UCSF Advocacy & Scientific Retreat

As part of my recent involvement as a breast cancer advocate at UCSF's Breast Cancer SPORE ("Specialized Program of Research Excellence", sponsored by the National Cancer Institute), I had the privilege of attending their annual Advocacy Retreat on Wednesday and their Scientific Retreat on Thursday and Friday. I say privilege because I got to hear about the latest and greatest of breast cancer research being conducted at UCSF as well as at other centers, with a couple of presentations given by researchers at Berkeley and MD Anderson Cancer Center.

I learned many new things about the disease, and was overwhelmed in the end with the amount of new information I (hopefully) absorbed. I wanted to give a highlight of some of the topics I heard about, so here it goes:

• I-SPY 2 Adaptive Neo-Adjuvant Trial: UCSF is spearheading a novel clinical trial design for breast cancer with the goal of determining the best possible agents for any given subset of the disease, with the ultimate goal of reducing the time for a drug in development to be approved and used by patients. During the trial, patients will be put into different regimens according to their diseases - it is clear that breast cancer is a heterogeneous disease and as such, requires heterogeneous treatment. For example, HER-2+ patients may get Taxol + Herceptin and maybe a new targeted agent (such as a Tyrosine Kinase Inhibitor like Tykerb or other agent in development), followed by AC, Triple Negative patients may get a PARP inhibitor from the start, and so on. It seems that the neo-adjuvant approach that I followed during my treatment (that is, chemo before surgery) has become more and more popular - especially for locally-advanced (like mine) and inflammatory breast cancers. The trial is adaptive because it will adapt the agents given to their patients during chemo - if a given agent is not working, another one will take its place, and so on. Seems to be a very good idea, one that I hope will attract lots of patients to make the trial successful. The trial will be run in quite a few places across the country, and has just started enrolling its first patients.
  

• Pharmacogenetic Studies in Breast Cancer - Tailoring Drugs to Fit Your Genes: I thought this to be a very interesting area of research, one that also makes total sense to me. This area basically tries to answer the question of why some drugs are effective in some patients, but not in others. Why is that? Because of how each individual's genetic make-up tailors the response to a given drug. The researcher presenting her work told us that the human genome has about 3 billion base pairs of DNA but just one base pair out of 1000 will be different between any two individuals (see, we are pretty much the same after all). The most common variations are what's called "single base pair differences" or "single nucleotide polymorphisms" (SNPs). She gave the example of the drug Tamoxifen that I take (and will take for 5 years) as one whose response varies depending on the presence and type of copy of a gene called "CYP2D6". It turns out that Tamoxifen is a drug that gets metabolized into endoxifen in the body by a process that depends on the CYP2D6 enzyme - it is the endoxifen that is effective in blocking the estrogen that fuels the growth of the tumor cells. Levels of a patient’s endoxifen in the blood are related to the CYP2D6 gene and variants thereof. One study she mentioned showed a 40 % survival advantage in patients having normal copies of the CYP2D6 gene. This gene is not present in about 7-8 % of the Caucasian population - for example, the first mapping of the human genome by Craig Venter did not show this gene because he did not have a copy of it. It was only later that researchers discovered its importance in the metabolism of Tamoxifen. Why is that so important? Because if a patient doesn't have this gene, it means that taking Tamoxifen will be of almost no benefit - another drug may be used in its place. I already did a blood test a month and a half ago and I'm now waiting for the results to find out if I have the gene or not.

• PARP Inhibitors: another talk that we heard focused on this new line of drugs that is showing great promise for those patients who are triple-negative (that is, those whose tumor cells do not have receptors for estrogen, progesterone, or HER-2). One very interesting finding is that some triple-negative cancers have a "basal-like" behavior (very aggressive), while others are apparently curable. So hearing that you have a triple-negative tumor is no longer as bad as it used to be because of all the research that is being put into those tumors and the new drugs and treatments that are emerging every year.

