CATHY TANGCO-ONG (CTO): What is Ovarian Ablation? And how does it help women? What are right medicines or aromatase inhibitors wrongs to take for women who are past menopausal stage. Well, to help us understand, we have a venerable Dr. Francisco Lopez, I'll tell you a little bit about him. Bare with me. I know he'll probably be shy. Dr. Lopez was a graduate from the University of Sto . Tomas in 1989, he completed his internal medicine and fellowship trainings in Medical Oncology and Hematology at the Brown University School of Medicines in Providence , Road island. He pursuit further training in Bone Marrow Transplantation at the city of Hope , Duarte California . After 8 years of training in the US , he returned to Manila in 2002. Of note, he is one of the two Bone Marrow Transplant Specialist in the country and performed the first Autologous Transplant in the country in this year.

 

He holds the following positions, Section Head of Hematology and Head of the Bone Marrow Transplant Program at the Asian Hospital in Medical Center . He's also the Chairman of the Oncology Center in the Dr. Victor R. Potenciano Medical Center and he is a Consultant for the Bureau of Food and Drugs Administration of the Philippines . “ Power of knowledge saves lives” A slogan that he together with the several of his patients Suzette Andrews, Ferdie Figaroa and Achilles Mina, will able to make tangible in the form of a magazine, The Big C. Doc Francis, as he is more fondly known is the chairman and one of the medical advisers of the Big C magazine, the first and only Cancer Magazine in the country. Please welcome Dr. Francisco Lopez.

 

DR. FRANCISCO LOPEZ (FL): Good afternoon! When Suzette called me by cell phone and she asked me for a one liner for my talk this afternoon. So I said, “The Role of my Ovarian Ablation”, and she said, “Ovulation with a letter O?” Then I said, “Suzette, Ablation with a letter “O” will stimulate hormones and not stop the hormones.

 

AUDIENCE (A): (laughs)

 

(FL): This table here shows us the incident and death rate of breast cancer in the United States . Caucasians lead the diagnosis of breast cancer, and then you have the African-American and so on and so forth. If we get the average of the death rate, it is roughly around 20%. If you look at the Philippine data now, this was taken form the Philippine Cancer Society, so it ranks first among women and it surpassed already Cervical Cancer and among all the cancers in women are comprises roughly 25%, In 2005, there will be 14,000 new cases and 6,357 deaths are expected, roughly 45%.

So I think we are far behind from the US data and perhaps we can do better. The survival here in the Philippines 5 years survival is roughly 50%, or 50% of the patients will be alive in 5 years, that another way of looking at it. And in 10 years only 32% of our breast cancer patients will be alive. This is Philippine data. It is a (audience laughing) we will do better, we will do better, believe me. (audience laughing) I think you are 32 in this room all of you 32 will do well. So, age is a risk factor for breast cancer. As you get older the incidence of breast cancer also increases. As you can see here by the time you reach 79, 74, it peaks. Breast cancer in young is not very common. It just that in my practice I happen to get younger patients. So by age 40 the chance of having breast cancer is one 1 out of 236, buy age 80, it 1 out of 9.

 

So when I was doing my training in the States, there was this lady who came to me and said “you know I thought I was safe, that I wouldn't get breast cancer because you were 9 ladies in the group, a group that would have tea, afternoon tea. . . And one already had breast cancer so I thought that I would be safe. Unfortunately, she was the second in the group. So, aside for the risk factors that were mentioned earlier this morning, in the morning lecture about the other risk factors. I will just focus on the risk factor particularly the hormones and the estrogens. If you take Hormone Replacement therapy for more than 5 years, it increases your risk by 1.1% to 1.4%. If your menses start at a young age, age of 10, it increases by 4.5% per year. If you have your menopause at an older age of 50 or older again it increases by 4.5% per year. If your first full birth is at the age of 35, it increases it to1.9%, if your first birth is at the age of 20 or less it's neutral. It's only 1% but if you have your ovaries removed this for whatever reasons prior to the age of 40, it has a protective effect, it's less than 1%, 0.5%. So, this picture I showed this morning, which I would like to show again today, when you look at your Pathology Report, you have what you call your Estrogen and Progesterone receptors. All normal breasts have estrogen and progesterone receptors, so here, you have the receptor and you have estrogen binding into the receptor. Some cancer cells keep the receptor, which we call this, a good feature of a cancer cells. If you lose the receptor, it's not a good feature. So, if it keeps the receptors it's a good feature for two reasons: It has a prognostic value, meaning for those who have it live longer and than those who don't have it and that's shown by data and also you can take the medicine Tamoxifen.

