By Christine Benjamin - October 23, 2012
Moving Forward with Metastatic Breast Cancer
MBCN National Conference
Saturday, October 13, 2012
On Saturday October 13, 2012 (Metastatic Breast Cancer Awareness Day) MBCN held its annual conference in Chicago. The conference is one day long and packed with information covering many topics. There are five general sessions, three breakout sessions, a couple of breaks and lunch.
1. The first general session was given by Virginia Kaklamani, M.D., Associate Professor, Division of Hematology/Oncology at Northwestern and it was entitled: Understanding MBC: How it is Followed in the Clinic and When to Use Standard Care or Clinical Trials.
Dr. Kaklamani discussed the definition of MBC, the pattern of spread based on the type of breast cancer, methods of diagnosis and follow up, and clinical trials. She reported on the difference between each phase of clinical trials and gave a list of questions for patients to ask when considering a trial. Here is a list of the questions she recommends:
- What is the reason for the trial? Why are you doing this trial?
- What phase is the trial?
- How many patients will be enrolled? From where?
- What kind of patients?
- What are the drugs being used in the trial?
- What kinds of tests are required?
- How do I know treatment is working?
- How often will there be CT scans?
- How many visits will the trial require?
- Where do I get treated?
- What is the cost to me?
- What is randomization?
- Is there a placebo?
- Do I know what I am receiving?
- Are there potential toxicities?
- What is the benefit of participating?
- Does the benefit outweigh the risk?
- How long will I be on the trial?
- What are my alternatives?
Dr. Kaklamani also suggested that potential participants be aware of whether the study is helping you or humanity in general. This she feels might help patients make a decision to participate or not.
Lastly, Dr. Kaklamani discussed a study that is evaluating whether or not prolonged survival will result from early local therapy comprising surgery of intact primary disease, as compared to local palliative therapy only in patients with stage IV breast cancer whose disease does not progress during initial optimal systemic therapy. More information about the study can be found here: http://www.clinicaltrial.gov/ct2/show/NCT01242800?term=nct01242800&rank=1
2. Next, I attended a breakout session on Triple Negative Metastatic Breast Cancer (TNMBC) by Dr. Rita Nanda from the University of Chicago.
Dr. Nanda states several known facts about TNBC, including the following: (1) TNBC has different subtypes; (2) research about TNBC is relatively new, and TNBC is defined by characteristics it does not have; (3) as TNBC's are genetically unstable, chromosomes are actively rearranging and gene alterations are ongoing. She concluded that being able to subdivide triple-negative breast cancers into subcategories will help researchers identify new targets for therapy.
Targets that are currently being investigated are: Parp inhibitors, Androgen receptor, Death Receptor 5 Glucocarticoid receptor, P13K/mTor inhibitors, Jak2 inhibitors and macrophages or the tumor microenvironment.
Dr. Nanda presented a slide entitled: Why has it been so hard to find a treatment? The slide goes on to state that "TNBC is not one disease, PARP inhibitors and anti angiogenic inhibitors likely benefit only some women with TNBC (and it is not know which women will benefit), Tumors are genetically unstable and newer technologies and clinical trials hold great promise."
The TBCRC 001: Randomized Phase II Study of Cetuximab in Combination with Carboplatin in Stage IV Triple Negative Breast Cancer by the University of North Carolina and the Translational Breast Cancer Research Consortium. The study "assessed the clinical efficacy of the EGFR inhibitor cetuximab alone or combined with carboplatin as first-line therapy for metastatic TNBC. Cetuximab alone had minimal activity in TNBC; only 6% of patients (2 of 31) responded, although these 2 responses lasted more than 40 weeks. In the combination arm, 18% of patients (13 of 71) showed a response." *
Some drugs that have been effective in the treatment of prostate cancer are being studied for the treatment of TNBC. Recently more doctors are prescribing Metformin (a drug used to treat diabetes) to treat TNBC as well as atenolol (a beta blocker used to treat high blood pressure, anxiety, migraine). Dr. Nanda states the platinum and taxane drugs are "usually the most effective."
3. The next presentation was given by Patricia Steeg Ph.D, from the NCI. In her lecture entitled: A Common Sense Approach to Mets Research to Achieve Results, she broke the talk down into three lessons.
"What it takes to eliminate a metastasis is fundamentally different from what it takes to prevent its formation."
"Most of the compounds that have been tested pre-clinically for metastasis prevent the formation of a metastasis but don't shrink established metastatic lesions. ie: They work on single tumor cells/micrometastases only."
Dr. Steeg spoke about a study involving a LPA1 Inhibitor which showed the primary tumor size was unaffected by the LPA1 Inhibitor. What the study did not report is that the tumor size was unaffected for the period of study which was ten days. At 70 days, however, significant changes in tumor size were noted. Seventy days was outside the scope of the study and therefore findings were not deemed significant.
In another study, Dr. Steeg showed a slide referring to Ki67 Staining of Primary Tumors. Dr. Steeg said this study "blew her mind" because a drug made by Debio, which was developed for fibrosis, caused significant changes in primary tumor. Debio gave us [who is "us?"] the license for the drug, but another pharma Amira had a similar drug that they sold to Bristol Meyers Squibb who declared they would not develop the drug for two indications. It was discovered another pharmaceutical company has a similar drug and is now in negotiations with the NCI.
