Carmen Calfa, MD, a Breast Medical Oncologist, Assistant Professor of Clinical Medicine and Associate Director of Community Outreach Breast Cancer Program at Sylvester Comprehensive Cancer Center in Plantation talks about the TAPUR trial.
Interview conducted by Ivanhoe Broadcast News in September 2018.
Is breast cancer as prevalent as it always has been? What are we looking at statistic wise?
Dr. Calfa: We still have more than two hundred thousand cases of breast cancer diagnosed every year. And unfortunately we continue to lose about forty thousand women to breast cancer every year. So as long as we lose one patient to breast cancer we haven’t done everything we need to do. And that’s what we are here for, to fight cancer, to conquer cancer.
Obviously we hear because so many of us have had relative, friends, dealing with breast cancer we hear treatments of radiation, treatments of chemotherapy but the truth is sometimes depending on the cancer these treatments don’t work or stop working?
Dr. Calfa: You are right and I think it’s important to share with the patients and the caregivers and anybody out in the community that breast cancer is really a very common disease. It’s really affecting one in eight women. When you really count in a big crowd you will meet a lot of patients that have had breast cancer. The stage ranges from stage 0, pre-invasive, which is curable almost always with the right treatment, to the advanced stage. For those diagnosed with stage 0, depending on the amount of disease, a patient can chose to have a partial mastectomy followed by radiation or a mastectomy, in which case radiation is not needed. To decrease the chances of a new cancer from happening in the same or the other breast, Tamoxifen or an Aromatase inhibitor ca be used for 5 years. The same medications are used to treat or prevent recurrences in estrogen positive invasive breast cancers.
The earlier the stage at diagnosis, the higher the cure rate.
Moving on to the invasive cancers, stage 1-3 is treated with curative intent. Unfortunately approximately a third of these patients can have their disease recur at different sites. At that point the disease become metastatic and the goals somehow change. The focus become quality of life and prolonged survival but the deeper focus is finding the cure for this advanced stage.
The treatment of early stage and locally advanced breast cancer involves a multidisciplinary approach. Surgery is always part of rendering these patients “cancer free”. Radiation, chemotherapy, hormonal therapy, anti Her 2 therapy are used depending on the type of cancer, the type of surgery and the amount of disease.
These therapies are very effective and are able to cure most patients. Clinical trials are ongoing, building upon the already approved treatments, in an attempt to increase the cure rate and further prevent the recurrences from happening. Immunotherapies or targeted therapies are being investigated and the future seems bright.
I advise patients not to delay their treatment looking for “alternative therapies”. Second opinions are good ideas but more opinions add time that a newly diagnosed patient should be carefully watching for.
Like I said the higher the stage at presentation the higher the chance of recurrence usually is.
Screening mammograms are crucial for early detection. Women should start screening with yearly mammograms at age 40 or 10 years younger than the youngest first degree relative diagnosed with breast cancer. Additionally, an ultrasound is recommended for screening when breast are dense.
For patients with a deleterious BRCA gene mutation or other genes, high risk lesions or increased risk due to family and personal history, MRI of the breast can be adjunct to the screening.
Guidelines no longer recommend self-breast exam, however, most of the patients diagnosed before age 40 presented with palpable complaints. We recommend that women know their breast and bring to the attention of their health care provider any significant change. The down side to breast self-examination is that it may create unnecessary anxiety. The way I see it is that it can save your life.
Unfortunately 6% of the breast cancer cases are diagnosed with late stage, with distantly metastatic disease, so called “de-novo stage 4”.
Added to the patients who have their disease recur, these are the patients in most need for novel, more effective therapies.
We’re seeing about five percent of those patients having long durable responses without having evidence of disease. So we are encouraged that some of those patients are cured but we don’t want to be overly optimistic and fail our patients, we would rather keep our eyes on that and just say “you’re great, I don’t see any evidence cancer, hopefully it will stay like that”. Those patients that live with cancer have the biggest need right now. That’s how the patients, those forty thousand, die every year because of advanced metastatic breast cancer that have stopped to respond to therapy.
So what happens when somebody is diagnosed with stage four? We again look at the prognostic makers, a biopsy from the recurrent, distant site should be performed to confirm the diagnosis. Cancer can change, the estrogen positive that was before now it can be negative, the HER2 that was positive or negative now can change again. It’s not the norm, it’s the exception, but it can happen. It implies a different treatment. So anybody that is facing a diagnosis of either a stage four, which is initial presentation with advanced stage or a recurrent breast cancer should have a biopsy to confirm histology. Patient then undergoes approved therapies or chooses to participate in a clinical trial. Treatments tend to be more effective and duration of response longer at the beginning of one’s journey. Every time we have to change a treatment we call that a line of therapy so a patient usually goes through several lines of therapy because cancer out smarts us, unfortunately.
Patients will receive “chronic treatment” with the goal to improve symptoms, quality of life and survival. But most of the time the therapy will eventually stop working and the disease will take over.
Is this were TAPUR comes in?
Dr. Calfa: Yes.
Go ahead.
Dr. Calfa: There are several patients who have gone through several lines of treatment. The more lines you use the less likely that the treatment will work. The side effects start building up and the patient becomes weaker and more tired with more side effects until the point where the patient is unable to tolerate or the chemotherapy no longer works or you have situation where the patient is doing great, she’s finished all the drugs that we have and she looks at you and says, I’m still feeling great what else can I get? And that’s where these new drugs are coming in. And you know we couldn’t be an oncologist if we weren’t really hoping every day that we’re going to wake up to something better and new that will help more than the therapy we had yesterday. Recently we’ve been able to map the human genome. Through genomic sequencing and research we are able to understand better the mechanism of cancer resistance and growth. Many patients say, yeah I had genetic testing. Well the genetic testing is looking at one person’s genes right? So the genes that are giving us the blue eyes, the blond hair or those than can protect us from developing certain cancers.
