E48 Masterclass Alison Laws On Neoadjuvant Therapy In Breast Cancer, ALND and Becoming a Patient

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Chad Ball  00:12

Welcome to the Cold Steel surgical podcast with your hosts Ameer Farooq and Chad Ball. We’ve had the absolute privilege of chatting with some amazing Canadian as well as international guests over the past year. While the topics have been brought in range, whether clinical, social or political, our aims for the podcast continue to remain the same. We hope to inspire discussion, creativity, scholarly research and career development in all Canadian surgeons. We hope you enjoy our second season as we continue to highlight some incredible guests, deliver detailed masterclass sessions on a myriad of clinical topics and introduce some fresh new features such as debate and companion formats. We hope you relish the podcast as much as we do.

Ameer Farooq  00:55

In this episode, we were lucky enough to be joined by Dr. Alison Laws. Dr. Laws is a breast surgical oncologist at Brigham and Women’s Hospital in Boston, Massachusetts. We delve deep into topics that many trainees struggle with neoadjuvant therapy for breast cancer, indications for axillary lymph node dissections in 2020, and an approach to recurrent breast cancer. Finally, Dr. Laws shared some deep insights with us on how her experience as a patient shaped her perspective as a surgeon. Dr. Laws, thank you so much for joining us on the Cold Steel podcast today.

Alison Laws  01:50

Thank you for having me.

Ameer Farooq  01:52

Can you tell us a little bit about where you grew up and what your training pathway was?

Alison Laws  01:58

Yeah, for sure. So I grew up in Markham, Ontario, which is a small suburb of Toronto. And then I did my Bachelor of Science at the University of British Columbia in Vancouver. I’ve moved around a lot. So I then went back to Ontario to medical school at McMaster University. And then in terms of my surgical training, I did my general surgery residency at the University of Calgary and and then and then I went on to do a breast surgical oncology fellowship, which I’ve just finished up this summer. And I did that in Boston, Massachusetts. And it was a combined training program between Massachusetts General Hospital and Brigham and Women’s Hospital. And then currently, I’ve accepted a breast surgical oncology position at Brigham and Women’s Hospital. So I’ve just started on there as junior faculty. And then I’m also concurrently over the next few years doing a Master’s of Public Health through the Harvard Chan School of Public Health. And so I’m kind of doing that concurrently with my first couple of years of practice.

Ameer Farooq  03:10

I remember, you know, you weren’t, if I recall, correctly, you weren’t completely sold initially on doing general surgery. Like I think you had initially planned on potentially doing obstetrics and gynecology. Is that correct? Yeah, yeah, that’s correct. What, what made you change directions and become their loss and our gain?

Alison Laws  03:31

Yeah, it’s a good question. I mean, I, I enjoyed sort of the clinical and technical aspects of both fields. And I actually, like I had done a bunch of obstetrics and gynecology rotations early on, and I liked it. And so I sort of just committed as a medical student, you know, I was at McMaster’s, it’s a three year program, you feel a little bit of pressured, I sort of commit early and make sure that you’re planning your clerkship, you know, appropriately so that you’re a competitive match, etc, etc. And I’ve planned out a couple of general surgery electives, just kind of later on, because I felt that they would, you know, give my profile a little bit of diversity and give me a little bit of exposure to, you know, semi related fields, you know, surgical field operating in the abdomen. And then I basically loved those four weeks of general surgery. And I think a lot of it was the people. I felt like, it was just sort of a, I felt that the general surgeons I worked with, at least for those four weeks, I just felt like I fit in really well with them. I liked you know, it was really kind of collaborative group general surgeons were fun. I just, I felt that it was kind of a better fit from that perspective. And I also really, you know, loved the clinical side of things and the technical side of things, and it kind of met all of the other criteria that I was looking for. But yeah, I really was the people that kind of changed changed my mind.

Ameer Farooq  04:57

Think that rings true for a lot of us. What advice do you have like, you know, obviously, you had done most of your electives in a different specialty. And then you wanted to apply to general surgery? How did you sort of manage that during your interview process during CaRMS? And what advice do you have to applicants who maybe change their mind late in the game, especially for three, three year medical students?

Alison Laws  05:22

Yeah. Yeah. I mean, it was, it was very stressful. And, you know, I think I was just tried to be as honest as possible. So, you know, made sure to address that fact, in my personal letter, I made sure to address it in the interviews. And I, what else, I mean, I think I really made it, I tried to make it very clear to the general surgery people that I had worked with, as a medical student that, you know, I really, truly had changed my mind and really kind of tried to seek out their support as well and made sure that they were kind of aware of that fact, so that they could potentially address that in reference letters. And, you know, make sure that the messaging was really consistent. But I think there’s no question that, you know, it’s a challenge when you change late in the game. And, you know, probably had fewer interviews as a result, and you know, you kind of just have to roll with it and, and do your best, but I, you know, have absolutely zero regrets. And I think it’s also really important that, you know, if you do change your mind, you need to know yourself, and you need to know what the right path is for you. And, you know, I was willing to accept that if it didn’t work out, you know, the match didn’t work out, then I would try again the following year. And but I really wanted to sort of commit to the to the path that I felt was right for me in the long term.

Ameer Farooq  06:43

Excellent advice. You know, you finish residency in Calgary, and then obviously went on to do breast oncological surgery in Boston, why you can I’m sure you could have done anything about any fellowship that you wanted. So why why breast surgery? What was it about that that drew you to the field?

Alison Laws  07:00

Yeah, I think. I mean, for me, I actually kind of gained and developed an interest in breast through clinical research initially. So I was got sort of hooked in with May Lynn Quan, who’s one of the breast surgeons in Calgary for an early research project inc  my first year of residency. And and I, you know, she became a mentor of mine, both from a clinical and research perspective. And as I sort of developed, you know, research profile in the breast umbrella, I think I just kind of naturally developed a clinical interest alongside that. You know, I had always had an interest in women’s health, that was part of my draw to obstetrics and gynecology. And so I think that piece sort of fit nicely with breast and as I moved through residency, it really became clear to me that I was looking for a field where I could not only sort of develop a clinical expertise in a single area, but also have a concurrent sort of research career. And I felt that breast really offered that opportunity. And, you know, that was also then kind of a motivator for pursuing the fellowship as well.