• Central Nervous Systems Metastases (aka brain mets): this to me was the most depressing part of the whole retreat. Depressing because while great strides have been made in the area, the numbers are still somewhat dismal. The researcher presenting her work - Dr. Michelle Melisko - told us that brain mets occur in about 44 % of lung cancer patients, 12 % of breast cancer patients, and 11 % of melanoma patients. The median survival time is only about 30 months from time of initial diagnosis for HER-2+ brain mets patients, but she did say that there are patients at UCSF being treated for brain mets who have been alive for 5-6 years. The distribution and presentation of brain mets include headaches (50%), focal weakness (50%), seizures (10%), and lesion site-specific (aphasia – unable to express, ataxia – inbalance, visual field defect – focal vision defect, encephalopathy – confusion, sleepiness, coma – unusual unless extensive, leptomeningeal disease – lining of brain/spinal cord). Unfortunately it appears that there is no statistically significant difference in survival for those patients that are screened and for those that are not. The treatment includes a combination of radiation therapy and surgery/radiosurgery (like Gamma Knife or Cyber Knife surgery), with systemic therapy (chemo) being explored. Longer survival is associated with age, primary tumor control, ER+, and HER-2+.
  

• The Bay Area Physical Sciences Oncology Center: this was by far my favorite presentation (it had math! Equations! Physics!). We learned about this very innovative and novel area of research that looks into the interactions of Physics, Chemistry, Biology, and Engineering and how those interactions shape and fuel tumors in any particular tissue. The National Cancer Institute has a new Physical Sciences in Oncology initiative that is currently allocating about $200 million a year to 12 centers (including Cornell, yay!) across the country. The goal is to foster a new field of research combining physical sciences with cancer biology and clinical oncology to establish the physical principles that shape cancer. It's all very new (the initiative started in August '09) and exciting. The presenters - Prof. Liphart from Physics at UC Berkeley and Prof. Weaver from UCSF - clearly explained how cancer needs to be understood not only from a biological perspective of single proteins, genes, genomes, or cells, but also from a mechanical/physical/systems perspective of the surrounding tissue (think lego pieces versus a functioning engine made of lego blocks). Made total sense to me. For example, the idea that breast density contributes to cancer risk is intrinsically related to the mechanical/physical forces in the tissue. In fact, as they explained, cancer has always been understood from very early on to be "stiff" tissue with a diagnosis based on shape and hardness (cancer cells tend to go where it's stiffer). Even the Egyptians in 1550 BCE knew about cancer in those terms. So far their research has showed that breast cancer cells migrate faster in a stiffer environment, different types of breast cancers have different structural organizations, and that breast cancers are often enriched for collagen which is highly cross linked and alters the material properties or stiffness of tissue. In their words, cancer is a combination of oncogenic transformation and a stiff microenvironment. I hope that funding in this area will continue to increase because it seems to be taking the right approach to dealing with the complex, system-like cancer problem from a physical perspective that is also rooted in biology.
  

• HER-2+ Breast Cancers: now this was very exciting to hear. Dr. Moasser, an expert in cell signaling at UCSF, is doing groundbreaking research on the Human Epidermal Growth Factor Receptor (HER) family of receptors including EGFR, HER-2, HER-3, and HER-4. His research has showed that this family of cell receptors function and signal as a unit, with its members working closely in pairs. HER-2, for example, is closely tied with HER-3. Drugs that have been successful in treating HER-2+ breast cancers (like Herceptin and Tykerb) target HER-2 by itself without much blocking of the HER-3 activity - with Herceptin being a large molecule (monoclonal antibody) that blocks the signals outside the cell and Tykerb targeting the downstream signaling inside the cell. Dr. Moasser went so far as saying that HER-2+ breast cancers will be eradicated and will be the first type of breast cancer that we will be able to cure. And why does he say that? Because HER-2+ breast cancers have a distinct driver - the overexpression of HER-2 - and as such, those cancers are simpler (of course if it were that simple it would be cured by now) and can be cured by blocking the effects of the driver. He gave the example of CML (a type of leukemia) that is driven by a BCR/abl protein. Gleevec, a drug that was developed specifically to target the effects of this protein, has completely changed the picture of this disease. Before Gleevec, patients had a dismal chance of being alive after 5 years. Now the rate at 5 years is at 95-98 % survival - as close to a cure as you can get. That is, if you can develop a drug against the cancer driver, you can cure it!!! According to his research, HER-2+ breast cancers have not yet been cured because the current drugs are not effective as blocking the HER-2/HER-3 signaling completely. For example, he showed that Tykerb, while theoretically supposed to shut off the whole cell signaling across the HER family, still leaves out some HER-3 signaling behind. His theory is then to develop drugs that more effectively target the HER-2/HER-3 signaling or that affect HER-3 by itself, combined with downstream drugs (like Tykerb), more potent drugs, or higher dose of drugs that completely block off HER-2. He talked about the fact that the dose of Tykerb given today is not effective at destroying the tumor completely in mouse models. He ran a study giving Tykerb intermittently one week on and one week off at 800 mg/kg/day instead of the currently prescribed 100 mg/kg/day and showed that at 8 times the dose, there was a much better chance of completely destroying the tumor. Of course, 8 times the dose of Tykerb would probably kill us of a heart attack or something else, so more research is still needed to find the optimal drug/dose combination to interrupt the HER signaling. He also talked about the potential for siRNA as a potent delivery system. One thing was clear from his talk - his belief (and mine too) in basic scientific research at the lab to come up with the cure.

