the tumor microenvironment of metastasis (TMEM) score, and a group of researchers from the Albert Einstein College of Medicine in New York City have shown that it is possible to correlate this score with the potential for breast cancer metastasis.
  • Tumor microenvironment of metastasis (TMEM), consisting of direct contact between a macrophage, an endothelial cell, and a tumor cell, has been associated with metastasis in both rodent mammary tumors and human breast cancer.

My Take: Currently used gene signatures (including MammaPrint and OncoType DX) are associated with the probability of distant disease recurrence and are in clinical use as prognosticators. These signatures are primarily driven by genes reflecting the amount of cancer cell proliferation and the presence (or absence) or hormone receptors in the tumor. Now we have the exciting promise of adding in characteristics of the tumor microenvironment to offer better prognoses. I think this approach represents a fundamental change in how we approach cancer. I’m Dr. Michael Hunter.

The small print: The material presented herein is informational only, and is not designed to provide specific guidance for an individual. Please check with a valued health care provider with any questions or concerns. As for me, I am a Harvard- , Yale- and UPenn-educated radiation oncologist, and I practice in the Seattle, WA (USA) area. I feel genuinely privileged to be able to share with you. If you enjoyed today’s offering, please consider clicking the follow button at the bottom of this page.

Available now: Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Both can be found at the Apple Ibooks store. Coming Soon for iPad: Understand Breast Cancer in 60 Minutes; Understand Colon Cancer in 60 Minute; Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Thank you.

References: 

  • Thomas E. Rohan, et al. JNCI J Natl Cancer Inst Volume 106, Issue 8
  • Solicited editorial: Dan G. Duda, Marek Ancukiewicz, Steven J. Isakoff, Ian E. Krop, Rakesh K. Jain. jnci.oxfordjournals.org. July 31, 2014.

Cut Your Risk of Breast Cancer Now

women walking exercise

What You Need to Know: This could be the simplest bit of health advice ever: Exercise reduces women’s risk of breast cancer, no matter what kind of exercise they do, how old they are, how much they weigh, or when they get started.

The Study: Researchers in France looked at studies that involved more than 4 million women around the world who participated in prospective studies from 1987 to 2013. They found that the more active a woman is, the better her odds of avoiding breast cancer. Women who were most active, with more than an hour a day of vigorous activity, got the most benefits, lowering their cancer risk by 12 percent.

But women weren’t as active saw reduced risk, too, notes Mathieu Boniol, research director at the Strathclyde Institute for Global Public Health in Lyon, France. More activity was better, but anything was better than nothing. He presented the data Thursday at the European Breast Cancer Conference in Glasgow.

“This decrease is the same whatever the country, whatever the age, whatever the menopausal status,” Boniol told Shots. And it didn’t matter if women were active in work, activities of daily living, or sports. “It’s very good news.

Women who were overweight or obese benefited a little less, but still lowered their risk by 10 percent overall.

And women who got moving after menopause also saw benefits from exercise.

“It’s not something to say, ‘Oh, I’ve never done sports why do that right now?’ ” Boniol says. “We now have evidence that it could still be beneficial. And it’s cheap. It’s a very cheap way to do prevention of breast cancer.”

My Take: Scientists don’t know why physical activity reduces breast cancer risk. There’s been speculation about exercise’s effect on hormones and inflammation, but no one knows for sure. Other studies have found breast cancer risk reductions as high as 25 percent from physical activity, but because of the huge number of women included in this analysis, the 12 percent reduction may be more accurate. So, no matter where you live, your weight, or your age, keep moving. Keep moving. I’m Dr. Michael Hunter.

The small print: The material presented herein is informational only, and is not designed to provide specific guidance for an individual. Please check with a valued health care provider with any questions or concerns. As for me, I am a Harvard- , Yale- and UPenn-educated radiation oncologist, and I practice in the Seattle, WA (USA) area. I feel genuinely privileged to be able to share with you. If you enjoyed today’s offering, please consider clicking the follow button at the bottom of this page.

Available now: Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Both can be found at the Apple Ibooks store. Coming Soon for iPad: Understand Breast Cancer in 60 Minutes; Understand Colon Cancer in 60 Minute; Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Thank you.

Reference: http://www.npr.org/blogs/health/2014/03/20/291894075/exercise-cuts-breast-cancer-risk-for-all-women-everywhere

Breast Cancer Spread: Can Dieting Reduce Risk?

overweight obese woman

What You Need to Know: Women with an aggressive subtype of breast cancer known as “triple negative” may be able to reduce the chance of disease spreading distantly by reducing their calorie intake. But… the data thus far is based on mice (and not human) studies.

