It's imperative that we stay informed as the conventional medical approaches to standardised care adapt and change.
Today we are joined by Dr Lise Alschuler who takes us through some of the updates to the medical guidelines for breast cancer management. She talks us through some of the new treatment approaches when it comes to ductal carcinoma in situ, lymphedema, surgeries, phytoestrogens and more. Dr Alschuler highlights that this knowledge is essential for integrative practitioners in order to best support our patients and help empower them to ask the right questions and make educated decisions about their treatment.
Covered in this episode
[00:47] Welcoming back Dr Lise Alschuler
[02:03] Updated breast cancer screening guidelines
[05:48] Scans and breast cancer survival risk
[07:16] Fine needle biopsy vs core biopsy
[10:57] Breast cancer in men
[12:22] Using vaginal oestrogen post-breast cancer
[15:27] Phytoestrogens: which ones to use and when?
[17:10] Can oestrogen be used as a treatment for triple-negative breast cancer?
[18:59] Updates on treatment of ductal carcinoma in situ
[25:21] Updates on treatment for lymphedema
[33:20] Advances in surgeries for breast cancer
[36:43] IV ketorolac to reduce recurrence
[39:56] Using post-operative anti-inflammatories
[40:51] Updates on treatment for triple-negative breast cancer
[42:15] Genetic testing for BRCA genes
[44:24] Updates in chemotherapy
[46:39] Breast density and risk of cancer
[47:54] Discussing tamoxifen
[49:47] Studies on iodine and survival rate
[52:34] Is there a risk from contrast MRIs?
Andrew: This is FX Medicine, I'm Andrew Whitfield-Cook. Joining us on the line today, again, is Dr Lise Alschuler. She's a professor of clinical medicine at the University of Arizona where she is the assistant director of the Fellowship in Integrative Medicine at the Andrew Weil Center for Integrative Medicine. Dr Alschuler is also the founding executive director of TAP Integrative, a non-profit web-based educational resource for integrative practitioners. She practices naturopathic oncology out of Naturopathic Specialists in Scottsdale, Arizona. And Dr Alschuler co-hosts a radio show, "Five to Thrive Live!" and is also a co-founder of the iTHRIVE Plan, a lifestyle app for cancer survivors. Lise is co-author of the seminal work, "The Definitive Guide to Cancer," now in its third edition and, "The Definitive Guide to Thriving After Cancer" for patients. And I warmly welcome you back to FX Medicine, Lise, how are you?
Lise: I'm very good, thank you so much. Glad to be here.
Andrew: Thank you so much for joining us again. I miss you.
Lise: I know. We haven't seen each other in too long, I agree.
Andrew: Now, we've got some important things to discuss today with regards to conventional medicine updates in breast cancer. Now, you know I was just reading the other day for a totally different reason from our podcast and it was basically like we had some major advances in breast cancer survival, and then it seems to have stalled. So, what are the updated breast cancer screening guidelines?
Lise: Well, you know, there's been, yes, quite a bit of activity in this regard, I think, over this last year. A lot of the associations and societies have been putting out new recommendations or, sort of, reviewing the data and making sure that the recommendations that they're putting out are current and so forth. So, there's still a little bit of difference, I would say, between one guideline group and the next. But generally speaking, so women at average risk are still recommended to get annual mammograms and really the preference now is very clearly to get 3D mammograms because they present, you know, much clearer images. So, starting at the age of 40, annual mammogram is still recommended for women with average risk. If a woman is at increased risk and one of the newer findings, if you know consensus-based findings of increased risk, is women with increased breast density.
Lise: So, breast density is now very clearly linked with increased risk of breast cancer. So, a woman who's 40 who has high breast density is recommended to not only get 3D annual mammogram but also to be considered for additional supplemental imaging, usually ultrasound, on top of that mammogram. And then that would be, of course, true for women with other reasons that, you know, have high risk for other reasons. But for women, say, who have something that would really elevate her risk, so she's had radiation to the chest wall at an early age, she has BRCA1 or BRCA2 positivity…
Andrew: Yep. Yep.
Lise: …or really a strong family history, anything that puts her lifetime risk over 20%. She's recommended to get not only annual mammogram but also breast MRI and typically that started at age 30 or 35. Sometimes even as young as age 25 if she has, you know, BRCA positive mutational status. So, you know, I think that really the bottom line these days is that...and these recommendations that I just went through come from the American Society of Breast Surgeons but they're pretty consistent with a lot of the bodies. And I think that what we're seeing is kind of coming back to more regular screening if you will. There was a little bit of a deviation for that a few years ago, but it's all coming back to, you know, again, the annual mammogram after the age of 40.
Andrew: Yeah. You mentioned radiation to the chest wall at an early age, what sort of radiation are we talking here, like multiple x-rays?
Lise: Oh, no, I'm sorry, radiation treatment, I should have clarified. So, just getting chest x-rays for diagnostic reasons, that wouldn't put you at high risk.
