The 2024 San Antonio Breast Cancer Symposium® closed Friday, December 13, with a final session summarizing key highlights and practical insights on how to best translate four days of data and developments into clinical practice.

The session, View from the Trenches: What to do on Monday Morning, will be available on demand for registered 2024 SABCS® participants until March 31, 2025.

The session was moderated by Joyce O’Shaughnessy, MD, Chair of Breast Cancer Prevention Research at Baylor Scott & White Charles A. Sammons Cancer Center. The panel included:

• Stacey Tinianov, MPH, BCPA, patient advocate and Executive Director of Advocates for Collaborative Education;
• Antonio C. Wolff, MD, Professor of Oncology at the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center;
• Cristina Saura, MD, PhD, Head of the Breast Cancer Unit of the Service of Medical Oncology of Vall d’Hebron University Hospital;
• Alastair Thompson, MD, MBChB, Professor and Chief of the Section of Breast Surgery at Baylor College of Medicine; and
• Atif J. Khan, MD, Attending Physician and Radiation Oncologist at Memorial Sloan Kettering Cancer Center.

Role of adjuvant pembrolizumab in patients with stage II/III TNBC

Neoadjuvant immunotherapy-chemotherapy combination has become the standard of care for patients with early-stage triple-negative breast cancer (TNBC).

“What role, if any, does adjuvant immunotherapy have in this setting for patients who may have had surgery first?” asked Dr. O’Shaughnessy. She reviewed data from relevant studies — KEYNOTE-522, NSABP B-59/GBG 96-GeparDouze (reported at the 2024 SABCS^®), IMpassion030, and A-BRAVE.

Drs. Saura and Wolff both emphasized the importance of working as a multidisciplinary team to ensure that eligible patients with early-stage TNBC are offered the opportunity to receive neoadjuvant immunotherapy before surgery.

Panelists cited immunotherapy-related toxicity and the lack of biomarkers for optimal patient selection as concerns/gaps that, at present, preclude routine use of adjuvant pembrolizumab in patients who received surgery but not neoadjuvant immunotherapy.

Potential anthracycline benefit in HR-positive, HER2-negative early-stage disease

Data from nonrandomized studies — such as the post hoc analysis of the TAILORx trial, shared at the 2024 SABCS^® and the real-world FLEX trial — may help clarify if, and in which patient subsets, anthracycline may improve outcomes when added to chemotherapy for hormone receptor (HR)-positive, human epidermal growth factor 2 (HER2)-negative early-stage breast cancer.

Even though these data pertain to nonrandomized studies, Dr. Saura said she would consider anthracycline for patients with a high-risk score. Responding to a question about the test for assessing risk, she noted that Oncotype DX is used more often in her practice in Europe.

Dr. O’Shaughnessy noted ordering the 70-gene MammaPrint test in her practice for patients who are in the “grey zone” with respect to the benefit of anthracycline.

Dr. Wolff pointed out that the recently activated SWOG S2206 study may help clarify the role of anthracycline in ultra high-risk patients as measured by MammaPrint.

Treatment for germline BRCA-mutated high-risk HER2-negative disease

Updated long-term data from OlympiA presented at the 2024 SABCS^® were consistent with prior findings that showed reduced invasive disease recurrence or death with one-year adjuvant olaparib in patients with germline BRCA1/2-mutated, early-stage, HER2-negative disease.

Dr. O’Shaughnessy asked panelists about their preferred approaches to offer patients in this setting — 1) only olaparib, 2) olaparib, along with consideration of sequential CDK4/6 inhibitor therapy in high-risk luminal patients or pembrolizumab and capecitabine for patients with TNBC, or 3) prioritize other listed therapies before olaparib — with a large majority of the audience selecting the second option.

Drs. Wolff and Saura noted that this “was a data-free zone.”

For very high-risk patients, panelists noted that offering CDK4/6 inhibitors after surgery, but prior to olaparib, or combining/sequencing of olaparib with pembrolizumab may be considered, although they acknowledged these decisions are challenging in the absence of supporting evidence.

Dr. Khan cautioned against concurrent use of olaparib and radiotherapy, such as in very high-risk patients, due to the concern of toxicities. He noted that, on the other hand, radiotherapy concurrent with pembrolizumab did not have the same toxicity concerns.

Impact of obesity on early-stage breast cancer prognosis

Several studies presented at the 2024 SABCS^® addressed the impact of obesity on outcomes in patients with early-stage breast cancer, including weight-loss interventions.

Dr. O’Shaughnessy asked, would treatment with a glucagon-like peptide-1 receptor agonist or other weight-loss approaches be appropriate for patients with high-risk early-stage disease?

“[Body mass index] is an imperfect marker, but that said, exercise is incredibly important,” Tinianov answered.