Ameer Farooq  08:15

I do want to make one comment about having watched you do research as a resident, I think you’re one of the few people that actually listen to advice from people who’ve gone before us and you picked a topic that you were able to generate a fairly big sort of database on, and then and then ask that database, multiple different kinds of questions. And it turned out to be a very kind of productive line of research. Can you sort of comment on that? And is that was that a deliberate sort of choice? Or is that something that you sort of recommend for people looking to do research in residency?

Alison Laws  08:54

Yeah, I mean, I definitely think so. I’m trying to think now, essentially, almost all of the projects that I did, as a resident did come from a single database that I basically built with chart reviews, sort of in my first and second year of residency. And so I think in the end, I had four publications out of that kind of single data set. And I mean, there’s lots of questions that really could be continued to ask from that. So yeah, I mean, I think it it worked out very well, I think it is. That’s not always it, I guess the field that you’re interested in, and the question that you’re interested in doesn’t always lend itself well to that. And I think, really what made me productive was the fact that I was truly interested in what the in sort of the questions that I was asking and the the field of research that I was pursuing, and I think that is probably the most important thing Above all, is that you pick something that you’re actually interested in. But certainly if you can sort of curate a data set that is, you know, complete and comprehensive and then allows you to ask multiple questions. I mean, that certainly worked for me. And I think it’s a great strategy as a resident.

Ameer Farooq  10:06

We wanted to take the opportunity to ask you some burning questions about breast cancer and breast surgery. As, as you will remember, we texted you many times while you’re studying for for her Royal College exams. I don’t know if it’s too too early for me to talk about the six hours. But they’re definitely breast cancer and breast in general can be a confusing topic for residents. And so we wanted to take the opportunity to just pick your brain about a few of the topics that I think consistently kind of come up as challenging topics. And I think the first one I wanted to start with is the sort of the new argument scenario. So you know, the scenario that they often will paint for you on an on exam is that your your, let’s say you get a 50-year-old female, who comes in with a new diagnosis of breast cancer and has a palpable clinical node or a positive clinical node on FNA? How do you go about sorting out who needs a neoadjuvant neoadjuvant treatment? And how do you sort of approach that in your head?

Alison Laws  11:15

Yeah, yeah, definitely, you know, a bit of a controversial topic and a confusing topic, I think, the way that I was taught to think about this in residency, and then further in fellowship, and you know, think there’s kind of one bucket that our patients with triple negative and her2 positive disease, and then there’s another bucket, are that our patients with hormone receptor positive her2 negative disease, and I think, you know, it’s, it’s important to think about those patients a little bit differently. So, you know, for patients are triple negative and her2 positive disease, we know that the majority of those patients are going to receive chemotherapy as part of their treatment. And, you know, there’s two important trials that I think are nice to be aware about as the surge and that have come out in the last couple of years that look at, you know, our ability to tailor a patient’s adjuvant systemic therapy based on their response to a standard neoadjuvant regimen. And so the two trials that I’m referencing, one is the CREATE-X  trial, and one is the  KATHERINE trial. And in both of these trials, so CREATE-X was her2 negative patients,  KATHERINE was her2 positive patients, people receive standard neoadjuvant chemotherapy, then if they had any residual disease in the breast or the axilla. So patients who did not have an overall PCR, they were then eligible to be randomized to either standard adjuvant treatment or a tailored therapy. So in CREATE-X that involved capecitabine and in KATHERINE that involved T-DM1 instead of trastuzumab, and they showed a survival benefit for people, for patients in the intervention arm. And I think these these two trials have really solidified the the value from a systemic therapy perspective of using a neoadjuvant approach. And these have been certainly two very practice changing papers, at least at my institution, whereby really sort of all patients with triple negative disease are strongly considered for neoadjuvant chemotherapy, and in her2 positive, you know, those with stage two and above disease. So either node positive disease or tumors greater than two centimeters in size, again, are kind of strongly considered for a neoadjuvant approach. We also know that in these subtypes, you know, those patients are the most likely to get potential local regional therapy benefits. So these are the patients whose tumors really shrink down and become amenable to breast conserving surgery if they were large to begin with. Or these are the patients who are most likely to have an axillary PCR and potentially be able to avoid an axillary lymph node dissection. So that would apply to the patient that you’ve, you’ve referenced, in your case, like a node positive patient. If they have triple negative disease, they have probably about a 50% chance of being able to avoid an axillary lymph node dissection with neoadjuvant chemotherapy. And with her2 positive disease, it’s even higher, you know, in the 60 to 80% range. So, you know, it’s become that there’s really a lot of advantages to a neoadjuvant approach. And certainly, I think anybody would triple negative or her2 positive disease, you know, it’s not unreasonable to consider a multidisciplinary consultation and really be thinking about any of these patients as potentially benefiting from neoadjuvant chemotherapy. And for patients with hormone receptor positive her2 negative disease, it’s a little murkier, because, you know, particularly in the era of genomic assays, what we’re learning is that, you know, both fairly substantial subset of both mode negative or node positive patients may not actually get a lot of benefit from chemotherapy. And so chemotherapy may not necessarily be a part of their treatment, and you don’t want to be over committing people to neoadjuvant chemotherapy and you know, potentially getting in this scenario where you’re over treating patients. And so I think we have to be particularly thoughtful in this group. And you know, that being said, a patient who’s node positive at presentation, really their only chance to avoid an axillary lymph node dissection is with the neoadjuvant approach. But we need to recognize that depending on sort of the features, the biology of their disease, so things you can look at the tumor grade, you can look at the histology, if you have a genomic assay available, you can look at that even over the core biopsy. And you know, depending on their biology, you can sort of get a sense of what type of response they’re going to have. And you know, in some cases, the likelihood of an axillary PCR is really small. And you might actually benefit from just an upfront surgery approach, you know, really get a sense of the stage of the disease so that your medical oncologist then has all the information they need to make their adjuvant therapy decisions. So, you know, I think, again, in a clinically node positive hormone receptor positive her2 negative patient, I certainly think a multidisciplinary consultation and consideration for neoadjuvant chemotherapy is reasonable. But I think we do need to be a little bit more thoughtful about sort of committing patients too early and over treating patients with that approach.

