Additional Info
- Audio File hadassah/hd002.mp3
- Doctors Peretz, Tamar
- Featured Speaker Tamar Peretz, MD
- Specialty Director of Hadassah's Sharett Institute of Oncology, Hadassah Medical Organization
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Guest Bio
Dr. Tamar Peretz is the head of the Sharett Institute of Oncology at Hadassah Medical Organization in Jerusalem. She is one of the premier breast cancer doctors/researchers in Israel and world-renown. She discovered the connection between the BRCA1 and BRCA2 gene mutation and Ashkenazi Jews.
Learn more about Tamar Peretz, MD -
Transcription
Melanie Cole (Host): According to the CDC, except for skin cancers, breast cancer is the most common cancer and the second leading cause of cancer death among women in the United States. The prevalence of this disease particularly among those of Ashkenazi descent, underscores the continuing importance of Hadassah Medical Organization’ breast cancer research. Here to speak with us today, about breast cancer and the latest advancements in genetic predisposition, is renowned physician professor Dr. Tamar Peretz. She is one of the premier breast cancer doctor researchers in Israel and is the head of the Sharett Institute of Oncology at Hadassah Medical Organization in Jerusalem. Welcome to the show Dr. Peretz. Explain a little bit about breast cancer. What are you seeing as far as incidence and awareness? Are more women getting screened?
Dr. Tamar Peretz, MD (Guest): Good morning. So, what we are seeing general that in the western world, there was until recently an increase in the incidence of breast cancer. And as you already said, it is the second leading cause of death in the United States and the first leading cause of death in Israel. In terms of awareness, we see that there is more awareness, but in my view, it is not enough. Women should know more about their family history, should do more screening, and should be aware of any changes that occur in their breasts or otherwise in their body.
Melanie: So, who is at risk? Is there a genetic predisposition, Dr. Peretz, and what role does this inherited trait play in developing breast cancer? Please tell us how you came to this conclusion.
Dr. Peretz: The fact that breast cancer runs in families is known more than 150 years. It was first discovered or told by French doctor and everybody knows the story that in several families that they know or they heard of; there was a story of breast cancer. Today, we know that it is not only breast which brings breast into the family, but there is a link between different cancers and not necessarily the same type of cancer will develop in specific individuals. What I mean, is that it is possible that the father or the grandfather had prostate cancer and then the mother had ovarian cancer or pancreatic cancer and the daughter may develop breast cancer. This is just an example. We know that it is not categorized only by a specific organ. It is estimated today, that about 5-10% of all breast cancers are inherited. In my view, probably it is higher because we still did not recognize all the genes which are responsible for this inheritance. But definitely, the number is not small. And the risk factors are obviously as I said, any cancer in the family, not necessarily breast cancer, young age, particularly diagnosis of breast cancer diagnosed in the family, bilateral breast cancer and other rare factors like previous radiation, a woman that was radiated for example, for Hodgkin’s Disease at a young age. It maybe that the Hodgkin ’s disease was in the genetic background and she is at higher risk also to develop breast cancer. But the main things, again, are history, particularly in a young age of any cancer.
Melanie: Dr. Peretz, women are confused. They hear the word BRCA gene in the media. Do all women have the BRCA gene and it is really just a mutation of this gene that is the risk? Please explain a little bit about it for us?
Dr. Peretz: So, the normal gene which has a lot of factors that are important in the development of the human being. The normal gene exists if every human being. Mutations, namely changes in the gene occur in a certain percentage of individuals, not necessarily women. The incidence of this change, the mutations in the BRCA 1 and in the BRCA 2, all together in the western world is 0.3%. However, in the Ashkenazi women, it was found that the incidence of the mutation is much higher. It is 2.5%. Which means and again, not only women, if we see 40 Ashkenazi women walking on the street, or men, it means that one of them is a carrier of this gene. Once a person is a carrier, it increases his or her risk to develop breast cancer as well as other tumors as well. The second is a variant but also there is a higher risk, but we know today, for pancreatic cancer, for colon cancer, for prostate cancer in men and maybe more tumors as well.
