Management of the Axilla in Early-Stage Breast Cancer: OH (CCO) and ASCO Guideline

An interview with Dr. Muriel Brackstone from London Health Sciences Centre and Dr. Tari King from Dana Farber and Brigham and Women's Cancer Center, authors on "Management of the Axilla in Early-Stage Breast Cancer: OH (CCO) and ASCO Guideline." This guideline addresses management & timing of surgical and radiotherapeutic treatment of the axilla in early breast cancer. Read the guideline at asco.org/breast-cancer-guidelines. Suggest a topic for guideline development at surveymonkey.com/r/ascoguidelinesurvey.

TRANSCRIPT

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SPEAKER: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care, and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

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BRITTANY HARVEY: Hello, and welcome to the ASCO Guidelines podcast series, brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all the shows, including this one, at podcast.asco.org.

My name is Brittany Harvey, and today I am interviewing Dr. Muriel Brackstone from London Health Sciences Center in London, Ontario and Dr. Tari King from Dana-Farber and Brigham and Women's Cancer Center in Boston, Massachusetts, authors on "Management of the Axilla in Early-Stage Breast Cancer" Ontario Health (Cancer Care Ontario) and American Society of Clinical Oncology Guideline." Thank you for being here Dr. Brackstone and Dr. King.

DR. MURIEL BRACKSTONE: Thank you.

DR. TARI KING: Thank you for having us.

BRITTANY HARVEY: First, I'd like to note that we take great care in the development of our guidelines in both the ASCO and Ontario Health Cancer Care Ontario program and evidence-based care. Conflict of interest policies were followed for this guideline. The full conflict of interest information for this guideline panel is available online with the publication of the guideline in the Journal of Clinical Oncology.

Dr. Brackstone, do you have any relevant disclosures that are directly related to this guideline topic?

DR. MURIEL BRACKSTONE: No, I don't have any conflicts to disclose.

BRITTANY HARVEY: Thank you. And Dr. King, do you have any relevant disclosures that are directly related to this guideline topic?

DR. TARI KING: No, I do not have any relevant disclosures.

BRITTANY HARVEY: Great, thank you. Then let's get into some of the content of this guideline. So first, Dr. Brackstone, can you give us a general overview of what this guideline covers?

DR. MURIEL BRACKSTONE: Sure. This guideline reviews how best to diagnose and treat any lymph node spread in breast cancer patients with early-stage disease. It also reviews the role of radiation and surgery in treating the axilla to reduce the risk of regional cancer recurrence in these patients.

BRITTANY HARVEY: Great, thank you. Then I'd like to review some of the key recommendations that this guideline covers. So this guideline addresses five specific objectives. So I'd like it if we could go through each of those.

So for each of these objectives, could you give an overview of those high level recommendations? First, Dr. King, the first objective is about which patients with early-stage breast cancer require auxiliary staging.

DR. TARI KING: Yes, thank you. So I think the two main takeaway points from this objective-- the first is that sentinel lymph node biopsy really is the standard of care for axillary staging for all breast cancer patients when it is felt that information about the lymph node status is necessary. So this really is in the majority of patients that we see and care for with early-stage breast cancer.

We want to know the status of the axillary lymph nodes. That's important in our subsequent treatment recommendations. And there's really no role for axillary lymph node dissection as a staging procedure any longer. Sentinel lymph node biopsy is the staging procedure of choice.

Now, there are some patient populations, however, where we may decide that we don't need the information from the axillary lymph nodes to make subsequent treatment recommendations. And one particular group which is called out in this guideline is for those women who are over the age of 70 with early-stage, again, clinically node-negative hormone receptor-positive, HER2-negative breast cancer, where the information from the sentinel lymph node biopsy is not going to alter subsequent systemic therapy recommendations.

And this is really based on several lines of work demonstrating that omitting sentinel node in these older women, again, with hormone receptor-positive, HER2-negative breast cancer, does not negatively impact their long term outcomes. And so this is an opportunity for us to tailor our approach to a particular patient population without having a negative impact.

BRITTANY HARVEY: Great, thank you, and thank you for reviewing for which patients this is specifically targeted to. So then for the second objective, Dr. Brackstone, is further auxiliary treatment indicated for women with early-stage breast cancer who did not receive neoadjuvant chemotherapy and are sentinel lymph node-negative at diagnosis?

DR. MURIEL BRACKSTONE: No. We use this guideline to confirm that in patients who have early-stage disease and go to surgery first, so they're not having neoadjuvant chemotherapy. And in those patients, if their sentinel lymph node excision for staging is negative, that no further axillary surgery is required. Now, with regards to axillary radiation, it may be considered in the subset of patients whose breast cancer risk is high for recurrence-- so the triple negative subtype, patients who are under 50 years of age, or those with medial tumors.

BRITTANY HARVEY: OK. And then Dr. King, for the third objective, which axillary strategy is indicated for women with early-stage breast cancer who did not receive neoadjuvant chemotherapy and are pathologically sentinel lymph node-positive at diagnosis after a clinically known negative presentation?

DR. TARI KING: Thank you. Yes, so this recommendation really addresses a very large population of our breast cancer patients. Those that present with clinical T1 and T2 but node-negative early-stage breast cancer, we take them to the operating room. We perform a sentinel biopsy, and about 20% to 30% of them will actually end up having positive lymph nodes.

And traditionally, we thought that we needed to do axillary lymph node dissection in the setting of positive nodes. But we now have multiple clinical trials that have addressed this question. And we now know that it is safe to avoid lymph node dissection in women found to have one or two positive sentinel nodes.

We've had trials that have compared lymph node dissection to axillary radiotherapy or lymph node dissection to observation alone. And with either of those strategies, we've seen excellent local control in the women who have not undergone lymph node dissection. And so it really provides us, again, an opportunity to dial back or tailor our therapies to the patient's individual disease burden.