Lise: But let's say you have lymphoma, non-Hodgkin's lymphoma at an early age or Hodgkin's lymphoma, you would want to...you would probably have received mediastinal radiation so then you would be in this higher risk group. Therapeutic radiation is what I'm talking about or thyroid cancer history or something like that.
Andrew: Right. Although there is an increased concern amongst clinicians, mainly doctors, with regards to the amount of scans that are being done, not necessarily relevant for breast cancer, but can we just cover that as an aside?
Lise: Well, you know, the whole concern with this is, you know, we do these scans and does it really make a difference in terms of overall survival? Because, you know, the number of women that would be diagnosed from a scan compared to the number of women that will get false positives, you know, it's a fairly fine line. So, I think that you can still...despite all of these societies coming back to recommending these regular screenings, you could still make a case for the fact that, you know, the chances of getting screen-detected breast cancer is fairly low and you're going to send a lot of women in for unnecessary biopsies.
The challenge is that even if it's a fairly low number that's going to be caught, if you're one of those women, you definitely want to be caught when you have the early-stage breast cancer when the treatment is potentially curative. So, I think that's the kind of sticky wicket with this is that, you know, societies are really not willing to give up the potential even if it's 2 or 3 women out of 100 or whatever the case might be. They want to make sure they catch those women and provide them with, you know, curative-intent treatment, then they can do that.
Lise: Mm-hmm. So, fine needle biopsy is good to just...all that tells you is this woman, or really man, whatever, has breast cancer. So, we know that there's breast cancer here and we know that it's invasive for DCIS but they don't get enough tissue to do really any molecular analysis on it. So, it doesn't help you get information like oestrogen receptor positivity, progesterone receptor positivity, HER2-positive or negative, KI-167, which is a marker for proliferation rate, lymphovascular invasion. These are things that are really important to get upfront because those, in turn, help to determine subsequent treatment recommendations. So, you know, just a fine needle biopsy might be done just to make a diagnosis but in most cases, I should say, women will probably be referred right away to the core biopsy so they can get all that additional information.
Andrew: Yeah. I've always wondered about that. And so, if this happens, you know, in most...let's concentrate on women because we're talking about breast cancer and it mostly occurs in women. I understand it's a very important condition in men. With regards to the number of women that have a fine needle biopsy and then progress to having a core biopsy, is there any point to doing a fine needle biopsy anyway?
Lise: I think that, not really unless there's a, you know, very...let's say it's really equivocal. We really don't know whether based on imaging whether this is cancer or not, and the woman is small-breasted and the core biopsy would take out a fairly sizeable piece of tissue. Then maybe in that case, doing the fine needle is appropriate just to determine “is this cancer and do we need to go further with it?”
Andrew: Got you.
Lise: But I think more and more, you know, it's rarer and rarer that I see fine needle biopsy reports in patients.
Andrew: Got you. So, there is a movement to going, you know, like, "Hang it. Let's just go to the one that gives us the information because we have a rough idea what we're dealing with."
Lise: Yeah. And I think that's particularly true because one of...you know, the management of breast cancer is always changing and one of the ways in which it's changing now is that there's a very significant movement to neoadjuvant chemotherapy. So, this would be basically before surgery, women will get chemotherapy, sometimes in the post-menopausal and then instead of chemotherapy it might be endocrine therapy for a period of time, like a year or so, in order to minimise the extent of surgery that's needed. And so, in order to do that, you really need to understand what you're dealing with and whether a chemotherapy is justified at that point before you've done surgical resection.
Lise: And, you know, as I said, this is really a new frontier, if you will, of breast cancer treatment and there's a lot of clinical studies that are not complete yet in terms of how this will change overall outcomes and whether it's advantageous or not. But, you know, really the movement started in part because this is an effort to try to minimise the extensive surgery that a woman will need.
Andrew: And what about breast cancer in men? What is the sort of, you know, relevant detection? You know, men aren't sent for mammograms regularly at any age. So, what message do we have to get out to men to be able to reduce risk of breast cancer in males?
Lise: You know, I'm not an expert in this actually but what I will say is that the men that are on the tightest surveillance are really the men who have a history of being BRCA positive. So, if they are BRCA positive, then they are going to be in pretty active surveillance, and I believe that they are used...I mean what's used is still mammography depending on the shape of their chest. They also get a lot of ultrasound as a way to do screening. And as far as, you know, the frequency and so forth, that's a little bit beyond my expertise.
Andrew: Yeah. But just going on that screening, would that be largely based on a family history of BRCA positive?
Lise: Yeah, yep. For the most part, yeah. Like if the man tests positive, if he's BRCA positive, then he's typically put into this. So, if he have a strong family history he should get tested, and then if he's BRCA positive, he would be put into screening.
