Category Archives: breast cancer metastasis

ASCO 2015: No change in metastatic breast cancer survival found at one Canadian institution, 1970 – 2013

This in itself is bad news, but the investigators also noted some alarming trends in the aggressiveness of metastatic disease once it emerged in later years.

The purpose of this study, not formally presented at the 2015 ASCO Annual Meeting but published in conjunction with the meeting,  was to look at survival of metastatic breast cancer patients from 1970 through 2013 at a hospital in Montreal.  Using a tumor registry, investigators found 1079 patients who had developed metastatic disease, and divided them into 4 cohorts according to the diagnosis of the metastatic disease (cohort 1: 1970-1995 (339 patients), 2: 1996-2000 (292), 3: 2001-2005 (249) and 4: 2006 plus (199)).

The median age of diagnosis of metastatic disease increased over time, from 54 to 58 years of age, and the time until metastatic diagnosis was significantly delayed, from 4.2 years to 5.7 years after initial diagnosis.  However, overall survival did not change, from cohort 1 to cohort 4 (initial diagnosis until death). So while the appearance of metastatic disease was delayed, this did not result in increasing survival.

The investigators hypothesize that a parallel increase in the use of adjuvant hormonal therapy, such as tamoxifen, might explain the delay in the development of the metastatic disease, but that perhaps this therapy was also leading to a drug resistance, making the metastatic disease harder to control.  A disturbing trend was that the aggressiveness of the disease when it appeared increased between cohort 1 and 4: the percentage of patients with visceral disease (metastatic disease appearing in organs such as the lung and liver) when first diagnosed with metastases increased from 33% to 45% between cohort 1 and 4.

The investigators conclude ” In our institution, no increase in overall survival was noted between the initial diagnosis and death throughout cohorts 1 to 4, but the significant increase in time to progression from initial diagnosis may reflect that adjuvant therapy delays disease progression.”

It’s been awhile since I’ve posted a blog entry.  I’ve been learning a lot about the trends in research and treatment directed at many other tumor types beyond breast cancer, as part of my job as an oncology news editor.  Now I’m hoping to occasionally stop by to share information and insights I’m gathering along the way that might be helpful for breast cancer advocates. I’m particularly interested in sharing developments in immunotherapy, or therapy aimed at boosting an individual’s unique defense against cancer development and spread.  When these therapies work – so far only in a subset of patients, particularly those with melanoma, lung cancer, or bladder cancer – they often work for the long haul, not just for a month or two.  These developments are causing a buzz in the oncology world, and I think offer the most promise for making meaningful differences in women’s lives, changing these dismal numbers for those who develop metastatic disease.  Several studies are currently underway to look at these therapies in breast cancer.

My Last Day

 “I’m convinced that eradicating breast cancer won’t happen until we understand a lot more about breast cancer metastasis, the spread of cancer to other parts of the body.  People die from the metastases, not the primary tumors, and understanding how and why it happens, and how to prevent it, should be a research priority.”

“Despite widespread awareness campaigns and massive fundraising efforts over the years, breast cancer is still the second leading cause of cancer death among women.  There have been small steps forward in combating the disease but we need much, much more.”

These are words I wrote back in 2009, when I launched this blog.  Today is my last day working at the National Breast Cancer Coalition, and I will be retiring my advocacy hat, at least for awhile. I felt compelled to look back at my early thoughts on breast cancer and advocacy.  I’ve had many experiences and learned so much over the last four years. I expected to cringe at my early words, that they might seem naive. And yet, these thoughts still ring true. In the end, what I learned was that the goals of my advocacy as a recent breast cancer patient, were not misguided or naive, but that money, politics, and influence are difficult drivers to navigate.

I was right about the breast cancer industry, that powerful influences were distracting us or preventing us from making progress. I just had the opportunity to experience some of that industry up close, and to understand the forces we are up against.  I learned that breast cancer advocacy is as often about a strategy to navigate around influence and ego as it is about the development of a research strategy. It is a combat sport, leaving bumps and bruises, and even a few scars.  I’m sure it is the same with any efforts to bring about major change.

But the need for change remains the same, four years later.  We do need to do much, much more.  We shouldn’t settle for small, barely noticeable improvement in breast cancer mortality, but hold out for significant progress against this disease. And we need to understand metastasis to do so. I was reminded of dear Maria as she commented on those early words on my blog, responding to my thoughts on metastasis with some information on research she had read about. “It’ll be fascinating research to follow,” she wrote.   Maria died from breast cancer metastasis this year and it was a tremendous loss for so many of us, as I wrote about in May.  But she was only one out of 40,000 to die from the disease this year, every one of those women with a circle of family and friends experiencing a terrible loss. I still believe that with all of the attention and resources focused on breast cancer, there must be a way to change this for the future, for our daughters.

