Cancer Survivorship on the Rise

In early 2012, there were 13.7 million of us in the United States.  By us, I naturally mean cancer survivors.  Within ten years, that number will rise to 18 million or so, according to a report, sponsored by the American Cancer Society and the National Cancer Institute and published online in CA: A Cancer Journal for Clinicians (2012).

Why are there so many of us?  Partly, it’s because we’re living longer, and the longer you live, the more chance you’ll get cancer.  (Some reward for a long life, huh?)  It’s also because treatments are improving, so more of us are beating cancer. (There’s your reward.)

But, according to the report, survivors are a worried lot, expressing concern about recurrence, second cancers, and late treatment complications without cancer recurrence.

The researchers used data from the Surveillance, Epidemiology, and End Results (SEER) program, the National Center for Health Statistics, and the University of California Berkeley's mortalitycohort life tables. Population projections were based on U.S. Census Bureaudata.

The findings, from the report:

• 6.4 million men and 7.3 million women who had been diagnosed with cancer at some point in their life were alive on Jan. 1, 2012.

• The top cancer for men was prostate, with 43 percent of the total, meaning nearly 2.8 million survivors.  

• Breast cancer was the leading cancer for women, with 41 percent of the total, and nearly 2.9 million survivors.  

• No other cancer contributed to more than 9 percent of the total in either sex. 

• In 2012, 8 percent of the women, or 606,910, had survived uterine cancer, second only to breast cancer. 

•In 2012, lung and bronchial cancer accounted for only about 3 percent of cancer survivors in both sexes, putting it eighth on the list.
•45 percent of all cancer survivors are 70 or older.

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SOURCE:  Siegel R, et al "Cancer treatment and survivorship statistics 2012" CACancer J Clin 2012;DOI:10.3322/caac.21149.

Be Part of My Presentation through the TNBC Foundation

I am honored to be the first presenter in the Triple-Negative Breast Cancer Foundation's (Un)Common Knowledge series.  My Webinar will air October 16, 2012, at 1 pm.  You can be part of the discussion by asking questions that will form the base of my presentation.  The Foundation is accepting those questions through September 24.   The details:

Please email questions to knowledge@tnbcfoundation.org. Questions that are succinct, and apply to more than one individual have a better chance of being included, as it may not be possible to address every question.

AACR Report Highlights TNBC

NEWS RELEASE

Washington, DC, September 12, 2012– The Triple Negative Breast Cancer Foundation® is proud to support the American Association for Cancer Research in their effort to raise awareness of the need for greater federal investment in the war against cancer. Representatives from the TNBCF and scores of other patient advocacy groups attended the unveiling of the AACR Cancer Progress Report 2012 here today.  [PAT'S NOTE:  You can download the report here.  Information about triple negative breast cancer from the patient's perspective is on page 40 and 68-69; other TNBC information can be found on page 17.]

“Private foundations like ours do a lot, but a strong federal commitment to breast cancer research is crucial to find breakthrough therapies for patients,” said Lori Redmer, Executive Director, Triple Negative Breast Cancer Foundation. “Besides policy and regulation, an important form of commitment is federal investment in research, and looming reductions are of grave concern to the more than 25,000 women in the US that will be diagnosed with triple negative breast cancer this year.”

Today’s report calls for legislation that provides alternative means for reducing our deficit while still protecting federal cancer research funds. This will require a concerted effort from the cancer research and advocacy community to urge legislators to work together to prevent sequestration of funds, resulting in reductions.

Over the coming months, TNBCF will be alerting its community about the situation, the risks to cancer research presented by budgetary sequestration, while urging its community to contact legislators encouraging them to find alternatives to cutting cancer research budgets.

Triple Negative Breast Cancer Foundation will also be attending a number of satellite events after the AACR Progress Report launch press conference, including an awards reception on Capitol Hill and a dinner for the honorees. TNBCF joins with the AACR in saluting those lawmakers who make cancer research funding a priority.