Ameer Farooq  16:18

There’s a couple of things, I think, to just highlight, again, what you’re saying. So I think that’s where it gets confusing. And you’ve made that distinction very beautifully, is that, you know, just because they’re node positive doesn’t necessarily mean that they they will benefit from getting chemotherapy, but, you know, for an exam purpose, it probably makes sense to at least say that you were going to send them to a multidisciplinary clinic to actually, you know, have everyone’s input, but but you know, that you have to be thoughtful a bit about who’s going to actually get neoadjuvant therapy.

Alison Laws  16:54

Yeah, for sure. And I think, you know, in in the real life setting, I think it’s also really helpful to know sort of what your local medical oncology practices are, to some extent, and I found this even doing electives as a resident, you know, did a few breast swatches, in Toronto and Vancouver. And then of course, I had experience in Calgary. And, you know, the, the sort of local institutional practice patterns do differ a little bit between those places. And so I think sort of being mindful of that, and having a good relationship with your medical oncology colleagues and, and knowing, you know, you can start to learn what types of things they’ll consider a good indication versus not a good indication. And, you know, educating yourself as a surgeon, I think is really helpful.

Ameer Farooq  17:39

Can you talk a little bit about what neoadjuvant chemotherapy involves? Like, what is the regimen that’s typically used? Sort of the mechanics, like, how many months does that workout to be? And even even the logistics? Like, do you always clip the primary tumor and the and the axillary node if they do have a positive axilla? Can you talk a little bit about what what’s done at your institution?

Alison Laws  18:04

Yeah, so again, variable depending on the subtype. So for patients with her2 positive disease, of course, and I’m their neoadjuvant therapy should involve some kind of her2 directed therapy. So kind of the standard therapy would be trastuzumab plus or minus there’s a second agent that is sometimes added called pertuzumab, depending sort of on the extent of disease and the disease features. And the chemotherapy backbone that’s given along with the her2 directed targeted therapy varies a little bit by institution. And so, you know, answering the question about kind of a typical regimen is a little bit tricky there, I think it’s the kind of probably what’s good to know, is just that there’s multiple different regimens, some that are a little bit more chemotherapy intensive than others. And, you know, the other approach is that sometimes they’ll start with sort of a more, you know, mini chemotherapy regimen, you know, assess the tumor response. So, maybe give something like just Taxol Herceptin, you know, assess response if the patient’s not having a great response, then they might add AC you know, towards the end of the regimen, so, it is sort of a little bit of a moving target for triple negative disease or hormone or hormone receptor positive her2 negative disease, typically, to the most standard regimen is ACT so anthracycline, cyclophosphamide and taxol. And, you know, again, the kind of exact timing and dosing varies a little bit but in general there are injections that are given, you know, every one or sometimes every two weeks depending on the medication and it’s usually sort of a three to four month course of treatment in total. The yeah so in terms of kind of surgical planning in a patient who’s going to receive neoadjuvant chemotherapy, you know, making sure that you’ve really worked up the extent of disease in the breast and the axilla at the outset is important. Certainly any sites of disease that are suspicious on whatever breast imaging you’ve chosen, should be biopsied. And anything that is a biopsy proven cancer should be clipped. And, you know, the practice of clipping lymph nodes is a little bit controversial, a little bit institution specific. At Dana-Farber, we do routinely clip lymph nodes that are, you know, any lymph node, that’s biopsied gets a clip. And then if that lymph node is it turns out to be positive and if the patient is then you know, has a good response and becomes clinically node negative by physical exam after their treatment, then they are, in most cases offered a central lymph node biopsy as well as a targeted excision of that clipped node. And we actually localize those with a radioactive seed. So that node gets excised based on the localization with the seed. And then we perform a sentinel lymph node biopsy with dual tracer concurrently.

Ameer Farooq  21:19

You know, you talked a little bit about genomic profiling. Can you talk a little bit about that? Is that something that’s pretty standard at Dana-Farber and BWH? Or is that something that you’re using selectively? And in those cases, where if you’re using it selectively who are using it?

Alison Laws  21:36

Yeah. So I would say so for patients who are clinically node negative, and have estrogen receptor positive her2 negative disease. And the majority of those patients are getting a genomic assay to help guide their adjuvant chemotherapy at Dana-Farber. And they follow the TAILORx trial that suggested the patients with a low or intermediate, we use the oncotype here the 21 gene requirement score. So patients with a low or intermediate score are typically not felt to have a significant benefit from adjuvant chemotherapy, whereas patients with a high recurrence score, again, you know, kind of generalizing would typically be considered for adjuvant chemotherapy. You know, there are other clinical features that can trump that. So I wouldn’t say, you know, we make decisions based on the genomic essay exclusively. But you know, it’s an important piece, I think, in guiding the decision making. And we don’t have the same sort of level one evidence for the use of the recurrent score in patients with node positive disease. However, there is sort of mounting evidence to suggest that it probably can be used in that setting as well. And there’s an ongoing clinical trial that will answer that question called RX-PONDER, but we’re not expecting results for still a few years. So it is being used selectively in node positive patients as well. We’re also starting to use it sometimes to help make neoadjuvant treatment decisions as well. So patients again with estrogen receptor positive her2 negative disease. And if it’s a patient who has a large tumor, and you know, we’re thinking about neoadjuvant therapy, maybe to help facilitate breast conservation, or if it’s a patient with node positive disease. And we’re thinking about, you know, can we downstage the axilla to avoid an ax dissection. Sometimes we’ll use an oncotype to help guide the approach of whether a neoadjuvant chemotherapy versus neoadjuvant endocrine therapy may be more appropriate. And particularly if your goal is breast conservation, and you know, neoadjuvant endocrine therapy, you can often help you achieve the downstaging that you need, and can potentially help with this issue of not over treating people by giving them chemotherapy early on, when you know, depending on the final features of the tumor at time of surgery, they may not actually need that therapy. And so that’s I would say a little bit more novel use of the genomic assay that, you know, I suspect will become more popular, but I think that’s sort of something that’s evolving.

Ameer Farooq  24:19

Is this are you talking about Oncotype DX? Or is this a different genomic assay?