 

So for the next few seconds lets talk about the premenopausal women. This might be a very busy slide, but I will walk with you through it. So, how is estrogen produced in the body? Okay, so… the brain, particularly the hypothalamus which is part of your brain, secretes a hormone called Luteinizing Hormone Releasing Hormone or LHRH , which then stimulates the pituitary gland which is also located in the brain to secrete follicle-stimulating hormone and luteinizing hormones. This in turn stimulates your ovaries to produces your estrogens and your progesterone. Now, in order to stop your estrogen production, which I will further explain later, Tamoxifen blocks the estrogen receptors, Zoladex, which I will explain later tells the brain to stop the secreting the FSH and the LH and of course if you remove the ovaries surgically, you stop also menstruating. And a drug Aromatase Inhibitors or Anastrozole, as an example of which, will prevent the peripheral conversion of your male hormones to your female hormones. So you are post-menopausal you are still producing hormones from the fat, liver, and bone muscles and other tissues, and your Aromatase Inhibitors work in that aspect.. So, in short, Aromatase Inhibitors should only be taken by women who are in post-menopausal. So if you're pre-menopausal and heavily menstruating and are taking Aromatase inhibitors, it's not supposed to be the case, because even if you are blocking this, you are heavily producing it in your own place , so that's the rational there.

 

So let look at a survival craft, this is old data but it just points out one thing. If you are diagnosed at the age of 35 or less, those who are positive tend to do not as good as those who are ER-PR negative. But those who are diagnose 35 years and above, those who are ER-PR positive did better than those who are ER-PR negative. I was also surprise when I attended this conference and they mentioned this data. In fact, the reason is the following; So how do we improve the survival, so perhaps if your ER-PR positive and you are still menstruating and you are talking Tamoxifen, perhaps that's the reason why the survival is not good because your receptors are still being stimulated by your estrogen production.

 

So, how do we improve the survival of pre-menopausal women who are still menstruating or producing hormones? So the notion of ovarian Ablation as stopping the estrogen production is nothing new... The first time it was done was way back 19 th century by Sir Jorge Beatson and what he did on a stage 4 metastatic patient. What he did was he removed the ovaries and when he removed the ovaries he noticed a regression in the tumor in this stage 4 patient. So this was the first documented Ovarian Ablation There are another two ways of doing the ovarian oblation, the other way is by radiating the ovaries. It takes only 10 sessions. For those of you who already had radiation sometimes it takes 33 sessions. This one only takes 10 sessions or two weeks. Then the declined of the estrogen level or the hormone level In fact, takes 2 to 3 months, then it becomes menopause. And the third way was called Medical Castration by giving the drug Zoladex. And if I bring you back to the picture, Zoladex will basically tell your pituitary gland to stop secreting your FSH and LH, that how it works.So, it inhibits your sex hormones. The estrogens level by suppresses in 21 ways and the effect is reversible when you stop the injections so when you stop the injection, there are 60% chances that menses will return. It my group of patients; I would say I think I had two that opted for radiation because it's the cheapest. Others opted for Ovarectomy (you remove the ovaries) or for total hysterectomy because they had other problems going on, like problems in the uterus or cervix, so they said might as well just have a Hysterectomy. Majority of my younger patients are receiving the Zoladex, especially those who are not yet married or who just got married for the chance that eventually they might want to have children.

 

So what happens when (this is a theoretical risk) a pre-menopausal women takes Tamoxifen? There could be a stimulation of the pituitary ovarian axis function leading to high plasma estradiol level, competing with Tamoxifen for the estrogen receptor binding site. So this is your receptor in your breast cancer cell and this is your Tamoxifen that's blocking it if you have this high peak of estrogen, there's a high risk that the estrogen will push out your Tamoxifen and then stay at the receptor. So in order to stop totally your estrogen production, this is what we call complete estrogen blocking. Some form of your ovarian Ablation and your Tamoxifen, a combination of both, to render the patient post menopausal right away. So in this data, they tried it on stage 4 patients and who were given the LHRH Zoladex together with Tamoxifen and Zoladex alone. And they show that women, metastatic women who got the Zoladex and Tamoxifen combination lived better than those who only got the Zoladex alone. This is in stage 4.