• Circulating Tumor Cells: a couple of presentations focused on the significance of circulating tumor cells (CTCs). CTCs, as explained nicely here, "are cells that escape from the primary tumor and settle down at a secondary site to cause metastasis". Dr. Park gave a presentation in which he said that the presence of CTCs in a patient's blood is correlated with an increased risk of distant recurrence and death from cancer. Papers (such as this) have concluded that the number of CTCs is an independent predictor of progression-free survival and overall survival in patients with metastatic breast cancer. Apparently about 60% of metastatic breast cancer patients have CTCs; the number is about 30% for non-metastatic patients. A study that was presented showed that Zometa, a drug that is used to treat bone mets and is on trials to evaluate whether it can be used to also prevent bone mets from occurring, when given to patients with CTCs, was able to reduce their number. It remains to be seen whether CTCs are indeed a valuable predictor of mets and disease progression/survival, and whether targeted therapies can be developed to obliterate them before they form a colony somewhere else in the body.
  

• Keynote talk by UCSF Chancellor: Dr. Susan Desmond-Hellman, one of my new heroes, gave an inspiring and motivational keynote talk in which she highlighted the importance of accelerating the cancer drug development process and the potential for the next decade to have an explosion of new drugs. The link above does a pretty good job describing her talk, so I won't go into too many details here. Suffice it to say that she mentioned that there are almost 900 cancer drugs in development, with about a fraction of those being approved each year at an average time of 15 years to market. Only 2 new compounds were approved by the FDA last year. The costs are still huge - $2B per approved drug, which includes the cost of all the failed drugs. Clearly this process needs to be made faster and better. But how? That's the million - er, billion - dollar question.

• Other highlights included a presentation on cancer stem cells, a discussion during the I-SPY2 and Athena talks about a measure called the Residual Cancer Burden ("RCB") and how well it predicts survival (RCB is measured after a neo-adjuvant chemo regimen by evaluating what's left at surgery), a presentation that clearly showed that functional limitations in a patient (e.g., smoking, obesity, hypertension) are independent predictors of survival and in part explain the survival disparity between African-American and Caucasian patients, the fact that 75% of the cancers found in young women (under 40) in the first I-SPY trial were aggressive cancers with a poor prognosis, and a discussion on Physics and cancer focusing on how environmental stresses work with evolutionary forces to shape cancer dynamics.

As you can see, it was packet full of interesting and hopeful information. I hope that I'll be able to take advantage of some of these new approaches if, God forbid, I ever need them.

Scary, Scary, Scary

An article posted on the New York Times web page yesterday exposed some appalling mistakes committed during radiation treatments. Patients were given huge overdoses of radiation that ultimately led to their death. I read the article (click here) last night and have been thinking about the patients and their families ever since. So much so that I felt out of sorts today, stressed, emotional, angry, a mixed bag of emotions all rolled into one.

I thank the New York Times for telling us the story. Hopefully the lives that were lost to the medical/technical mistakes committed will bring new levels of oversight in radiation rooms everywhere.