Alison Laws  24:24

Yeah, Oncotype DX, or sort of the 21 gene recurrence scores the other sort of more generic name for it. Yeah, so that’s the one that we use. And I mean, there’s lots of data coming out about some of these other assays, PAM50, etc. But the one that I’m most familiar with just because we use it at Dana-Farber’s

Ameer Farooq  24:44

Obviously, the way you’re thinking about these issues are is at a fairly high level, fairly sophisticated kind of way where you’re really trying to think about what the evidence is behind the various treatment options and the patient in front of you. And obviously, you know, the multidisciplinary kind of discussion about these things are super important. You know, in the rectal cancer world, that also seems to be a big move where, especially now that we’re having things like total neoadjuvant therapy, that that’s that’s becoming increasingly important. Do you think that we’re going to get to this point where you know, all breast cancers need to be discussed at a multidisciplinary meeting? Or do you think that would be too overwhelming? Like, what are your thoughts on that? Like, do you think breast cancer is going to become an increasingly specialized kind of rarefied specialty that you really can’t practice unless you’re doing a high volume of it?

Alison Laws  25:41

Yeah, I think, you know, I think so. I mean, I can tell you the model at Dana-Farber is that all new breast cancers are seen in a multidisciplinary setting. So all new breast cancers are scheduled both with the breast surgeon and with a medical oncologist at the first visit. And it was similar at Mass General, except that their multidisciplinary setting at the first visit always involved the visit with the breast surgeon and with the radiation oncologist actually, and then they would see the medical oncologist as well at that visit, if it was sort of a patient that the surgeon had flagged as you know, potentially needing some neoadjuvant systemic therapy. So that is the model that we use, I don’t know that I feel that that’s absolutely necessary for every breast cancer patient. I mean, the reality is, there’s still a lot of these run of the mill, you know, postmenopausal ER positive her2, negative node negative screen detected cancers, where, you know, upfront surgery is still very much the standard. And I think most surgeons are pretty comfortable in that sphere. And, you know, how much those patients really gained from a multidisciplinary visit at the first meeting? You know, I’m not I’m not sure it’s, it’s totally necessary. And I agree, I mean, I think there’s some risk there of sort of overwhelming patients with too much information at the first visit, right. Like, in some instances, you’re dealing with three providers, maybe you have genetic testing that day, like it’s a lot, I think, for patients to take in. But certainly in triple negative and her2 positive disease. And, you know, I kind of gave my bias earlier, I think that, you know, I think a multidisciplinary visit for any patient with that subtype is quite reasonable. And I do think that, you know, the care is becoming more and more nuanced. And so, you know, even as a provider, having the opportunity to meet in a multidisciplinary setting, and just be able to discuss the case with your colleague and kind of bounce ideas off of each other and come up with a plan that sort of somewhat laid out from the outset, I think is nice. I mean, it gives me comfort as a provider, and I think, I think it does make sense for some patients.

Ameer Farooq  28:00

Yeah, I think that’s an under emphasized point in the multidisciplinary conferences is that how how, like how helpful it is for you, as a surgeon to actually be able to talk about it with other other clinicians and make sure you’re doing sort of the right thing. Okay, so I think that was an a fantastic overview of sort of an approach to neoadjuvant therapy. I think another related topic that gets people all twisted up is sort of the indications in 2020 for an actual lymph node dissection, and I really think, honestly, it’s probably more helpful to think of it in that way, like, who are the people that actually still should be getting an actual lymph node dissection, as opposed to the other way around? Because it’s just such a rare occurrence. And I think, you know, most general surgery residents probably don’t see very many of these through their career. So break it down for me, how do you sort of think about who is getting an actual lymph node dissection in 2020?

Alison Laws  28:58

Yeah. So I mean, I think there’s kind of two branch points that I think about, I think the first is whether we’re talking about upfront surgery setting versus post neoadjuvant chemotherapy setting, because the algorithm kind of really is different for those two spheres. And so if we think about upfront surgery setting first, then I think your next branch point is sort of is the patient clinically node negative or are they clinically node positive. And that’s defined by your physical exam, as well as by any imaging identified abnormal lymph nodes that are then biopsied and found to have disease like that patient I would put in the clinically node positive pocket. And so if they’re clinically node positive and we’re talking about upfront surgery, that patient needs an axillary lymph node dissection, so that’s a pretty easy one. If they’re clinically node negative and upfront surgery, then most of those patients are eligible for sentinel lymph node biopsy. That’s usually your first step. And if the sentinel node is negative, then that’s easy. They don’t need an axillary dissection. It’s when the sentinel lymph node is positive, this bucket is kind of, I think, the most confusing one. And it’s because you sort of need to know what are the clinical trials where there’s been investigation of, you know, it’s safe to omit and axillary lymph node dissection in under these criteria. And I think, you know, the two trials, two, three trials, I guess to know about would be the ACOSOG Z0011 trial, the AMAROS trial, and then the IBCSG 23-01. So the last trial that I referenced, basically, if patients have only micro metastatic disease in the central node, they don’t need an axillary lymph node dissection. If patients have had breast conserving surgery, and had a T1 to 2 disease to begin with, and then they have one or two positive sentinel nodes, that’s basically the criteria for ACOSOG Z0011. And those patients don’t need an axillary lymph node dissection. If they have three or more positive nodes sentinel nodes, then they don’t meet those criteria, or if they have T3 or T4 disease to start with, then they don’t meet those criteria you would with node dissection. The AMAROS trial was very similar except that it also included patients with mastectomy. However, in that trial, patients received axillary radiation. So in that case, if you’re if you’re talking about a mastectomy patient, and again, T1 to 2 disease with only one or two positive central nodes, they don’t necessarily need an axillary lymph node dissection, as long as they are candidates for post mastectomy radiation where the axillary lymph node will be radiated. So that is kind of the confusing bucket, I think, and you just kind of have to commit those criteria to memory, you know, for the exam. And in real life. If we’re talking about post neoadjuvant chemotherapy, I almost think this is a little bit easier. So you people who were clinically node negative prior to their treatment, and who remained clinically negative after treatment would have a central lymph node biopsy. And if it’s positive, any number of nodes any volume of disease, they need an axillary lymph node dissection. And basically, the same goes for patients who were clinically node positive at the outset. So if they are now have converted to clinically node negative and you do the sentinel lymph node biopsy and remove the clipped node, again, any number of positive nodes, any volume of disease, we need a ax dissection, and then the final category are patients I guess, who are clinically node positive, get their neoadjuvant chemotherapy and are still clinically node positive. And really, I kind of define that as still positive physical exam, then those patients need an ax dissection, we typically, you know, don’t offer  sentinel lymph node biopsy if you can still feel abnormal disease in the axilla. So, you know, unfortunately, there’s just not a really super easy way to break it down. But that is kind of the branch points that I think about. And hopefully that gives people somewhat of an approach.

