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Breast Cancer Index, Extended Endocrine Therapy | Elizabeth Ott, PA | 2022 West Oncology APP Updates

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In this session, Elizabeth Ott, PA from West Cancer Center, discusses an important issue, the use of extended endocrine therapy in breast cancer and the role of the breast cancer index in this decision.

Good afternoon and thanks for tuning in for this talk on the breast cancer index abiomarker for extended endocrine therapy benefit my name is elizabeth ott i am a physician assistant in breast medical oncology at the west cancer center for those of you who don’t practice in the breast cancer space i thought i would give you just a brief overview of the subtypes

To give you a little bit of context there are three main subtypes that we talk about with breast cancer triple negative her2 positive and hormone receptor positive which you’ll also hear called er positive sometimes triple negatives are fairly aggressive and typically require chemotherapy plus or minus immunotherapy likewise her2 positive breast cancers while also

Aggressive and they typically require her to targeted therapy which often involves chemotherapy er positive breast cancers are a little bit different they are more slow growing and they can receive chemotherapy in some settings but the mainstay of treatment for these patients is endocrine therapy which attacks the estrogen driven process for increasing the metabolism

Of these cancers typically this endocrine therapy which is an oral medication is taken for five to ten years for a higher risk stage three patients they can even go up to 15 years but for the purposes of our talk today we will be discussing early stage patients while early stage er positive breast patients do have a good overall prognosis for the patients that do

End up having recurrence over 50 percent of these actually occur after the five-year mark just to put that in perspective for a triple negative patient that highest risk of recurrence is within the first two years so this is a rather different process that we see you’ll also remember that we talked about these patients being on their endocrine therapy for five to

Ten years so for early stage patients who were getting five years of therapy as planned obviously if you’re they’re recurring after that five-year mark that brought up some questions about would more medicine be better there were several trials that looked at whether or not an additional five years of endocrine therapy would be beneficial for these patients and they

All showed consistent results of about three to five percent absolute benefit from that extra five years of therapy what they didn’t tell us however is which of these patients is most likely to get benefit from that further therapy now it’d be easy to and convenient to say that all patients should get another five years of therapy to get that extra five percent

Benefit but unfortunately these medications are not always easily tolerated there’s about a 10 percent chance of adverse event with either bone toxicity such as osteoporosis thromboembolic events and even endometrial cancers also these are not easy medications for people to tolerate about 50 of patients have tolerability challenges which i think is a conservative

Number uh hot flashes joint pains vaginal issues and many other problems can make these medications quite difficult to tolerate for five years in the first place let alone 10 years traditionally we would use clinical pathologic factors to help determine which patients should get more therapy such as tumor size and grade and patient age but these are helpful for

Prognostic indicators but they don’t actually help predict which patients get benefit from further therapy it’s helpful to know the difference between prognostic and predictive factors in this setting so prognostic factors help correlate with outcome meaning that a patient with higher risk features typically has a poorer outcome whereas predictive factors help us

Determine whether or not a patient-specific tumor would be more likely to receive benefit from a specific intervention in this case extended endocrine therapy which is where the breast cancer index comes in so this is a genomic assay which is performed on the original primary breast tumor this is essentially two tests in one it’s a predictive test as well as a

Prognostic test both of these are based on the hi biomarker as well as an algorithm of that ho biomarker with several other genes the predictive value gives us a high or a low on the test that will be denoted as a yes or a no so whether or not this patient is likely to benefit from endocrine therapy it also gives us a prognostic score of the risk of recurrence in

Years 5 through 10. so let’s look at her a uh an example case to just get an idea of what we’re really looking at here so that predictive value for this patient they were predicted to get benefit from a further five years of endocrine therapy their prognostic score was 11.1 percent so for this patient if she was to receive another five years of endocrine therapy

She would reduce that risk from about 11.1 percent to somewhere about 3.8 percent based on a 65 percent relative risk reduction foreign ly this patient was bci low so they would not get benefit from a further five years of endocrine therapy and their risk of recurrence is 2.2 percent and years five through ten regardless of what this patient did that five to ten