I’m encouraged to see some change in focus since 2009.  There is more discussion about metastasis, a recognition of the importance.  Groups are coming together to focus on the needs of women dealing with metastatic disease and on the need to understand and prevent metastasis to achieve real progress against the disease.  I suspect there will be collaborations across cancer groups as we learn more about the biology of cancer, that there will be a recognition that the similarities across sites probably outweigh the differences.  I’m hopeful that this change in focus, and the new energy and collaborations involving advocates will not just create another arm to the industry, but will result in real change in the future.

As for me, I am returning to medical journalism. I am going back to the International Medical News Group, a place I worked during my twenties as a medical reporter.  I will be a managing editor for oncology.  I’m looking forward to working with friends from many years ago and with new colleagues, and learning more about the broader world of oncology.  I’m not discounting the possibility that learning more about all types of cancer, new treatments and approaches, will help me in some way as a future advocate, but for now I am taking a break.

I do hope I continue to cross paths with the many wonderful, and passionate, advocates I have met along the way. It is your energy that will bring about change for our daughters.  And I want to thank Fran Visco, president of NBCC, who has been doing this for so many years, for taking a chance, and giving me the opportunity to work as a telecommuter to offices in DC.  Her fortitude continues to inspire.

May 2014 bring good things to us all.  Happy New Year everyone!

Inaugural Advocate Leadership Summit: Where are we in 2013?

 

These were comments I gave during the opening plenary session on the breast cancer world in 2013. My presentation followed presentations by Dr. Silvia Formenti, Dr. Susan Love, and Dr. Dennis Slamon and our session was moderated by advocate Amy Bonoff.

Photo: Group Photo from the Inaugural Advocate Leadership Summit

Good morning.  So we’ve heard a lot about where we are today with breast cancer, and a little bit about where we need to go.  It’s clear that a lot needs to change. Over 300,000 women will be diagnosed this year with in situ or invasive breast cancer but at least one third of those women will have been overdiagnosed, put at risk of toxicities from treatments they didn’t need.  And though screening has led to an increase in the diagnosis of early breast cancer, particularly DCIS, the rate of those diagnosed with Stage IV disease has not declined, but instead has been holding steady at the same rate for the past 30 years. I would tell you the rate of women diagnosed with recurrences every year, but I don’t know.  It’s not tracked.  But I do know that the median survival for all women with metastatic breast cancer has also remained constant, at about three years. 

The good news is that we are preventing some recurrences – we have seen steady, incremental declines in breast cancer mortality since the early 90s – but the bad news is we don’t really know why.  We do not know how to save the lives of individual women. The overall picture of recurrences is murky, we don’t know much. As I said, we don’t track these women. It’s like the world wants to ignore the true nature of breast cancer, a disease that can hide out for a few years or many before reappearing.  No medical oncologist can truthfully tell an individual woman how to prevent a recurrence, or if she is indeed “cancer free” once she has had a diagnosis of breast cancer.  As patients ourselves and watching our friends, I think most of us would agree, it feels like a crap shoot.  Good luck or bad luck. 

And so there is much that must change.  We need fewer women being diagnosed with breast cancer in the first place.  We need to understand prevention, prevention of lethal disease, and just as importantly, we need to understand how to prevent those with non-lethal disease from being brought into the system, lowering their quality of life, putting them at risk for toxicities needlessly, some of those toxicities deadly, and straining the health care system with increased costs.  And we need to understand how to prevent recurrences and metastasis.  So much focus is on the primary disease, ignoring the fact that the majority of women die of metastasis, and most of those experienced metastasis after a recurrence.

So why has so little changed?  I’ve spent a lot of time thinking about this, and I think it is because the world of breast cancer has grown exponentially, explosively, and in so many directions, way beyond the disease itself.  So many people have become invested in breast cancer and everything surrounding it, way beyond the patients themselves. All of this attention has caused distraction, misguided focus in the wrong places, and worse yet, brought tremendous investment in the status quo. 

Because breast cancer has garnered a lot of attention it has attracted so many people to attach to it – many businesses have thrived directly, mammography providers, biopsy device businesses, hospitals, pharmaceutical companies, oncologists, to name a few. And then there are businesses with no direct connection but that use cause marketing to drive profits, or to counteract bad PR, and this is where we get more bizarre partnerships each year – we can vacuum, pump gas, drink hard liquor, and bake for the cure. Breast cancer is the mother of all cause marketing.

