Multidisciplinary Management Stands at the Forefront of Breast Cancer Treatment

In Partnership With:

Partner | Cancer Centers | <b>Mayo Clinic</b>

Judy C. Boughey, MD, shares criteria for omission of sentinel lymph node surgery, the importance of not altering treatment based on identification of variants of uncertain significance, and the potential value of trastuzumab deruxtecan in HER2-low metastatic breast cancer.

Advances in the surgical management of breast cancer stem from developments across the surgical and multidisciplinary oncology field, with surgical approaches being increasingly tailored to complement patients’ responses to neoadjuvant therapies, according to Judy C. Boughey, MD. Expanded germline genetic testing capabilities further influence management recommendations and identify patients who might benefit from some newer therapies.

“There are continuously evolving data regarding management of patients with breast cancer, both from the systemic therapy [perspective] and from the local regional therapy [perspective]; this field is rapidly advancing,” said Boughey following an OncLive® State of Science Summit™ (SOSS), which she co-chaired with Matthew P. Goetz, MD, of Mayo Clinic.

In an interview with OncLive®, Boughey shared some top insights from the meeting, including criteria for omission of sentinel lymph node (SLN) surgery, the importance of not altering treatment based on identification of variants of uncertain significance, and the potential value of fam-trastuzumab deruxtecan-nxki (Enhertu) in HER2-low metastatic breast cancer. Additionally, she highlighted upcoming advances in breast surgery, including potential methods for identifying patients who can avoid breast surgery and the possibility of improving sensation after nipple-sparing mastectomy.

Boughey is a breast surgical oncologist, division chair of Breast and Melanoma Surgical Oncology and chair of the Breast Cancer Disease Group at Mayo Clinic.

OncLive®: Could you review the main points from your presentation on de-escalating surgical management in breast cancer?

Boughey: It was a pleasure to talk at the OncLive® SOSS. [My presentation] focused on changes in surgical management of breast cancer, many of which are coming about through improvements in systemic therapies.

Historically, breast cancer was treated with modified radical mastectomy, and over time, treatment evolved to total mastectomy, and now increasingly to breast conservation surgery and even nipple-sparing mastectomy. In terms of lymph nodes, we’ve also evolved from a complete axillary lymph node dissection, where all the lymph nodes [are removed], to just removing 2 or 3 lymph nodes with SLN surgery.

Now, increasingly, we’re asking the question: Do we need to remove any lymph nodes in some patients with breast cancer? I covered several specific patient populations in which we can look at avoiding axillary surgery. In particular, the Choosing Wisely® guidelines from the Society of Surgical Oncology recommend against routine SLN surgery in women aged 70 or older with hormone receptor [HR]–positive disease. I discussed how [those recommendations] can be successfully implemented into clinical practice to allow us to de-escalate or avoid the use of axillary surgery in older women with disease that is responsive to hormone therapy and unlikely to be treated with chemotherapy.

I also talked about the [phase 3] Z0011 study [NCT00003855], which has dramatically changed clinical practice, allowing patients to forego a full axillary lymph node dissection [if they are] receiving breast-conserving surgery for tumors up to 5 centimeters and only have 1 or 2 positive lymph nodes at the time of SLN surgery. These findings have been nicely implemented into clinical practice across the country. I also discussed the same situation for patients undergoing a mastectomy and how we can try to de-escalate the use of axillary lymph node dissection in patients with a mastectomy who have only 1 or 2 positive lymph nodes.

The final topic I focused on was patients treated with neoadjuvant chemotherapy. There’s been a significant frameshift from requiring axillary lymph node dissection for patients who have known node-positive disease prior to chemotherapy, allowing us to tailor our surgery based on the tumors’ responses to neoadjuvant systemic therapy. If those patients have a response in the tumors in their breasts and lymph nodes, we can consider doing SLN surgery along with resection of that initial biopsy-proven positive node and avoid automatic full axillary lymph node dissection, as long as those SLNs have converted to node-negative after chemotherapy.

It’s nice to see how improvements in systemic therapy are allowing us to de-escalate surgical [approaches] in the axilla.

In which patients would you avoid axillary surgery?

With the Choosing Wisely® guidelines recommending against routine SLN surgery in women aged 70 and older with HR-positive, HER2-negative breast cancer, this is still a relatively broad category. [At Mayo Clinic, we’ve implemented this by] routinely omitting SLN surgery in the lowest-risk group within that cohort, patients with a grade 1 tumor up to 2 centimeters or a grade 2 tumor up to 1 centimeter. In those who have larger tumors or higher-grade disease, we are considering the use of SLN surgery on a case-by-case basis together with our multidisciplinary team, in particular, considering whether the findings from SLN surgery would affect any adjuvant recommendations.

What alternative approaches would you recommend for patients in whom you would avoid these surgeries?

[Patients aged 70 and older in whom axillary SLN surgery is avoided] will then go on to meet with radiation oncology. I am pleased that at my institution, we have done this in a multidisciplinary group. The radiation oncologists are not escalating their radiation management based on the surgical decision to omit SLN surgery. This is a true multidisciplinary approach. Those patients would then go on to receive radiation if indicated, but this is also a group of patients that frequently meets criteria for the consideration of radiation therapy omission. [These patients] would continue to be followed as per the usual standard; we don’t escalate the imaging surveillance based on the omission of SLN surgery.

What does the future look like for surgical approaches and potential surgical omission in breast cancer?