Triple negative breast cancer accounts for about 15% percent of all breast cancers, and is often more aggressive than other forms of the disease, while also disproportionately striking some populations such as women under 40, African Americans and Latinas. Unlike other breast cancers, triple negative breast cancers lack three specific proteins, or receptors, and as a result generally do not respond to existing targeted medicines commonly used to treat the disease. Since no targeted treatment exists yet, women with triple negative breast cancer usually receive surgery, chemotherapy or radiation. Treatment options remain limited if these interventions are not effective. Triple Negative Breast Cancer Foundation is focused solely on this dangerous form of breast cancer and is investing in research to find a targeted therapy.

About Triple Negative Breast Cancer Foundation
The Triple Negative Breast Cancer Foundation was founded in 2006 in honor of Nancy Block- Zenna, a young woman who was diagnosed at age 35 with triple-negative breast cancer and died two and a half years later in 2007. In response to Nancy's diagnosis, her close friends launched the Foundation. Our mission is to raise awareness of triple-negative breast cancer and to support scientists and researchers in their effort to determine the definitive causes of triple- negative breast cancer, so that effective detection, diagnosis, prevention and treatment can be pursued and achieved. For more information about TNBCF, visit www.tnbcfoundation.org.

About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR’s membership includes 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes seven peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the Scientific Partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of individual and team science grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit www.AACR.org. 

Help the TNBC Foundation

 

The Triple Negative Breast Cancer Foundation has the chance to win a share of $5,000,000 from Chase Community Giving.  Help by voting before Sept 19.  Chase customers get bonus points by checking in with your online credentials.  And you can add votes by getting folks to click your Tweets. (Such a silly phrase, isn't it?  Click your tweets.)  Vote here.  There is so much good the Foundation could do with this funding.

Clear Margins Especially Essential for TNBC

Patients with triple-negative breast cancer face an increased risk of residual cancer after a lumpectomy, making the need for generous margins especially important, according to research published in the Journal of the Academy of Physician Assistants.  Some details:
• Surgical specimens from 369 women with invasive breast cancer were examined.
• 51 percent of those with TNBC had invasive cancer in their surgical specimens.
• 30 percent of those with non-TNBC had invasive cancer in their surgical specimens,
• This means that clear margins are especially essential for those with TNBC.   Patients without clear margins might need re-excisions.

Remember: This is one study, of only 369 women.  In it, the odds of residual disease are high for all those studied—those with TNBC and those with non-TNBC.  Yet most women typically survive at far higher odds than in this study.  One reason for this may be that these specimens were taken before chemotherapy and radiation, which kill residual disease.

The bottom line: Clear margins are essential.

Additional Note:  A new device might help determine the existence of cancer on surgical margins.  In a paper  presented at the  2012  American Society of Clinical Oncology Breast Cancer Symposium in San Francisco, researchers demonstrated that the MarginProbe device found positive margins and reduced the need to re-exisions in a large, prospective trial.  Check out the article on Cancer Network.

Breasts and the Earth

Two mountains rise from the plains near Walsenburg, Colorado, twin peaks that point up to the sky like giant breasts. Native Americans —the Utes, Comanches, and Apache that once called this area home—named the peaks Wahatoya, which means Breasts of the Earth.  The Europeans who settled the region were less poetic and less graphic and called them the Spanish Peaks, and that is their official name now, the easternmost peak being, logically, the East Spanish Peak and the western one the West Spanish Peak. 

Native Americans believed that the peaks protected those who lived in their shadow. Of course, that didn’t quite work out—people still got sick, died, fought, lost money, had their hearts broken, and faced the same hardships and pain as those in less blessed areas.

We have a summer cabin in the shadow of the East Spanish Peak, so when I got breast cancer, I especially grumbled at this healthy myth.  No health protection for me. Nor for Dominick and Ruth, neighbors we have recently lost to cancer.  And no, I did not appreciate the irony of getting breast cancer when the breasts of the earth were supposedly keeping me healthy. 

Protection comes in many forms, though, and I believe my summers in this beautiful mountain valley have been important in regaining my health after my diagnosis.  We get our exercise by climbing the dikes that are scattered throughout the peaks—walls created by molten lava that radiate from the two mountains like wheel spokes.  We hike in firs, pines, and aspens that are a palette of greens in the summer and a mix of yellows, oranges and reds in the autumn.  And this is all under an azure sky.

