Here is Helen Schiff's (NYC-based advocate) speech as she made it in the first Plenary session examining Major Advances in Breast Cancer. My job today is to look at the “major” advances made in breast cancer in 2005, to see from an advocate's perspective if they really are THAT major. Here they are Herceptin in the adjuvant setting. 2) Avastin for metastatic breast cancer. 3) The mammography modeling study that Gil Welch talked about. 4) New findings about breast cancer prevention. But first I would like to step back and examine what HAS been achieved since President Nixon declared the war on cancer in 1971. Examining our past gains gives us a good yard stick with which to measure the recent advances. You can see from the graph that in the first 20 years 1971-1990 the mortality rate did not budge. See the line is completely flat. In 1990 we see a small yearly drop in mortality rates of 2.3% each year up to 2003 the most recent year that statistics are available. That comes to a total drop of nearly 30%. In real figures this means that while in 1971 30 women out of every 100,000 women in the US population died of breast cancer by 2003 the deaths from breast cancer declined to 26.4 deaths per 100,000 women. So 4 less women per 100,000 died from breast cancer in 2003 compared to 1971. Much of the breast cancer community is satisfied with this progress, but I look at it this way. If it took 32 years to reduce mortality rates by 30% it will take us, at this same rate, another 70 years to reach a zero mortality—rate. We don't want to wait that long-that's for sure. What is responsible for this drop in mortality. Most experts think its mammography and chemo or hormonal therapy. It is the increase in the numbers of women over the years who have received mammography screening and adjuvant therapy that are responsible for the yearly drop in mortality over the nineties and into the 21st century. Once there are no more new women to reach with these modalities, mortality rates will stop falling. That is where we find ourselves now. At least almost. The only way to keep the mortality rates falling is through the development of new therapies for women both with early and advanced stage breast cancer. So let me start with Herceptin, Peter Ravdin showed you the data from the Herceptin adjuvant trials. Adjuvant means for early stage breast cancer right after primary surgery. You can see the reason for enthusiasm. I have looked at two year results from major trials past and present and nothing compares. And what makes these finding all the more impressive is that Her2 positive breast cancer is so aggressive. Remember 25% of the women in the non Herceptin arm of the 2 combined American trial became metastatic within 3 years of diagnosis. But before we get carried away with these results, as many have, we should be cautious. Why? Several reasons. 1) Because 19 % of women who were on Herceptin and Adria had to stop treatment due to heart toxicity. If women can't remain on Adria and Herceptin they obviously don’t benefit from it. It is interesting to me that the heart toxicity was so minimized. 2) 3-4% of these women had symptomatic congestive heart failure and % had asymptomatic heart toxicity. We don’t know what does the future hold for those who have asymtomatic heart toxicity. Fortunately, we know from one of the adjuvant trials-- the one sponsored by the Breast Cancer International Ressearch Group called the BCIRG Trial --that Herceptin is not cardio-toxic when carboplatinum and Taxotere were substituted for Adria. We don't have mature enough data to know if it as effective as the Herceptin - Adria combination. The results from this International trial were also the first to show that the cardiotoxicity with Herceptin-Adria appears to be irreversible. This is contrary to what we had been told for years. This heart toxicity is no surprise. It was seen in the metastatic setting almost ten years ago. Advocates ask the question: why then did the two American trials that were eventually combined only look at Adria-Herceptin and no other combinations? Do they think that heart toxicity is the price you have to pay to treat breast cancer? The early stopping of all but the BCIRG trial will prevent long term follow-up to answer such important questions as how damaging is the heart toxicity and how long will Herceptin work for? Another unresolved question is duration of treatment. None of the four major trials looked at a shorter than 1 year duration of treatment. I have been told that one year was arbitrarily selected . I ask why did none of the trials look at a shorter duration . Indeed, a small trial in Finland has shown that 3 months of Herceptin is a as good as one year. Think of the money saved, the toxicities avoided, to say nothing of the convience of a shorter course of Herceptin. Many argue that looking at the proper dose or duration of treatment by adding more arms to a trial would make a trial take more time. Many Advocates, doctors, and drug companies want to get drugs to market as soon as possible. I think it is worth the wait. If we knew a year or two from now that 3 months of Herceptin is just as good as a year the extra time it might take to recruit to an additional arm of a trial the drug will be affordable to many more people in this country and around the world. There would be less heart toxicity. Extending a trial a year or two to find the proper dosing or length of treatment can save more lives than rushing it to market. So it is clear that there are many unanswered questions but the Herceptin data does show that adding targeted therapies to traditional chemotherapies can lead to important advances-- a larger treatment effect than we have ever seen. Also targeted therapies spare a lot of women unnecessary expense, toxicity, and inconvience because treatment is limited to specific types of tumors. This is a big change from the last 35 years which was treating the many to save the few. This was good for the few but not for the many. They suffered the treatment and its toxicities without any benefit. But a targeted therapy is limited by how many women have the target. Luckily, 60% of women’s tumor have estrogen receptors and can use hormonal therapy. Herceptin is only potentially useful for 25% of women with breast cancer- those who over-expresses HER2. Furthermore, from preliminary data, the adjuvant trials show that only 50% of those women benefit from Herceptin. And, we don't know for how long this benefit will last. It is definitely not a cure for most women with breast cancer and it is too early to speculate on how long it will keep women with Her2 positive tumors from beoming metastatic. Avastin like Herceptin represents an important break from our 30 year reliance on chemotherapy. Although, for now, both drugs are being given in combination with chemotherapy. Avastin and taxol given to women with metastatic breast cancer has resulted in an additional 4.6 months time to progression compared to taxol alone . That so much of the breast cancer community sees that as a big advance is only a testament to how little progress has been made in the treatment of advanced disease. It remains to be seen how well Avastin will work in the adjuvant setting-trials with and without chemotherapy are being planned. It is true that