Melanie: So, who should get tested for this genetic mutation? That’s a question many people have and do you feel that all women should be tested, but more specifically women of Ashkenazic descent?
Dr. Peretz: Okay, so first of all, it is important to understand that the BRCA gene, the mutation in the BRCA gene is responsible only for about half of the genetically predisposed breast cancer cases. Which means that if a woman develops breast cancer and in her family, there are cases of breast and other cancers and it is obvious for us that her breast cancer is on a genetic background. Only in 50% of such cases, the BRCA gene will be found. Other genes also exist. I will not mention them now, but today, we go more and more into the testing of panel of genes, namely not only BRCA. This is on one hand true for all the western and also for the eastern world.
As for Ashkenazi women, because of the high incidence of the BRCA gene in Ashkenazi women; it is questionable whether all Ashkenazi women will be tested. The situation today, is that even women that have a family history of other tumors as well are not being tested and I think that first of all, we should make an awareness of the importance of BRCA testing in any woman that has or had a family history of any cancer in her not only mother but even grandmother or a sister of a grandmother. The question whether all Ashkenazi women should be tested is a very difficult question. The reason is, that we know today, what the expectations are or what may happen to a woman that is a BRCA carrier with a family history. We do not have enough information for women that are tested as BRCA carriers and there is no family history in the family.
We know that if there was a history of ovarian cancer in the family, a BRCA carrier will develop more ovarian cancer. So, there is importance also of the family history. So, a woman that is tested with the genetic background or family history in her family, we know what to tell her and obviously, she should be tested. As for the other Ashkenazi women, they should consider to be tested, but they should know this is what also should be included in the counseling, that the recommendations are not as I would say scientifically based as for those with a family history. So, in summary, I suggest that all Ashkenazi women will be tested, knowing that the information that will help for those without family history is not complete enough as of today.
Melanie: And now the big question is what do you do with the info and how do they use this information to make informed decisions? What must go along with this testing?
Dr. Peretz: So, there are several issues. I think the most important one, is the fact that towards the age of 40 and this depends on the specific mutation but I will not go now into details. We recommend that the woman will have preventive oophorectomy. The reason is that today, we don’t have good means to diagnose ovarian cancer at an early stage. We know that ovarian cancer is a devastating disease, so we recommend prophylactic oophorectomy as prevention.
Obviously, the consequences of that recommendation are tremendous. Because if a woman wants to plan her family life, how many children she wants to have, if we recommend to have oophorectomy at the age of 38, she should start planning her life earlier, how she would like to see her life. It is important to mention that today there are many means to preserve by IVF, by other technologies to preserve an oocyte or part of the ovary and we do have cases that women that did get pregnant with their own fetus after they had an oophorectomy. But anyway, the factor of oophorectomy is the most important one and respect of planning of life.
The second thing is the question of mastectomy, which is open, although in many cases, we recommend it. It is also important to say that although women have a preventive oophorectomy, we do give them hormone replacement therapy which we know that it does not make any harm. So, many women think that if they will have a preventive oophorectomy, they will go into early menopause, it will affect all their life and sometimes this is a reason to hesitate not to have testing or not to have the oophorectomy. So, this is not the case. Obviously, it goes along with a list of tests to again a regular follow-up, to see a doctor every six months and there are specific recommendations based on the specific mutation and on the family history.
Melanie: So, what does current research indicate for future developments in treatment? Give us a little blueprint, for future research and what you are doing specifically.