Lise: Yes. So, this is kind of interesting, too, because it's becoming more and more accepted even in kind of conventional circles, if you will. It appears that the risk of, you know, elevating oestrogen levels high enough from vaginal oestrogen is very, very low. There's very little elevation of systemic oestrogen from vaginal estradiol or estriol treatment. And it's a very effective treatment for some women with vaginal dryness, painful intercourse, so it can be really helpful from the symptomatic standpoint. So, it's becoming, you know, again, more accepted among conventional oncologists, which is great because it's really giving some options.
Now, there's some other options as well. There's some drugs that had been...I guess drugs, topical medications that had been developed that use EAGA instead of oestrogen and that can be very effective towards these same issues, and again, very low risk of raising serum oestrogen levels. There are also just some interesting work, a couple of studies looking at testosterone and topical application of testosterone in women taking aromatase inhibitors, and there's a suggestive synergistic effect in terms of lowering the risk of recurrence, which is interesting. Plus, the testosterone vaginally is also very effective for some of these same vaginal symptoms.
Lise: But, you know, some of the latest research has really found there's no difference in women who are getting vaginal oestrogen in terms of recurrence rate compared to women who are not. So, that's good news for most of these women.
Andrew: Yeah. Now, I'm assuming that this is to allay any fear with regards to oestrogen-positive cancers, correct?
Lise: Right, yes, correct, yes. So, I didn't make that clear, but absolutely. Now, I want to be very clear, we're talking about vaginal oestrogen. Oral hormone replacement therapy in women even with early-stage breast cancer and taking tamoxifen. So, tamoxifen is something that blocks oestrogen receptors. But even in those women, they increase their risk of breast cancer by like 300% when they're taking oral oestrogen so that's still a no-no.
And we don't know, studies aren't long enough to say, "Well, does that impact overall survival?" But we do know for sure that oral oestrogen therapy in women with oestrogen receptor-positive, regardless of whether they're on an anti-oestrogen type therapy or not, is not recommended. And that's true, you know, for natural oestrogens, these so-called bioidentical oestrogens, as well as conventional oestrogens. But vaginal oestrogens, totally different situation.
Lise: So, yeah, it's a good question. So, phytoestrogens, you know, they're not...one size doesn't fit all with phytoestrogens, so I think of phytoestrogens as a continuum.
Lise: So, there are some phytoestrogens like soy which binds to the oestrogen receptors, preferentially to the beta sub-type which is actually an anti-proliferative receptor. And in fact, soy, you know, even with that oestrogen-binding effect, probably more of an anti-proliferation effect along with all the flavonoids in soy ends up having an anti-cancer effect. And it's used for...its consumption is associated with reduced risk of breast cancer recurrence.
However, there are other phytoestrogens that are really much more stimulatory to the oestrogen receptor alpha, which would be things like Medicago, or red clover is another one, Angelica, these are ones that I would not use in somebody with a history of oestrogen receptor-positive breast cancer because they do elevate serum oestrogen levels. And any elevation of serum oestrogen levels in somebody with a history of oestrogen receptor-positive breast cancer is really considered inappropriate.
Andrew: It's a really important point to make that medically, phytoestrogens are lumped together and yet we're eating them. You really need to know about what type of phytoestrogen, or flavonoid, or flavonol that you're taking.
Lise: Right, absolutely.
Andrew: Okay. So, am I right in did I see a paper that was talking about a potential for oestrogen for triple-negative breast cancer, that it actually might be a therapeutic thing?
Lise: I am not sure what paper you are referring to but I know that there are...I've read some papers recently that have looked at the rate or the rather common change of tumours over time, so that tumours that start as maybe triple-negative can actually later on...if it's, you know, active metastatic disease or even a recurrent disease, can recur with a different receptor status. Also, tumours can de-differentiate so they can start out as oestrogen receptor-positive and then become negative. So, there's a lot of, I think, more change in these tumours than we would expect. So, you know, I don't know if that is related or not to what you've read in terms of...
Andrew: Certainly be a caution.
Lise: Yeah, a caution because, you know, I mean I think the reason I brought that up is that even though somebody is oestrogen receptor-negative, they might still have some oestrogen receptors that are being expressed. And I think that what we know about breast cancers and, you know, cells in general, but if breast cancer cells are in an oestrogen-rich environment, they're going to up-regulate receptors to whatever is available. And so, I think the risk of, you know, doing something like that, using oestrogen in a triple-negative breast cancer, is that you might encourage that change in morphology and then actually be feeding the proliferation of the tumour. But I think until we are really clear on, you know, what happens clinically, I would just say we're playing with fire.
Andrew: Now, you know, when is treatment needed, when is it not, when is it watch and wait?
Lise: Right. So, you know, DCIS is quite a conundrum for practitioners and so there's been some recent data that's been published looking at, you know, this whole issue. So, first of all, about one-fifth, one out of every five, you know, mammography-screened, detected breast cancers are DCIS. So, about one in five women are dealing with the diagnosis of DCIS, and then they're diagnosed.