 

So let as look at the data on stopping your menses in pre-menopausal women in the adjuvant setting, the early stage of breast cancer. So, this were women who got chemotherapy CMF chemotherapy, and as most of you know … after you get a chemotherapy specially if you are already in your mid 40's or late 40's or sometimes even early 40's. When you get your chemotherapy there's a big chances to become a menopause already after you're complete. But there's still some patients that their menses will recur. Especially if you're young, in your 30's or 20's, your menses will become back. In fact some of my patients there's 20's, their menses don't even stop in spite of 6 rounds of chemo, their menses continue. So, this data shows that after receiving CMF chemotherapy, for those patients whose menses completely stopped after the chemotherapy did better than those whose menses continued. Amenorrhea means wala nang menses. So amenorrhea, those whose menses stopped did better than then those whose menses did not stop. Approximately 15% or 20% difference in terms of survivals so that's big. (pointing to a visual presentation) Here's also another study that looked at the same data, this time those who are were amenorrheic or no menses up to 36 weeks when the chemotherapy was given, and again it shows the same thing. Yes and no. Yes, they are amemorate, and no they were not, again a big difference. Some 15-20%.

 

So, next question is when do we start some form of ovarian ablation? I think that those twp grafts have shown that by stopping the menses there is a benefit already. So, the next question when do we stop the menses? Do we stop it immediately after the chemotherapy, or do we wait for the few months after to which the patient is already menopause or do we wait for the next menses to come back and then only then stop it. There's no clear-cut answer yet as to when is the best timing. In the international conferences, these are the same question that is always being asked. When do we start? There is on going trial looking at this and yung ginagawa nila is 6 months after completion of chemotherapy, Chine-check nila yung hormone level. When they check the follicle stimulating hormone and the estradiol level to see if the patient is menopaused or not, kung hindi then we can start the treatment. Take note, even if you're not menstruating your hormone levels can still be in the pre-menopausal level, Sometimes it takes one year for your hormone levels to drop to post-menopausal level, after your last menses.

 

The next question is how long you do we keep you, especially for those who are you going to be in the injections, okay lang kung after your Ovarectomy tapos na. your ovaries have been removed. But how long are you going to be on the injection. Again, there is no concrete answer yet if some studies use two some studies use three, and some studies use five, but the ongoing trials now, is five years of the injection together with the Tamoxifen. How about the use of Aromatase Inhibitors now that the patients is already menopaused, can we use Aromatase inhibitors together with the Zoladex and ovarian ablation. Again, the studies are still on going so we don't have yet the answers if ovarian ablation together with Arimidex better than ovarian ablation and tamxifen. We don't still have the answer as of today. There's still on going trials looking at that. And we have to be careful of osteoporosis; before I do anything I always asked the patient their family history of osteoporosis. That's very important because if you are only 28 years old and you are were going to render them as menopaused, there is a very increased risk developing osteoporosis and sometimes osteoporosis can be very debilitating, you can have fractures. So, this is the on going international study looking at all of these questions. So (pointing at the visual presentation) this is the Zoladex plus Tamoxifen, Zoladex plus arimidex, and they give the drug Zumeta. Zumeta is an intravenous drug by Vovartis and its supposed to strengthen the bones even twice a year and so, in order to prevent osteoporosis they included Zumeta in their studies.

 

So, there are 4 arms of this study trying to answer the question, which is better or which is the best part, and also to prevent osteoporosis. Maybe 5 years from now or 3 years from now, we will have some answer. There is also another international study sponsored by Pfizer and there are three arms in their study. One group of women to take the Tamoxifen, another group to take something similar to Zoladex by the brand of Pfizer, and Tamoxifen and again together with Exemastane. Exemastane, which I will explain later is also an aromatase inhibitor manufactured by Pfizer, it called Aromasin.

 

So, let's move on to the post-menopausal women. So as I said, estrogen is being produced even if you're post-menopausal... It's being produce by the fat tissue, by the muscles, by the bone and also by the breast. So, that is the reason why the recommendation I said earlier, low fat diet, it's because Adipose tissue or fat can be converted to estrogen. So what Tamoxifen does, it blocks the estrogen and progesterone receptor and it also can kill your cancer cell. Tamoxifen has been considered as the gold standard for the past decades, 10 to 20 years, Tamoxifen is and old drug. It's around thirty years na po. And it is given to woman with any tumor with any size that are estrogen receptor, positive or progesterone receptor positive. And if the adjuvant setting it is given for 5 years. It has not been proven that giving Tamoxifen for more than 5 years is of any benefits. So at 5 years you stop. This is an old data showing the benefit of Tamoxifen, so as you can see in your node-postitive patients there was a 8% benefits among those who took Tamoxifen versus those who did not and in the node negative, there was a slight improvement of around 3% for those who took Tamoxifen than for those who did not. So, Tamoxifen has been considered as a standard of therapy for all those years. Tamoxifen may be considered as a standard therapy but is it the gold standard at this time?