drugs that show a small benefit in metastatic disease show a much bigger benefit in the adjuvant setting so Avastin could prove to be another Herceptin. But that still remains to be seen. Avastin currently costs 100,000 dollars a year. This price is outrageous. It doesn't matter how GOOD a drug is if people can't afford it. Compounding the problem, last year Congress passed legislation prohibiting the federal govt from negotiating discounts for the Medicare and Medicaid enrollees to pay the full price for drugs. As drug prices skyrocket the gap in access to quality healthcare is widening. Even those with insurance will have problems affording the copay for Avastin and Herceptin. Such high prices mean that dose and duration of treatment-which is unknown with Avastin- should be established before a drug comes to market not after. Only drug companies benefit from sellings drugs at higher dosers and longer treatment duration. Number 3: (show slide 9) Gilbert Welch has covered the recent findings in mammography screeining. I was appalled by the fact that the findings of the modeling study were used to justify WITHOUT question WITHOUT reexamination the continuation of our policy of yearly mammograms for all women over 40. It was as if no one heard what Don Berry, the lead investigator, said in and interview in the Dec. ? NY Tiimes. He said “mammography causes a 30% overdiagnosis of invasive breast cancer. This means that nearly one-third of all the somen who breast caners were diagnosed on a mammogram have a type of breast cancer they they didn't need to know about. Their cancers would never have progressed had they gone undetected. To me it is frightening to think that of all the women in this room, assuming that we are a representative sample of all women with breast cancer and had mammograms starting at age 40 almost 1/3 of us were told we had breast cancer needlessly. So we have suffered the toxicities of treatment, the expense, and the psychological trauma for nothing. Certainly, women should be informed of these new findings which show that the benfit is small anywhere from a 5-15% mortality reduction and the harm is large. It might be that the huge sums of money spent on mammography- along with the large number of unnecessary biopsies, and needless treatment-- could be better spent on women who ALREADY HAVE breast cancer for drugs like Avastin and Herceptin that they can’t afford. Number 4: (show slide 11) Breast Cancer Prevention is the best way to lower mortality rates. If women don't get breast cancer they can't die of it. It is that simple. Unfortunately, a lot of resources are diverted from prevention to chemo-prevention. Let me make it very clear that prevention and chemoprevention are two very different things. Prevention means finding the causes of breast cancer and then eliminating them. Chemo-prevention is the development of DRUGS to prevent breast cancer. Why is that so bad. Well just look at the Tamoxifen Prevention Trial. For many women in that trial especially older women the incidence of life threatening toxicities like uterine cancer, pulmonary embolism, deep vein thrombosis, and stroke were equal to the number of breast cancers that were prevented. We do not see that as progress-lowering the incidence rates of breast cancer but raising the incidence of other diseases. I call that disease substitution. Leslie Bernstein reported here on the studies she present at SABCS that showed that lack of exercise and obesity raises a woman's chances of getting breast cancer. Certainly this is an important finding from a public health point of view. But I look at it from the point of view of the individual women. The average women's chance of getting breast cancer is about 8% in the course of her life. A 30% reduction of an 8% risk is less than a 2.4%. I'm not sure we can get women to diet or exercise so that they will reduce their risk of getting breast cancer by 2.4%. It will take multidisciplinary teams from different institutions working together to shed more light on what causes breast cancer. Only collaborations of basic scientists, epidemiologists, toxicologists, geneticists, endocrinologists can begin to figure out this puzzle. The NIEHS grants for four centers that are looking at different exposure in very young girls is an important beginning as are the centers of excellence that have been proposed by the NBCC. It is good when speakers can end on an optimistic note. I wish I could. But as I prepared for this presentation I began to realize how daunting a job we have ahead of us. We can feel encouraged about the development of two new drugs-Avastin and Herceptin. At least some of the research community has realized that it is not just a matter of finding the right dose of chemotherapy, the right combination of chemotherapies, and the right duration of treatment. And I am heartened by the fact that the NBCC played an important role in making this happen, much sooner than it would have, through its partnership with Genentech on the Herceptin and Avastin trials. We have shown that Advocates CAN make a difference. The question remains is why the two scientists who played key roles in the development of Herceptin and Avastin-Dennis Slamon and Judah Folkman had problems getting a hearing and/ or getting funding for their work over the years. I wonder how many important ideas, findings and drugs are still being dismissed out of hand? Is advocate involvement in the department of defense breast cancer research program helping in this regard? We can’t make up for the lack of creativity and good science of those who apply for DOD grants. We have much bigger challenges ahead. The most important is guaranteeing everyone the best healthcare available. We are in fact being taken in the opposite directions by politicians who are in the pockets of the drug companies instead of their constituents; Drug companies whose bottom line is more important than developing effective drugs and who set prices that make drugs unobtainable to so many; Research grants that are based on competition between individual scientist when what we really need is broad cooperation and coordination; Weakening of the FDA resulting in drugs coming to the market without knowing if they work and if they do, for whom; advocates being used by drug companies to make their case for early approval of drugs; And a media that misleads the public with its hype of medical breakthroughs. To take on these forces we will have to be much larger, stronger, and much more educated than we are now. We have to educate the American people about the importance of evidence based medicine, the problems of stopping trials early, of accelerated approval. But before we can do that effectively we have to educate our selves. Everyone in this room should take project lead-all three courses and continue their education after that by participating in discussions on leadgradsonline-we have been having a hot discussion right now on the value of Herceptin; Continuing to attend the NBCC advocacy conferences. I made of a bibliography of good books to read and websites to be on. Letter sent January 2008 Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. Support our work with any size DONATION - see left side of any page - for how to donate. You can help raise awareness of CAM.