Ameer Farooq  33:16

The the one thing we didn’t mention that I think it’s just important to clarify that inflammatory breast cancer, those people are going to have to be referred for neoadjuvant chemotherapy, and then and then all of those people will get an axillary node dissection, right?

Alison Laws  33:32

Yeah, that’s correct. So that’s really none of the trials looking at the safety or sorry, I shouldn’t say the safety, none of the trials looking at the feasibility and false negative rates of sentinel lymph node biopsy, after neoadjuvant chemotherapy in a node positive patient have included inflammatory breast cancer. So that is really still an area where yes, and triple therapy approach so neoadjuvant chemotherapy followed by a modified radical mastectomy followed by post mastectomy radiation is still the standard of care.

Ameer Farooq  34:05

The one thing I was hoping you could also do is to briefly go over your high level kind of thought process on an approach to the axillary dissection, because I think, again, this is something that’s going to become an increasingly rare thing for general surgery residents to do. So sort of in you know, 10 steps or less, sort of, if you could summarize how you approach ax dissection.

Alison Laws  34:29

Yeah. So yeah, I mean, this was definitely an area where fellowship training was useful, because, you know, I agree, I think I’d only done sort of a handful of axillary node dissections and actually most of the ones that I’ve done as a, as a resident were for melanoma. So, you know, general approach, so I think, you know, I usually make an incision sort of along the anterior axillary hairline, I use sort of a curvilinear incision. You know, the reality is, you actually don’t need a really large incision. I think the key is that you then get down and widely excise the clavipectoral fascia. And I remember that something that I learned sort of memorizing as a resident to talk about this surgery. But until you’ve done a few, you don’t really realize what the value of that is. And so I think, you know, real life advice is that you know that why like excising the clavipectoral fascia is really what gets you good visualization at the axilla. There are then a couple of, I guess, surgical approaches, I prefer sort of a medial to lateral approach. So I like to start by identifying the pectoralis major muscle and I sort of widely, you know, dissect along that muscle, so I’ve really nicely exposed it, I then follow it down so that I’ve exposed pec minor, and I’m really kind of down on the chest wall, and it started to loosen up that tissue, it really got into that axillary fat. I then worked my way superiorly and identify the axillary vein, this can often really just be done with blunt dissection, particularly if you’ve kind of started that medial dissection, just blunt dissection with your finger on a sponge or a sponge stick, you know, whatever instrument you like. And once you’ve identified the axillary vein, I usually leave about a centimeter. So I work sort of about a centimeter interior to the vein and just work my way along medial to lateral, there will often be some crossing branches that need to be ligated, work my way all the way along, really until I’ve identified the latissimus. And then I come down the latissimus. So this is you know, network, kind of the lateral side, and I fully dissect along the latissimus. And so that I’ve now kind of really defined my medial, my superior and my lateral border. And then at this point, I go back to the medial to the chest wall. And again, really using exclusively blunt dissection, if you’ve kind of gotten down to the chest wall, you can sweep all of that axillary tissue off of the chest wall until you’ve identified your long thoracic. You know, confirm that you’ve identified it, I do like to do this with the patient’s not paralyzed. So that I can be really confident that I found my nerves and, and then I basically work my way now, sort of superiorly you’re now working, like, I think that I’m kind of working towards the patient’s back. So you’re kind of working straight down until you’ve identified subscap. And you’re just peeling that tissues sort of inferiorly and off of the subscapularis. And here is where you’ll ultimately come across your thoracodorsal bundle, obviously, that you want to preserve that. And I continue to clear the axillary tissue, even lateral to the thoracodorsal really all the way to the lat, which I’ve already identified. So this is actually the pretty easy part of the operation, you’re just kind of peeling everything within those borders that you’ve already created. And, you know, the inferior aspect of the axilla is kind of a nebulous border, there’s not an obvious anatomic landmark, but really, you know, your lat and your chest will almost kind of start to converge. And that’s how, you know, you’ve gotten to the inferior aspect of the axilla. And I, you know, typically this all comes out kind of in one block, that’s really level one, often you’ve kind of got some of level two, but I then do, you know, make a note to really make sure that I felt with my fingers sort of under the pec minor, and if you know, particularly if there’s anything gross that I can feel sort of, you know, dissect out any additional level two nodes that I’ve missed in my initial dissection.

Ameer Farooq  38:32

That was a brilliant description. What do you think are the big pitfalls that or technical tips that you have for getting yourself out of trouble when doing this?

Alison Laws  38:43

Yeah, I mean, I think that early exposure is really key. And so that is sort of what I was harping on, I guess about that clavipectoral fascia. And then I think, like, for me, I just find it really helpful like the the pec is a really consistent, easy landmark. And that’s why I like to start there. I think like sometimes you can get a little bit lost in the axilla and I think just really is systematically identifying those three landmarks the pec, the axillary vein and the lat will really keep you oriented. And, and then, you know, the nerves from there are actually the nerves, you know, the clavo thoracic nerves or the thoracodorsal bundle, from there, you know, are pretty easy to identify.

Ameer Farooq  39:27

The last topic that I’m going to pester your about or ask you about is on recurrent disease because I think that was something that we also struggled with a lot with setting for our exam. You know, that they’ll they’ll give you different sort of scenarios. You know, the isolated axillary recurrence, the isolated subclinical recurrence, maybe we can start with sort of your general approach. You know, you have a patient who has previously had surgery for breast cancer now comes back in with let’s say, a isolated supraclavicular node, how do you approach that patient?

