ASCO: A shift in thinking on causes of metastasis?

It’s easy to get lost in the sea of abstracts and presentations at the annual meeting of the American Society of Clinical Oncology (ASCO).  The amount of data being presented is overwhelming, with 30,000 people milling from halls to exhibits to poster sessions, trying to take it all in.  But what makes it easier for me is to keep an eye out for what is really sounding different or new, and what could have a major impact on the course of breast cancer for women.  Not the drug studies hyped in the media or at the fancy pharma exhibits, not the association studies on the posters, but what really has the potential to change the course of breast cancer for women? 

There has been a lot of talk in the media about the focus on personalized medicine at this year’s meeting here in Chicago – finding out the genetic fingerprint of a tumor and finding the drug that will match up with the patient’s tumor.  Sophisticated science, yes, a boon for pharmaceutical companies, yes, but great for patients?  Not so much.  These high tech, targeted treatments are adding months, not years to patients lives, at great expense.   Focusing only on the genetic drivers of tumors is not enough.  Cancer, particularly advanced cancer, usually finds a way to work around any of the road blocks thrown its way.  More mutations and resistance are almost always inevitable.  We need something more, a different approach.  We need to cut cancer off at the knees before it gets threatening at all.

The presentation that picqued my interest the most as possibly opening the door to something game changing was a presentation by Dr. Robert Weinberg of the Whitehead Institute for Biomedical Research.  His talk was entitled The EMT and the pathogenesis of high-grade carcinomas.  He spoke of new insights from his lab and others on how cancer may come to eventually metastasize and take lives, and how the biological changes that are occurring may be foreshadowed extremely early on, like maybe 30 to 40 years before the cancer causes death.  Dr. Weinberg presented data to show that differentiation of the cells very early on determines their future metastatic potential.  An idea that goes against conventional thought.  It may not be because of genetic mutations occurring late in the stage of cancer, as many believe and where much of the research is currently focused.  His theory is that the cell of origin plays a role in determining future tumor morphology and behavior.

And his second point was that the interaction between the cancerous cells and the surrounding tissue or stroma also plays a crucial role in the development of metastases.  Signals from the surrounding tissue cause some of the cells to undergo changes, a  biological program, called the epithelial-mesenchymal transition (EMT).  This transformation, he said, causes cells to take on traits that make them highly malignant, such as increased motility, invasiveness, and heightened resistance to apoptosis or cell death.  These changes make the cells like stem cells, cells that can self renew.  It is these cells, Dr. Weinberg speculates, that lead to metastatic growth of tumors. 

Most importantly, Dr. Weinberg showed convincing data to indicate that current cancer treatments aren’t effective against these cells that have undergone the EMT transformation, becoming more deadly.  Traditional chemotherapy agents are effective at wiping out the non-stem cell like cancer cells, but not those that have taken on the traits necessarly for self renewal at distant sites.  This could help explain the reappearance of cancer after dormancy, and the eventual spread of disease after removal of primary tumors.   Dr. Weinberg also showed data to indicate that non-stem cell like cells have the ability to spontaneously go through the EMT process and become stem like.  The implication for effective treatment of cancer, he emphasized, is that treatment must address both stem cells and non-stem cell like tumor cells.

I hope that some other laboratory groups and those in industry shift some resources toward following this line of thought – it makes sense based on what we now see happening to patients with cancer, and it provides a game changing possibility for really curing people of the disease.  That is an exciting possibility.

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ASCO Annual Meeting

The 47th annual meeting of the Annual Society of Clinical Oncology is coming up next week in Chicago, June 3-7, and is expected to draw 30,000 attendees.  Results from over 4,000 cancer research studies will be released.  A bit overwheming for a cancer research advocate – how do you find the useful and meaningful results?  A start is to look at what the press office is highlighting ahead of time, though we can’t always be sure these are well done studies, and are the most important ones.  This years’ press release highlights seven studies, three of which are relevant to breast cancer patients.  The one that caught my eye was a Phase II study of Cabozantinib for patients with advanced, progressing tumors.  The researchers found the drug was helping slow some tumor growth, but a surprise finding was its impact on patients with bone metastases.  Fifty-nine of 68 patients with bone metastases (including patients with breast and prostate cancers and melanoma) experienced either partial or complete disappearance of the cancer on bone scans, often with significant pain relief and other improved cancer-related symptoms.  Independent review by radiologists confirmed that bone metastases disappeared in the majority of patients who had bone metastases when they entered the study.

I look forward to learning more at the meeting.  Most of the research abstracts are currently online and can be searched here.  Please leave a comment if you find or hear about an interesting study to be presented at ASCO.

