The 2024 San Antonio Breast Cancer Symposium (SABCS) concluded with a “View from the Trenches” panel discussing the clinical implications of key findings presented during the symposium. Bringing medical, surgical, and radiation oncology specialists together with a breast cancer thriver turned patient advocate, the conversation explored how these latest findings might alter how clinicians navigate the complexities of breast cancer treatment.
From leveraging genomic testing to refining adjuvant therapy, to reconsidering surgical approaches and embracing new treatments for metastatic disease, the discussions emphasized a personalized, patient-centered approach. With these insights, clinicians left San Antonio better equipped to navigate these complexities and make informed decisions as they return to their clinics.
Refining Adjuvant Therapy in Early-stage Breast Cancer
The session first turned to the role of pembrolizumab (Keytruda) in stage 2/3 triple-negative breast cancer (TNBC) following surgery. Ideally, these patients should get checkpoint inhibition and chemotherapy before surgery, noted moderator Joyce O’Shaughnessy, MD, from Baylor University, Texas Oncology, and Sarah Cannon Research Institute (SCRI).
But what happens if, for some reason, they had surgery first?
Results from the NSABP B-59/GBG-96-GeparDouze study unveiled at SABCS 2024 tempered enthusiasm for adjuvant pembrolizumab in these patients who have already had surgery. Medical oncologists Cristina Saura, MD, PhD, from the Vall d’Hebron Institute of Oncology, and Antonio Wolff, MD, from Johns Hopkins Medicine, said that they would not use immunotherapy in this adjuvant context. And 75% of the audience agreed.
Saura noted that while the treatment might not be effective, the risk of toxicity is still there, and also underscored the importance of biomarkers to identify potential responders and gauge side effect risks. Wolff was reassured by the audience responses, suggesting that clinicians should no longer have to worry about missing the window for checkpoint inhibition after surgery, pointing to other cancers where “we have evidence that the drug works with the presence of tumor versus when tumor is removed.”
Providing input from the integral patient perspective, Stacey Tinianov, MPH, BCPA, reframed the conversation, suggesting that rather than talk about de-escalation, care teams should emphasize “right-sizing” treatments to fit individual patients appropriately.
The talk next turned to genomic testing to determine recurrence risk in patients with human epidermal growth factor receptor 2 (HER2)-negative early breast cancer, and whether they should receive anthracyclines in addition to standard-of-care chemotherapy after surgery. Results from two nonrandomized, registry-based studies—TAILORx and FLEX—presented at SABCS 2024 showed that patients classified as high genomic risk benefited from anthracyclines, with higher scores associated with greater benefit.
In the light of this clear evidence of benefit for some patients, Wolff admitted that perhaps he had been too reticent in prescribing anthracyclines, while still acknowledging their known risk of hematological and cardiovascular complications. Tinianov echoed the delicate nature of the decisions a patient must make with their doctors, urging that the conversations should focus on potential risk, benefit, and impact.
The OlympiA study update reinforced the importance of PARP inhibitors in BRCA-mutated cases, and the panelists and audience said they would now prioritize olaparib (Lynparza) over other adjuvant treatments, though 70% of the 93% who agreed indicated they would also consider sequential treatment with pembrolizumab or CDK4/6 inhibition.
Panelists cautioned against the “kitchen sink” approach without evidence to support such combinations. As a radiation oncologist, Atif Khan, MD, from Memorial Sloan Kettering Cancer Center, advised delaying PARP inhibitors, as well as potential CDK4/6 inhibition, until after radiotherapy to avoid potential adverse interactions, for which there is insufficient data.
Obesity, Weight Loss, and Surveillance Strategies
The panel addressed obesity’s impact on breast cancer outcomes and weight loss interventions, noting diet and exercise outperformed GLP-1 receptor agonists. The Breast Cancer WEight Loss (BWEL) Study showed that weight loss was linked to improved metabolic markers, insulin resistance, and inflammation, whereas analyses based on the MD Anderson database showed no direct benefits of GLP-1 receptor agonists on disease-free survival. Consequently, 69% of the audience said they would recommend diet and exercise alone, compared to 30% who also supported the use of GLP-1 receptor agonists.
New results from the ZEST trial demonstrated the challenges of using circulating tumor DNA (ctDNA) technologies to surveil for recurrence and provided some lessons. Most importantly, while early ctDNA detection was possible, it was still too late, as half of patients already had metastatic disease at the time of their first positive result.
Given that higher baseline ctDNA was linked to faster recurrence, regardless of when detected, intervention opportunities were limited. With 86% of panelists opposing routine ctDNA surveillance in high-risk patients with no evidence of disease, Wolff summarized the sentiment: “The concept is there, but we are not yet ready for asymptomatic surveillance outside of clinical trials.”
Evolving Surgical and Radiotherapy Practices
Next, the group, led primarily by Khan and Alastair Thompson, MD, MBChB, of Baylor College of Medicine, focused on “right-sizing” options for patients when supported by evidence.
One area became a bit murkier in light of new data. Whereas a study from last year’s meeting showed that breast-conserving therapy proved as effective in preventing recurrence as double mastectomy for BRCA mutation carriers, an analysis from the BRCA BCY Collaboration study seemed to show the opposite: that BRCA mutation carriers diagnosed with breast cancer at or before age 40 had lower rates of recurrence and death after risk-reducing surgeries. Stepping back from the statistics and focusing on the human angle, Tinianov made a point everyone can appreciate: “Sometimes individuals feel better if the organ that has developed a tumor is completely gone, and that’s okay.”
The COMET trial revealed that active monitoring is an acceptable option for some patients with low-risk, hormone receptor-positive ductal carcinoma in situ (DCIS), in terms of both risk of recurrence and quality of life. Emphasizing the importance of incorporating patient-reported outcomes (PROs), Tinianov noted that some of these stress-related factors are themselves known to impact cancer progression and response to treatment. Thompson also credited the conference for including the PRO portion of COMET in the feature presentations.
Electronic PROs also emerged as a valuable tool for patients in the PRO B study, which highlighted reduced fatigue and improved survival with electronic symptom monitoring, though only 42% of panelists currently use these systems in practice, indicating an area for potential growth.
The INSEMA trial reinforced the safety of omitting sentinel lymph node biopsy (SLNB) in clinically node-negative patients, though Khan cautioned that radiation planning becomes more complicated without nodal biomarkers. For patients achieving pathological complete response after neoadjuvant chemotherapy, SLNB was preferred over axillary clearance, reflecting a shift toward preserving the axilla.
There was also evolution in terms of radiotherapy decisions based on the 10-year results from the BIG 2-04 MRC SUPREMO trial, with Khan stressing, “Postmastectomy radiation therapy (PMRT) should be very rare in node-negative patients.” He added that there is no evidence to suggest that node-positive patients should omit radiation therapy.
The EMBER-3 and PATINA trials set new standards for metastatic HER2-positive and ESR1-mutant breast cancers. Over 90% of panelists agreed to integrate these therapies—imlunestrant and palbociclib (Ibrance), respectively—into first-line treatment. That the PATINA trial took so long to mature into a positive study reinforces the need for us to have patience with these large-scale, long-term trials, according to the panelists.