She encouraged oncologists to engage their patients in conversations about exercise, even though it may seem obvious. Also, given that patients with severe obesity tend to experience worse side effects with chemotherapy, she said, “there is value in having these conversations, period.”

She also pointed out the value of a survivorship clinic-like support mechanism to facilitate exercise and mental health counseling, for initiating and sustaining beneficial lifestyle modifications.

Lessons from the ZEST study of MRD-adapted treatment

Dr. Saura said that although the ZEST study was negative, the concept of minimal residual disease (MRD)-adapted treatment is a valid approach. Her key takeaways were that the patient population for such a trial needs to be refined and that the MRD testing, which was based on circulating tumor DNA (ctDNA) detection in ZEST, needs to be validated and standardized.

ZEST findings were reported in General Session 3 at the 2024 SABCS^®.

There was agreement among the panelists that routine surveillance of ctDNA in asymptomatic patients was not appropriate outside of a clinical trial.

‘Right-sizing’ surgery for breast cancer

Dr. Thompson led the discussion on optimal surgical approaches in breast cancer. He reviewed conflicting findings from two large retrospective studies — the first presented by Kelly Metcalfe, RN, PhD, at the 2023 SABCS^® and the second by Matteo Lambertini, MD, PhD, at the 2024 SABCS^® — on the impact of risk-reducing mastectomy on extending overall survival.

Dr. Thompson said that an analysis of pooled data from such large studies is needed to clarify the impact of risk-reducing surgeries on survival outcomes in breast cancer.

The panel then considered the value of active monitoring in low-risk ductal carcinoma in situ (DCIS), based on the COMET study results. Dr. Thompson, who was involved in the COMET study, noted that some of his patients with low-risk DCIS prefer active monitoring over surgery, at least for the first two years. Dr. Khan has not yet incorporated the active monitoring approach, per COMET, in his practice but noted that he may consider it going forward.

Dr. Thompson flagged the imminent publication of revised American Society of Clinical Oncology guidelines for managing the axilla, which would include discussion of the de-escalation approach in the INSEMA study.

Optimizing radiotherapy

Dr. Khan discussed the implications of the combined analysis of pooled data from NRG/RTOG 9804 and ECOG-ACRIN E5194.

“Do these data mean that we should more uniformly adopt endocrine therapy in [patients with ‘good risk’ DCIS], and forgo radiotherapy?” he asked.

Dr. Khan said that, going forward, he intends to recalibrate his message to patients based on these data and advocate more strongly for endocrine therapy, especially for patients who are considering omission of radiotherapy.

 “There is no ‘good risk DCIS’. Let’s call it low risk,” Tinianov said.

She added that, in her experience with medical oncology consultations, statistics regarding endocrine therapy are presented in terms of relative risk, which may be terrifying for people unfamiliar with risk terminology. She encouraged clinicians to include absolute risk when discussing data with their patients.

The SUPREMO study showed no difference in outcomes with post-mastectomy radiotherapy in patients with intermediate-risk breast cancer. However, Dr. Khan noted that given contemporary standards of care, with predominant use of sentinel lymph node biopsy, patients who have undergone mastectomy and have macrometastases in the axilla currently require a complete axillary lymph node dissection and/or post-mastectomy radiotherapy.

Practice implications of evolving data in the metastatic setting

“EMBER-3 is a very important trial,” Dr. O’Shaughnessy said, discussing the findings presented at the 2024 SABCS®.

“Assuming availability, will we use imlunestrant as monotherapy in patients with ESR1 mutations, and as combination with abemaciclib in patients regardless of their ESR1 status?” she asked.

A poll of the audience showed overwhelming acceptance of these approaches.

The AFT-38 PATINA study, also presented at the 2024 SABCS^®, showed that adding palbociclib to anti-HER2 and endocrine therapy extended progression-free survival by over a year in patients with HR-positive, HER2-positive advanced breast cancer.

Dr. O’Shaughnessy alluded to PATINA as “the number one study that will change our practice on Monday morning,” asking the panelists and the audience whether they would add palbociclib maintenance, per the PATINA study.

While panelists seemed to broadly agree on the addition of palbociclib, Tinianov exhorted clinicians to discuss the potential for higher grade diarrhea with patients as a potential palbociclib-associated toxicity.

Dr. O’Shaughnessy rounded out the discussion, asking for Tinianov’s perspective on the alert-based patient-reported outcome (PRO) monitoring protocol used in the PRO-B study.

“This study was fascinating,” Tinianov said. “Every individual, whether they have cancer or not, wants to be seen, heard, and held.”

She encouraged breast cancer-focused clinicians to review the studies conducted by Ethan Basch, MD, MSc, in the lung cancer space, which mirrored the findings of PRO-B.

“Feeling connected, staying connected, being connected saves lives,” she said.