Breast Cancer Metastasis – Changing the Conversation

Though it is the spread of breast cancer, or breast cancer metastasis, that ultimately takes the lives of women who die from the disease, only a fraction of the research into the disease is aimed at a greater understanding of this process. And the public dialogue, including government officials, is too often focused on screening mammography as the best or only solution, with the false claim that metastasis could be eliminated simply through widespread use of mammography.1 Sure, industry continues to focus on metastasis – nearly 2,000 drugs for the treatment of cancer are under development. 2 But these drugs can win FDA approval and generate huge profits while providing little or no meaningful benefit for patients. Think of Avastin, costing approximately $8,000 a month,3 showing no increase in survival from breast cancer in randomized clinical trials but increasing a risk of death from side effects. 4

It is time to change the conversation. We need to talk about why and how metastasis happens. And then figure out how to prevent it. Let’s face the reality that mammography is not enough. Women, even those receiving mammograms, will continue to be diagnosed with metastatic breast cancer, sometimes years after an initial “early” breast cancer.5 And for these women, drugs that may or may not add a few more weeks or months of life, and can have lethal side effects of their own, are not enough. We must do more.

Since setting Breast Cancer Deadline 2020 last fall, NBCC has begun taking steps to change that conversation. We have pulled together a diverse group of 20 advocates and scientists who are working to plan a Metastasis Summit, to be held August 24-26, 2011. The Summit will bring together 35-50 stakeholders, leading investigators, regulators, and advocates, to develop a strategic plan to answer the question: what must be done to determine, by 2020, how to prevent breast cancer metastasis and save women’s lives?

Members of the Metastasis Summit Planning Committee are beginning their work by looking broadly and identifying a wide range of ideas worth investigating and researchers worth interviewing. Advocates on the committee will be conducting interviews over the coming months with the identified investigators, and then the work will begin to narrow the focus, and to identify the topics and participants for the Summit. The goal of the Summit will be to identify the key questions to carry into catalytic workshops in 2012, in order to get the research accomplished and translated to the clinic as quickly as possible.

But changing the conversation around breast cancer and metastasis must be much more than our Summit. The conversation needs to change in laboratories and classrooms, in the media, in the workplace, the halls of Congress, online, at the kitchen table. We want to hear from you. How are you changing the conversation? What do you think needs to happen to meet Breast Cancer Deadline 2020?

Work has also begun on NBCC’s other major focus for Breast Cancer Deadline 2020 – prevention of breast cancer all together. Look for information on the Prevention Summit in a future blog.

 

NBCC Breast Cancer Deadline 2020 Metastasis Summit Planning Committee

  • Shirley Brown, Advocate
  • Frank Calzone, PhD, Amgen, Inc.
  • Suzanne Fuqua, PhD, Baylor College of Medicine
  • John Glaspy, MD, PhD, UCLA Medical Center
  • Sherry Goldman, Advocate
  • Kathleen Harris, Advocate
  • Patricia Haugen, Advocate
  • Michelle Holmes, MD, DrPH, Harvard School of Public Health
  • Debbie Laxague, Advocate
  • Debra Madden, Advocate
  • Silvano Martino, DO, The Angeles Clinic & Research Institute
  • Musa Mayer, Advocate
  • Marlene McCarthy, Advocate
  • Shirley Mertz, Advocate
  • Laura Nikolaides, NBCC
  • Patricia Steeg, PhD, National Cancer Institute
  • Fran Visco, NBCC
  • Sandy Walsh, Advocate
  • Danny Welch, PhD, Kansas University Cancer Center
  • Maria Wetzel, Advocate

References

1”But under the law, every American who buys a new plan can access free preventive care like Pap smears and mammograms. That means women are no longer going to have to put off breast cancer screenings, taking the risk that their cancer could be caught late – when chances of survival can be as low as 23 percent – instead of early – when the survival rate is 98 percent.” Secretary of Health and Human Services Kathleen Sebelius in a blog post on Huffington Post, Protecting and Strengthening Women’s Health, Feb. 18, 2011.

 2 “Since the introduction of Herceptin® in 1998, manufac¬turers have been flocking to oncology, creating an R&D arms race. Several large pharmaceutical companies (some of which have little or no prior experience in cancer thera¬peutics) have committed more than 20% of their late-stage pipeline projects to oncology molecules.…. Nearly 2,000 individual molecules for the treatment of cancer are under development—a measure of the indus¬try’s determination and ongoing commitment to finding new and innovative treatments for cancer.” The Oncology Pipeline: Maturing, Competitive, and Growing by Steven J. Gavel. http://www.imshealth.com/imshealth/Global/Content/Web%20Article/The_Oncology_Pipeline3.pdf

3 http://www.washingtonpost.com/wp-dyn/content/article/2010/08/15/AR2010081503466.html