And so, there's been some look at, well, what happens if you don't treat DCIS? And there's been a big retrospective study that looked at that. And, by the way, now we classify DCIS more specifically so we look at the pattern of DCIS and we can determine if it's low grade, or intermediate, or high grade. And really, only when it's intermediate or high-grade DCIS do you see a separation of the lines in terms of risk of breast cancer-specific survival.
So, low-grade DCIS, there's really no advantage to receiving treatment, which is kind of interesting, that's new. So, all DCIS is no longer treated equally and that, you know, by at least its respective data, it appears that a low-grade DCIS is very safe to just do what's called active surveillance. Now, women who have DCIS, low-grade DCIS, are on active surveillance, what that means is they need annual mammograms. And as long as they get that, they're fine. Now, if a woman has intermediate or high-grade DCIS then there is a little bit, not dramatically, it's, you know, probably at best like...I don't have the exact statistics but it's certainly less than 10% difference in disease, breast cancer-specific survival with treatment.
Lise: You know, there's a difference so that's something that women would potentially want to do. And then if the question becomes, "Well, what treatment should they get and are there any other characteristics that we can look at that will help us figure out of those intermediate and high-risk DCIS, who really is going to go on to develop invasive breast cancer and who isn't?" And so, those are trials that are still ongoing but in the meantime, just in terms of some really interesting resources, there's a new, very well-validated test that's available and it's called the Prelude Test, Prelude Diagnostic Test. And it actually predicts an individual patient's benefit from radiation therapy. So, DCIS is typically treated with surgery and then the question is “does this woman additionally need radiation therapy and endocrine therapy?”
So, radiation is kind of the variable that's most often either yes or no. So, this new Prelude Diagnostic Test very carefully and very clearly reclassifies women into women who would benefit from radiation or not. And so, this is great because it's actually...when it's being used, it's saving a lot of women from getting radiation therapy who would have otherwise been recommended to get radiation just based on the initial grade of a tumour. So, that's exciting.
Andrew: Yeah. I've got to ask the question about fear though. I mean if a woman was told that she had a diagnosis of DCIS, I can't imagine many women going, "Yeah, we'll just watch and wait." How does a clinician broach that?
Lise: Yeah. I mean you'd be surprised, actually a lot of women don't want treatment. They do want to watch and wait…
Lise: …and they feel like they can...you know, it's an opportunity that they have to reverse things. And really the, you know...But to be fair, you know, there's some women who will be like, "I don't even...you know, I don't want to watch and wait. Let's just take care of it," which is fine. I think what the data is saying is if that woman has low-grade DCIS, whether she treats it or not is not really going to impact her overall survival, or her risk of dying from breast cancer one way or another.
So, she can get a treatment for, you know, kind of peace of mind but she could also...if she doesn't want to, that's a very evidence-based decision, if you will. But to your point, yes, I think that there are some women who are just going to be like, "I don't even want to deal with this. I just want to get it taken care of." And they will still, of course, be treated.
Andrew: What I was thinking of is that ongoing hypervigilance and the stress that that places on the body, and I'm thinking biochemically.
Andrew: I’m thinking about catecholamines being a driver of metastases.
Lise: Right. Yeah. I think that, you know, these are good questions and, unfortunately, we don't really have...I don't have a data-driven answer for that. And, you know, I think that the main benefit or the main role that practitioners really can play for these women is to share the data with them to really kind of give them as much information, in a digestible way, as possible so that whatever decision a woman makes, she's making a decision that's based on really having a good sense of the available information at the time so she shouldn't look back later and say, "Gosh, if I'd only known that I didn't need treatment, or that I did," you know?
Because I think that's a part of the decision, "Do I want to expose my breasts to this degree of, you know, radiation through screening on this regular of a basis? Do I want to know that I have this DCIS in my breast and I'm choosing not to treat it?" I mean those are things that she needs to put it into the decision-making, whatever, buckets that she has.
Andrew: Yeah. Let's move on to lymphedema. This is a big one for me because I've seen, you know, various attempts of reducing lymphedema. And then I've also met patients who have been given absolutely no advice on lymphedema, post-breast surgery.
Lise: Yeah. I mean it's really interesting. And, you know, by the way, I have a wonderful opportunity to go to attend the American Breast Surgeon Society's Annual Conference this year and I can't tell you how impressive it was to me how many presentations were focused on lymphedemas. So, these are breast surgeons who are causing a lot of the lymphedema…
Andrew: Yeah. Yeah.
Lise: …and they are really invested in trying not to do that. And there was a lot of, I mean a high level of recognition of the challenges that lymphedema presents to quality of life. And, in fact, one of the keynote speakers was Kathy Bates who is a famous actress, you might recognise her name and...
Andrew: Ah, yes, yes.