But then we also have scientists who are pursuing new knowledge about cells, genetics or biochemistry, whatever their interest, which is great – but they know there can be good avenues for their funding if they somehow link their interests to breast cancer, and they do.   And non-profits with various agendas find ways to link their cause to breast cancer, knowing concern about breast cancer will drive their own influence and fundraising.  Politicians even get into the act for the women’s vote, whether they help light up pink bridges or express outrage at new mammography guidelines, they can show their support for women’s issues.

Breast cancer is so much more than a disease, it is an industry, a feel good cause, a fear for all women, an inspirational journey for women’s magazines.  In fact, I would argue, you couldn’t dream up a better consumer situation for profit and growth with strong forces for maintenance and keeping the status quo.  Let me see if I can explain what I mean:

With breast cancer we have half the population at risk, the half that is most compliant, most likely to defer to authority.  They are at risk of something that is very scary, that can take away so much, parts of the body, sexual identity, hair, and worst of all life. They are constantly reminded of that risk when they shop, go online, read a magazine. They have very little reliable information about the causes of breast cancer, so it will seem almost random, creating great anxiety and fear, and creating a great market for doing something, anything, to protect oneself and to contribute to a cure. 

That fear, the compliance, the trust of authority all leaves women vulnerable to overdiagnosis and overtreatment, but is a boon for business.

Think about treatment decisions.  Women are the caretakers.  We are willing to take it all, add it on, add it up, give me everything, anything that contributes one iota to more time with our families.  At whatever the cost, to ourselves, our bodies, our bank accounts, no matter how small the promise of benefit.

And then the disease itself contributes by being so complex; it is not one disease, though portrayed as if it is to the public. There is no easy answer.  There is tremendous opportunity for scientists, who are in the business of discovery, of finding something new, exploring the seemingly infinite number of mutations and pathways associated with breast cancer.  The more we learn, the more it seems that each individual tumor is unique, with its’ own unique fingerprint, most likely unique causes, and most definitely unique responses to treatment.  And these tumors aren’t frozen in time, but continue to evolve and change.  A fascinating playing field for science.    No question, a lot of resources dedicated to discovery in breast cancer, but not so much in translation to the clinic. And, not so much to discovery upstream, earlier on in the disease or in the normal breast, the kind of discovery that could lead to prevention of the disease.  But who does that benefit besides our daughters?

So much change is needed.  Don’t get me wrong, there are many hardworking, dedicated people focused on making positive change for women and future generations.  But they often face difficult challenges within the system.  So this is where you all come in.  WE, all of us together, can be one strong, powerful voice calling for change. 

And so now I want to talk a little bit about breast cancer advocacy.  Where we have been and where we need to go.

First of all, what is an advocate? An advocate is defined as someone who speaks, writes, or stands up for something or someone; someone who supports or promotes the interests of another. 

In the early days of breast cancer advocacy, this is exactly what was done.  There was a need to bring attention to the disease, bring it out of the closet.  And this was done successfully. Women can speak openly and freely about the disease.  But advocates went on to do so much more than this, speaking out about the needs of breast cancer patients.  And in particular NBCC advocates, spoke out and were successful in obtaining increased access to medical care for women with breast cancer, and increased federal research funding directed at the disease.  Scores of women and men have been empowered and educated, and now have a seat at the table where decisions are being made that impact those with breast cancer.

But now we need to kick it up a notch.  We need to be the advocates for change in the breast cancer world.  We must see ourselves as not only advocates, but activists, defined as those who take direct, vigorous action to bring change.

You as our leaders must understand this better than anyone.  Breast cancer advocacy has become diluted by so many who seek to use advocates to promote their own agenda.  Be wary of who or what you are advocating for when you are recruited as a breast cancer advocate.  Put the task through the BCD2020 lens.  Am I seeking change here?  Will this contribute to ending breast cancer?  Or am I contributing to the status quo? Things have gone awry in the breast cancer world and we, as activists, must seek to turn things around, seeking change rather than protecting the status quo. We need to demand more focused research with the end results in mind. We need more translational research. We need to focus more upstream, even to the normal breast, so we can understand prevention.  And we need to measure what matters.  And that is what this Summit is all about.  We will be learning, we will be brainstorming new ideas, and we will be making plans for that direct, vigorous action that will bring change.