 

Now let as move on to the aromatase inhibitors. Which is now a new drug that is available and which has shown more benefit that Tamoxifen. So, what is an Aromatase inhibitor? In post-menopausal women as I mentioned earlier, you produce estrogens and the way it's produced, yung male hormone your androgens, females also have male hormones, the androgen are converted to estrogens and they are converted through help of this protein called aromatase. So what the aromatase inhibitor does is it inhibits the proteins that convert your male hormones to female, so it blocks it there. (pointing at the visiual presentation) There are three brands available in the country. You have Anastrozole which is Arimidex by Asrosenica. You have Letrozole which is Femara by Novartis, and Exemastane Aromasin by Pfizer.

 

All of these three drugs, for obvious reasons have never been compared to each other, because it would be fatal for the drug company if they did study comparing one to the other, but suffice to say that in metastasic patients in stage 4 patients, if you have failed Arimidex or Femara and you take Aromasin, it can still work… there's data to show that. There's no cross re-activity. So if you have failed Femara or Arimidex and then shift to Aromasin it can still work, and there's data and literature to support that study. But in the in the adjuvant setting they have not been compared neck to neck. So, there have been three landmark studies already that have been puiblished in the early 2000 using the three drugs. The first one is the ATAC trial where women, were randomized or were grouped to receive Arimidex, the other group to receive Tamoxifen and other group received both. In summary the study shows that the Arimidex arm was better than Tamoxifen and better than the combination arm. Perhaps they're saying that if you take Arimidex and Tamoxifen the effectiveness basically just cancels out. So there really is no benefit. The MA17 study randomized women who took Tamoxifen for 5 years and then asked to take a placebo or a sugar pill for another 5 years. And the other group took Tamoxifen for 5 years and then Femara for another 5 years for a total of 10 years of tablets. In the IES study randomized women to Tamoxifen for 5 years versus Tamoxifen for 2 to 3 years and then midway shift to Aromasin for another 2 to 3 years. These have all been published in the leading medical journals today. And the summary of all this trials are as follows: There's a 20 to 30% reduction in the risk of relapse, which means the breast cancer spreading to another organ. 40 to 50% relative reduction in the risk contra-lateral, when you say contra-lateral, the other side with breast cancer. If you have breast cancer you have a risk of developing breast cancer in the other side. And taking the Aromasin decreases by 40 to 50% and and absolute gain of 2 to 5% in diseases-free survival. Meaning I have a 5% chance better of being alive without breast cancer if I take Aromasin or Arimidex better than taking Tamoxifen. Also in the ATAC trial they show that if you are any of this one to three (meaning hormone receptor posistive) you can take it. If you are ER-PR negative you don't benefit at all , so this are only for those who are hormone receptor positive, but the group that tend to benefit the most are those who are ER-PR positive, where there was a 52% reduction in recurrence. So if you look at it in a graph form this is a Anastrozole or Arimidex two things to point out in this graph. This is the recurrence graph for hormones positive population. Two things to point out, number 1… as you can see here by the time you hit one year, or a year in a half the graph starts to diverge, naghihiwalay na sila. So ibig sabihin yon by the time you hit one year, you have more patients in the Tamoxifen arm prelapsing or recurring versus those in the Anastrozole arm. And it usually starts by one year. Second point to emphasize here is that yung benefit ng Arimidex or any of these aromatase inhibitors continuous even after 5 years of taking it. As you can see the graph continually splits, nagda-diverge pa rin sila, so you have more patients failing in Tamoxifen arm even after 5 years of taking the drug compared to the Arimidex arm. When the first study first came out 2002, their analysis was still very short. It was only I think 3 years. So there wasn't seen to be very enthusiastic in making the shift because by 3 years the only difference is 1.70%. But as you can see as we move to the 6 th year the benefit increases. Also by taking one of the aromatase inhibitors as you can see, you have almost 50%, less chance of invasive carcinoma on the other side; on the contra-lateral breast almost 50% reduction. In the Tamoxifen arm there was 48 patients and in the Arimidex arm there's only 21. So, what do you gain out of taking an aromatase inhibitor? If you don't take any hormonal therapy after your chemotherapy you have a roughly 38% chance that it's going to come back, or no adjuvant treatment at all, I'msorry, no adjuvant treatment at all, early breast stage you have a 38% chance that your breast cancer will come back if you don't do anything after surgery. If you take Tamoxifen and you are ER-PR positive, it brings it down to 50%. So, if your risk is 38% and say 50% reduction and 38% goes down to 19. Now, if you say there's still another 26%… so 26% of 90 is only 14. So, at the end of the day when we take an aromatase inhibitor, your 38 goes down to 14… that's basically what it translates to.