Now, certainly, patients that have more than one or two positive nodes, and the guideline specifically states how to manage patients with three or more positive nodes. And those patients do need additional axillary treatment, either in the form of lymph node dissection or lymph node dissection plus axillary radiotherapy and in some scenarios. Also, the guideline is very clear to define that there are some differences in the level of recommendation for women undergoing breast-conserving surgery and found to have one or two positive nodes as opposed to women undergoing mastectomy and found to have positive nodes.

So certainly, we have the larger body of data in the breast-conserving therapy group, but the guideline is very clear to also highlight the data that is available for the mastectomy group. And again, the overall recommendation is that not everybody with positive nodes needs additional lymph node dissection. And that we have alternatives which we know minimize the morbidity of our treatments.

BRITTANY HARVEY: Great. Thank you for addressing the evidence base behind both of those recommendations as well. So following that, Dr. Brackstone, for the fourth objective, what axillary treatment is indicated? And what is the best timing of axillary treatment for women with early-stage breast cancer? And when is neoadjuvant chemotherapy used?

DR. MURIEL BRACKSTONE: Right. So this guideline was really used to formalize a recommendation against repeating the sentinel lymph node biopsy procedure twice in patients, before and after chemotherapy. We really found that the risk of false negativity in a repeat procedure was too high. So for patients who are having neoadjuvant chemotherapy-- so patients with higher risk cancers-- the axillary ultrasound is useful to guide a biopsy of any suspicious lymph nodes to document if they're positive.

If the clinical exam and the ultrasound are both negative, then the sentinel lymph node excision should be done at the time of surgery after chemotherapy. If they do have a positive lymph node that's confirmed by biopsy before their chemotherapy, and those lymph nodes respond really well to chemotherapy and are no longer palpable, then their staging can occur by sentinel lymph node procedure at the time of surgery. And that avoids what we have standardly done up to now, which is the axillary dissection and the risk of lymphedema that comes with that.

If the sentinel lymph nodes are negative when you're doing your surgery after neoadjuvant chemotherapy, then we are recommending that no axillary lymph node dissection is required. If any of the lymph nodes are positive after neoadjuvant chemotherapy through the sampling technique, then a completion axillary lymph node dissection is still recommended, at least for now, until the results of some ongoing clinical trials looking at avoiding axillary node dissection are completed, which will be in the next several years. In both of those scenarios, however, locoregional radiation is still recommended.

BRITTANY HARVEY: Great, thank you for providing some clarity around those specific scenarios. So then finally, Dr. King, regarding the fifth and last objective, what are the best methods for identifying sentinel nodes?

DR. TARI KING: Thank you. Yes, so this objective encompasses several different clinical scenarios as well. The first being, when you are performing a sentinel lymph node biopsy procedure, do you need to use single tracer or do you need to use dual tracers to help you identify the lymph nodes? We know that in the up upfront surgery setting that you can absolutely identify the nodes with a very low false-negative rate with a single tracer. And this guideline highlights that single tracer is appropriate in patients who are undergoing upfront surgery.

The guideline suggests that the physicians start with radiocolloid, and if there is a good signal, then blue dye can be omitted. In contrast, though, in patients that are receiving neoadjuvant chemotherapy, the data there supports really that the use of dual tracer is important and improves the identification rate, as well as decreases the false-negative rate of the procedure. This recommendation also includes guidance on when ultrasound should be used.

As you just heard from Dr. Brackstone that they do recommend ultrasound prior to neoadjuvant chemotherapy. But in patients undergoing upfront surgery, again, with early-stage disease, clinically node-negative disease, the guidelines states that preoperative axillary ultrasound staging is not recommended. But in anybody who has suspicious or potentially abnormal nodes, then preoperative axillary ultrasound is recommended to confirm nodal status.

And then finally, it is important to note that nodal staging cannot be solely performed with axillary ultrasound. So sentinel lymph node biopsy is still, again, indicated even if the ultrasound is negative. There are many clinical trials going on around the world right now to address that question.

But right now, the evidence still certainly supports that we cannot rely on a negative axillary ultrasound, and sentinel lymph node biopsy should be performed.

BRITTANY HARVEY: Great. Well, thank you both for reviewing those key recommendations around the objectives. So then Dr. Brackstone, in your view, what is the importance of this guideline? And how will it both impact clinicians and patients?

DR. MURIEL BRACKSTONE: Thank you. I would say for clinicians that the guideline was written in an effort to collate all of the clinical trial data and the variable practice patterns across institutions in an effort to standardize treatment. In order to deescalate therapies that don't improve patient outcomes. And hopefully, provide some clarity for clinicians who treat breast cancer.

For patients, I would say that deescalating treatments that are entrenched as standard, but where data demonstrates no known significant disease-free survival or overall survival benefit, that these are important because patients can suffer long term side effects from treatments, such as lymphedema, that could potentially be avoided if they're not clinically indicated.

BRITTANY HARVEY: Great. Thank you both so much for your work on these evidence-based recommendations. And for taking the time to give a summary to our listeners, Dr. Brackstone and Dr. King.

DR. TARI KING: Thank you.

BRITTANY HARVEY: And thank you to all of our listeners for tuning into the ASCO Guidelines podcast series. To read the full guideline, go to www.asco.org/breast-cancer-guidelines. Additionally, our annual survey for guideline topics is open for submissions.

Suggest a topic for guideline development at www.surveymonkey.com/r/ascoguidelinesurvey by August 1. The link is also available in the episode notes of this podcast. If you have enjoyed what you've heard today, please rate and review the podcast, and be sure to subscribe so you never miss an episode.

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