Year risk of recurrence would not change in response to additional endocrine therapy that 65 percent relative risk reduction is fairly specific and that comes from the proof of concept study in stockholm but there was also seen in ma-17 trans atom ideal and b42 as well so there’s a little bit of variation in between these but they all kind of center around the 65

Percent risk reduction which is what i quote to patients that prognostic score was also validated validated in several trials both in node negative patients as well as node positive patients they can have up to three lymph nodes positive now we already discussed that clinical pathologic features are insufficient to predict benefit from extended endocrine therapy

This was illustrated in the ideal study in which bci identified patients that had high-risk clinical features but got no benefit from that full 10 years of endocrine therapy it also identified low-risk clinical features with patients who experience significant benefit from that additional five years of therapy we’ve also seen that quantitative er and pr staining

Does not show a significant correlation with the benefit from further endocrine therapy only that bci hi biomarker actually shows a meaningful correlation with extended endocrine therapy benefit so because of this bci is now recognized by nccn and asco guidelines to guide decision making regarding extended endocrine therapy this is the nccn guidelines for gene

Expression assays for breast cancers er positive breast cancers and determination of their adjuvant systemic therapy you’ll notice there are two tests which do have predictive value in this setting and that is the oncotype which helps predict the likelihood that they would benefit from chemo and then also the bci which helps predict whether they would benefit from

Another five years of endocrine therapy foreign these tests are great complements to each other they are certainly not meant to replace each other and bci is a great test after oncotype because it also helps prognosticate a patient’s risk in years five through ten so we’ve talked about data let’s talk about patients so we’ve already discussed that patients really

Struggle with side effects with these medications a lot of the time so if we’re going from five years of therapy to now 10 years of therapy it’s even longer for them to develop issues as well as adverse events it’s estimated that 40 of patients are non-compliant with their extended endocrine therapy and obviously poor compliance affects the outcomes negatively these

Patients don’t do quite as well if they don’t take their medication it’s obvious that these side effects can be a big reason for these patients to discontinue the medications but i want to just call out this 22 percent here in the gray box that 22 of these patients weren’t even sure if their medication was helping them and a yale decision impact study on patients

It showed that 82 percent of patients studied that were recommended for extended endocrine therapy stated that they would be more likely to be compliant based on bci results and that’s really significant it also showed that the bci results changed physician treatment recommendations regarding that extra five years and 30 percent of patients which stated another

Way that means that almost a third of patients would have been either either over treated or under-treated regarding extended endocrine therapy this is a little bit of a busy slide and we’ll talk more about who’s clinically indicated in this uh for this test but i do want to talk about the decision uh marked around year four here i typically order bci around year

Four the way that i like to do it in my practice is for my patients who are already on a six-month schedule and their fourth year of endocrine therapy i will mention that there is a tiebreaker test that we would consider doing coming up on year five to determine whether or not they would benefit from another five years of endocrine therapy when i come back for

Their next six month follow-up we would talk about it a little bit more in depth that this test would help them make the determination from whether or not they would get benefit or not from that additional five years and then it would give us a risk of recurrence in years five through ten if they were likely to benefit from endocrine therapy it would reduce that

Risk by 65 if they’re not likely to benefit it wouldn’t do anything to that risk so these are the patients that you can order bci in it is indicated in both pre and postmenopausal patients they can have up to three positive lymph nodes or be lymph node negative you can use it in t1 through t3 size tumors grade one through three you can actually use this in her2

Positive patients as well as her2 negative as long as they are er or pr positive they can have received chemotherapy as their original adjuvant treatment but it is important that you send an untreated specimen for testing obviously we want to be running this test on patients who are not already metastatic and it can be tested on ductal or lovular histologies so to

Help kind of put this in perspective of practice i’ve put some cases together these are my own patients with their actual results that we’ve talked about in our clinic case number one was 62 years old at time of diagnosis with an infiltrating globular carcinoma t1cn0 grade 2 erp are positive part two negative she had an oncotype recurrent score of 22 and received