If certain mutations occur, the gene responsible for a function is unable to do it and, as a consequence, it increases the risk of developing some cancers. So that’s where we’re looking when we do genetic testing. The genomic testing leads to understanding what’s happening in the tumor itself. This genomic testing has become available and we have learned that tumors have certain mutations that are contributing to the tumor growth, metastasis or drug resistance. We look at different options and we look at blocking more than one pathway at the same time. Because when you block one it’s almost like you close one door and the cancer finds two other doors and gets in and becomes stronger, it’s almost like a hurricane, it just gets speed as it goes through. I hate cancer, I hate cancer with a passion.
I hate cancer too.
Dr. Calfa: Every one of us hates cancer. There is just not one of us that hasn’t been affected by cancer in one way or another so we’re all together into this. We learned that our immune system it’s really not doing its best when the cancer happens. The question is how to get the immune system involved in the fight against the cancer? Instead of going after the cells and just getting rid of them it’s just sitting there like nothing happened. So that’s where the new therapies come in to play. Vaccines or checkpoint inhibitors either make the cancer cells recognizable by the immune system or they “take the brake off” and unleash the immune system.
We don’t have to get in to all that.
Dr. Calfa: going back to genomic testing and genomic alterations. If we have certain mutations then there are certain drugs that work and there are certain drugs that already have an FDA approval for that particular mutation in a certain type of cancer that it was studied for. This is where TAPUR comes in. There are patients getting these genomic testing with results potentially showing an alteration/mutation for which a drug was already approved for by FDA, for a different cancer type. Giving the drug off a clinical trial is tempting but not feasible in most cases due to cost.
So what ASCO, our national leading force in the country, American Society of Clinical Oncology did was to partner with seven drug companies and come up with the TAPUR study.
So it’s basically using a drug that has an FDA approval for a different cancer type and giving it to cancers that have that specific mutation. So no longer cares about where is the cancer coming from it just cares if that mutation is actionable and it has a drug that already has an FDA approval.
And that would allow you to be part of the TAPUR trial?
Dr. Calfa: That would allow you to be part of the TAPUR trial. Patients have to be in relatively good shape and have relatively normal vital organ function. Their physician believes that the standard treatment options are not promising or they had exhausted standard treatment options. They have the genomic testing that shows that they have a mutation and that mutation is actionable then TAPUR comes in. The drug is provided by the study and patients are monitored to assure that it’s working and its safe. That’s the goal of TAPUR.
UM is one of the sites but there are several sites across the country right?
Dr. Calfa: TAPUR study started in two thousand sixteen and started really small with one site and they added the second. There are several sites now with Sylvester Cancer Center being the only site in Florida. We offered the trial at different locations as we wanted the patients to be as close as they can with being home. We really have it over the span of Dade and Broward County and accessible to all patients with solid tumor types. I’m the Principle Investigator for our Sylvester site and I oversee anybody’s inclusion, exclusion to make sure that the appropriate candidates are participating.
There is one beautiful thing about this, that there are a lot of minds that look at every case. So it’s really the model, the best example of personalized medicine where you no longer look and say “its breast cancer”, but you found a potentially actionable mutation and a study that would give the drug to the patient.
So, you know how you hear people saying, well my case was discussed at the Tumor board and this is what the conclusion was and all that. Those tumor boards traditionally engaged all the disciplines involved in the care. So radiology to show how the breast looked on mammogram, surgeon to tell if a patient can keep the breast or not, what to do with the lymph nodes. Then the medical oncologist-which I am one of them-comes in and says she needs or she doesn’t need chemotherapy or what the treatment would be. Radiation oncologists talk about who needs radiation and who does not and several other people are part of that care, it really does take a village for every patient from the diagnosis to the survivorship and throughout their life and their journey. And surviving is really from the day of diagnosis I say to patients if you survive that day you know you’re a survivor. It’s just probably the hardest day just being hit with that diagnosis. So that Tumor board now has become even more sophisticated and for patients living with cancer we have now the molecular Tumor board. It takes the question to a deeper level to find out what the molecular makeover of the tumor is and what a trials could look like. And if it’s not TAPUR we have several other precision medicine trials. Some of them are Phase I. TAPUR is a Phase II. Phase II means that we already have safety data, we already know the dose that we have to use for the drug.. Through that molecular tumor board we really identify what’s best. Many patients come with more than one mutation and there could be more options just based on TAPUR or other trials. So the precision medicine and the molecular tumor board discuss the case and we develop the algorithm and make recommendations. The good news is you actually can re-visit this trial. The best news is that we have seen some amazing responses so there is definitely hope.
END OF INTERVIEW
This information is intended for additional research purposes only. It is not to be used as a prescription or advice from Ivanhoe Broadcast News, Inc. or any medical professional interviewed. Ivanhoe Broadcast News, Inc. assumes no responsibility for the depth or accuracy of physician statements. Procedures or medicines apply to different people and medical factors; always consult your physician on medical matters.
If you would like more information, please contact:
Diana Gonzalez, PR Sylvester Comprehensive Cancer Ctr
305-243-8219
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