Side effects, I have listed here the side effects of your aromatase inhibitors. This was the ATAC trial compared to Tamoxifen. You have less hot flashes, vaginal bleeding and vaginal discharge, endometrial cancer, less strokes and less blood clots when you take Arimidex. However you tend to have more joint symptoms or joint pains and joint fractures when you take Arimidex over Tamoxifen. But again it is not exclusive; you can also have joint symptoms and fractures when you take Tamoxifen. I've had some patients who are on the Arimidex who shifted to Femara and say that there's less joint pains but I don't have any solid data. This is just personal comments from patients. The risk of fracture after taking Arimidex begins after 1 year of taking Arimidex and it increases, by the time you reach the third year. The risk of fracture of Tamoxifen and Arimidex are almost the same. So, how do we prevent the fracture? Again… calcium, some more between 1200-1500mg a day, Vitamin B, somewhere between 400-800mg daily, aerobic weight base exercises and I also recommend a Bone Density test yearly just to make sure you don't have any have any osteopenia or osteoporosis. Once I see osteoporosis, then I start injection of Fosamax. For those who want the Zumeta there's also another option, it's just given a twice a year.

 

So what do we do now? What do we start off with? I gave this similar lecture to the Bosom Buddies a few months ago. So, do you start on a aromatase inhibitors immediately or do you wait after 2 to 3 years or if you're already completed 5 years of Tamoxifen, will I still take the 5 years of Femara? Taking an aromatase inhibitors is really no joke to your pockets. That's the cost ranges from P 7,000 to 9,000 depending on the brand that you get. So for 5 years that's that's roughly somewhere between 450,000 to 500,000 if you're going to take it for 5 years.

 

So, let us look at the risk of recurrence. If you have not take anything after your surgery by one year the risk of the recurrence increases to around 10%. If you don't do anything and then after that you tapers off. So in the question earlier, once you further away, what is your chance of recurrence? The lady asked this morning... that what are my chances of recurrence after so many years after. It becomes less as we go to one or 5 years or 10 years, but the highest risk of recurrent is here. And if you take Tamoxifen as you can see in this graph, there's still that sudden bump of that risk of recurrence then it platoes then theres a sudden increase again. Why increase here? Well your'e making me think, its afternoon (laughs). I'm just joking. The answer there is because they notice that for women who stop taking Tamoxifen after 5 years, they notice in studies that there was a sudden increase of stimulation of the estrogen receptors. So that since there was sudden increase in number and in activity of the estrogen receptors and perhaps that the reason why the continuous estrogen secretion in the body stimulated these receptors. So that's why we still have those re-failures of breast cancer even after five years. So that's the rational why Femara is given 5 years after the tamoxifen. So, that is the rational there because after 5 years there was an increase and that's because the number of receptors and perhaps also that there are receptors that would have mutated instead of becoming a blocking, they get stimulated by the Tamoxifen. But when you take the aromatase inhibitors it seems to be a little bit blunted compared to the sudden rise in your Tamoxifen, therefore, potentially saving these patients from relapse. In the last concluded American Society of Oncology last June, They presented a model based and they looked at all the studies that were done and they looked at what is the best way of starting this medicine. When. So, we said that if you are ER PR positive, patients who are ER PR positive, if they will collapse they tend to relapse later, not earlier. So, if that's the case start the first in Tamoxifen then later on shift to Arimidex or one of aromatase inhibitors. Now, if you are ER positive, PR negative you tend to relapse sooner. You relapse mas maaga, not later, therefore, you are best starting right away to the aromatase inhibitor. Because pinakita ko kanina, the bump is highere in the beginning. Now, they didn't mention anything about ER-negative and PR-positive, but in my practice, if I see that, I tend to suggest to my patients to start also an aromatase inhibitor sooner rather than later.

