Tari A. King, MD, FACS, FSSO, FASCO
Collaboration between surgeons and medical oncologists is driving advances in breast cancer management, including tailoring preoperative therapies and reducing the need for axillary surgery in carefully chosen patient populations, according to Tari A. King, MD, FACS, FSSO, FASCO.
In the interview, King discussed the importance of a multidisciplinary approach in de-escalating breast cancer treatment and the potential to omit axillary surgery in certain patients, particularly those with hormone receptor (HR)–positive, HER2-negative breast cancer and negative axillary ultrasounds.
King shared additional insights about locoregional breast cancer management strategies in another article.
King is chief surgical officer for the cancer service line and codirector of the Glenn Family Breast Center at Winship Cancer Institute of Emory University and Emory Healthcare in Atlanta, Georgia; as well as a professor and chief of the Division of Breast Surgery in the Department of Surgery at Emory University School of Medicine.
OncLive: What is the importance of multidisciplinary collaboration when de-escalating breast cancer treatment?
King: The way we have managed breast cancer over the past decade and a half or so has laid the groundwork for true multidisciplinary collaboration. As we have learned more about the importance of the different molecular subtypes of breast cancer, we’ve learned more about the opportunities to use some systemic therapies in the neoadjuvant setting. We’ve also learned how the response to that neoadjuvant therapy dictates long-term outcomes and treatment recommendations postoperatively. Understanding the biology and the expected response to different treatments in different biological subtypes of breast cancer has helped us promote this multidisciplinary team, with the surgeon and medical oncologist working together to decide which patients would benefit from a preoperative therapy approach vs going to upfront surgery.
When we consider the benefits of preoperative therapy, from a surgical point of view, preoperative therapy allows us to shrink tumors, so we can perhaps perform a smaller lumpectomy or dual lumpectomy when we might have thought we had a patient who would have required a mastectomy without tumor shrinkage. Preoperative therapy also allows us the opportunity to downstage the axilla—eradicate breast cancer from the axillary lymph nodes. This allows us to potentially avoid axillary lymph node dissection, which is an important goal given that axillary lymph node dissection is a strong risk factor for the development of lymphedema. Working with the multidisciplinary team, we can identify which patients may benefit from a preoperative approach, both from a surgical perspective and a long-term survival perspective.
We now have good clinical trial data showing that in some breast cancer subtypes, [there are benefits to using] particular medicines in the preoperative setting. [For instance], in the triple-negative population, combining immunotherapy with chemotherapy preoperatively results in improved survival for patients compared with giving them chemotherapy alone. [This collaboration] also helps us tailor adjuvant therapy.
The trials that demonstrate improved survival in triple-negative breast cancer with the addition of immunotherapy also continued that immunotherapy postoperatively. Oncologists like to assess what disease is left after preoperative therapy. We go to surgery, and that helps them understand how well that treatment worked. Then they can tailor therapies on the back end.
From a medical oncologist’s perspective, multidisciplinary care helps identify patients who are going to benefit from preoperative therapy; then that preoperative therapy informs long-term prognosis and subsequent treatment decisions. From a surgical perspective, that multidisciplinary approach allows us to identify patients who would get additional gains from preoperative therapy, such as shrinking the tumor or eradicating disease in the nodes. Not all patients are good candidates, though, so we need to work together to decide who should go to upfront surgery vs who should go to preoperative therapy. However, we’ve come a long way in our understanding of that interaction and the importance of us all working together to consider these options for patients.
Are there cases in which axillary surgery can be omitted completely?
The new frontier is to identify patients who can avoid axillary surgery completely. We made a big difference throughout the 1990s and early 2000s with avoiding axillary lymph node dissection using sentinel node staging. However, now we are moving into an era where we’re trying to identify populations that don’t even need axillary surgery at all, so no axillary staging.
There was an important trial called CALGB 9343 that demonstrated that in women [at least] 70 years of age with early, clinically node-negative, HR-positive breast cancers, omitting sentinel lymph node staging or axillary surgery did not result in significant increases in rates of axillary recurrence and [resulted in] no difference in disease-free survival [DFS]. Patients in that age group are most likely to just receive hormonal therapy, so this information was not critical for determining their subsequent therapy recommendations. Although [results from] that trial [were published in 2004, this approach] has not been met with widespread adoption, and there are still a lot of older adults in whom we could safely omit lymph node surgery who are subject to lymph node surgery, mostly out of fear of undertreatment.