Lise: She shared her...Yeah, yeah. And she shared her story. She has significant lymphedema and she's the spokesperson for a lymphedema society, it's called lymphaticnetwork.org, a wonderful organisation. And she's doing a lot of public policy work and, you know, appealing to legislators because in the United States, lymphedema is not recognised as a disease state so it doesn't get covered by insurance.
Lise: …so the treatments don't get covered by insurance in the same way. So not only are there a lot of women who have lymphedema from their treatment but when they get it, there's really very little options for them in terms of what's covered.
Lise: So, it's a very challenging situation but that being said, you know, there are some advances if you will. So, from a...just first, before we get into some of the surgical advances, it's important to keep in mind that when we have patients, we need to be thinking about prevention, which one of the biggest risk factors for lymphedema is obesity. So, obese women are at a much higher risk for developing lymphedema and so, you know, anything that we can do to help women manage their weight, especially going into surgery, and now post-surgery is very important.
We also know that women who are sedentary have a high risk of lymphedema so, you know, anything we can do to encourage people, women, to get active is also very important. And then in terms of prevention, too, there's a great role for physical therapy and there are physical therapists that have special training in lymphedema work and they're really the ones that you want to try to find and get into your referral network because these physical therapists have learned very specific techniques.
They're very good at instructing patients on how to do some elements of self-massage and they can counsel the patient about, you know, when they can start exercising, how much weight can they lift at what point after surgery, I mean all of that is really important. So, a lot of times that is not set up for women when they go into surgery. So, the ideal time to start having that conversation with somebody is when they know they're going to get breast surgery and they're going to have some lymph nodes removed or they might have lymph nodes removed. They should have an appointment set up with a lymphedema physical therapist or specialist post-surgery so they can get on that pretty quickly.
Andrew: There was also, was it physical therapy combined with, I'm going to say strapping, but compression bandaging?
Lise: Yeah. So, compression bandaging is really more of a treatment that the preventive benefit of compression stockings or sleeves is still debatable. But women who have had severe lymphedema develop in their arms generally report that when they engage in something that they know that triggers lymphedema, which can be flying is the most obvious one, but even high stress can cause it to happen. Anything that increases the oxidative stress in the body will increase the chances of, you know, lymphedema to develop. So, those women usually report that they benefit from some kind of compression sleeve and women can be fitted for those sleeves post-surgery. But from a data perspective, the prevention is a little bit, you know, equivocal.
Lise: That being said, treatment-wise, it's really critical that women...you know, lymphedema, when it accumulates, they have to get some external compression but that needs to be done very carefully depending on how severe the lymphedema is, you know, they might need to be actually bandaged for a while first and then eventually progress to the compression sleeve as the lymphedema revolves. For really severe lymphedema, there's special pneumatic compression devices that they need. And so, there's a lot of...you know, there's kind of an order and an intelligence to how that compression is done.
Andrew: Would that be combined with diuretics at all?
Lise: Sometimes diuretics are used and they can be helpful, yeah. And that, you know, depends a little bit on, you know, the blood work in the women and the weight of the women and so forth, but yes, that can definitely be used.
Now, from a surgical perspective, there's some really interesting techniques that are just starting to make their way into, kind of, more breast surgeon facilities. Not all breast surgeons have the training, specialised training or equipment to do this, but one of the things that I'm really excited about is something called axillary reverse mapping or it's called ARM for short. So, in women who get...So, usually, women who go in for their first surgery will have sentinel lymph node axillary dissection. So, that occurs by the breast surgeon injecting...usually, it's a blue dye or sometimes a radioactive tracer, but injected into the breast and then they open up the axilla enough to see which nodes are blue, so they're collecting the dye.
Lise: And those are kind of the first nodes that collect from that tumour and those are the only nodes that are removed. If those nodes are negative, the surgeon doesn't take any more axillary nodes and everything is said and done. On the other hand, if those nodes are positive, then typically, and this again is changing, but still some women will then have more nodes removed depending, you know, on how and what kind of positivity there are in the nodes will determine to some extent how many more nodes are removed. But one of the things that some surgery centres are now doing, is that in addition to injecting that dye in the breast, they inject a different dye into the upper arm and then when they open up the axilla they can see which nodes are creating the ARM.
And it's uncommon for a node to drain both the breast and the arm, so they can visually see which nodes they don't need to take out…
Lise: …even if they have to do more than sentinel node dissection, which is great because it helps to preserve the lymph flow from the hand, which is where lymphedema happens.
Lise: And then there's some other techniques they can use to reconnect channels if they do happen to have a node that they need to remove. But that's something that I think we're going to start to see more widely implemented because it really has a potential to make such a difference to these women.
Lise: Gosh, there's so much. It was really exciting. I just, you know, am very pleased with what's happening with breast surgery. So, you know, surgeons are really trying to put themselves out of a job, basically. No, that's not really true but they are really doing whatever they can to make surgery as minimally invasive as possible. So, for example, mastectomy. You know, there's a presentation at this breast surgeons' conference where this gentleman who's been a breast surgeon for, I think, 50 years or something show slides of what mastectomies used to be and it was just horrific. Like, women would literally have their chest removed, you know, down to the bone.