 

How about switching to aromatize inhibitors after 5 years of Tamoxifen? Some of you may be nearing your completion of Tamoxifen and I think that's the next question, Should I be on aromatase inhibitors? I think, there's number one, there's data to prove hit, but should anybody be on aromatase inhibitors after 5 years. I think yung recommendation do doon would be in a case-to-case basis. If you have very small tumor, stage one, very good features then maybe you don't have to go to aromatase inhibitors. But if you were a patient with poor features I probably will suggest might as well go on for another 5 years. So there on going trials answering the following question. Tamixifen versus 3 groups, Tamoxifen for 5 years, making the switch for a total of 5 years or aromatase inhibitors for 5 years. Another study looking at Tamoxifen then aromatase inhibitors then placebo, 5 years then 5 years and placebo for another 5 years versus Tamoxifen and aromatase inhibitor for another 10 years... so, for a total of 15 years of tablets. Of course these studies are sponsored of the makers of the drug Femara. So all those women who joined the AM17 trial, they are now really randomizing them to received another 5 years of Femara or another 5 years of placebo so we wont know that answer to the question probably another 5 years from now.

 

So in summary, Ovarian Ablation plus Tamoxifen is an acceptable treatment for pre-menopausal women. Aromatase inhibitors have shown that they are better than Tamoxifen. So Tamoxifen is not anymore the good standard but perhaps it's still a standard of therapy. We Doctors will not be faulted if we recommend if to our patients and there are still more questions to ask and more answers for us to find out the best way to treat our patients.

In the Big C magazine last March and April, we wrote an article on aromatase inhibitors and this coming issue we will going to talk a little bit more on the recommendation of if you are ER-PR Positive, the best to start it with Tamoxifen etc. so, Thank you for your attention. We are now open for questions.

 

(CTO): Thank you very much Dr. Lopez

 

(Q1): You talk about Tamoxifen and Arimidex, which are given after your treatment, chemo. Is there any benefit taking it even before your surgery, once you've been told you have cancer and you have surgery, is their benefit in taking that, lets say, together with your treatments?

 

(FL): For patient with big tumors, you can go what they call Neo-adjuvant. Whether its chemo or hormonal therapy, before you go into surgery, and then you also complete rest of the treatment. Puedo ho yon.,. Mauuna muna yung chemotherapy. There was a study that looking at Letroxole or Femara given before surgery and went on to surgery and proceed to the rest of the treatment. So, that can be done again but if you are going to take Femara for one week and then stop as you going to surgery I think there's no benefit at all because aromatase inhibitors take time before they work. It's not like if you take one and after uy lumiliit na yung tumor. Unlike if you take chemotherapy, you can really see the tumor shrink every time you get the chemotherapy. So, there's no benefit, I know some surgeons who do that, they give them and then take then into surgery but again there's really no clear benefit in doing that.

 

Number 2, you don't take Tamoxifent together with chemotherapy; there who study done. It showed the negative study. It was not only neutral it was negative and it was even detrimental.

 

(Q2): Upstairs this morning I don't know if it was you who mentioned it or Dr. Mark Kho mentioned, Herceptin. Can this be taken together with Tamoxifen or aromatase inhibotor?

 

(FL): There is no study yet done using Herceptin together with aromatase inhibitors. The studies that were done, there were done exclusively alone. The Herceptin is a new drug used for a patient who expresses the her2neu protein, if you look your pathology report. There's data saying that they could take Herceptin for one year. So, there's no data yet, combining both as of today.

 

(Q3): So, if you are ER positive, PR negative but her2neu positive, it is more beneficial to just take Herceptin for one year then afterwards take the…

 

(FL): If confronted with a case like that. Probably you heard the price I heard many women fainted when they heard the Herceptin, is P64,000 per session.

 

(Q3): Can you answer my question? (laugh)

 

(FL): (laugh) …It takes Six or seven years before the patency expires, and then there will be other companies manufacturing the drug Now, the Herceptin just came out of the market so still have to wait for 5 years before another company will come up with the same drug so that's why it is expensive. The Arimidex can be somewhere 7,000 plus I think the Femara and Aromasin is like around P9000 plus

 

(Q4): You said the exact phrase “if you fail Femara and you fail Arimidex” what exactly do mean by failing?