We relax on our deck, looking at the mountain.  Just looking, seeing the formations caused by trees and boulders that look like a pirate’s face, a skull, an eagle.  And we watch eagles fly above us, bears walk the meadow across from the cabin, and hummingbirds fly in our faces when we don’t keep their feeders full enough.

Some folks like to call this God’s Country and it does feel especially blessed. But it’s not like God saw this pretty place, gave it a nod, and then shirked the rest of the world:  This is my country, and the rest of you can just deal with it. No, I think our blessings are where we are and are what we make of them.   Some of us are given more to work with—I give thanks every day for this beautiful spot—but I don’t think we’re given these gifts to just soak them in selfishly and be smug about our good fortune.  We’re given them to appreciate, to savor, to share, and to protect. 

You can’t help but get over yourself in land like this.  On the one hand, you see how lowly you are—when you stand next to a mountain, you are literally and figuratively tiny.  At the same time, you recognize your importance, because you are a caretaker of this great treasure.

It’s the same thing with our bodies.  We’re caretakers of these wonders.  We seldom contemplate the reality that we inhabit miracles every second of the day, until illness demonstrates that especially strongly.  When our cells stop behaving properly and turn cancerous, we have to really step back and try to comprehend the complexity that we live in. That’s one of those truths we seldom consider—that our bodies are natural wonders.  It takes a malfunction to make us recognize that.  It's a frightening awaking at first, but it can grow into an awesome respect.  

After my diagnosis, I realized that I needed to take care of this body better than I had been doing in the past. I needed to nurture it with nutritious foods, good exercise, and a healthy environment.

It’s all a circle of protecting, of caretaking.

As I sit and look out at the East Peak, at this breast of the earth, I think of my own breasts, my own tiny natural peaks, and I breathe in the mountain air, envision it filling those breasts with health.  Then I go eat some blueberries before my mountain hike in the protection of the Wahatoya.

PHOTOS: Top: The Wahatoya, with the East Spanish Peak on the left, West Spanish Peak on the right. Center:  The East Spanish Peak from our cabin, with clouds building in the meadow.

Is Pakistani Herbal Tea a New Cancer-Fighter?

Folks in rural Pakistan might be on to something.  They have long used extracts from a common herbal tea ingredient, the plant Fagonia cretica, known as virgin's mantle, to treat breast cancer. Now researchers at Aston University, Birmingham, England, and Russells Hall Hospital, Dudley, England, have evidence that this is more than folklore—an extract of the plant might actually work to repair cell damage in cancer cells without affecting healthy cells.  So far, their studies have been confined to laboratory analysis, but they hope to now determine what elements in the plant are the active cancer-fighters, with the hope of eventually beginning clinical trials.

In previous laboratory research, virgin's mantle repaired damage caused by p53 expression, which is associated with triple-negative breast cancer.  

In a news release, Professor Helen Griffith of Aston said,  "More research is needed to establish the role of the extract in cancer management and It now needs to be demonstrated that this extract is as effective in killing cancer cells inside the body as it is within laboratory."

Virgin's mantle is found in arid regions of Pakistan, India, Africa and parts of Europe.

Sharing Good News One Case at a Time

Here's one face of TNBC as I have seen it this week:

A reader wrote that his 36-year-old wife, who had been diagnosed in February with stage 3b TNBC, just got a glowing report from the doctor after a mastectomy and 8 rounds of ACT: Her chances of long-term survival are excellent.  They are meeting with the radiation oncologist soon.

So thanks to Walt for keeping me current and lifting my spirits.    When I first heard from him in late March, they were reeling from the diagnosis, and she was sleeping off the anti-nausea drugs. (I stopped taking them because they did little for nausea and made me feel worse.)

Walt says they modified their diet after her diagnosis.  Here's what he says about their new approach: 

I started juicing for us nightly.  I usually throw in: Kale, carrots, celery, blue berries, ginger, cucumber, and apple.... Also, we've dropped milk from our diet, and switched to decaf coffee and decaf tea.  Otherwise, we were pretty healthy before so not much has changed—oh, less red meat (but that wasn't a lot to start with).