Lise: And they would emerge with the skeletal kind of cavitation as a result and that's how mastectomies were done not too long ago. And where it's come now is the new emerging standard of care is what's called oncoplastic surgery. So, even if a woman needs a mastectomy, so the removal of the entire breast tissue, they are developing ways to do this with one small lumpectomy-sized incision. And they can still pull out the entire breast tissue through that small incision and then insert the implant at the same time. And so, the woman comes out of surgery with basically a breast that looks the same, more or less, and with one small incision. And that is just tremendous.
Lise: And not all tumours qualify for that but there are some all the way up to a, you know, certain size. Then there's robotic surgery, which is really interesting. This is definitely not widely available yet but with robotic surgery, through that small incision, the robotic kind of arm, if you will, goes in and the surgeon is operating this robotic arm. But what this allows is the surgeon can actually see, with magnification, the inside of the breast tissue. So, this robotic arm comes with little snippers…
Lise: …and so the surgeon can kind of snip away very precisely around the tumour. So, for say a lumpectomy, can get just the amount needed, you know, based on the dye spread and so forth without having to get any healthy tissue, so very precise way to do surgery and they can actually see what they can't otherwise see with their naked eye. So, you know, these things are kind of exciting because it's just giving women options to have surgery in a less disfiguring way.
Andrew: Obviously, as you said before, there's limitations regarding, you know, the size of the tumour, where the tumour is, whether there's peau d'orange, whether there's areola involvement, that sort of thing, yeah?
Lise: Yes, right, yeah. And just the availability of it, too, is still limited so depending on where a woman, you know, has to get her care, the centre near may not offer some of these techniques. But it's good to be aware of as practitioners because if women have options and these are some of the questions that she can ask and look around to find, especially the oncoplastic surgery, she's looking at a mastectomy.
Lise: Yeah. You say ketorolac, we say ketorolac over here.
Lise: Yeah, this is really interesting, too, because I'd heard about this a while ago and then just heard this last year there was a study that came out. So, ketorolac is an anti-inflammatory basically, and it's given intravenously. And we know that inflammation is really the driver for tumour regenesis because, you know, it creates that inflammatory tumour microenvironment which unleashes the proliferative potential of cells, creates that invasiveness, all the things we don't want to have happen.
So, there's always been a concern that when a woman is undergoing surgery, it's a very inflammatory event, not necessarily at the time of surgery but in the healing process, and could that then encourage later metastasis if there are, you know, some breast cells that were left behind because now they're in this very inflammatory environment? So, the idea has come about, well what happens if we give a very strong anti-inflammatory just prior to surgery, would that impact this risk of distant recurrences?
Lise: And the most recent study on this actually found that there's a 45% reduction in the risk of distant recurrences when one dose of IV ketorolac was given just prior to surgery. And this was most evident in women who are obese or overweight. So, women who have BMI of over 25, which makes sense because obese women have more inflammatory cytokines, so they're more likely to be affected by this, especially with leptin, you know, really should definitely ask their surgeon about this.
Ketorolac is basically just a COX-1 and COX-2 inhibitor. And there's been some other research that's shown that ketorolac specifically inhibits some of the cytokines that are directly involved in cell motility and adhesion and invasion. So, really kind of designed to prevent this kind of inflammatory-induced invasiveness. And all of those cytokines, by the way, are also specifically up-regulated by leptin, which is why the obese women are at higher risk…
Lise: …for this effect. There's studies that are looking at this and have so far shown similar benefits for ovarian cancer. So, women getting ovarian tumour removals also have a lower risk of recurrence with pre-surgical ketorolac. And lung cancer, too, there's some good data there.
So, I hope we start to see this kind of filter into being standard of care but I now encourage...If I have the good fortune to see somebody before surgery, I encourage them to talk to their surgeon about their willingness to do a dose of IV ketorolac. There's no...doesn't appear to be any adverse effects of the ketorolac on the surgery or the surgical outcome or complications.
Lise: Yeah. And it does, you know, beg the question, right? So, we don't have any good clinical data on it but I certainly think that that should be a mainstay of our integrative approach.
Lise: And for the post-surgical period, you know, I'm all about high doses of bromelain for example, very specifically, to try to minimise this inflammatory cytokine milieu. I even sometimes go so far, if there's no bleeding risk, to recommend non-steroidal anti-inflammatories over the counter, NSAIDs, or you know, sort of going back to some of our integrative therapies, essential fatty acids, I think, have a really important role in reducing post-operative inflammation. I think probiotics have a role in this. I think these are all really doable, important therapies post-operatively.