Well, it does work for mice: The study published in the Journal Breast Cancer Research and Treatment, used mice models to investigate the impact of diet on triple negative disease, which is found in about one in five women with breast cancer. It found that when mice were given 30 per cent fewer calories, changes occurred in the body in the way cells were regulated. Mice on restricted diets produced more protective proteins in the tissues around the tumour, which make it harder for cancer to spread, the study by Thomas Jefferson University found.

My Take: We know that in among some groups of women (for example, women who are post-menopausal), obesity increases the risk of breast cancer. Unfortunately, treatment such as chemotherapy (and steroids) can cause weight gain. This weight gain can lead to worse cancer outcomes. Human trials are examining the impact of calorie restriction on outcomes. For now, I advise my patients to try to achieve, and maintain, an optimal Body Mass Index (BMI) of 20 to 25. I’m Dr. Michael Hunter.

The small print: The material presented herein is informational only, and is not designed to provide specific guidance for an individual. Please check with a valued health care provider with any questions or concerns. As for me, I am a Harvard- , Yale- and UPenn-educated radiation oncologist, and I practice in the Seattle, WA (USA) area. I feel genuinely privileged to be able to share with you. If you enjoyed today’s offering, please consider clicking the follow button at the bottom of this page.

Available now: Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Both can be found at the Apple Ibooks store. Coming Soon for iPad: Understand Breast Cancer in 60 Minutes; Understand Colon Cancer in 60 Minute; Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Thank you.

Reference: http://www.telegraph.co.uk/journalists/laura-donnelly/10856597/Dieting-may-reduce-chance-of-cancer-spread.html#source=refresh:

Breast Cancer Spreads to brain By Disguising Itself as Brain Cells

Often, several years can pass between the time a breast cancer patient successfully goes into remission and a related brain tumor develops. During that time, the breast cancer cells somehow hide, escaping detection as they grow and develop.

Breast cancer cells disguise themselves as neurons, becoming “cellular chameleons,” found the scientists from City of Hope in Duarte, California. This allows them to slip undetected into the brain and then develop into tumors. The discovery is being heralded as “a tremendous advance in breast cancer research.”

Although breast cancer is a very curable disease—with more than 95% of women with early-stage disease surviving after 5 years—breast cancer that metastasizes to the brain is difficult to fight. Only about 20% of patients survive 1 year after diagnosis.

“There remains a paucity of public awareness about cancer’s relentless endgame,” said Rahul Jandial, MD, PhD, a City of Hope neurosurgeon who headed the breast-cancer-and-brain-tumor study, published in the Proceedings of the National Academy of Sciences (2014; doi:10.1073/pnas.1322098111). “Cancer kills by spreading. In fact, 90% of all cancer mortality is from metastasis,” Jandial said. “The most dreaded location for cancer to spread is the brain. As we have become better at keeping cancer at bay with drugs such as herceptin, women are fortunately living longer. In this hard-fought life extension, brain metastases are being unmasked as the next battleground for extending the lives of women with breast cancer.”

He added, “I have personally seen my neurosurgery clinic undergo a sharp rise in women with brain metastases years—and even decades—after their initial diagnosis.”

Jandial and other scientists wanted to explore how breast cancer cells cross the blood-brain barrier—a separation of the blood circulating in the body from fluid in the brain—without being destroyed by the immune system.

The researchers’ hypothesis was that,  given that the brain is rich in many brain-specific types of chemicals and proteins, perhaps breast cancer cells that could exploit these resources by assuming similar properties would be the most likely to flourish. These cancer cells could deceive the immune system by blending in with the neurons, neurotransmitters, other types of proteins, cells, and chemicals.

Taking samples from brain tumors resulting from breast cancer, the scientists found that the breast cancer cells were exploiting the brain’s most abundant chemical as a fuel source. This chemical, gamma-aminobutyric acid (GABA), is a neurotransmitter used for communication between neurons.

When compared with cells from nonmetastatic breast cancer, the metastasized cells expressed a receptor for GABA, as well as for a protein that draws the transmitter into cells. This allowed the cancer cells to essentially masquerade as neurons.

“Breast cancer cells can be cellular chameleons (or masquerade as neurons) and spread to the brain,” Jandial said.

He added that further study is required to better understand the mechanisms that allow the cancer cells to achieve this disguise, and he hopes that, ultimately, unmasking these disguised invaders will result in new therapies.

// // //

New Breast Cancer Stem Cell Findings Explain How Cancer Spreads

breast cancer tumor

Breast cancer stem cells exist in two different states and each state plays a role in how cancer spreads, according to an international collaboration of researchers. Their finding sheds new light on the process that makes cancer a deadly disease.