And I want to end with the positive.  We do have some of this happening already.  Particularly, with NBCC’s Artemis Projects, we are demanding focused research with the end results in mind.  These are experiments that will try out a new way of doing things, and hopefully be a model for others.  We will have an opportunity to hear about some of these efforts in the next session.  But we have only just begun. And we need so much more to happen.  We are counting on all of you to work with us to help make it happen.  So let’s get it done.

 

 

 

Remarks at the Collaborative Summit on Breast Cancer Research

Collaborative Summit

I attended the Collaborative Summit on Breast Cancer Research in Washington D.C., held January 31- February 1. The goal of the Summit was to gather researchers, funders, advocates, and industry representatives together to assess the breast cancer research landscape and to develop collaborative projects for moving forward. Below are the remarks I gave during the opening plenary panel on the breast cancer research landscape and on NBCC’s current projects and priorities.

I am excited to be here and to have the chance to talk about the bigger picture of breast cancer research, where we have been and where we should be going. So much of the year is spent down in the weeds when it comes to breast cancer research, when we attend the ASCO meeting or SABCS, or when we review grant proposals, so it is gratifying to have this opportunity to for all of us to pull our heads up from the weeds and to discuss the long view.

And for me, the long view, means thinking about my 13-year-old daughter. Where do we need to be by the time she and her friends are adults? Are we on track? Will things be dramatically different in ten, twenty, thirty years when it comes to breast cancer? Or will mothers, grandmothers and young women and even men still be dying of breast cancer? Will we know by then why breast cancer cells can lay dormant for 15 years to reemerge and metastasize? Will we know how to eliminate those dormant cells from the beginning? And what about women who have aggressive disease from the get-go. Will we understand why it developed and more importantly know how to stop the progression for the long-term?

Unfortunately, I don’t see dramatic change on the horizon with current approaches. The ACS predicts that over 300,000 women will be diagnosed this year with in situ or invasive breast cancer. Dr. Gil Welch and others predict that between 30 to 50% of those could be considered overdiagnosis. We continue to add more women into the equation, putting them at risk of harm from treatments, and yet, are we seeing a difference in the measures that matter? Yes, we have seen steady, incremental declines in breast cancer mortality since the early 90s, but there has been no acceleration in this decline. And do we know what this really means? What IS working for women and what is not? Do we know how many women have died from the treatments? Do we know if death from breast cancer is being delayed rather than prevented? Are we really any closer to knowing how to prevent breast cancer or a breast cancer death for an individual woman?

What we do know is that the rate of diagnoses of Stage IV disease has remained constant for 30 years. What we do know is that 40,000 women and men will die from the disease again this year. What we do know is that the median survival for metastatic breast cancer has remained constant, at about three years.

With billions in resources and decades of effort, we see discovery of new targets, and development of new agents, that extend life by three to four months at a time, if we are lucky. We are learning a lot about the DNA of breast tumors, and the layers of complexity involved, but are we really gaining a better understanding of the why and how of breast cancer? The kind of understanding that will allow for development of gamechangers?

A pharma analysis report prepared a few years ago concluded that with what is currently in the pipeline, and based on historical trends, the median survival for metastatic breast cancer will inch forward from three years, to three years and six months by the year 2021. Important progress and critical efforts, yes, but is it good enough? No, it is not good enough. We can and must do better. We need new approaches to complement the old ones. We need new ways to look at the disease. We need to find approaches that give us hope of doing better. Targeting of mutations alone, in a disease that constantly grows and mutates, will never be enough.

In 2010, NBCC set a deadline. By the end of the decade we need to understand much more about metastasis and about development of primary breast cancer, so that we can prevent deaths and end this disease. The deadline is a tool to cause disruptive change. The purpose is to shift the focus, to look at the disease differently, to consider new approaches that give us hope of doing better.

How do we get there? To achieve success we have to do more than bring everyone together who works in the field, increase funding, and see what happens. We need to demand more focused research with the end results in mind. We need to bring new perspectives to the table. We need more translational research. And we need to measure what matters. It may just take having specific goals in mind, timelines, and yes, deadlines to get us there.

Many say to us, that’s not how science works. But, I know how science works. I did graduate work in nutritional biochemistry at Cornell University, I carried out a large thesis project involving lactating rats, looking at the impact of malnutrition on milk composition. I know that science works by asking questions, and figuring out how to test theories about the answers to those questions.