Lise: So, triple-negative major advances, well, there are some newer trials that are...some of them are still going on but there's some new combinations of chemotherapy drugs. I think one of the more exciting areas is immunotherapy for triple-negative cancer combined with chemotherapy and there's some good initial trials that are showing some pretty good responses for those women. And, you know, because of course, these women are, it's unfortunate in some ways because they don't have that hormonal-based target. So really, the only thing they have going for them, or the only thing they have available to them I should say...
Andrew: Yeah, to those, yeah.
Lise: ...typically is chemotherapy. But with the addition of immunotherapy, it appears that there's a more durable response to chemotherapy and a greater response rate, so in other words, more women appear to respond to the chemotherapy. I think that's kind of a big direction that triple-negative treatment is heading.
Andrew: Now, you were mentioning the BRCA previously. What's going through my head is this, you know, genetic testing that's freely available to the consumers and this is fraught with difficulty because of accessibility without appropriate counselling. So, what's your thoughts on consumer genetic testing and can it accurately identify and indeed should it be used to test for BRCA, for the BRCA genes?
Lise: Yeah. You know, it's super tempting, right, to use these consumer genetic tests to just avoid the whole issue of having to get the insurance to cover the BRCA testing and all of that. The problem is that there was actually a study that looked at the accuracy of those consumer-based tests and there was an extremely high false-positive rate.
Lise: So, there was actually a 40% false-positive rate.
Lise: And so the only thing these tests were 100% accurate for were what's called the founder mutations in the BRCA gene. But the evolution of BRCA testing has, you know, evolved many times. So, even if you were BRCA tested six years, you probably need to get retested because the test is now testing for different mutations.
So, the testing has gotten a lot more sophisticated but these consumer-based testing have not kept up. And so, they're very inaccurate in terms of false-positives and it's because of the way that they test. So, the consumer-based testing is basically using single nucleotide polymorphism arrays and they're not doing full genetic sequencing. So, they're not able to really pick up all of the potential variants. So, I think it's basically two-thirds of the BRCA mutation variants that are associated with increased risk are not picked up as well, from these genetic consumer-based testing. So, it's really not a good way to screen for these BRCA mutations.
Andrew: And what about tailoring results with regards to chemotherapy as well? You're talking about these new advances which can reduce the severity, if you like, or the extent of surgery. What about being sparing with chemotherapy? Are there certain women…
Andrew: Yeah, that can be spared or have less dose?
Lise: Yeah. So, the big, big news that everybody has been waiting for who, you know, treats a lot of breast cancer is the result of the TAILORx study. So, people are probably somebody with the Oncotype DX test, which is a test that looks at gene expression pattern of a certain number of identified genes in breast tumour tissue and that expression pattern classifies women into low, intermediate, or high-risk groups. And up until the TAILORx, we didn't know what to do with the intermediate group. We knew that the low women, women in the lowest group did not need chemo, didn't offer them any survival advantage, and we knew that the women in the high-risk group did have a significant survival advantage from chemo. But we didn't really know what to do with the intermediate group so we just gave them chemo too.
So, with the TAILORx, we now know what to do. So, it's basically it's taken the score within that intermediate score, which is a score between 11 and 25, and we can now essentially say that a score from under 25, endocrine therapy only. Score over 26, equal or over 26, you need chemotherapy, except if you're young. So, if a woman is under the age of 50 and her score is between 21 and 25, so it's a much narrower range, she would get, with the addition of chemo, about a 6.5% additional reduction in her risk of recurrence.
Lise: If she is below that, 16 to 20, so still in that old intermediate category, there's a little bit of risk reduction, it's only 1.6%, so not very much.
Andrew: Got you.
Lise: So, it's just this has been really helpful. It's taken a lot of women again and reclassified them to a category where they really don't benefit from chemotherapy.
Lise: Yes, we can. So, high breast density is more common in women who have a history of hormone replacement therapy, so that's one area that we can modify. Women who eat a Western diet are at higher risk for increased breast density. Women who drink more than seven servings of alcohol a week, higher risk of breast density. And there are genetic factors but the modifiable risk factors are basically what we talk about all day long to our patients, eating a healthy diet, moderate intakes of alcohol, and potentially avoiding hormonal replacement therapy. And if a woman has a really high risk of...I mean she has really high breast density, she actually could be a candidate for tamoxifen therapy. Tamoxifen therapy reduces breast density by about 10% but that translates to about a 63% reduced risk of recurrence. So, you know, there is some potential there but generally speaking, Mediterranean diet, decrease the alcohol is kind of the mainstays.
Andrew: Got you, okay. Just a point on that tamoxifen. So, you know, tamoxifen's got basically, you know, a time of let's say confidence and outside that time is a veil drawn over it because it's a selective oestrogen receptor modifier, whereby it blocks oestrogen at the breast tissue but it doesn't block oestrogen receptors in the uterus, and can lead to subsequent issues with the uterine lining. So, with regards to that preventative tamoxifen therapy, if you like, is there a caveat there to how long they can take it for?
Lise: Well, I think they would take it really only as long as they needed to get the breast density reduced.