Digital Mammography Delivers Significantly Less Radiation Than Conventional Mammography and Saves Lives!

"Data from one of the largest mammography trials in history demonstrates that overall the radiation dose associated with digital mammography is significantly lower (averaging 22 percent lower) than that of conventional film mammography and that the reduction could be greater in women with larger and denser breasts, according to a study published in the February issue of the American Journal of Roentgenology.

"The ability to reduce the radiation dose for many women is another step forward for breast cancer screening with mammography - which saves thousands of lives each year," said R. Edward Hendrick, PhD, lead author of the study.

The American College of Radiology Imaging Network (ACRIN) Digital Mammographic Imaging Screening Trial (DMIST) published in 2005, enrolled 49,528 women and found that digital mammography detected significantly (up to 28 percent) more cancers than film mammography in women younger than 50 years of age, premenopausal and preimenopausal women, and women with dense breasts.

In this latest DMIST study, published in AJR, technical data from 5,102 DMIST participants were evaluated, demonstrating that the dose received by women imaged with digital mammography was significantly lower than that received by the same women imaged with standard film mammography.

"The average breast radiation dose per view was 2.37 mGy for film mammography and 1.86 mGy for digital (22 percent lower for digital than film mammography)," said Hendrick.

Digital mammography is similar to conventional except with digital, X-ray images are collected on a digital detector and stored on a computer rather than being collected and stored on film. "While the radiation dose from both film and digital mammography are low, further dose reduction is an added benefit of digital mammography over and above its ability to better detect cancers in women with dense breasts," said Hendrick.

Access to digital mammography continues to increase. More than 60 percent of U.S. breast imaging facilities offer digital mammography and more are acquiring digital services each month. "As digital mammography has now been shown to significantly lower the radiation dose, it is likely that access to it will continue to grow," said Hendrick."

Source: Heather Curry
American College of Radiology / American Roentgen Ray Society

Anti-Cancer: A New Way of Life

I had the privilege of attending a talk on Friday at UCSF by Dr. David Servan-Shrieber, author of the book entitled "Anticancer: A New Way of Life". Dr. Servan-Shrieber is a two-time brain tumor survivor (17 years out), co-founder of Doctor Without Borders in the US, a leading researcher in psychiatry, and an all-together amazing man, contributing so much to the anti-cancer cause.

I had gotten his book (in Portuguese) as a gift from my parents, when they came over last year from Brazil to help me during chemo. At the time when I read it (I got through most of it, but never finished it), I was somewhat overwhelmed and feeling guilty that I could have somehow controlled this and avoided getting cancer. The guilty feelings were made worse by comments and all the things that people say, like it must have been your diet, it must have been your stress, and on and on. I heard it all in the beginning and it was a little too much to handle. But I've come a long way and no longer think that getting cancer was my fault (although sometimes my mind still plays games with me and tells me otherwise). The author has a whole chapter somewhat devoted to this guilt and blame issue - he hints at emotional stresses in his life contributing to his brain tumor.

In any case, his book is full of supporting data and evidence for doing all the right things that we hear about - avoid sugar, change the omega-6s/omega-3s balance in your body and so on. Keeping in mind he's not an oncologist, but a psychiatrist and 17-year survivor of a brain tumor, here's a summary of some main points I was able to write down on my iPhone during his talk:

• We all carry cancer cells in our body. Cancer is a natural part of our human biology. We're all exposed to cancer promoters in our lives - 1/4 of people will succumb to it, the other 3/4 will be protected from it by the body's own natural defenses. Our natural defenses must therefore be strengthened for both prevention and recurrence avoidance purposes. Classical oncology: destroy tumor. Integrative oncology: also strengthen terrain.
• Cancer promoters he talked about: sugar, trans fats and omega-6s/omega-3s balance favoring the omega-6s, chemical exposure, sedentary lifestyle, lack of social support, lack of sun exposure and vitamin D
• He showed a study linking a high glycemic load to ER+/PR- breast cancers
• Avoid soy oil (the one widely used in Brazil for cooking for example), meat that is not grass-fed (grass is very rich in omega-3s, if cows don't eat grass and eat corn they only get omega-6s), eggs today have 20 times more omega-6s than omega-3s so when eating non-organic eggs avoid the yolk and try to get farm-fresh, cage-free, organic eggs, avoid atrazine pesticides (prohibited in Europe but not in the US), air out dry cleaning to prevent the chemicals from being stuck inside the plastic bag and impregnating the clothes, avoid BPA of heated plastics, avoid pesticides and inseticides, avoid chemical cleaning products, avoid skin contact with aluminum
• Vitamin D is crucial for everyone, he suggested 60 ng/ml for cancer patients (Lappe 2007 study - 1100 UI a day reduced risk in 78% in the studied population)
• Studies that he mentioned validating the power of diet, exercise, and stress management: Ohio State study by Andersen (2008) showing a 68% reduction in mortality, Cancer magazine/journal (I'll look it up when I have a chance and post it here); Pierce (2007, Jnl of Clin Oncology) - exercise and dietary changes by themselves do not show an impact on survival, but when combined they do; Surth 2003 study published on Nature
• The power of green tea: Zhang 2009 Int. J. Cancer study - 89% reduction in breast cancer rate with mushrooms (have to check the study to find out what kind) 2-3 times a week and green tea 3 cups a days
• The anticancer plate: 80% vegetables (add turmeric powder, garlic, onions, thyme, oregano, marjoram, rosemary), the rest whole grains and small fish (sardines in olive oil are great), a fruit or some squares of 70% dark chocolate for dessert is ok (Yay, I'm a chocolohic and find it hard to give it up)
• Stress by itself does not cause cancer (Lillberg 2001 Int. J. Cancer study with Finish women, Visintainer Seligman 1982 Science study on stress in rats)
• Do not understimate the power of a good support network of friends and family (Kroenket US nurses study)
• Mobile phones and blood brain barrier study (Salford 2003) - especially for children under 12. When talking on a cell phone, use a blutooth device and headphones and keep it away from your head
• In short, cancer=loss of equilibrium between the cancer promoters and the cancer inhibitors. Promoters: sugar, tobacco, alcohol, omega-6s, chemical pollution, sedentary lifestyle, powerlessness without social support, lack of sunshine. Inhibitors: anticancer phytochemicas, omega-3s, detox phytochemicals, physical activity, social support network, sunshine/vitamin D.

As you can see, it was a talk packed full of information. UCSF will make it available online at some point and I'll post the link here when they do. While I'm not following all of his guidelines by any means yet, I'm trying to adapt myself to them as soon as possible. I'll read his book again and recommend it for anyone who believes on an integrative approach to fighting (or preventing) the disease.

The Crosses We Carry

Courtesy of a fellow blogger and breast cancer survivor:

We complain about the cross we bear but don't realize it is preparing us for the dip in the road that God can see and we cannot.

Whatever your cross, whatever your pain,

there will always be sunshine after the rain...

Perhaps you may stumble, perhaps even fall;

But God's always ready, to answer your call....

He knows every heartache, sees every tear,

a word from His lips, can calm every fear...

Your sorrows may linger, throughout the night,

But suddenly vanish, by dawn's early light...

The Savior is waiting, somewhere above, to give you His grace,

and send you His love.

Be kinder than necessary, for everyone you meet is fighting some kind of battle!

Herceptin # 9 and Record Breaking Delay Day

Yesterday I believe I broke my record for waiting to be seen by my oncologist: a whopping 3 hours! I had arrived at the Stanford Cancer Center early, mistaken that my appt for a blood test was at 9:40 am when in fact was at 10:40. I waited around a bit, and then got the needle inserted into the port, vitals, and blood work done by 11 or so. I then went downstairs to the clinic to wait for my appt with the oncologist at 11:40. The clinic was full, so I wasn't expecting to be seen early, but hopefully at least on time or just with a little delay. Around 12 or so, I was called on by the nurse and thought great, looks like they're on time today!

Little did I know that that was not the case at all - I waited and waited and waited and saw my oncologist close to 3. Good thing I had brought a couple of magazines along (finished them in the waiting room), a great book ("Half the Sky" by Nicholas Kristoff and his wife), and my iPhone with my new favorite app installed: Kindle by Amazon (currently reading "The Breast Cancer Wars", another great book). She apologized for the delay as usual, and given that I'm used to it already, I didn't complain or was upset at all. I had taken a nap, and had read quite a bit undisturbed.