  • First, on the outside of the tumor, a type of stem cell exists in a state called the epithelial-mesenchymal transition (EMT) state. These stem cells appear dormant but are very invasive and able to get into the bloodstream, where they travel (metastasize) to distant parts of the body.
  • Once there, the stem cells transition to a second state that displays the opposite characteristics, called the mesenchymal-epithelial transition state (MET). These cells are capable of growing and making copies of themselves, producing new tumors.

“You need both forms of cancer stem cells to metastasize and grow in distant organs. If the stem cell is locked in one or the other state, it can’t form a metastasis,” Wicha says.

The findings, which are published in the January 2013 issue of Stem Cell Reports, raise a number of questions about how to treat or prevent metastatic breast cancer. Researchers must now understand whether new therapies must attack both forms of the stem cell to be successful. Different pathways regulate each type of stem cell, which suggests that effective therapies must be able to target multiple pathways.

In addition, current tests that look at tumor cells circulating in the blood to help determine whether the cancer is spreading do not appear to capture the EMT stem cells, which are the cancer cells that travel through the blood. U-M researchers are working with colleagues from the U-M College of Engineering to develop new tools to isolate the EMT stem cells from the blood of cancer patients.

“Now that we know we are looking at two different states of cancer stem cells, we can use markers that distinguish these states to get a better sense of where the cancer stem cells are and to determine the effectiveness of our treatments,” Wicha says. The study looked specifically at breast cancer stem cells but the researchers believe the findings likely have implications for other cancer types as well.

I’m Dr. Michael Hunter.

The small print: The material presented herein is informational only, and is not designed to provide specific guidance for an individual. Please check with a valued health care provider with any questions or concerns. As for me, I am a Harvard- , Yale- and UPenn-educated radiation oncologist, and I practice in the Seattle, WA (USA) area. I feel genuinely privileged to be able to share with you. If you enjoyed today’s offering, please consider clicking the follow button at the bottom of this page.

Available now: Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Both can be found at the Apple Ibooks store. Coming Soon for iPad:  Understand Breast Cancer in 60 Minutes; Understand Colon Cancer in 60 Minute; Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Thank you.

Reference: Suling Liu, Yang Cong, Dong Wang, Yu Sun, Lu Deng, Yajing Liu, Rachel Martin-Trevino, Li Shang, Sean P. McDermott, Melissa D. Landis, Suhyung Hong, April Adams, Rosemarie D’Angelo, Christophe Ginestier, Emmanuelle Charafe-Jauffret, Shawn G. Clouthier, Daniel Birnbaum, Stephen T. Wong, Ming Zhan, Jenny C. Chang, Max S. Wicha. Breast Cancer Stem Cells Transition between Epithelial and Mesenchymal States Reflective of their Normal CounterpartsStem Cell Reports, 2013; DOI:10.1016/j.stemcr.2013.11.009

Breast Cancer in Brain: Cancer Masquerading as Neurons

cancer cells tumor

Breast cancer cells masquerade as neurons, allowing them to hide from the immune system, cross the blood-brain barrier and begin to form ultimately-deadly brain tumors, the researchers found.

“The most dreaded location for cancer to spread is the brain,” said Rahul Jandial, a City of Hope neurosurgeon who led the study, available online and slated for print publication in the Proceedings of the National Academy of Sciences in February. “As we have become better at keeping cancer at bay with drugs such as Herceptin, women are fortunately living longer. In this hard-fought life extension, brain metastastes are being unmasked as the next battleground for extending the lives of women with breast cancer.”

Jandial and other City of Hope scientists wanted to explore how breast cancer cells cross the blood-brain barrier — a separation of the blood circulating in the body from fluid in the brain — without being destroyed by the immune system.

“If, by chance, a malignant breast cancer cell swimming in the bloodstream crossed into the brain, how would it survive in a completely new, foreign habitat?”Jandial said. Jandial and his team’s hypothesis: Given that the brain is rich in many brain-specific types of chemicals and proteins, perhaps breast cancer cells exploit these resources by assuming similar properties. These cancer cells could potentially deceive the immune system by blending in with the neurons, neurotransmitters, other types of proteins, cells and chemicals.

The Study: Taking samples from brain tumors resulting from breast cancer, Jandial and his team found that the breast cancer cells were using the brain’s most abundant chemical as a fuel source. This chemical, GABA, is a neurotransmitter used for communication between neurons. When compared to cells from non-metastatic breast cancer, the metastasized cells expressed a receptor for GABA, as well as for a protein that draws the transmitter into cells. This allowed the cancer cells to essentially masquerade as neurons. Jandial offers:

“Breast cancer cells can be cellular chameleons (or masquerade as neurons) and spread to the brain.”

He says that further study is required to better understand the mechanisms that allow the cancer cells to achieve this disguise. He hopes that ultimately, unmasking these disguised invaders will result in new therapies. I’m Dr. Michael Hunter.