Dr. Peretz: So, basically, there are two aspects. One aspect is the question of early detection and prevention and this is regarding the healthy women. In my research, in my group, is trying to identify a possible way to further identify who are the women that are very high risk. Namely, if a woman is a BRCA carrier, she is 22 and we are asking ourselves how will look her future. We are looking at a possibility that by specific testing of the DNA in her circulation, we can predict who will develop breast cancer or who will develop ovarian cancer. We try to identify very early stages of the development of the possible development of cancer years before in the blood. And this will refine our recommendations, who should have oophorectomy, who should have mastectomy and at what age. This is the research that is at very early stages, but this is also connected with the fact that also in cancer patients, we are trying to identify today, DNA of specific organs or specific tumors in the blood. So, by specific blood testing, not a very sophisticated to test, not MRI, not CT scan, but a blood test or circulating DNA. It may be that we will – it will be possible for us to predict what kind tests or what kind of preventive surgeries a woman will have. So, this is one aspect for women that are healthy. This is also true for men.
The other aspect is how the presence of BRCA affects therapy. We know today, that the specific type of tumor that develops depends on the genetic background of the patient, namely breast cancers that develop on the background of BRCA mutation. The cancer is different than the cancers that developed in women that are not a BRCA carrier. And the consequence of this is that there is a different therapy. What we are doing today, we are looking at the molecular profile of the tumor of women with the BRCA mutation and not BRCA mutation and we are trying to identify what specific therapies are better for those women or another one and this is another refinement of the precision medicine when we try to select for each woman or for each individual the best treatment for the cancer that she is carrying. This is fascinating and this opens new horizons for better cure for cancer.
Melanie: It is absolutely fascinating, Dr. Peretz, and in summary, what would you like women to know about breast cancer awareness, the latest advancement in genetic testing and asking the right questions, being their own best health advocate and taking care of themselves?
Dr. Peretz: Yes, so, I think the first thing is to be aware of your body, to see whether there are any changes. The second thing is to learn more about your family history. The third is to look for genetic testing, genetic counseling which will fit into this profile of my body, my family, myself and then follow the recommendations. It is very important to say that in terms of prevention, it is quite clear today, that what is good for other diseases is good for cancer as well, namely to have a healthy – to follow a healthy lifestyle, to have physical activity and not to be overweight, to have a good night’s sleep. We know more and more especially now that you probably know that the Nobel Prize was given to three scientists that found the biological cloak and we know today that the biological cloak effects many hormones and many factors that develop in the body, so I stress again how although it sounds very simple to have a good night’s sleep and again physical activity and not to be overweight. On top of all the other scientific things.
Melanie: Thank you so much Dr. Peretz, for being on with us today. This is Hadassah On Call New Frontiers in Medicine brought to you by Hadassah, the Women’s Zionist Organization of America. The largest Jewish women’s organization in America. Hadassah enhances the health of people worldwide through medical education, care and research innovations at the Hadassah Medical Organization. For more information on the latest advances in medicine please visit Hadassah.org, and to hear more episodes in this podcast series, please visit Hadassah.org/podcasts, that's Haddasah.org/podcasts. I’m Melanie Cole. Thanks so much for listening. - Hosts Melanie Cole, MS
Additional Info
- Audio File hadassah/hd001.mp3
- Doctors Lotem, Michal
- Featured Speaker Michal Lotem, MD
- Specialty Head of the Center for Melanoma and Cancer Immunotherapy at the Sharett Institute of Oncology, Hadassah Medical Organization
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Guest Bio
Michal Lotem, MD, is the Head of the Center for Melanoma and Cancer Immunotherapy at the Sharett Institute of Oncology of the Hadassah Medical Organization in Jerusalem, Israel.
Learn more about Michal Lotem, MD -
Transcription
Melanie Cole (Host): Melanoma is the most dangerous form of skin cancer. It occurs when there is damage to the DNA that controls cell growth. And it is most often caused from sunshine or tanning salons. While melanoma is the 19th most common cancer worldwide; its rates are higher in countries with sizeable fair skinned populations including Israel, where it is among the ten most common cancers. In the US, the rates of melanoma have been rising for the last 30 years. In 2017, it is estimated that there will be up to 87,000 new cases of melanoma in the United States and up to 9.000 deaths from the disease. Here to speak with us today about melanoma is Dr. Michal Lotem. She is the head of the Center for Melanoma and Cancer Immunotherapy at the Sharett Institute of Oncology of the Hadassah Medical Organization in Jerusalem Israel. Welcome to the show Dr. Lotem. What is melanoma? How is it different than normal skin cancer and why is it so deadly?