That is similar to my approach, but I do have some milk—always low-fat organic. And I have my blueberries whole in the morning, not as party of my nightly juice.

I love hearing from readers and will start sharing bits of it with all of you who are on the same journey.

More Genetic Research Helping Define TNBC: Oncogene FAM83B

NEWS RELEASE

Newswise — A team of researchers at Case Western Reserve University School of Medicine, led by Dr. Mark W. Jackson, have developed a novel method to identify genes that, when overexpressed, make normal cells behave like cancer cells. Using this method, the Jackson laboratory has identified a new oncogene, which is a gene that contributes to the development of cancer, named FAM83B.

“We made our discovery in a model of breast cancer,” said Mark W. Jackson, Ph.D., Assistant Professor, Department of Pathology, Case Western Reserve University School of Medicine, Case Comprehensive Cancer Center. "Using an unbiased screening approach, we let the biology of cancer formation tell us what genes are important and FAM83B was one of the genes that came out of our screen. When FAM83B was overproduced in normal breast cells, it transformed the normal cells, causing them to behave like breast cancer," stated Jackson.

There are relatively few oncogenes that are critical to breast cancer growth, and only one other breast cancer oncogene has been identified in the last 6 years. Breast cancers are classified clinically into subgroups based on the presence of specific proteins, including estrogen receptor (ER), progesterone receptor (PR), and HER2.

"Analysis of breast cancer revealed that elevated FAM83B expression is associated with the more aggressive, triple negative subgroup which lacks ER, PR and HER2,” said Jackson. “In short, patients with triple-negative breast cancer would benefit most from the development of new therapeutics.”

Novel oncogenes provide opportunities for drug development that may expand the number of therapies available for eradicating cancer and extending the life of patients. "Our discovery provides the foundation for developing new therapies that can inhibit FAM83B in these aggressive cancers, which have traditionally been difficult to treat." We are currently trying to identify drugs that that can inhibit the function of FAM83B." stated Jackson.

This study will appear in The Journal of Clinical Investigationand will be co-published with a discovery from the laboratory of Dr. Mina Bissell at Lawrence Berkley National Laboratories. Dr. Bissell’s laboratory discovered an oncogene called FAM83A. Both FAM83A and FAM83B belong to an eight member family of genes that both laboratories propose may drive tumor formation and therapeutic resistance.

Dr. Jackson is the principal investigator leading a multidisciplinary team with investigators that include: Rocky Cipriano, James Graham, Kristy Miskimen, Benjamin Bryson, Ronald Bruntz, Sarah Scott, H. Alex Brown and George Stark. Additional support for the research came from the Case Comprehensive Cancer Center, the United States National Institutes of Health (R01CA138421 to M.W.J; T32CA059366 to R.C), the Department of Defense Breast Cancer Research Program (M.W.J), the American Cancer Society (RSG-10-072-01-TBG to M.W.J) and the McDonnell Foundation (to H.A.B).

The pharmaceutical company EntreMed has announced a Phase 2 study of ENMD-2076 in triple-negative breast cancer.  

Jennifer R. Diamond, MD, of the University of Colorado, says, 

"We are encouraged by the data from the Phase 1 study of ENMD-2076 in patients with advanced solid tumors, including triple-negative breast cancer. ENMD-2076 has also demonstrated significant anti-tumor activity against preclinical models of breast cancer with more robust activity against triple-negative breast cancer alone or in combination with standard chemotherapies. This single-agent Phase 2 study is designed to determine the activity of ENMD-2076 by the clinical benefit rate in patients with previously treated locally advanced or metastatic triple-negative breast cancer."

For more information, check out the news release.

What We Can Learn From Hospice Patients

NOTE:  The article below is essentially a press release about a new book, and I don't normally share these things until I can read the book.  However, I like what Gourgey has to say about the qualities of dying patients--essentially they demonstrate how we all should live, especially the part about love not being self-interested.  

Does our society hold too narrow a view of what defines strength? 

The things many would point to as indicators – youth, wealth, a fully capable body – fall short, says Charles Gourgey, a veteran hospice music therapist and author of Judeochristianity: The Meaning and Discovery of Faith (www.judeochristianity.org), a book that explores the unifying faith elements of Judaism and Christianity. 