Lectures all alone she tolerated that with mild hot flashes and joint pain and was able to tolerate it quite well we ordered bci around five years after her diagnosis coming into that fifth year of endocrine therapy and it resulted with a no in terms of her likelihood to benefit from that additional five years of therapy her risk of recurrence in years five through

Ten was 2.6 percent this patient is now off of her endocrine therapy and on annual follow-up this is the dream scenario obviously that we get to move out to annual follow-up and not be on any more medications but let’s talk about somebody who would get benefit from further therapy foreign years old at diagnosis she had an infiltrating doctor carcinoma a t1c and

Zero grade one erp are positive for two negative she was treated with ai alone she initially was started on a nash resolve which she developed significant joint pain with she was changed to letrozole which she was tolerated well she unfortunately did develop osteoporosis during her endocrine therapy course and was started on tenosumab for this it was around that

Time that we decided to go ahead and send a bci to determine our best next steps in terms of her therapy so this patient is likely to benefit from that extra five years of endocrine therapy her risk of recurrence in years five through ten was 5.7 percent and if she took that extra five years of therapy that risk reduces to about two percent uh this patient continues

On lessrozole and did not with good tolerance and is planned to continue until you attend so those were fairly low risks of recurrence so we’ll look at people with a little higher risk our third patient was 53 years old at a time of diagnosis she had an infiltrating ductal carcinoma t1c n1a so a node positive patient grade 3 tumor er positive pr positive cartoon

Negative she received adjuvant dose dense act followed by an ai she was originally started on a nashville but developed significant joint pain with this so we changed her to let result this patient unfortunately struggled with multiple comorbidities from the time that we met her at her diagnosis she had a dbt has had issues with chronic pain which was then exacerbated

By the ais she’s also had renal insufficiency so she can’t take nsaids quite as rarely as some of our other patients and then she ended up having a stroke which necessitated a four-year uh holiday or four year a four-month holiday from her endocrine therapy and before we ordered this test she actually asked me how much longer do i have to take this medicine um so

We were rounding the corner into her sixth year of endocrine therapy and her sorry into her fifth year of endocrine therapy and her bci showed that she would not benefit from any further endocrine therapy past that five years her risk of recurrence is 11.9 in years 5-10 which makes sense she has a lymph node positive patient but further therapy would not do anything

For this patient other than give her more side effects when she’s already having a lot of medical issues this patient is slated to come in next month as she’s finishing up that extra four months that she missed when she had her stroke and she will discontinue endocrine therapy at that time our fourth and final patient was 67 years old at time of diagnosis she had

An infiltrating dental carcinoma which was t2 and n0 it was erpr positive as well as her2 positive so she received agent paclotaxial address to the map with maintenance trust usumab she came to us with significant baseline arthritis and obviously struggled to tolerate endocrine therapy because of this she was tried on anastrozole and then eximesting and ultimately

Changed to tamoxifen due to the joint symptoms unfortunately she developed stiata hepatitis with cirrhosis while she was taking tamoxifen and she elected to discontinue after four and a half years of endocrine therapy for concern for her liver about a year and a half after we discontinued that endocrine therapy i was seeing her in routine follow-up and she asked

How important is it for me to be on endocrine therapy so we ordered a bci to see really what’s it worth to you uh she actually would get benefit from being on it for the full 10 years her risk of recurrence was 15.6 which is one of the higher risks that i’ve seen if she was to go ahead and take that full 10 years of endocrine therapy her risk would be reduced to

5.5 percent this patient actually elected not to continue with endocrine therapy she stated that that 15 was fairly close to what she was quoted for her her2 positivity in the beginning and for her the risk of side effects did not outweigh the benefits of uh sorry for her the risk of side effects outweigh the benefits of uh continuing on endocrine therapy and i

Think that really demonstrates the utility of the bci that you can give your patients the right information to make the best choice for them so they can take an active role in their care thank you for listening and let me know if you have any questions

Transcribed from video
Breast Cancer Index, Extended Endocrine Therapy | Elizabeth Ott, PA | 2022 West Oncology APP Updates By Total Health Conferencing | Oncology