Dr. Michal Lotem, MD (Guest): So, Melanoma is a skin cancer that starts with the normal pigment producing cells of the skin and we need these cells in the normal situation to induce tanning. Tanning gives our protection from the sun, from the ultraviolet rays of the sun. And those melanocytes which are our protectants can transform into a malignancy and the name of the malignancy is melanoma which is quite – in the sense that most situations this is the black or brownish type of a skin lesion and so for this reason, it is not too difficult to diagnose as long as there is suspicion. And why is it deadly? This is a good question. And not always do we know why a certain malignancy would be more aggressive than others and maybe it is because after years and years of exposure to ultraviolet rays, then the melanocytes gain many, many mutations. The mutations are defects in the DNA control that add and add and accumulate and endow the cancer with more aggressive traits and features.
Melanie: So, how is it identified? When should you go to the doctor to find out if something might be melanoma? Would we spot this on ourselves, Dr. Lotem?
Dr. Lotem: Part of the public education is to identify moles but it is quite difficult and I think the thing we must be very much aware of is the changing mole. A change is something that should attract our attention. In situations that we have many spots on the skin, some of them from the sun, some of them are completely benign tumors. In these situations, it is always very helpful to have a specialist do a skin examination. Dermatologists are helped by dermoscopy. Dermoscopy is a magnifying device that helps dermatologists see all of the tiny details and diagnose melanoma. I would recommend that any person should have his or her skin checked at least once a year and if the dermatologist then says this is a problematic skin then do it twice and even three times a year. Because it can never be too much.
Melanie: That’s great advice and so if somebody does get that diagnosis, which can be very scary; what is the typical first line of treatment once it is identified?
Dr. Lotem: It is very important to remember that actually the majority of patients diagnosed with melanoma will be just fine with a simple excision, surgery, simple surgery taking the melanoma out with a safety zone around the melanoma of normal skin and most of the patients with need nothing. I even hesitate to use the word patient. It is people diagnosed with melanoma. It is the minority of people diagnosed with melanoma that eventually develop metastases and the treatment that we would advise can either be prevention treatment we generate in order to reduce the risk that the patient will develop metastases and then we have of course treatment for those unlucky people who did not have early enough diagnosis of the melanoma and eventually developed metastases.
Melanie: So, you are working on some research regarding strengthening the patient’s immune response to a tumor with vaccines. Who is this for? Tell us about this research doctor.
Dr. Lotem: We try to follow the example of infectious disease. If you look to what happened to many deadly infectious diseases that we actually generated a vaccination and thus we induced immune protection and most of the people in society will never have this disease. In the situation of cancer, and especially in the situation of melanoma; this is not simple because melanoma has a lot of similarity with the normal tissues of the body. So, number one what we do right now is generate a vaccine that is made by the patient’s own unique tumor. Today, we know that there is a unique single gene to every individual cancer and it is not just that we can have a general melanoma vaccine, but we need to have the exact features of every patient’s melanoma. This is possible only to patients with advanced melanoma, like metastases to the lymph nodes. The lymph nodes are removed and the patient is fine. There is no sign of disease existing at the time that we offer to receive the vaccine. But we know that these patients are under danger of developing disease which can be as high as 75%. So, one of the scientific efforts that we are doing right now is to deliver a unique individual vaccine to melanoma patients and this probably in the end will not be a sole means of prevention but it will have to be combined with other drug class that is called immune check point modulators and that is very powerful proteins that are given to patients by infusions and these proteins can invigorate, strengthen the killing capacity of immune cells and what we try to do is initially generate immune cells against melanoma and once they have been formed; we strengthen them using the immune check point modulators to have a strong and effective protective immune response.