4 Treatment Related Mortality with Bevacizumab in Cancer http://jama.ama-assn.org/content/305/5/487.abstract

 5 Soliman H. Developing an effective breast cancer vaccine. Cancer Control. 2010 Jul;17(3):183-90.

Misconceptions about Breast Cancer Deadline 2020

It’s been almost two months now since NBCC set a deadline for the eradication of breast cancer.  We set a  deadline of January 1, 2020 as a tool to change the conversation around breast cancer.  Researchers, industry, the government, advocates, and the public have all become complacent.   Breast cancer has led to powerful industries of research, screening, diagnosis, pharmaceuticals, and even advocacy.  And many more industries gain through cause marketing of the disease every year.  NBCC set a deadline to change the status quo, to stand up and say this is no longer acceptable. NBCC declared a deadline to end breast cancer for everyone.  NBCC’s deadline campaign is focused on metastasis and primary prevention.

Thousands of people have listened, and heard, and new conversations are beginning.  Imagination has been sparked and people are allowing themselves to imagine a world without breast cancer and considering what it would take to get there.  But many others have also expressed doubt or even disappointment.  Some say it is too long to wait – why should we wait that long for a cure, they say.  Others say they are disappointed because they believe our focus is on prevention only. 

We used neither the word “cure” nor prevention when we declared the deadline.  We simply set a deadline to eradicate breast cancer.  To us, this means we need to learn how to prevent deaths from breast cancer metastasis and we need to learn how to prevent the disease from developing.

Some scientists have said it sounds like a gimmick or marketing campaign and it doesn’t fit with NBCC’s reputation and respect for science.  They say ten years won’t be enough time and it is naive.  They want to see our detailed plan.

But our deadline wasn’t set because we already have a detailed scientific plan on how to get there and just needed a target date to finish.  The deadline was set to change the conversation.  And to focus work on a deadline.  To bring urgency to our work. To end breast cancer. Business as usual is not working.  Progress in preventing deaths from this disease, or in preventing the disease all together, has been slow and incremental, if at all.  Too many resources have been focused on the wrong areas. 

We do have a detailed plan, but it is a plan for starting a new conversation and for changing and focusing research.  Our strategic plan is to engage all of the stakeholders around the goal. Scientists, regulators, industry representatives, and advocates have been and will continue to be invited to meetings focused on specific areas that will be crucial to achieving the goal with an emphasis on removing barriers and encouraging collaboration.

Two strategic summits will be held in 2011, one each on the topics of Metastasis and Prevention. Major issues that are ripe for further work and that would have a significant impact on breast cancer in a five year time frame will be identified. Catalytic workshops will then be held around these issues in 2012 and beyond.

 We could have kept on doing what we were doing, and I think we can guess where we would have been on January 1, 2020.  Or we can set a deadline to bring urgency – the catalyst we need for change.  We chose to declare a deadline.  Are you with us?

To find out more visit www.stopbreastcancer.org.

Hoping for a Cure

After I was diagnosed with breast cancer I wasn’t sure how I felt about pink ribbons.  They were suddenly everywhere I turned.  A lot of people seemed to care about breast cancer and there were certainly a lot of people hoping for a cure.  There were plenty of businesses getting on board too.  I could shop for the cure, bake for the cure, drive for the cure, even vacuum for the cure.  But something made me uneasy about all of this pink and hope.  If all of this shopping and hoping was making a difference why did I get breast cancer out of the blue in the first place?  And why was I being treated with the same toxic treatments of the past that may or may not prevent the cancer from returning?  The best I could do after eight months of surgeries, chemotherapy, and radiation was wait around and see if I died of something else to know if it had worked.  Not a lot different than what happened to women who were diagnosed with breast cancer decades before me.  That didn’t seem like much return for the millions of dollars being raised on pink ribbons and hope for a cure each year.

If hope was enough we would have cured breast cancer years ago.   But instead of curing breast cancer all of this hope and pink has created a huge economy that feeds on the disease and is sustained by people’s fears of the disease.  Cause marketing led to $1.55 billion in spending in 2009, with breast cancer being the greatest netting cause.  And the business of breast cancer extends far beyond cause marketing. The mammography business is expected to surpass $1.1 billion by 2015, according to a report by Global Industry Analysts, Inc.  The US market for vacuum assisted breast biopsies is expected to net $350 million by 2012. Pharmaceutical company Roche brings in $1 billion in revenues each year from Avastin for the treatment of metastatic breast cancer, despite the failure of studies to show it increases survival.

It is time to move beyond hoping and shopping for an end to breast cancer.  We must shift the status quo from the business of breast cancer to the end of breast cancer.  We must replace the complacency. We must bring back the urgency to end this disease.  We must demand accountability from those making a profit off breast cancer, and ensure that resources and efforts are focused in the right places to bring about eradication of this disease.