Alison Laws  40:08

Yeah, so I remember a lot of the, the scenarios you worry about for the exam, you know, clinically in real life are actually really rare. But nonetheless, I think you know, anybody with local regional recurrent disease, it’s reasonable to first sort of stop, take your time. I do believe in distance staging for all of these patients, I think NCCN does recommend that. So really restaging you know, biopsying suspicious things, and really identifying the extent of disease because there is a significant proportion of patients who will present with concurrent distant metastatic recurrences at the time of a local regional recurrence. And you don’t want to miss that. I think local or regional recurrences is really an area where multidisciplinary review is critical. You know, I think here is definitely an area where involving medical oncology, involving radiation oncology, you know, all of your subsequent treatment decisions are largely dependent on what previous treatment the patient has had. And so, you know, having the colleagues who have administered those therapies previously involved in really understanding sort of where this patient stands is critical. And the isolated supraclavicular recurrence, you know, I think, again, it’s, it’s really dependent, like if a patient has already had regional nodal radiation, then they’re not necessarily eligible for that again. And so in that case, you may be thinking more about systemic therapy. And I think if they haven’t had prior, regional nodal radiation, then, you know, radiation first approach is often the way that we’ll go, although it does depend a little bit on the extent of disease, because, you know, radiation is really most effective for small volume disease. And so, you know, again, a little bit dependent on the presentation, I think it’s important to know for the exam that, you know, we don’t, typically we don’t, surgically resect supraclavicular disease that is not typical therapies. So, really sort of radiation or systemic therapy is your first step. The same goes for internal mammary nodes, those are not really thought of as surgically resectable disease. Isolated axillary recurrences, you know, if it’s an operable lesion, then typically the first step would be an axillary lymph node dissection. And then followed by, you know, potentially axillary radiation, again, depending on what the patient’s had previously, plus or minus systemic therapy, depending on what the patient’s had previously, and the extent of the recurrence. And then for locally recurrent disease, I guess would be sort of the last scenario. And here again, their previous surgical therapies really important. So a patient who’s had previously breast conserving surgery and has a local recurrence. You know, the standard therapy would be a mastectomy. And typically we do try to restage the axilla. Its still a little bit of a data free zone but in a patient who has previously had a sentinel lymph node biopsy, you know, our practice certainly is to try a repeat central node biopsy and it actually will map the majority of times. And patients alternatively, who have already had an axillary lymph node dissection, we do not routinely restage the axilla in those patients unless there’s something grossly abnormal on their exam. And then if patients have had a prior mastectomy and have a chest wall or a skin recurrence, again, if it’s all horrible disease, then typically an excision to negative margin would be your first step. And then sort of adjuvant radiation, systemic therapy, depending on all of those other factors.

Ameer Farooq  43:51

I guess I guess one of the things that we struggled with was sort of the the sequencing sometimes of what therapy you’d get, particularly for the supraclavicular lymph node recurrence, it seemed like there was some difference, depending on what resources you’d read about whether to chemo first versus radiation first, does that really matter? Or is that sort of just institution dependent type of issue?

Alison Laws  44:16

Yeah, I mean, I think, to be honest, I feel like it’s a little bit outside of my area of expertise. My understanding is that, you know, depending on the bulk of disease, and, you know, the radiation oncologist can help determine whether they feel that their radiation therapy can effectively, you know, can effectively treat that volume, or if the patient may benefit from some cytoreduction from systemic therapy, such that the radiation therapy can then be more effective. So that, I think is where the sequencing piece does become a question and I think, you know, again, outside of my area of expertise, but you know, involving those two colleagues, I think that why it’s so critical.

Chad Ball  45:02

You know, it’s interesting to listen to you guys talk about not doing that many axillary dissections in residency because I’m not that old, I don’t think but I certainly remember doing them sort of every day, on general, general surgical rotations, it’s interesting to see how far things have come in, it’s always fascinating to listen to that because it seems in terms of progress, and treat treatment progress and philosophy to change within breast oncology, maybe even at a pace greater, or certainly a sustained pace that’s greater than most other fields. One of the things I remember, Dr. Laws was being told very early in my residency, which again, is a little bit ago now that soon one day, breast oncologic management would be entirely nonoperative. That’s clearly not the case now. What’s your what’s your vision, or your or your your belief in terms of if that’ll ever happen? And maybe what that will look like in another 15 years from now?

Alison Laws  46:01

Yeah, yeah, it’s a really interesting thought. You know, again, I think there’s real sort of differences amongst breast cancer subtypes with this question. And so, you know, particularly patients with triple negative or her2 positive disease, who are, you know, more and more commonly treated with their neoadjuvant systemic therapy, which is usually chemotherapy up front, you know, chemotherapy has gotten so good that it does really have this ability to melt away disease in a significant proportion of patients. And we’re seeing that sort of even at great percentages now, and there’s, you know, better systemic therapy coming down the pipeline, you know, we just had sort of some early data about immunotherapy in the neoadjuvant setting for triple negative breast cancer presented at ASCO this year. And, and, you know, we’re seeing even greater rates of of complete pathologic response with that therapy. And so, you know, I have to believe that this systemic therapy is just going to get better and better. And, you know, in the setting where it’s done, first, you know, I could see that I could see that we are eventually going to get to a part where surgery may not have a role in all patients with breast cancer. You know, there’s already been a lot of interest in this in these subtypes, in particular, and unfortunately, thus far, you know, there’s not any one imaging modality that seems to be able to predict a PCR with enough reliability. There’s also, you know, after that was kind of determined, there’s now been more recent efforts looking at, you know, can we do multiple core biopsies of the tumor bed and cannot be acting, you know, have a reasonable enough false negative rate that we can identify patients who don’t need surgery. And unfortunately, those early efforts have not suggested that that’s the case. And we’re not quite there yet. But certainly in those subtypes, in particular, I can, I can see that coming. You know, in the hormone receptor positive her2 negative disease, I’m not as sure. I think if anything, the movement in the systemic therapy world has been, you know, trying to pull back a little bit on how many patients we are giving chemotherapy to, you know, as you know, we’ve, as we’ve talked about today, and genomic assays have really helped us to identify a large subset of women who don’t get a lot of benefit from chemotherapy, and who have excellent long term outcomes with endocrine therapy alone. And, you know, even if we were to think about moving endocrine therapy to the neoadjuvant setting, we know that endocrine therapy doesn’t really melt away disease the way that chemotherapy does. And so I you know, my gut is that in those patients, there’s always going to be a role for surgery. But, you know, who knows? I mean, I totally agree, it’s amazing. You asked me Ameer and I were talking earlier that just, you know, things have changed in breast since I wrote my exam, you know, a year ago, it’s just the pace of changes is extremely rapid. And I think you know I think it could go in many number of ways.