Melanie: Absolutely fascinating. So, what does current research indicate for future developments and treatments? Give us a little blueprint Dr. Lotem for future research in immunotherapy, targeted therapy, combination therapies. What are you doing?
Dr. Lotem: it is important to know that a lot of the advances in cancer development are actually achieved by the drug companies, by Pharma companies and of course we participate in many clinical trials that are initiated by the leading Pharma companies testing, leading new drugs. Most of them are in the class of immune modulators. These are biologicals that aim to help the immune system be strong enough in order to effectively fight against cancer cells. What is more futuristic and more imaginative is to try and for those patients in whom you cannot induce immune response; to generate for them premade immune cells that are actually you endow with the capacity to kill. So, what you do, is you take a blood sample, by the way, this is research that is done in living centers. It is not yet in our hands in the phase of clinical trials but it is a direction for the future. You take cells from the blood of a patient and during genetic engineering, you give these cells the capacity to recognize cancer in a totally artificial manipulation but you end up with a cell that is a good anticancer killer. This is an effort that we are right now establishing together with the department of bone marrow transplantation and Dr. Polina Stepensky in that department.
What we kindly do before we will be more capable in the genetic engineering is remove metastases for melanoma patients that failed all existing treatments and from these metastases using special growth conditions, we grow and expand immune cells. And in the beginning, those immune cells are very few and very weak. But outside of the body, of the patient, we give them idealized conditions. We incubate them and we can expand them until we receive trillions and trillions of these cells and we infuse them back to the patient. The cells called T to more infiltrate in the lymphocytes and the technique is called adoptive transfer. So, we transfer into the patient immune cells that the few initiating cells will actually take and form the cancer then outside of the body, they will expand that to very large numbers and then now that they are in the huge number, now we give them back and -
Melanie: Wow, are you thinking about extending some of these treatments to patients with colorectal tumors, ovarian malignancies and those of the lung and breast possibly?
Dr. Lotem: So, we know that there are tumors which are more likely to induce effective immune response and there are tumors which are less likely to do so and so the colon – the colorectal cancers tumors that develop on the basis of defects in DNA damage repair. Those tumors are excellent candidates for immunotherapy and yes, we have a vaccine program for colorectal cancer. We have a vaccine program for ovarian cancers. Unfortunately, for breast cancer, at the moment, it is much more difficult to induce immune response and probably the triple negative type of breast cancer will be the first where we will see more and more immune approaches offered to patients.
Melanie: What is your best advice, in summary, Dr. Lotem, for prevention? Is putting on sunscreen enough and is it true that melanoma has become more common since sunscreens were developed?
Dr. Lotem: Well, first it is important to realize that some of our patients develop melanoma totally regardless of sun exposure. Those melanomas are in protected areas and part of the reason for their development is genetics. So, genetics plays a role in melanoma development and sometimes you know it is just fate and we should not blame ourselves for that. Part which is about 50% of the melanomas which develop on the basis of excessive sun exposure, the number one problem is when there is a sunburn. It is very important not to get burned and that sunscreens are protective and are helpful. I do not think that there is a rise in melanoma incidence because of sunscreens and most of the community believes that they are necessary and that is probably is my best advice. Do not burn in the sun.
Melanie: Thank you so much. Dr. Lotem, for being on with us today. This is Hadassah On Call, New Frontiers in Medicine brought to you by Hadassah, the Women’s Zionist Organization of America. The largest Jewish women’s organization in America, Hadassah enhances the health of people worldwide through medical education, care and research innovations at the Hadassah Medical Organization. For more information on the latest advances in medicine please visit Hadassah.org, and to hear more episodes in this podcast series, please visit Hadassah.org/podcasts, that's Haddasah.org/podcasts. I’m Melanie Cole. Thanks so much for listening. - Hosts Melanie Cole, MS