However, now we have additional modern prospective randomized trials of patients—including women over the age of 70 years but also in women much younger—with smaller tumors that are clinically node negative and an ultrasound of the axilla that is negative. In these 2 trials—SOUND [NCT02167490] and INSEMA [NCT02466737]—patients with negative axillary ultrasounds were randomly assigned to undergo sentinel node surgery or no sentinel node surgery. The [percentages of] women who underwent sentinel node surgery were consistent across the 2 studies. [13.7% and 11.4% of patients in those respective trials] had positive sentinel nodes, but there was no difference in long-term outcomes between patients who had that disease identified and those who did not have that disease identified.1,2
Most of the women in these studies were postmenopausal. Most of the women had smaller tumors of the HR-positive, HER2-negative subtype, so their treatment decisions could be made without nodal information. The oncologists identified the patients who they were simply going to give endocrine therapy to vs the patients who they might want to give endocrine therapy plus chemotherapy without nodal information. [These findings opened] the possibility of omitting axillary surgery altogether in a broader population of women, not just those over the age of 70 years, but even some younger, predominantly postmenopausal women, as long as we have that negative axillary ultrasound and our oncology colleagues don’t feel like they need the nodal information to make systemic therapy decisions.
That’s [most applicable in patients with] estrogen receptor [ER]–positive, HER2-negative disease, because in patients with HER2-positive or triple-negative disease, having positive nodes has a big effect on subsequent treatment recommendations; chemotherapy comes into the recommendations with node-positive disease in those subtypes. However, in a large number of women with ER-positive, HER2-negative breast cancer, just having a positive node isn’t enough to require additional systemic therapy. Most of those women can still be treated with endocrine therapy alone.
We also now live in an era where in those patients with ER-positive, HER2-negative breast cancer, we’re using genomic testing to determine their risk of recurrence and help understand the potential benefit of chemotherapy in addition to endocrine therapy. Therefore, the nodal information is not as important anymore for treatment decisions in the ER-positive, HER2-negative group. Now we have those 2 prospective, randomized trials selecting patients with negative axillary ultrasounds for omission of central node staging without any difference in axillary failure or DFS. This is an exciting time for us to be de-escalating even further to reduce the morbidity of procedures for patients.
What is your main message for surgeons and medical oncologists regarding axillary management?
The management of the axilla in breast cancer is one aspect of treatment that has changed dramatically over the last 2 decades. It’s been rewarding to bear witness to these well-designed clinical trials that have resulted in our ability to appropriately de-escalate or escalate therapy. These trials have addressed a wide number of questions regarding proper management of the axilla and are now at a place where the body of data is so vast that there are not many exceptions anymore.
It doesn’t matter whether a patient is having breast conservation or a mastectomy. It doesn’t matter whether a patient is older or younger. It doesn’t matter if they have micrometastatic or macrometastatic disease. We now have data that encompass all the nuances we see in clinical practice.
We have come so far in being able to de-escalate axillary treatment, and I am privileged to have the opportunity to focus my practice on women with breast cancer. Keeping up with this body of data is a challenge if you don’t have the time. It can be hard to keep up with all the additional trials, but it’s wonderful for our patients and for our teams to see the progress that’s been made in de-escalating axillary surgery through the design and conduct of well-done clinical trials.
References
- Gentilini OD, Botteri E, Sangalli C, et al. Sentinel lymph node biopsy vs no axillary surgery in patients with small breast cancer and negative results on ultrasonography of axillary lymph nodes: the SOUND randomized clinical trial. JAMA Oncol. 2023;9(11):1557-1564. doi:10.1001/jamaoncol.2023.3759
- Reimer T, Stachs A, Veselinovic K, et al. Axillary surgery in breast cancer – primary results of the INSEMA trial. N Engl J Med. 2025;392(11):1051-1064. doi:10.1056/NEJMoa2412063