 

(FL): These were stage 4 patients by the way, this study was done on stage 4, not on adjuvant setting, because in adjuvant setting, when you say fail it has come back, but these were metastasic patients who are given Arimidex and then when the drugs stop to responding the they tried it on Aromasin and they worked. There was some response.

 

(Q5): I'm Cecille Locsin Alba from Bacolod . I have a breast cancer support group there. I was placed on Arimidex one year after I was on Tamoxifen by then my doctor because she thought that this must have been the reason why after I was given an MRI, the MRI expert read the results said that I had metastasis on the bone meaning that my breast cancer, has gone to the bone. Okay. So, she shifted me to Arimidex, and I've been on Arimidex for almost 4 years now, and recently my orthopedic onco told me to stop taking Raloxifen which my oncologist before prescribed for me. He said that Arimidex and Raloxifen are not good together but he could have give me a reason and I said if there's any data about this, but of course since I was apprehensive, I stopped.

 

(FL): In my opinion… a background on Raloxifen.

 

(Q6): … because I have osteoporosis so he shifted me to Fosamax instead.

 

(FL): Ok Backgrownd of Raloxifen. Raloxifen is a drug that is similar to Tamoxifen. There was a study that was done in the late 1990's. I was still in the States then when they came out showing that Raloxifen, Evista has benefit in osteoporosis. And the drug was really use for osteoporosis and in fact it was FDA approved a year ago in the United States for osteoporosis alone. Now when they published their study in the journal, the last two paragraphs of the article siningit nila yung statement, Oh we also notice the decrease in breast cancer recurrence in women taking the Raloxifen. So, that's how it ended. Then there was a star study I think is called looking at using Raloxifen in the preventions of breast cancer. Not in the adjuvant setting. So Raloxifen never made its way, has never been FDA approved in the treatment of breast cancer.

 

Now, your question, your oncologist is true there's no data saying that taking Raloxifen and Arimidex is bad. There's none. But if you look at the ATAC trial that I just showed you earlier, when they combined the Tamoxifen and Arimidex, there was really of no benefit. Arimidex was still better. So you want to extrapolate it from that. Again Raloxifen is not an exclusive blocker. It can also have some estrogen-like properties, because just like Tamoxifen it stimulates. It's blockage from your receptors, and also stimulates your other organs namely your bones, your uterine lining, that's why you have the uterine thickness or bleeding. It can also stimulate your liver. Now, going back to your question, I personally, why do you have to take the risk? Because I can give another drug anyway for osteoporosis. Why do I have to settle for Evista, I won't want to take the risk. In fact (pointing to another patient in the crowd) that's exactly what she asked me because her OBGYN was recommending Evista for her. Though she's not on any medicine because she is ER-PR negative, I just felt uneasy doing something that, I have this breast cancer patient I'm giving her a drug and it has not been studies carefully on breast cancer patients. Will it add any benefit or no benefit when I had another drug that will make me sleep well at night that I am not harming my patient. So in that case I probably would have just settled for a Fosamax and Arimidex.

 

(Q7): My name is Tina Gutierrez. Doctor, logic lang. I have a question about Tamoxifen. Kasi if you had total hysterectomy and yet they still recommend Arimidex or Tamoxifen after having total hysterectomy…

 

(FL): Because as I said earlier, even if you have a total hysterectomy, you are still producing estrogens. If you look at this picture, pre-menopausal, majority of your estrogens come from your ovaries. But in your post-menopausal women, after you have your hysterectomy or ovarectomy, you are still producing estrogens in the fat tissues, muscles, bones and also in the breast. Though, the secretion of your estrogens is now on a very stable, low fashion unlike in pre-menopausal women where you have these sudden surges of estrogen, you are still producing. That is the reason why you still recommend Tamoxifen.

 

(Q7): Can you switch to Tamoxifen, Arimedex then to Tamoxifen?

 

(FL): So the Example you gave me are like the politicians, the keep on switching parties. (laugh) Just a joke only! But, if you're going to make the switch, it's a permanent switch. Who was that lady who asked me outside; yes you asked me that question. Yes it's a permanent switch. When you read the literature of the study its not three months you're here, one month there, no, it's after you make the switch you stay with that drug. That's what the switch means, it's not ok this month I will be with Tamoxifen, next month I will be with Arimidex, its not that way.

 

(Q8): But it's allowed?

 

(FL): What do you mean it's allowed?

 

(Q9): Tamoxifen, Arimidex and then Tamoxifen.