So what if we can all agree on what those questions should be? Questions that will help drive us to an understanding of how to prevent deaths from breast cancer? Science can work towards meeting goals and yes – even meeting deadlines. I know I had to answer my research questions in a certain time to finish my thesis and graduate. Scientists meet deadlines all the time. Right now, in the field of breast cancer research, we have many people asking many questions in an infinite number of directions. We are producing incredible volumes of information. But for all of that effort we are seeing minimal benefit for women. Something has to change. We need leadership and coordination of efforts, sharing of information, all of us working together on common goals. We need the will to ask the right questions, and the resources to explore those questions. And then we have to measure what matters to judge success.

NBCC has spent the last two years exploring how to do this on a small scale with what we call Artemis Projects. These are a series of collaborations among patient advocates and researchers from diverse perspectives. The purpose of the collaborations is to develop strategies, research plans and timelines for answering key breast cancer questions. Patient advocates are there to make sure efforts are always focused on the end result.

The first of our Artemis Projects was launched in 2011, bringing together a group of advocates and scientists to take a strategic, systematic yet broad approach to the development of a breast cancer preventive vaccine within five years. We bring together a group of close to 40 each year to assess progress and to readjust plans. We also hold smaller meetings to bring together experts to bear on particular issues as needed, and have an online community for the project to keep things moving in between meetings.

As most of you know, we don’t typically fund research directly. But through the generous support of National Philanthropic Trust (NPT), NBCC has awarded two seed grants as part of this project, one to Dr. Paul Spellman and Dr. Joe Gray of Oregon Health and Science University to identify possible vaccine targets using existing and developing human genomic data within different breast cancer subtypes.

And a second seed grant was awarded to Dr. Paul Ewald at the University of Louisville, and Dr. Vladimir Belyi of The Cancer Institute of NJ to look at infectious agents and breast cancer. Bioinformatic tools will be used to take a systematic approach to intersect the genomes of known viruses and a broad array of cellular pathogens to identify their presence and prevalence in breast cancer genomes relative to normal breast tissue. Initial data from both of these seed grants will be presented at the next annual meeting in March.

We will also be kicking off a second Artemis Project on Metastasis in June to focus on tumor dormancy. As with the Artemis Project on the Preventive Vaccine, our goal is to bring together investigators with diverse perspectives to brainstorm and develop innovative strategies for accelerating progress.

In summary, I think we do have the will and the resources to come together on asking the right questions. We have heard from others this morning about new initiatives focused on prevention and metastasis. I see positive steps being taken to prove that pharma analysis wrong. If we can keep the end result in mind, where we want to be when all of those 13 year olds are 21 year old adults and beyond, I feel hopeful we can change the course. I look forward to the rest of the meeting for further discussion on how we are going to get there. Thank-you.

Random Acts of Science and Business: Reflections on the San Antonio Breast Cancer Symposium

After attending my fifth San Antonio Breast Cancer Symposium it seems, once again, that we are inching forward ever so slowly in improving survival for some women, but at a great cost to many.  Much effort is going towards breast cancer research, but these efforts seem diffuse, with a hit or miss strategy.  Many results never reach the clinic.  Those that do may or may not lead to marginal improvements for some, but most often add risk of toxicities for many. Thousands of researchers and oncologists once again gathered to hear about studies focused on comparing different doses, different schedules, different combinations of treatments, with some showing marginal improvements in survival, most showing no difference.  Very few presentations focused on how to reduce the risk of toxicities from treatment for the increasing numbers of women being diagnosed with early breast cancer, many of whom may have been fine with no treatment at all.  Almost no presentations focused on preventing the disease in the first place.

I like to imagine how different it could be if there was a mission-driven approach to breast cancer research, and everyone was coming together to strategize about achieving very specific goals, rather than diffuse pursuits in many directions.  What if there was a coordinated effort throughout the year to answer a few directed questions that could lead to understanding how to prevent deaths from the disease?  How exciting it would be to come together each year to hear about that kind of progress.

Instead, the presentations I heard often seemed driven by the needs of pharma or business, but not women.  How can we recapture the market for a drug going off patent? Or how do we move the drug to another stage of the disease and capture a new market?  Or the needs of scientists.  Many presentations this year looked at associations between genomic profiles and various factors of the disease or treatments.  This is elegant science, which leads to papers and new lines of laboratory research for next year, but I didn’t hear much evidence that this work was leading to benefits for women.