"The Clinical Trial System is not set up to validate a metastasis prevention drug (unless it also happens to be a cytotoxic or synergize with chemo). If done right, metastasis prevention drugs could prevent initial metastasis in high risk patients and limit the development of more metastases in metastatic patients."
Basically Dr. Steeg feels that "we are approaching metastasis from two different directions," where oncologists want to shrink the tumors of patients with metastatic disease while other researchers want to prevent the formation of mets and additional mets.
4. Living with Metastatic Breast Cancer for those Under 40
Moderated by Roz Kleban, L.C.S.W, Memorial Sloan-Kettering Cancer Center
A panel of four young women living with MBC talked about their disease, their lives, their fears and hopes. The conversation was opened up to the audience and most of the young women in attendance participated. One woman stated that once she was diagnosed with MBC she was "no longer part of a community where I was once embraced," referring to the broader breast cancer community. Others expressed concern about leaving their children, worrying about children with special needs, wondering if their kids will remember them. One woman talked about the stress of losing friends to the disease, saying "when my friends die, it's like watching my own death." Many discussed their feelings of jealousy towards friends not living with MBC as they plan their weddings and births of their children.
5. How Do I Find a Clinical Trial?
Elly Cohen, Ph.D
Program Director, Breastcancertrials.org
Dr. Cohen discussed the different phases of clinical trials and gave a live demo of the newly designed Breastcancertrials.org and how best to find a clinical trial.
6. Treating Pain and Neuropathy
Judy Paice, Ph.D, RN
Director, Cancer Pain Program at Northwestern
Dr. Paice discussed different types of pain including nociceptive pain which is the aching, throbbing sort of pain one might feel in the bones. There is visceral pain that is associated with cramping. She states it is important to be able to describe pain accurately to doctors so the right medication can be prescribed. Dr. Paice suggests keeping a diary or journal indicating the type of pain, time of day, location of pain, what it feels like, intensity, medication taking, dosage and any other information that might be relevant.
Chemo Induced Peripheral Neuropathy is a common occurrence with certain types of chemotherapy. CIPN usually occurs in the hands and feet and can affect balance as feet may not feel the floor as they have before. There are some agents that may be helpful to some who have CIPN: Calcium, Acetly Carnitine, Duloxetine, Glutathione, Oxcarbazepine, Zaliproden, Venlafaxine.
In addition to opioids and non-opioid drugs that may help CIPN, Dr. Paice discussed non-pharma therapies such as integrative therapies like acupuncture, physical measures such as PT, OT and exercise, and cognitive behavioral therapies. She stated it is important to exercise or keep moving.
7. Dr. Steven Rosen
Emerging Research-Hope for Improved Outcomes for the Future
Genevieve Teuton, Professor of Medicine
Director, Robert H. Lurie Comprehensive Cancer Center, Northwestern
Dr. Rosen discussed Biological Response Modifiers (BRM's). According to Medterms.com, biological response modifiers are "substances that stimulate the body's response to infection and disease. The body naturally produces small amounts of these substances. Scientists can produce some of them in the laboratory in large amounts for use in treating cancer, rheumatoid arthritis, and other diseases."
BMR's include monoclonal antibodies, recombinant toxins, vaccines, adoptive immunotherapy, interferons and cytokines, hormonal agents, signal transduction modifiers, transcriptional regulators, anti-sense compounds, angiogenesis inhibitors, proteasome inhibitors, metabolism inhibitors and DNA repair inhibitors.
There are currently a few FDA approved monoclonal antibodies including Herceptin (Trastuzumab), Perjeta (Pertuzumab) and the newest monoclonal antibody drug conjugate Trastuzumab Emtansine or T-DM1 discussed in the EMILIA trial.
Recombinant toxins are proteins made by genetic engineering consisting of a toxin fused to a ligand which binds selectively to a target cell. Recombinant toxins used for cancer treatment generally contain either a growth factor or a recombinant fragment of a monoclonal antibody fused to a truncated bacterial toxin, derived either from Pseudomonas exotoxin or from diphtheria toxin, according to Pubmed.gov. One recombinant toxin linked with diphtheria toxin is approved for clinical use in advanced stage T-Cell lymphoma. Dr. Rosen showed the slide below of a patient covered with lesions before receiving treatment and a photo of the patient after treatment. There was great improvement in the number of lesions.
Next Dr.Rosen discussed vaccines which produce "modest benefits" but did refer to a vaccine for prostate cancer that has been approved by the FDA. He also talked about epigenetics which controls genes and the identification of a second layer of controlling genes that is being looked at in leukemia drugs.
Antisense Oligonucleotide Inhibitors essentially "turn off" genes by binding to the messenger portion of the RNA and inactivating it. Dr. Rosen says Isis Pharma is developing a drug for large cell lymphoma that is showing "great results."
Dr. Rosen also discussed metabolism inhibitors, DNA repair inhibitors and nanotechnology or nanoconstructs which are FDA approved including Abraxane.
8. The last session of the day was presented by Shirley Mertz, MBCN Board Member and woman living with metastatic disease. The session was entitled, Advocacy: Use your Voice to Change Outcomes for MBC. Shirley spoke about the AIDS movement as a model for advocacy in action.
All presentations will be available on-line on the MBCN website: www.mbcn.org
Christine is the Breast Cancer Program Director at SHARE.