Chad Ball  49:11

That’s so true. It’s it’s really remarkable. It’s probably a good model of not only envy, but really something we should all aim to in other subspecialty diseases it’s it’s awesome. If you don’t mind alley, we wanted to touch on just a short list of things. Again, more about you and and move on from, from the importance of of your breast comments. With regard to oncologic care, you know, both you and Ameer have spent time in Boston at various parts and as we heard your you continue to be there right now. And maybe forever, who knows, hey, but I’m curious, you know, everybody I’ve ever known who’s gone to do some segment of training in Boston from really undergraduate all the way through medical school and fellowship, training and staffdom has absolutely loved that experience. So first to you and then also to Ameer what it is, what is it about Boston that, that is so enriching and so unique and so awesome.

Alison Laws  50:13

Yeah, it’s very true. I mean, I feel the same way about my training. And now my, my position here, I think, you know, there are really a large concentration of sort of the thought leaders in the field of breast cancer concentrated at Brigham and Women’s and Dana-Farber. And getting to work alongside those people in sort of the clinical care of your patients on a day to day basis, and then also in your academic efforts, and you just can’t help but learn from them. I mean, there’s just, there’s so much knowledge. And not only is there so much knowledge, but it’s, it’s an environment where they really promote education, and they really are focused on, you know, the senior, more senior colleagues mentoring the junior people in the department and the amount of sort of time and focus and attention, I think that’s given to making sure that everybody’s is learning and moving forward. And kind of this idea of lifelong learning is really just epitomized in the group as certainly the breast oncology group. And so I think I have been so grateful for that. I mean, just, you know, the amount of time that people dedicate to sort of mentoring you and making sure that you’re progressing as a clinician as a, as an academic, you know, there’s a really strong focus on that. And that is makes all the difference as a trainee or as a junior faculty.

Chad Ball  51:52

That’s, that’s so well said, You know what, it’s interesting, one of my best friends, who’s a neurosurgeon in the US now, did a PhD at the University of Alberta. And he was a pretty good heavyweight, I mean, his first two papers are published in Science and his third in Nature. And he went down to Harvard and did a postdoc down there, and then did med school. And then and then left, and I asked him the same question. I said, what’s the difference between U of A, you know, in the biochemistry world, which was superb and Boston. He said, well, the difference is, you can walk down the hall and talk to three people that have won a Nobel Prize on that topic. I was just like, oh, my God, that that is truly amazing. And I wish we could all experience that.

Ameer Farooq  52:32

I just echo what both of you’re saying, I think it’s just the ability to have rich conversations with people from many different backgrounds, who really care about what they’re doing, and really believe that they can make a difference and change things. That it’s just a it’s a very intoxicating kind of experience. And it’s really enjoyable. I we wanted to talk to you a little bit about one of the topics that we’ve talked about on the show before, which is the concept of regret. So Tim Pawlik, who’s obviously the heavyweight in, in surgery down at OSU has written a lot about this topic of regret. And this is particularly important in breast cancer, where there’s a lot of different factors that patients have to think about, including cosmesis, but also, you know, oncologic considerations like recurrence. How do you approach these very challenging discussions in clinic with patients?

Alison Laws  53:32

Yeah, so yeah definitely very applicable. And, you know, I think this comes up a lot when you’re counseling patients about breast conserving surgery versus mastectomy. And I think this is probably even more relevant when patients are thinking about a contralateral prophylactic mastectomy. And I think, you know, we’re fortunate in breast that there’s actually been a lot of interest in incorporating patient reported outcomes into some of the research efforts that have been done in those areas. We actually do have some reasonable data that we can talk to patients about, and I do I do explicitly address that with patients. You know, for patients thinking about bilateral mastectomies. There’s a really nice position statement that’s been put out by ASBRS that sort of summarizes some of that data and, you know, we tell patients that so like I said, as I talk quite explicitly, so I first sort of focus on my oncologic recommendations, and what I think you know, is is good treatment options for the patient from an oncologic perspective. And then I always turn the discussion to, you know, what are the implications for you otherwise, of a masec of a mastectomy or have of a bilateral mastectomy. And we know fortunately, you know, not a lot of patients express significant regret about their decision, although there are probably somewhere in the range of five to 10 percent of patients who do regret whatever decision they make. But there are you know, that 25 to 35% of patients that if they choose mastectomy are unsatisfied with their outcome in some way. And, and I think patients don’t appreciate that about a mastectomy. And when I say unsatisfied, that’s things like you’ve identified, so because you know, I’m unhappy with the cosmetic result, what I think patients appreciate even less is the impact on their body image, their sexuality, and that’s been, you know, well documented in some of these studies that have that have asked patients and, you know, we have data from large numbers of people on this. And so I pretty explicitly talk about that with people. And I find if if you’ve kind of given you know, the oncologic information, and then some of this PRO data, I think, from there, patients do self select a little bit. And I think, you know, at the same time, I trust that most patients know themselves pretty well. And that’s probably why we see, you know, relatively low, low rates of true, you know, regret, with a decision, I think, you know, I think people kind of self select from there as to whether, you know, what, you know, the balancing of these oncologic considerations versus these other real quality of life outcomes with more aggressive surgical treatments. But, you know, some patients are more receptive than others. And so, you know, the conversation is very different every time. And, you know, sometimes I feel better about it at the end than other times. So I think still something that I’m sorting out to be honest.

Chad Ball  56:43

That’s, that’s well well said Allison. And then the last thing we wanted to talk to you about, and again, thank you for your your time, and your expertise and your candor. The last thing was was about your experience, really on the other side of the knife, or the table, or the curtain, or whatever terminology you’d like to use, but as a patient who underwent surgery. And I mean, I’ll just point out for the listeners that we did clear this with you before, and we’re really privileged that you’re willing to talk about it. I guess my questions are sort of maybe threefold. The first is, just broadly, what was that experience like, in hindsight. I’m curious, also how it may have altered or probably did alter, uh, your, your view of surgery and your development as a surgeon in general. And then I’m curious, in particular about, you know, for somebody like me, to be honest, who, you know, had a knee procedure done, but that’s not saying a lot, someone who has a more invasive or high risk procedure, what are some of the things that you think, you know, we need to be cognizant of and improve upon as, as surgeons and physicians in general, for the for the patient?