Andrew: Right, I see what you mean.
Lise: And that would not be my first therapy, by the way. I just mention that because that's kind of the, that's what conventional oncologists, that's the tool that they would have.
Lise: But, you know, I think from the integrative perspective, we would go diet first, but that is potentially out there. Speaking of tamoxifen, I just want to throw out one thing which I'm excited to hear about, I can't wait for more data. There's a little trial that was presented in 2018 at the San Antonio Breast Conference, it's like the big breast conference where all the research findings are presented and there was a...it's a retrospective study, which is not the best study design, but it indicated that low-dose tamoxifen...
So, normally, tamoxifen is dosed at 20 milligrams a day, so it's what I call very redundant dosing. It's, you know, way more than we need to block all of our oestrogen receptors where they are blocked by this drug.
Lise: And so, in this retrospective study, they found that a dose of 5 milligrams of tamoxifen may be as effective. Enough so that they are proposing some prospective clinical trials, so we'll see because that would be great.
Lise: We could lower the dose, theoretically improve tolerance, less harm for the mitochondria and all those good things.
Andrew: Yeah, yeah, yeah. What about iodine? I remember an old, very old trial. Forgive me, not a trial, a paper talking about iodine. And I do believe in this very old paper, it was Lugol's solution which was used, but I remember something about it being used for non-cyclical mastalgia.
Lise: Yeah. So, speaking of iodine, actually, there was just a paper that I was circulated to today that I just saw. This was a randomised pilot so it was really kind of two studies in one but they looked at two groups of women. One were women with early-stage breast cancer who were managed surgically and they gave them 5 milligrams of iodine and then surgery. And then they had a second small group of women, and I'm talking like it's about 15 to 17 or something in each group, small groups, advanced, so stage three breast cancer getting chemotherapy, and they also got 5 milligrams of iodine. And although this is a small trial and we still don't know really what this tells us in terms of overall survival, in the women, advanced-stage breast cancer women who were getting chemo with the iodine in this five-year disease-free survival rate was significantly higher than in women who did not get the iodine.
And there's an indication that that effect was also seen in the early breast cancer stage group so it appears that 5 milligrams of iodine, you know, might actually be beneficial. And these researchers are going to go on to a phase three clinical trial in advanced breast cancer, so I'd be looking that for sure. I just want to caveat this to say that there's other research prior to this that had looked at various iodine dosages. And generally speaking, 5 milligrams is within what we call the safety range. So, you don't get thyroid storm effects, you don't have disrupted metabolism in a deleterious way, so it generally would be considered safer dosing. So, this is not justification for high-dose iodine therapy. I know some alternative practitioners recommend, you know, 100, 200 milligrams of iodine.
Andrew: Yeah, way too high.
Lise: And I think that that, personally, is very dangerous and not what the study is about, but it's encouraging, so I think encouraging data here.
Andrew: Oh, that's really exciting. But can I ask though, that was used 5 milligrams over what period?
Lise: Yep, orally. And this was a month for the early stage and 170 days for the advanced stage. So, about over about six months or so.
Lise: Yeah. So, this is, you know, kind of...I hear this, I don't know if you run across this, but I hear this from patients who are needing to get breast MRIs because their tissue is dense and the mammogram isn't good enough. And so, their, kind of, screening tool of choice is breast MRI so they get concerned because the contrast agent used in MRI, gadolinium, is deposited in the brain and there's been a few reported cases of people who, you know, have cognitive issues, they feel, as a result of this deposition. And the reality is, we don't really know, you know, what the impact of retaining gadolinium over a long period of time is. We know, for example, that the risk of Parkinson's disease increases about 4% per contrast MRI. So, whatever your starting risk is, that's relative risk, so that's not a hugely impactful number but it does obviously say there's some negative impact on the brain.
So, you know, that's kind of the concern but I think that right now what most surgeons anyway are saying is that the risk is not great enough to not get the contrast MRI. Now, the alternative is a non-contrast MRI and the sensitivity for that is actually pretty high, that's about 97% sensitive for breast cancer detection. Specificity is not great, it's about 83% specific, so it wouldn't necessarily differentiate between a malignant versus a non-malignant lesion. But I would argue that it's probably better than nothing if somebody's really quite concerned about a high, let's say, familial risk or individual risk of Parkinson's or something like that.
Andrew: I got to say, Lise, I always learn something new and useful whenever I speak with you. And I just thank you so much for just enlightening us on the new developments with conventional medicine updates in breast cancer, so thank you so much for taking us through those today.
Lise: You're very welcome. I hope that was helpful. You know, I think this stuff is very important for us to know as integrative practitioners because we can often be that interface for patients in trying to help them translate, directing them to the right questions to ask. And so, even though it's not exactly in our wheelhouse, I think it's important for us to be aware of what's happening out there.
Andrew: This is FX Medicine. I'm Andrew Whitfield-Cook.