We’ve never set a deadline before.  It is time. Ten years to get it done.  Breast Cancer Deadline 2020.   www.breastcancerdeadline2020.org

KnowBreastCancer.org and Advocacy Training Conference

Lots happening this week at NBCC!  KnowBreastCancer.org, our new breast cancer research website has just been launched.  Find in-depth information on controversies in breast cancer, breaking news from research conferences, and access to original research articles.  Check it out!

The Annual Advocacy Training Conference begins this weekend in Washington DC.  Over 90 speakers will be presenting information on breast cancer research and public policy.  Topics range from Pregnancy Associated Breast Cancer to Breast Cancer and the Media – Who Gets in Right? to Update on PARP Inhibitor Research.  See the program here.  If you are not able to be there, sign up to get email updates from an e-advocate!  Find out more here.

Eat fried chicken to cure breast cancer!

Wow.  This is wrong on so many different levels.  KFC is going pink this month for breast cancer awareness.  First of all, is going pink and promoting breast cancer awareness going to invade every month of the year?  But even more disturbing is Buckets For the Cure.  Money will be donated to Susan G. Komen For the Cure for every pink bucket of fried chicken purchased.  KFC is hoping to make the “largest donation ever in the fight against breast cancer.”

The Colonel says pink is the new red.  Is he trying to distract us from heart disease and obesity maybe?

“Another year and I could have been in big trouble”

“Everyone gets busy, but don’t make excuses. I stay in shape and eat right, and it happened to me. Another year and I could have been in big trouble.”

Martina Navratilova was talking about her diagnosis of Ductal Carcinoma in Situ (DCIS) following a mammogram.  She will no doubt be learning the facts about DCIS and breast cancer as she goes through treatment and beyond.    Unfortunately, the public will be stuck with the misinformed messages that Martina has sent out during the early days of her diagnosis.  She will probably learn that DCIS shouldn’t be called breast cancer.  She may learn an NIH consensus panel on DCIS has recently called for a name change to remove “carcinoma” in order to prevent the exact reaction exhibited by Martina – the anxiety, shock, fear, and misunderstanding. 

Cancer means abnormal cells have become invasive.  In most breast cancers, this means abnormal cells have moved out of the milk ducts into surrounding tissue.  DCIS are abnormal cells that haven’t become cancerous or invasive yet.  They may in the future, but often do not.   Researchers estimate that up to 50% of DCIS won’t ever go on to become invasive, and there is some research suggesting that DCIS may even disappear over time.

DCIS is a product of mammography.  The diagnosis was relatively rare before the widespread onset of mammography.  Now, for every four women diagnosed with invasive breast cancer, one is diagnosed with DCIS.  Has this really meant preventing more invasive breast cancer?  Probably not.  There hasn’t been a corresponding  drop in breast cancer incidence following the dramatic rise in the incidence of DCIS.   There has only been a dramatic rise in the number of women experiencing the fear and anxiety, surgery, and radiation therapy that Martina is experiencing.

Thoughts on Collaboration

It’s been an interesting conference here at the NIH campus on collaboration between academia and industry.  There was lots of talk of the “valley of death” or the wide expanse left between basic research and good ideas, and translation into the clinic.   NIH is trying to help by creating these Clinical Translational Science Awards (CTSA), which are actually consortiums organized around the country to move ideas into the clinic. There are currently 26 CTSAs with plans for 60.  They work to move drugs, devices, and diagnostics from the lab into the clinic.

What I found relevant for breast cancer advocates, is the important role they can play in ensuring that the work stays focused on the health needs.  Some of the directors from the CTSAs spoke of the need for the “pull” from the consumers to drive these collaborations and the translation, rather than the “push” form the scientists or businesses.   As these CTSAs continue to form and evolve, there may be a great opportunity for advocates to get involved and to have influence.

For more information and to find out if there are participating institutions in your area check out the website at  www.ctsaweb.org.

NIH Forum on Collaboration

I’m hoping the snow we are having today doesn’t prevent me from traveling early tomorrow morning.   I’m scheduled to fly to DC for a day in the office, and then out to Bethesda for a forum at the National Institutes of Health (NIH) on Wednesday and Thursday.  The forum is entitled “Promoting Efficient and Effective Collaborations among Academia, Government and Industry.”   NIH director Francis Collins will be opening the forum, and then there will be several panels and breakout sessions.  I’m particularly interested in a breakout session on biomarkers and diagnostic tests for diseases including cancer.  I’m also looking forward to the posters showing good examples of collaborations.

If I make it there, I’ll let you know what I find out!