“Youth is ephemeral, abundant wealth is for just a few, and we all experience some kind of disability, usually at several points in our lives,” he says. “A car accident, the loss of a job or a home, grief over a loved one’s dying: such things can happen to anyone and easily destroy our happiness.” 

Gourgey says some of the greatest strength he’s ever seen was demonstrated by certain of his patients facing imminent death. 

“Some people have complete love and grace when facing death – it’s how they’ve lived their lives, and at the end of their lives, it’s what supports them,” he says. “Those who, at the end, are peaceful, grateful and confident share some common characteristics.” 

They are: 

• Their love is non-self-interested. When we have awareness of and deepest respect and reverence for the individuality of others, we overcome the high walls of ego and experience a tremendous sense of freedom, says Gourgey. He says he continues to be inspired by patients who cared more for the well-being of others, including their fellow hospice patients, than themselves while facing their own mortality. Non-self-interested love – loving others for themselves without expecting or needing anything in return – is the greatest form of love, he says. 

• They had an unwavering faith that transcended religious dogma. Faith is the knowledge that there is more to life than the apparent randomness of the material world; a sense that we are known to a greater reality and will return to that reality. No matter what their religion, the patients who were most at peace with their life’s journey were those who had faith in something higher than themselves. The problem with many concepts of faith, Gourgey continues, is that people attach specific doctrines to it, which means some people will always be excluded. A unifying faith – that all people are connected and love is the force that binds us – allows for trust, compassion and caring. 

• They were motivated by an innate sense of what is good. They didn’t get mad at themselves; they didn’t beat themselves up for mistakes they might have made in the past. That’s because they were always guided by their sense of what is good, and they made their choices with that in mind. That did not prevent them from making some bad choices or mistakes over the course of their lives, Gourgey says. But when they erred, they addressed the problem with the same loving compassion they extended to others. “Their compassion overcame even any self-hate they may have experienced.”

Many patients left lasting impressions on Gourgey, and taught him valuable life lessons. He remembers one in particular. 

“She was in hospice, a retired nurse who had developed a rare, incurable disease,” he recalls. “She would go around every day, checking to see what she could do for the other patients. She fetched blankets for a 104-year-old lady who always complained of cold feet. She sat with and listened to patients who needed company and someone to talk to. She had an attentive awareness about her, like she was fully in touch with her soul.” 

Gourgey was with the woman when she died. 

“She was radiant, she just glowed. She kept repeating how grateful she was for her life,” he says. “It was as if the life of love she’d lived was there to transport and support her at the end.” 

About Charles “Carlos” GourgeyCharles “Carlos” Gourgey, PhD, LCAT, MT-BC, is a board-certified and New York state-licensed music therapist. He has more than 20 years of experience working in hospices and nursing homes, and for 10 years was music therapist for Cabrini Hospice in New York City. He has published articles on psychology and religion in various journals.

Botanical Formula Shows Promise in Fighting Metastatic TNBC

A botanical formula that includes medicinal mushroom, flavonoids, botanicals, and extracts of cruciferous vegetables may be effective against triple-negative metastases, according to a study published in the  journal Oncology Reports.

The study was conducted at the Cancer Research Laboratory, Methodist Research Institute, Indiana University Health. It was presented at the annual meeting of the American Academy for Cancer Research.  Its publication in Oncology Reports marks the third peer-reviewed study demonstrating the anticancer effects of the formula.

Researchers implanted triple-negative human breast cancer cells in the breast tissue of mice.  The tested group was given the formula orally for four weeks; the control group received no treatment.  

According to a news release from Indiana University Health:

The cancer metastasized to the lungs in only 20 percent of the treated group as compared to 70% of the untreated, control group. Furthermore, in the treatment group that did metastasize, the number and size of the lesions was dramatically reduced in comparison to the control group. 

Gene analysis showed that the formula down regulated (suppressed and reduced) two genes implicated in cancer metastasis -- PLAU (urokinase plasminogen activator, uPA) and CXCR4 (C-X-C chemokine receptor-4). These results further substantiate previous cancer cell studies published on this formula, which similarly demonstrated a down regulation of these cancer promoting genes. 