A few presenters said we may be going about it all wrong.  Dr. Fatima Cardoso, in a presentation on treatment guidelines for women with metastatic breast cancer, said we need to think of metastatic disease as a different disease and study it as a different disease, not as grounds for studying adjuvant treatment of early breast cancer.  The current model is to develop a drug that shrinks tumors, prove its efficacy in the metastatic setting, and then move it into the adjuvant setting to prevent recurrences.  And add it on to existing standard of care to see if it improves survival.  The problem, said Dr. George Sledge in a presentation on tumor dormancy, is that agents that can halt progression in a metastatic setting may be completely different from those that can remove residual disease after surgery for early breast cancer, or that maintain tumor dormancy and prevent a reemergence of the disease.  I would also say that another problem of this add-on approach to breast cancer treatment is that while sometimes bringing marginal benefit, this approach continues to escalate the risk of treatment toxicities.

Our work must continue as advocates for women, to right this ship, getting researchers to focus on the appropriate questions that will lead to meaningful progress and lower toxicities.  This year, we remain hopeful that a new class of drugs, antibody-drug conjugates (ADCs), will alter cancer care, bringing greater efficacy and at the same time greatly reducing the harms of treatment.  These ADCs can deliver chemotherapy directly to cancer cells, resulting in cell death, while avoiding harm to normal cells.  But they must be evaluated on their own, and not simply added to regimens of systemic chemotherapy.  We continue to advocate for the company  (Genentech), that developed an ADC for HER2+ breast cancer called T-DM1, to evaluate the new drug in early breast cancer without systemic chemotherapy, to finally give the promise of targeted breast cancer treatment, with lower toxicity, a chance to be achieved.

Specific findings reported at this year’s symposium:

CDK-inhibitor

This was one bright spot at the meeting.  Encouraging results were presented from a small study of a new agent, done in two parts, with just under 200 women who had ER+ advanced breast cancer.  The agent, which is identified as PD 0332991, was developed from the work of Dr. Dennis Slamon and colleagues, funded by a DOD Innovator Award. It is an inhibitor of cyclin-dependent kinases (CDK), necessary for DNA synthesis.  In the first part of the study, women were randomized to receive PD 0332991 with letrozole, or to receive letrozole alone.  In the second part of the study women were screened for a biomarker, abnormal levels of the CDK protein.  The good news is that women who took the CDK inhibitor had a median progression free survival of 26.1 months, compared to 7.5 months for the women who took letrozole alone. The disappointing news was that the effort to identify a biomarker of response beyond ER was not successful.  More low white and red blood cell counts were reported with the new drug, but were readily managed and produced few complications for the women.  A phase III trial of the CDK inhibitor begins in 2013.

Avastin

Though FDA approval for Avastin in the metastatic breast cancer setting was revoked last year, clinical trials of the drug are continuing, and we continue to get reports.  I wonder how many women are still receiving this drug and what it would take for researchers to stop these trials.  Two studies were presented this year – the BEATRICE trial, looking at Avastin to prevent recurrence in women with triple negative disease, and the LEA trial, looking at Avastin in combination with hormonal treatment for first line treatment of metastatic breast cancer.  In BEATRICE, a trial of over 2500 patients, the three year recurrence rate was virtually the same for both arms of the study, with greater toxicity in the Avastin arm.  In LEA, investigators were hoping to show that Avastin if given without chemotherapy, would be more beneficial.  But results from the trial of 380 women showed no differences in overall survival, and in fact, there was a trend toward lower survival in the Avastin arm, though this wasn’t statistically significant.

Eribulin

Results were reported from a phase III trial of eribulin mesylate for women with previously treated metastatic breast cancer, showing no significant improvement in overall survival, when compared to capecitabine.

Letrozole for Lobular Carcinoma

Lobular carcinoma accounts for approximately 10% of invasive breast cancer, and is usually ER+.  An analysis from BIG I-98, a study comparing letrozole with tamoxifen for preventing recurrences in post-menopausal women, was presented showing that women with lobular cancers were deriving greater benefit from letrozole, than women with invasive ductal carcinoma. Previous results had failed to demonstrate an overall survival advantage with letrozole for all of the women in the study, but this subset analysis did find a greater overall survival advantage with letrozole vs. tamoxifen for women with invasive lobular carcinoma.

Faslodex

Results from CONFIRM, a study of different doses of Faslodex for recurrent or metastatic breast cancer, were presented showing a median overall survival of 26.4 months for the higher 500 mg dose of Faslodex compared to 22.3 months for the smaller dose of 250mg. At least one serious adverse event was experienced by 8.9% of the women receiving the higher dose, compared to 6.7% receiving the lower dose.