The small print: The material presented herein is informational only, and is not designed to provide specific guidance for an individual. Please check with a valued health care provider with any questions or concerns. As for me, I am a Harvard- , Yale- and UPenn-educated radiation oncologist, and I practice in the Seattle, WA (USA) area. I feel genuinely privileged to be able to share with you. If you enjoyed today’s offering, please consider clicking the follow button at the bottom of this page.

Available now: Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Both can be found at the Apple Ibooks store. Coming Soon for iPad:  Understand Breast Cancer in 60 Minutes; Understand Colon Cancer in 60 Minute; Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Thank you.

Reference: J. Neman, J. Termini, S. Wilczynski, N. Vaidehi, C. Choy, C. M. Kowolik, H. Li, A. C. Hambrecht, E. Roberts, R. Jandial.Human breast cancer metastases to the brain display GABAergic properties in the neural nicheProceedings of the National Academy of Sciences, 2014; DOI:10.1073/pnas.1322098111

Younger, Early Breast Cancer Patients Often Undergo Unnecessary Staging, Imaging Procedures

bone scan

More than one third of younger, early stage breast cancer patients undergo unnecessary imaging procedures — including position emission tomography (PET), computed tomography (CT), nuclear medicine bone scans (NMBS) and tumor markers (TM) — at the time of staging and diagnosis, according to research from The University of Texas MD Anderson Cancer Center.

Presented at a poster session at the 2013 CTRC-AACR San Antonio Breast Cancer Symposium by Carlos Barcenas, M.D., assistant professor in MD Anderson’s Breast Medical Oncology, the study is the first to look at the issue of over-use of staging procedures, including imaging and tumor markers in the diagnosis setting, specifically in younger, early-stage breast cancer patients.

Over-testing and unnecessary procedures extends beyond cancer care across the healthcare continuum. To help address the issue, the American Board of Internal Medicine began “Choosing Wisely®,” an initiative encouraging physicians and patients to have conversations that encourage its reduction.

As part of its participation in the national campaign, last year, the American Society of Clinical Oncology (ASCO) generated a “top five list” which recommended against the use of CT, PET, TM and bone scan in the diagnosis and staging of early-stage breast cancer at low risk for metastasis. Rather, treatment guidelines clearly state that for women with early-stage breast cancer, the proper procedures for diagnosis include mammogram, ultrasound, clinical exam and blood work, said Barcenas.

Study Design: For the retrospective study, Barcenas and his colleagues analyzed claims from a national employer-based database of 42,651 women between 2005 and 2010 with an initial diagnosis of breast cancer. All were younger than 65 years old and had undergone a mastectomy, lumpectomy and sentinel lymph node biopsy. Patients who underwent axillary lymph node dissection were excluded from the study because this is considered a surrogate for node-positive disease. Claims for imaging and tumor markers were analyzed between the specific period of three months prior to surgery and one month post-surgery. Researchers stratified for age, geographical location, treatment and insurance coverage, HMO or PPO.

Results: The researchers found that 37 percent of early stage breast cancer patients had at least one claim for an unnecessary staging test, with minimal change in rate of that average over the five-year period. Of note, said Barcenas, 18 percent of the woman had tumor markers performed, which is a staging procedure with no role in the non-metastatic diagnosis setting. Undergoing chemotherapy had the highest association with overuse of staging procedures, with hormone and radiation therapy also associated with overuse.

Barcenas and the team also found regional differences in overuse trends, as well a higher rate of unnecessary procedures in women with PPO insurance coverage compared to those with HMO. Also, women with breast cancer under 35 years old were at higher odds of having one of these tests, he explained. Yet when diagnosed at such a young age, this patient population is perceived by the physician to be at higher risk of metastatic and/or aggressive disease.

My Take:  These findings clearly support the need for the ASCO recommendations. We must shift our focus to doing what matters for the patient and what’s proven to improve outcomes, rather than testing for the sake of testing I’m Dr. Michael Hunter.

The small print: The material presented herein is informational only, and is not designed to provide specific guidance for an individual. Please check with a valued health care provider with any questions or concerns. As for me, I am a Harvard- , Yale- and UPenn-educated radiation oncologist, and I practice in the Seattle, WA (USA) area. I feel genuinely privileged to be able to share with you. If you enjoyed today’s offering, please consider clicking the follow button at the bottom of this page.

Available now: Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Both can be found at the Apple Ibooks store. Coming Soon for iPad:  Understand Breast Cancer in 60 Minutes; Understand Colon Cancer in 60 Minute; Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Thank you.

Reference: University of Texas M. D. Anderson Cancer Center (2013, December 13). Younger, early breast cancer patients often undergo unnecessary staging, imaging procedures.ScienceDaily. Retrieved December 28, 2013, from http://www.sciencedaily.com­/releases/2013/12/131213092852.htm