The  formula includes ingredients that have been shown in previous research to have anti-cancer properties:

• Medicinal mushrooms Trametes versicolor, Ganoderma lucidum, Phellinus linteus reduce cancer growth and invasiveness.• Extracts from the botanicals Scutellaria barbata, Astragalus membranaceus and Curcuma longa induce programmed cell death (apoptosis) and reduce cancer metastasis.•The flavonoid, quercetin, reduces cancer cell proliferation and helps suppress tumor growth.• DIM (3, 3'-Diindolylmethane), an active component of cruciferous vegetables, reduces cancer growth, migration and invasiveness.

      Source: Jiang J, Thyagarajan-Sahu A, Loganathan J, Eliaz I, Terry C, Sandusky GE, Sliva D. BreastDefend prevents breast-to-lung cancer metastases in an orthotopic animal model of triple-negative human breast cancer. Oncol Rep. 2012 Jul 26. doi: 10.3892/or.2012.1936.

Protein Kinase Thwarts TNBC Cell Migration and Invasion

NEWS RELEASE

ScienceDaily (Aug. 1, 2012) — By identifying a key protein that tells certain breast cancer cells when and how to move, researchers at Michigan State University hope to better understand the process by which breast cancer spreads, or metastasizes.
When breast cancer metastasizes, cancer cells break away from a primary tumor and move to other organs in the body, including the lungs, liver and brain. In work published recently in the journal Cancer Research, MSU researchers Kathy Gallo and Jian Chen show a protein called MLK3 (mixed lineage kinase 3) is a critical driver of breast cancer cell migration and invasion.More importantly, Chen and Gallo showed that in triple-negative breast tumor cells, which are more aggressive and for which targeted therapies are needed, it is possible to thwart that cell migration and invasion."While the classical approach to cancer drugs has been to find drugs that kill tumor cells, there recently also is an interest in finding drugs that interrupt metastasis," said Gallo, a professor in MSU's Department of Physiology. "The hope is that such drugs in combination with conventional therapies may lead to better outcomes in patients."As part of their study, Gallo and Chen, a biochemistry graduate student, also found that eliminating MLK3 prevented tumors in animals from metastasizing to the lungs, providing the foundation for future research on targeting MLK3 pathways as an approach to preventing the spread of cancer.The researchers identified how key cellular proteins were instructed by the MLK3 protein -- through the addition of molecular tags called phosphates -- to interact with one another, leading cancer cells to move. Specifically, MLK3 promotes the addition of phosphates to another protein called paxillin, which is known to control how cells move.Gallo and Chen then stopped cell movement in breast cancer models by eliminating MLK3 altogether or using a drug called CEP-1347 to block MLK3's ability to add phosphates to other proteins. The experimental results indicate that when certain cancer cells lose MLK3, the ability to add phosphates is impaired, eventually crippling the cell migration machinery and diminishing cell movement."Our research suggests that the intracellular pathways involving MLK3 that control cell movement could provide new targets for the treatment of patients with metastatic cancer," Chen said. "Drugs developed for combating the MLK3 activity may be useful in reducing the spread of breast cancer."Gallo added that MLK3 is a protein kinase, and these types of proteins have proven to be good drug targets in cancers and other diseases."While drugs such as chemotherapy kill all cells, research has shown drugs that inhibit kinases often can be effective with fewer side effects," she said.The next step for the researchers is to test whether an MLK3 inhibitor can prevent cancer from metastasizing in animal models."Cancer is a very complex collection of diseases, but we believe that certain types of cancers may be sensitive to MLK inhibitors," Gallo said, "and targeting MLK3 may provide a very useful weapon in the fight against cancer."The team's research was supported by grants from the Department of Defense's Breast Cancer Research Program and the Elsa U. Pardee Foundation. The MLK inhibitor, CEP-1347, was provided by Cephalon Inc., a wholly owned, indirect subsidiary of Teva Pharmaceuticals Industries Ltd.