Alison Laws  57:56

Yeah, it’s very interesting. So I had this experience, you know, as a laparotomy, was my operation for urachal tumour that turned out to be benign, but there was some diagnostic uncertainty. And I was 20 years old, I was in third year university. So this was really sort of premedicine. And I’m very grateful, honestly, to have had that experience before having any exposure to the medical world. Because I definitely think that it has given me insight, you know, definitely insight into what it’s like, as a patient who’s not kind of in it and who’s, you know, naïve to the whole medical sphere? You know, I think it was, it was a stressful experience. I think it was stressful, partly because of my other life circumstances, like I was sort of in the middle of applying to medical school, and in the middle of exams, and it all happened very quickly. And, you know, I was living where I didn’t have any family. And so, you know, I think, I think having, I think I have a definite appreciation for how sort of your other life context can shape the experience of having to go through a major operation, and sort of prepare for it mentally, have it, recover from it, all of these things. It definitely shaped you know, definitely shapes the way that I care for patients. And I think it was interesting, I don’t know that it largely influenced my decision to pursue surgery. But you know, the fact that I did choose general surgery, I think it has kept the whole experience a little bit fresher in my mind than it otherwise may have been. And sometimes I’m surprised at the level of detail that I still remember about the whole experience. And I think, you know, being in the surgical world and sort of becoming really attuned to all of these things on the other side has has helped me to kind of remember and keep it fresh in my mind. I think, you know, the way that it has shaped how I provide care, there’s a couple of things, there’s a couple of like key moments that I remember. One was the feeling of sort of entering the operating room. And, you know, to be honest, I hadn’t I wasn’t particularly afraid, I felt, okay, I felt kind of mentally and emotionally ready, pretty much until that moment where I was rolled into the operating room. And I remember, like, the whole environment just suddenly felt very foreign, I felt a lot of fear, you know, you suddenly had people kind of touching every part of your body, right? Like, people are putting things on your legs and your arms and your face, and lots of people are talking at you. And, you know, I remember that being just very overwhelming. And I, you know, so now as a surgeon, it’s something that I actually talk to patients about in the, in the pre-op therapy area, I sort of warn patients, you know, listen, when you get in the room, there’s going to be a lot of bodies, you might hear a lot of talking, you’re going to hear monitors, people are going to be putting things on your body. So, you know, I don’t know if that helps, maybe that’s just makes people more worried. But I think, you know, that was really surprising to me and kind of took me took me by surprise. And it’s something that I do now communicate to patients ahead of time. I think it also has made me really cognizant about that period of time in the operating room, you know, as a surgeon, or a trainee or the nurse working in the room, I mean, it’s kind of just another day in the office. And I think sometimes, you know, there can be personal conversations, there can be laughter, there can be you know, can be a little easy to just kind of not be laser focused on our professionalism. And I think those moments, I now really think about that, and strive to kind of keep that, as, you know, try not to add any more overwhelming piece to that experience for patients. And you know, it’s a short period of time between when they come in the room and when they’re anesthetized. And I think really kind of controlling the environment and maintaining our professionalism during that time is really critical. And it’s something that I think about, I think, based on my own experience.

Ameer Farooq  1:02:18

But you know, having been on the other side of the table as well, too, I really wanted to echo one thing that you said about just realizing like how important this moment is to that person you have lying on the table. Like I felt exactly the same to you, which is interesting, even though I had a totally different operation. That I just didn’t want anyone like laughing like I now it’s funny, because I I recognize that, like when people are relaxed, that’s actually a good sign. But I didn’t want that when I was having my surgery, like I just wanted people to be like, totally focused on me and just really like, treating me like I was, you know, the most important person in the room. So, you know, it’s just funny, like how these little things when you become a patient, you really notice and they’re not necessarily the same things that you think matter to you as a surgeon, right? Like, you know, as surgeons, we’re thinking about recurrence and mortality and morbidity and these very hard outcomes, but it’s like sometimes these very little things that really bother patients. How do you think that we can go about getting better a better sense of what really matters to patients? And then trying to, to address those things just as much as the big things that that we’re always concerned about?

Alison Laws  1:03:42

Yeah, it’s a good question. I mean, so a good example of this, I guess, for my surgery was, you know, remembering the preoperative consultation, you know, you talked to me about everything, you’re involved in the surgery, and I, you know, whatever, kind of went through all the details, went through the expected recovery, and then he had me get up on the examination table, and he examined me and then while he was examining my abdomen, he kind of showed me like, okay, here’s what your incision is going to look like. And, you know, I have it was like, umbilicus to suprapubic bone, basically. So it’s a pretty big incision. And I remember like, all of a sudden being like, oh my gosh, like, wow, this is this is real, like, this is a big operation. And I’m almost embarrassed to admit this, but then the second thing I thought about was, oh my gosh, like, I’m gonna have this huge scar. And, you know, I had to have my umbilicus resected as part of his operation and so then he’s telling me you’re not gonna have a belly button anymore. And you know, those things mattered to me at that point in my life. I you know, I was sort of like, oh, wow, okay, so you know, what can I do to sort of make the scar heal well and make it look like I you know, normal if I wear a bathing suit and these kind of things. And I think about it now and I’m sure you know is this you know, your logic on call oncology surgeon and he’s like, Oh my goodness, this girl, you know, cares more about her incision than anything else. But, you know, he allowed me time for that narrative. And he listened and you know, he gave me a monocle closure and, you know, some other little things and and if they go, you know, that really helps build rapport. And I really appreciated him for that, and I still do. And so I think, you know, I think we have to respect you know, what our patients tell us and you know, when possible, try to accommodate that and be aware of the fact that they may be worried about things that we’re not, you know, aren’t necessarily front and center in our mind. But, you know, I bet most people who go through surgery have a story like that of, you know, something that they were a bit fixated on that the surgeon sort of wasn’t, and, you know, within reason, and I think we want to allow patients, you know, time to express that and sort of accommodate.

Ameer Farooq  1:06:10

You’ve been listening to Cold steel, the official podcast of the Canadian Journal of Surgery. If you’ve liked what you’ve been listening to, please leave us a review on iTunes. We’d love to hear your comments and feedback. So feel free to email us at podcast.cjs@gmail.com or connect with us on Twitter @CanJSurg. Thanks again.