 

(FL): Your question is ‘how about the other way around?' You started at Arimidex. How about make a switch to tamoxifen. There is a study looking at that. But we don't know the answer. There a study looking at what sequence is better Tamoxifen to Arimidex or Arimidex to Tamoxifen. We don't have that answer yet. We have to wait for 5 years to get that answer.

 

(Q10): My question to you is, the result of my ER-PR is negative – positive. After my chemo, after 9 months I am expecting Arimidex so my first question is the length of the time I took the medicine, is there an effect on that and my second question is I have pain here. I was talking to my oncologist and he told me that was the effect of the medicine. But I have a sister telling me you have to find out what is the cause.

(FL): Let me answer the second, Arimidex can have a side effect of joint pains. So what you can do is, yes I agree you have to investigate. One way of investigating is do a bone density. Because for all you know you are having osteoporosis.

 

Q11): I did and it's negative.

 

(FL): It's negative. So you're not having osteoporosis. So this might be side effect of the drug. Some of my patients claim if they switch to Femara they tend to have less bone pain. At least one or two of my patients have told me that. Now whether there is any literature to support that or not, I don't have. I'm just telling you what my patients have told me. Next what you want to do in the adjuvant setting is you want to start your treatment right away. There is a study done saying that after your surgery, you want to do your chemotherapy at least four weeks from your surgery. For those who did it more that four weeks they tend not to do as good as those who had it right away.. Why? Because you are allowing the cancer to cells to grow. The whole rational for adjuvant is Wala akong decease ngayon, tinangal yung breast ko, tinangal yung kulani ko, I don't have any cancer but I want to prevent it from coming back. So if you have one or two cancer cells left behind, na hindi pa natin nakikita, and you prolong the adjuvant treatment than you are allowing these cancer cells to grow. So what you want is to start right away. If fact, there is one study that said, if you are ER-PR negative, you don't even have to wait four weeks to start right away. So that delay of nine months I cannot answer you if that did you good or bad but suffice to say in adjuvant, we want to always start right away.

 

(Q12): I want to ask about the side effects of Tamoxifen and Arimidex. I know they are also toxic to our liver. And it's not stated in your slide. And since I have high liver enzymes should I take the Tamoxifen or do they both act on the liver also.

 

(FL): The reason why it is not listed there is that it is not a very common side effect. But yes I agree. I have had patients who have had increase in the liver enzymes when they take Tamoxifen. I don't see it as much when they are taking Arimidex, but Tamoxifen yes. That's one reason why I always take the SGPT - SGOT levels when they come for their regular checkups. That's one thing I always do plus the fact that they may be taking other supplements, herbal or things like that, and I want to make sure the liver is okay for that reason.

 

(Q13): I included CT Scan already because of my high enzymes, but it normal so could you lower the dose of your 0Tamoxifen or the 20 mg is really the..

 

(FL): Well the 20 mg is really the recommended dose. What I do is, this is my strategy, I stop first the Tamoxifen and wait and see if the liver comes down then I resume still at 20 mg. Or if not, I make the switch, I tell the patient, look your liver is affected, let's try the Arimidex.

 

(Q14): Good afternoon Doctor, operated ako last year, modified radical mastectomy. ER-PR negative, her2 positive 3. Pero wala natatake ako. Yung pinatake lang ako yung Bonefos. Okay yun? Bonefos 800 mg once a week. Wala akong maintenance.

 

(FL): Anong stage ka?

 

(Q15): Stage 2.

 

(FL): Nag chemotherapy kayo after surgery?

 

(Q16): Yes

 

(FL): Anong chemotherapy nyo? May pula?

 

(Q17): Oo.

 

(FL): Tatlo o dalawa?

 

(Q18): Tatlo – six sessions.

 

(FL): So it means you probably got CAF times six. Yun na po yung treatment ninyo. You are not a candidate to take Tamoxifen or Arimidex because you are ER-PR negative. Why your doctor is giving you Bonefos, maybe to prevent osteoporosis. If you want mag pa second opinion kayo, saan ka na opera?

 

(Q19): Sa Chinese General

 

(FL): What I always do if I have a patient who has ER-PR negative, send it for another opinion just to make sure because yung pagka stain ng slide ginagawa po ang isang tao. Kung mali yung pagka stain mali rin yung pagbasa ng pathology. So if you really want to be sure, I always tell my patients, second opinion yung ER-PR.

 

(CTO): Lets give a round of applause to Dr. Lopez. (clapping)