Drug Combo May Stop TNBC Growth

From Medical Daily

Two drugs approved by the Food and Drug Administration for blood cancer treatment may also be used to treat triple negative breast and kidney cancer. researchers say.

The drugs are romidepsin and decitabine. Together they can activate a gene sFRP1 (secreted frizzled related protein one) that can stop the growth of cancer cells. 

"We now have the basis for a clinical trial aimed at providing effective therapy for two drug-resistant cancers and perhaps many more tumor types in the future," said Dr. John Copland, biologist from Mayo Clinic. The trials were conducted on cell lines of cancers where the combination of drugs was effective in halting the cell growth. 

"Individually, each drug did not induce any form of cell death but, together, they killed all of the different cell lines of kidney and triple negative breast cancer that we tested in the laboratory," said Simon Cooper, a Mayo Clinic molecular biologist who specializes in renal cancer and lead author of the study. 

Nearly, 80,000 people are affected each year by these two types of cancers in the United States.

It was observed that certain types of cancer suppress the gene sFRP1. Activation of this gene by the drugs can stop the growth of cancer cells. Even cancers that affect colon, ovary and lungs grow by suppressing this gene.
Researchers say that this gene could act as a biomarker to test the effectiveness of the combination drug therapy on certain kinds of cancers. 

"But now, not only do we have a very promising lead on future therapy, but if this combination treatment works as we hope it does, we will have a biomarker to be able to test which patients might benefit the most. In other words, a biopsy test could identify patients whose tumors had lost sFRP1 function," said Edith Perez, MD, deputy director of Mayo Clinic Cancer Center and co-author of the study. The combination therapy can help fight cancers that have become resistant to other drugs and as these drugs are clinically approved the human trial phase would be faster.

 "This type of interdisciplinary preclinical research effort is important, not only because of the value of the science, but also because the drugs are already in the clinic and that will facilitate translational efforts and hopefully confirm the preclinical findings in patients with advanced malignancies," said Michael Menefee, MD, an oncologist and co-author of the study.  

The study was published in Molecular Cancer Therapeutics. 

Tumor Suppressor Gene Linked to Improved Response to Chemo in TNBC and Other Breast Cancer Patients

NEWS RELEASE

PHILADELPHIA—Breast cancer patients whose tumors lacked the retinoblastoma tumor suppressor gene (RB) had an improved pathological response to neoadjuvant chemotherapy, researchers atThomas Jefferson University Hospital and the Kimmel Cancer Center at Jefferson report in a retrospective study published in a recent online issue of Clinical Cancer Research.

Many breast cancer patients undergo neoadjuvant therapy to reduce the size or extent of the cancer before surgical intervention. Complete response of the tumor to such treatment signifies an improved overall prognosis. Today, no marker is applied to identify tumors which will respond to such treatment, and as a result, only a subset of patients exhibit benefit from it.

"We found that loss of RB was associated with better pathological response rates in breast cancer patients—at various stages and representing multiple molecular subtypes—who were administered neoadjuvant chemotherapy," said Agnieszka Witkiewicz, M.D., Associate Professor of Pathology, Anatomy and Cell Biology at Thomas Jefferson University.

Erik Knudsen, Ph.D, Professor of Cancer Biology and the Hilary Koprowski Chair in Cancer Biology, was excited that discoveries from his life-long research on the RB-pathway were making their way into the clinic.

"This represents a potential new biomarker that could be used to tailor treatment plans for women considering neoadjuvant therapy and is a testament to the importance of cancer research," he said.

For the study, researchers, including Gordon Schwartz, M.D., Director of the Jefferson Breast Care Center and Adam Ertel, Ph.D., Bioinformatics Specialist, Department of Cancer Biology, performed a combination of gene expression profiling to identify those with RB loss and direct histological analysis in over 1,000 breast cancer patients who had undergone neoadjuvant therapy. These patients represented distinct subtypes of breast cancer and were treated with multiple different therapeutic regimens.

RB loss was associated, the team found, with an improved response to all the neoadjuvant regimens investigated in the major subtypes of breast cancer.

