The Genetics of Breast Cancer: The Research Starts Here

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
• 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