Dose Dense Chemotherapy

A ten-year follow-up analysis of adjuvant dose dense chemotherapy, given every two weeks and at a higher dose, instead of the standard dose every three weeks, showed a benefit in overall survival.  In this study of over 1200 women with 4 or more positive lymph nodes, 10 year OS rates were 69% for those on the dose dense regimen, compared with 59% for those receiving the standard regimen.  Nine cases of leukemia were reported in the dose dense arm vs. two in the standard arm.

Leukemia risk from treatment for early breast cancer

From clinical trials results we know that adjuvant treatment for breast cancer increases the risk of developing leukemia.  A review of the records (a NCCN database) from over 20,000 women treated for early breast cancer found an overall cumulative risk of developing leukemia after ten years of 0.27%.  The women who developed leukemia tended to be older, and the risk increased in those receiving chemotherapy vs. no chemotherapy, and for any radiotherapy vs no radiotherapy.  No increased risk was observed if a taxane was added to an anthracylcine chemotherapy regimen.

Herceptin

Results were presented at this symposium and earlier this year at a European meeting on the optimal duration of Herceptin treatment for HER+ early breast cancer.  The HERA trial found no difference in recurrence or survival between one or two years of treatment, and the PHARE trial, which was designed to determine if six months did not give a worse outcome, had inconclusive results.  One year of Herceptin treatment remains the standard of care.

Tamoxifen

The ATLAS study (Adjuvant Tamoxifen – Longer Against Shorter) was the one most covered by the media this year.  In this study, over 6800 women who had completed five years of treatment with tamoxifen for early breast cancer were randomized to continue tamoxifen for five more years or to stop treatment.  Compliance was approximately 80% and a benefit was found for the longer treatment, but it didn’t show up until after it was completed, in years 10-15 following diagnosis. The benefit was modest and the risk of side effects did increase.  Breast cancer mortality was 15% for those women who stopped tamoxifen at five years, compared to 12.2% for those who continued for ten years.  The cumulative risk of recurrence was 21.4% for women who took tamoxifen for ten years, compared to 25.1% for those who stopped.  The rate of endometrial cancer was 3.1% in the ten year group, compared with 1.6% in the group that stopped at five.  There was also an increased risk of pulmonary embolism in the ten year treatment group, though there were no differences in the risk of stroke.

Radiation Therapy

Several studies on radiotherapy were presented.  Most notably, ten year follow-up from the START trial demonstrated that three weeks of treatment is at least as safe and effective as the standard five-week schedule of treatments.  Researchers with the TARGIT-A trial, looking at a single dose of radiation delivered internally vs. whole breast externally delivered radiation, presented preliminary results showing no differences in breast cancer deaths but a decreased mortality with the single dose from cardiac related deaths and second cancers.

Summit on Prevention of Metastatic Breast Cancer

When NBCC set a deadline for ending breast cancer, we knew a key to reaching that goal would be gaining a better understanding of metastasis, and learning how to prevent the process from taking women’s lives.  This weekend we are taking an unprecedented step to reach that goal by bringing together scientists from different fields with passionate, knowledgeable advocates, to challenge each other to look at the issue broadly and in new ways, and to seek attainable solutions.  We are bringing together investigators who are currently looking at the biology of breast cancer metastasis – the genetics, the cellular mechanisms, and the role of the immune system – with others who have created mathematical models of metastasis, or have been applying evolutionary theory to cancer progression, or are problem solvers from other fields, such as a former DARPA project manager and physicist.

This will not be a typical scientific meeting.  There will be no formal presentations.  The 31 scientists and advocates will divide into groups to first diverge, and explore all of the different ways to view breast cancer metastasis and prevention.  Then we will converge, as a large group, to determine the most viable approaches for moving forward, and develop recommendations for next steps.  We will work together to see how different perspectives can intersect and complement each other, and ultimately, lead us to an understanding of how to prevent breast cancer metastasis from taking women’s lives.  We are not interested in incremental change.  We want to see leaps and bounds.  We believe this requires a broad, systemic look at the problem, and bold new ideas.

Science writers will document the work of the summit and produce a report on the recommendations.  After the summit, NBCC will determine how best to further the recommendations in 2012 and beyond.  Stay tuned.

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.

Metastatic Tumors ARE Different From Primary Tumors

Great research published today in Nature.  Canadian researchers have identified the complete genetic code for a metastatic breast tumor and compared it to the genetic code for the primary tumor.  This was in human breast tumors (the metastatic tumor found nine years after the primary) – not in a mouse or laboratory cell line.