The oncologist fellow that had seen me before my oncologist had also apologized for the delay, and I shrugged it off, saying that they must be really busy with lots of cancer patients. She added that they had a lot of difficult cases that day, with some patients who are not responding to treatment and need to evaluate new treatment options with the doctors. So I felt fortunate again in the scheme of things, thinking that hey, I got 3 hours of life, 3 hours spent waiting, but 3 hours nonetheless. 3 Hours that are so precious for cancer patients who are wondering how much more time they have left, 3 hours during which thousands of people lost their lives in Haiti. So now you see how my perspective has changed, and I don't stress or complain about things like delays in doctors' ofices anymore. For I am alive and well, and truly have nothing to complain about. I am blessed to be here enjoying every second of the day, every precious moment that is given to us.

I reflected on this during my hike this morning, when I saw a most gorgeous rainbow between two clouds when I reached the top of the hill. Life is so beautiful and precious and we truly have to appreciate every little bit of it. I was very sad yesterday for the victims of the earthquake (including 20 Brazilians so far, mostly soldiers on an UN mission, but also the head of a children organization that had done so much for poor and indigent kids in Brazil), and for a family that I had read about in the Stanford Medicine newspaper available at the Cancer Center. A family that lost a brilliant man, a Stanford anesthesiologist and professor, at the ripe age of 34, to colon cancer. A son, a father of a 3-year-old boy, a husband, a researcher, a professor. So many people gone yesterday, to cancer, to earthquake, to heart attacks, and so on. I more than ever truly believe that all of us have a responsibility to ourselves and to others to live life to the fullest and to improve upon the conditions of life on our planet. Life is too precious to be wasted away in meaningless pursuits. But I digress.

All is well with me. My visit with the oncologist went very smoothly. We talked about the fact that I've been feeling very bloated lately and my doctor thought it prudent to order a Metabolic Panel blood test to check my liver (in the morning I had done a blood test to check my CYP2D6 to see how well I metabolize Tamoxifen, more on that later). We talked about whether I should repeat any CT/PET scans (I haven't done any since my diagnosis) but we all (my doctor, her fellow, and I) agreed to wait. I seem to be doing great, and we're going to operate on the assumption that the cancer that was in my body is indeed all gone. I had no indication of it being present anywhere else when I was diagnosed, and certainly no indication of it being present now.

I was also lucky to have bumped into my research nurse on the hallway. I hadn't seen her in a long time, and it was great to catch up. She said that they now have 18 patients on the clinical trial I was a part of (when I started there were only 6) and that all of those patients are doing great. So far no one has recurred, including a woman who had a gigantic tumor like me that was also in the lymph nodes in her neck (she's 3 years out from diagnosis). She told me to continue to be hopeful and optimistic, that there were new drugs on the arsenal being developed, especially for HER-2+ breast cancers like mine. It was great hearing all the positive results from the last Breast Cancer Conference in San Antonio that happened in December.

I asked her some other questions of studies I had read and then I was all set to go back to the ITA room upstairs to get my blood work and my 90 min Herceptin infusion. It was then that I learned about the Earthquake, and was able to follow it on CNN while getting my treatment. My blood work turned out fine, and I left the center after 7 pm, sad for those that lost their loved ones, sad for those that lost their lives, sad for those battling much worse cancers than me, and happy to be alive.

Not "Every Woman Counts" in CA

CA has become the first state to follow the new misguided recommendations for mammograms starting at age 50. The state has decided to cut $10 Million from its "Every Woman Counts" initiative to provide mammograms and cervical-cancer screening to low-income women. What this means is that from now on only those low-income women who are 50 and older will be able to have free access to these life-saving tests.

I find this appalling. What is this saying to low-income women everywhere? That they're not valuable enough to count? That they are not worthy of being screened when they need to? It's now up to the non-profits, advocacy groups, and religious organizations everywhere to help these women get the tests they need. Hope this doesn't repeat in other states.