[At Mayo Clinic,] we participated in a trial looking at eliminating surgery from patients who have an exceptional response to neoadjuvant systemic therapy. This was a trial run out of [The University of Texas] MD Anderson Cancer Center that focused on patients with clinical T1 or T2 tumors that were either HER2 positive or triple negative. If patients had neoadjuvant systemic therapy with an excellent imaging response, they could undergo vacuum-assisted percutaneous core needle biopsy. If no disease was identified in the core needle biopsy, these patients could omit surgery on the breast and proceed directly to radiation therapy. We’re excited about the future results of this trial, as well as [findings from] other trials that we hope will be developed in this space looking at [the possibility of avoiding] breast surgery in patients who have a phenomenal response to neoadjuvant chemotherapy.

Similarly, in terms of axillary surgery, [I highlighted] patients with triple-negative or HER2-positive disease in whom the disease has been successfully eradicated from the breast who have a breast pathologic complete response [pCR], and were clinically node negative prior to chemotherapy, have a low rate of positive nodes, less than 2%, after chemotherapy. This may be a group where we could avoid axillary surgery altogether, if we can reliably predict which patients will obtain a breast pCR.

These are some exciting future opportunities for us to be much more selective [when deciding] which patients we need to operate on post-neoadjuvant therapy.

Your colleague, Siddhartha Yadav, MBBS, MS, of Mayo Clinic, presented on new breast cancer treatment strategies in patients with germline predisposition gene mutations. How helpful is the classification of variants of uncertain significance, and what cautions should still be taken with this information?

It was exciting to hear all the advances in this area. For years, we’ve looked at trying to identify patients with germline mutations, predominantly because identification of a BRCA1 or a BRCA2 gene [mutation] would change the surgical counseling of patients. [For instance,] patients with unilateral breast cancer [could be counseled about] contralateral prophylactic mastectomy because of their elevated risk of contralateral breast cancer.

What’s exciting is that the identification of germline genetic mutations now affects the surgical recommendations, and the systemic therapy recommendations are different for patients with germline genetic mutations. That’s been a nice advance in terms of the importance of germline genetic testing for these patients.

It’s also been great to see the decrease in the cost of performing these sequencing tests. They are now often cheaper than a mammogram. For years, we were cautious about who we recommended genetic testing for. However, now, the breast surgery guidelines are such that we should make sure genetic testing is available to all patients with breast cancer who are interested in proceeding with genetic testing.

[Patients with] variants of uncertain significance have always been a challenging population. The textbook guidelines and the rules that we should adhere to say that variants of uncertain significance should not alter [a patient’s disease] management. We should not be recommending more aggressive surgical management or changing the systemic therapy based on a variant of uncertain significance.

It is important, though, that these patients are followed. Frequently, the variant of uncertain significance will be reclassified either into a pathogenic variant, in which case we would consider alternatives to offer to that patient, or, more commonly, a benign variant that can be reassuring for that patient.

What are your thoughts on the significance of trastuzumab deruxtecan in metastatic breast cancer, as outlined by David Potter, MD, PhD, of the University of Minnesota, in his presentation on the treatment of HER2-positive and HR-positive/HER2-negative breast cancer?

Dr Potter presented a talk looking at the exciting new therapies available for patients with HER2-positive breast cancer. One study that was recently reported was the [phase 3] DESTINY-Breast04 trial [NCT03734029], which showed that trastuzumab deruxtecan was valuable in patients with HER2-low, unresectable, and/or metastatic breast cancer. This was the first time that we found a HER2-targeted therapy that demonstrated improved outcomes in patients with HER2-low breast cancer.

This is an exciting advancement for the field, and [this agent is] something that we will start seeing included in medical therapy for metastatic disease in the near future. We’ll continue to see how trastuzumab deruxtecan makes its way further into the treatment algorithm for breast cancer.

One of the key things Dr Potter highlighted was the potential for toxicity associated with trastuzumab deruxtecan, including lung disease and the importance of treating this adverse effect [AE] with steroids. As more oncologists become more familiar with this drug, we will all be learning more about the AEs of trastuzumab deruxtecan and its potential dosing limitations.

What main message would you like colleagues to take away from the meeting overall?

This was an exciting meeting. It’s great to be interchanging with local community oncologists and academic oncologists and talking about advances in care. It seems like every meeting there are new treatment algorithms available on the market specifically for triple-negative and HER2-positive breast cancer.

It’s always important for the multidisciplinary team to consider how the advances in 1 modality affect the advances in other modalities, such as how radiation interacts with surgery, how surgery interacts with medical oncology, how medical oncology interacts with radiation, and how all the advances we’re seeing in all 3 of these fields are improving patient outcomes, which is always the focus of these trials and our clinical practice.

It’s an exciting time to be working in breast cancer. It’s important to stay up-to-date, and these OncLive® seminars are a good way to get the latest and greatest data.

What exciting breast cancer research is being conducted at Mayo Clinic?

We’re currently exploring 2 exciting advances in the surgical arena for patients with breast cancer at Mayo Clinic. One is looking at trying to improve the sensation patients have in the long run after a nipple-sparing mastectomy. We advise patients to not expect any sensation in the nipple areola complex after nipple-sparing mastectomy. However, early results indicate that the process of neurotization, which is placing a nerve graft from an intercostal nerve to a subareolar nerve, may help improve sensation in patients after nipple-sparing mastectomy.

We’re exploring this in appropriately selected patients, and we’re keen to see how these patients do in the long run. This is an exciting approach, especially for young patients who are looking to pursue a nipple-sparing mastectomy. In the future, we may be able to preserve some sensation to the nipple-areola complex.

In another FDA-approved clinical trial, we’re evaluating robotic-assisted nipple-sparing mastectomy; this is a relatively stringent trial, and it is only for patients proceeding with risk-reducing surgery, not for those who have a malignancy in the breast. [It is only] for patients who have a cup size of C or less. These patients will be eligible to consider a robotic approach to their nipple-sparing mastectomy, which may potentially have some significant advantages in the future. We’re delighted to be able to offer this as a novel approach to nipple-sparing mastectomy for motivated patients.