"Together, these data indicate that the loss of RB, which occurs relatively frequently in locally advanced disease, could be a useful tool for defining patients who experience an improved response to neoadjuvant chemotherapy," said Dr. Witkiewicz. "Based on these findings, we have initiated a prospective clinical trial at Jefferson, evaluating the association of RB and another marker, PTEN, with the response to neoadjuvant chemotherapy."

###

The clinical trial is open to patients who have a diagnosis of triple negative breast cancer and are eligible for neoadjuvant chemotherapy. (clinicaltrials.gov/ct2/show/NCT01514565).

Seeing the Trees in The Forest, And Where We Fit In

A little evergreen tree has died alongside our road and, as we walked by it yesterday, my husband wondered why.  All the other trees around it are healthy and it did not look like it had been hit by lightning or damaged by wind or attacked by bugs.

The tree is about eight feet tall, so it lived several years.  We are in the Rocky Mountains and this little guy took root on its own, taking seed and growing in that place by the road.

The trees all around it are scrub oak, so maybe the soil was not right for an evergreen.  Maybe it just grew in the wrong place, in soil that could not sustain it.  Still, there are evergreens nearby that soar to the sky, so maybe this little tree was just too weak to begin with.

Could we have done something to save it?  If we were in the city, would we have babied it and maybe kept it alive?  Or would it have died sooner there?

These are the same questions we ponder about why some people get sick, why one disease affects one person more than others, why people who live healthy lives still can’t beat some illnesses, yet people with deplorable habits keep going and going.

It’s the old nature versus nurture argument.  Bad genes or bad environment?  Or both?

I am sort of over being angry at people who have dodged major illnesses—largely because, frankly, there aren’t that many of them.  Seems like most people I know have something to contend with—debilitating arthritis, diabetes, heart disease, Alzheimer’s.  But when I first got cancer I did look around at people who obviously were not living as healthy as I was and wondered, Why me and not them? And then I realized that I had no idea what they were dealing with and I should just stop being so angry and judgmental and get over myself.  It was not their fault I got sick.

Still, you have to wonder about this poker game we all play with our health.  Some seem to be dealt a good hand to begin with, some make the best of a poor hand, some try but can’t make a straight out of a pair of twos, and some look at their cards and just fold. 

I have one friend who never exercises and has a diet full of fat, yet she is in her mid-80s, hale, hearty, and youthful-looking.  Another smoked all his life, drank, and never exercised, yet he is pushing 80 and has nothing seriously wrong physically, although I do think he looks back at his life with serious regret.  Still, the big C didn’t get him, nor did any major illness.  I wouldn’t swap places with him, though, even if I knew my cancer would return.

I also know a wide variety of cancer patients—fighters who refuse to let the disease get the upper hand, questioners who search for their own information rather than listening to the docs, accommodators who go along with whatever the doctor says, worriers who can’t get beyond the fact that they might die.  Most of us are a mix of these traits, fighting one day, living in worry the next.  But we are all built differently, both physically and mentally, so we all react to our disease differently.  Nobody is right, nobody is wrong.  We’re all just us, being our own little trees fighting our own little battles.

We cannot escape our genes—they make us prone to certain diseases, give us the strength to fight others, and offer a blueprint for either a long or a short life.  Still, we can change some of that—the science of epigenetics demonstrates that lifestyle and environmental factors can influence our genetic makeup so that, by improving things such as diet and physical activity and by avoiding unhealthy environmental pollutants including stress, bad air, and chemicals, we can eventually build a healthier DNA.

I was born into a history of cancer.  My grandmother and both of my parents had forms of cancer, although none of them had breast cancer.  I was the pioneer there.  But both parents lived into their 80s and remained in their home until they died, surrounded by their family.  So, I might have a tendency toward cancer, but perhaps my genes also mean I will hang around for a couple more decades.  And my particular mix of nature and nurture has given me an ability to love, to laugh, to process health information in a way that might make me proactive, and to keep going, assuming all will be well, at least at some level.

Maybe I won’t end up as one of the stronger trees in the forest, maybe I will be the gnarled, crooked one.  Maybe disease might slow me, but I feel I am rooted deeply in decent soil—family, friends, community—so I am going to push on, grow how I can, and, in the process, help shade and nurture the other trees around me.