Why is this exciting?  Because there were differences in the codes.  There were 19 additional mutations in the DNA of the metastatic tumor that weren’t there in the primary tumor.  The next step is for scientists to figure out what these differences mean.  How are these changes in genotype (or DNA) changing the behavior of the tumor cells?  Once scientists know that, targeted therapies can be developed to interrupt the metastasis or spread of these tumor cells.

For those of you who want the scientific jargon, the investigators sequenced the genome and transcriptomes of an estrogen-receptor positive metastatic lobular breast cancer and found 32 somatic non-synonymous coding mutations present in the metastasis. They then measured the frequency of these somatic mutations in DNA from the primary tumor of the same patient. Five of the 32 mutations (in ABCB11, HAUS3, SLC24A4, SNX4 and PALB2) were prevalent in the DNA of the primary tumor removed at diagnosis 9 years earlier, six (in KIF1C, USP28, MYH8, MORC1, KIAA1468 and RNASEH2A) were present at lower frequencies (1–13%), 19 were not detected in the primary tumor, and two were undetermined.  The authors conclude that a low to intermediate grade primary tumor goes through significant mutational evolution during the metastatic process.

Great research, eh?

Surgery May Increase Survival in Stage IV Breast Cancer

Study results presented today at a European Cancer Organization conference in Berlin  may give physicians a reason to rethink the standard of care for Stage IV or metastatic breast cancer.

Treatment for women who are diagnosed from the beginning with a Stage IV breast cancer, or one that has spread to other parts of the body, is  typically focused on systemic, or whole-body treatments, such as chemotherapy.  Surgery to remove the primary tumor is usually not a priority in the treatment of metastatic disease.

However, researchers in The Netherlands found significant differences in survival between those who had had surgery to remove the primary tumor versus those who had not. In a retrospective study of 728 patients, the researchers discovered that those patients who had received surgery survived an average of 31 months, compared to 14 months for those who did not receive surgery. The five-year survival rates were also significantly different – 24.5% for the surgery group, compared to 13.1% for the non-surgery group.  Having had surgery was an independent prognostic factor even after adjusting for age, period of diagnosis, the number of metastatic sites and different types of treatment.

The researchers suggest that removal of the primary tumor reduces the number of circulating tumor cells in the rest of the body, or perhaps reactivates the immune system.  They are doing further analysis to determine if those who received surgery presented with less severe symptoms and perhaps had less severe disease.  They also plan to expand the study to look at the records of 10,000 patients over the last ten years.  In addition, the researchers would like to work with the Dutch Breast Cancer Research Group to set up a national randomised controlled trial to prospectively study the effect of surgery in Stage IV breast cancer patients.

Lots more work needs to be done to address the needs of women with Stage IV metastatic disease.  But this is one, small, encouraging step forward.

Research results presented today in Berlin, by Dr. Jetske Ruiterkamp, a surgeon from the Jeroen Bosch Hospital, Den Bosch, The Netherlands, at a European cancer congress, ECCO-15 and ESMO-34.

Prevention of Metastasis?

I’m convinced that eradicating breast cancer won’t happen until we understand a lot more about breast cancer metastasis, the spread of cancer to other parts of the body.  People die from the metastases, not the primary tumors, and understanding how and why it happens, and how to prevent it, should be a research priority.

Commentary published online today in the Journal of Clinical Oncology makes some interesting points about breast cancer metastasis and raises some good questions.  Last year, researchers were surprised by findings in a study of bishphosphonates for bone loss in early breast cancer – the premenopausal women who took the bisphonsphonates had  not only less bone loss, but less bone metasases,  less loco-regional spread of the disease, and less spread to other parts of the body.

Dr. Philippe L. Bedard and Dr. Martine J. Piccart-Gebhart, in the article published today,  Sowing the Soil for Cure?  Results of the ABCSG-12 Trial Open a New Chapter in the Evolving Adjuvant Bisphosphonate Story in Early Breast Cancer,  ponder what the results mean and introduce several important questions.

Do breast cancer treatments that decrease bone density make the bone fertile ground for bone metastasis? Do bisphosphonates prevent this?

But why did the bisphosphonate drug appear to decrease the risk for loco-regional recurrence and spread to other areas besides bone?  Does the drug do more than just destroy the fertile ground for tumor growth? Does the bisphosphonate perhaps destroy tumor cells that were spread very early in disease, even before the growth of the primary tumor became apparent?

Very important questions indeed.  Let’s hope the surprise results from last year continue to stimulate discussion, questions, and most importantly research.