Cancer Updates GI and Breast NJ: Breast Cancer Updates from SABCS 2024 with Dr Teplinsky
Presenter:
Eleonora Teplinsky, MD, Valley Health System, Icahn School of Medicine at Mount Sinai
Conference:
Cancer Updates GI and Breast New Jersey
Introduction
At the 2025 Cancer Updates: GI and Breast, New Jersey Conference, Dr. Eleonora Teplinsky from Valley Health System and Icahn School of Medicine at Mount Sinai provided a comprehensive review of key findings from the San Antonio Breast Cancer Symposium (SABCS) 2024, highlighting six key studies covering a range of topics, including novel treatment strategies, genetic risk reduction, and new paradigms in disease monitoring.
Highlights from SABCS 2024
PATINA – CDK4/6 inhibitors in HER2+ metastatic breast cancer
BRCA BCY – Risk-reducing surgery in young BRCA carriers
OlympiA – Long-term follow-up of adjuvant olaparib in BRCA+ breast cancer
EMBER-3 – Novel oral SERD Imlunestrant in HR+/HER2- breast cancer
ZEST – ctDNA-guided intervention in breast cancer
COMET – Active surveillance for low-risk ductal carcinoma in situ (DCIS)
PATINA: CDK4/6 Inhibition in HER2+ Metastatic Breast Cancer
Background: Dr Teplinsky noted that the current standard first-line therapy for patients with Human epidermal growth factor receptor 2 positive, hormone receptor positive (HER2+/HR+) metastatic breast cancer generally includes a taxane chemotherapy with dual anti-HER2 targeted therapy (i.e., trastuzumab + pertuzumab), followed by maintenance HER2 therapy with endocrine therapy (ET). The PATINA trial explored whether the addition of palbociclib, a cyclin dependent kinase 4/6 inhibitor (CDK4/6i) to maintenance therapy could improve outcomes in these patients.
Trial Design: Patients in the PATINA trial were randomized 1:1 to palbociclib + ET + anti-HER2 therapy versus standard maintenance therapy, with the primary endpoint of progression-free survival (PFS).
Key Findings: Dr Teplinsky noted a PFS benefit of 15.2 months over the comparator with the addition of palbociclib to the regimen, with a hazard ratio (HR) of 0.74. In addition, she noted findings of the interim 5-year overall survival (OS) analysis, showing an OS of 74.3 months versus 69.8 months with addition of palbociclib versus the comparator (HR=0.86). There were no new safety signals associated with the regimen, with the most common toxicity being neutropenia. Dr Teplinsky noted that findings from PATINA could potentially set a new standard of care for patients with HER2+/HR+ metastatic breast cancer, although FDA approval of the regimen for this indication is awaited.
“[PATINA] was one of the most practice-changing studies at SABCS… A 15-month improvement in PFS is huge.”
BRCA BCY: Risk-Reducing Surgeries and Survival in Young BRCA Carriers
Background: Patients with BRCA mutations have a high risk for both breast and ovarian cancers. The BRCA BCY study examined whether risk-reducing mastectomy (RRM) and/or other risk-reducing strategies, particularly salpingo-oophorectomy (RRSO), could improve survival in young breast cancer patients with BRCA mutations.
Trial Design: Patients in the trial (N=5,290) were BRCA mutation carriers, diagnosed with stage I to III breast cancer aged 40 years or below. The median follow-up in the trial was approximately 5 years.
Key Findings: Results from the trial showed that RRM reduced mortality risk by 35%, with 2,910 patients having had RRM, while 2,380 patients did not. Similarly, RRSO reduced mortality risk overall by 42% in the study, with a greater benefit seen in BRCA1 carriers as compared with BRCA2 carriers. Notably, the benefit was also more pronounced in patients with triple-negative breast cancers (TNBC).
Implications: Overall, Dr Teplinsky thought the study provides strong evidence to recommend RRM and/or RRSO to young BRCA carriers. Dr Teplinsky also noted the need for discussion on hormone replacement therapy (HRT) in patients undergoing RRSO.
“This study [BRCA BCY] is incredibly important data for counseling patients. We now have concrete survival benefits to support these risk-reducing surgeries.”
OlympiA: Long-Term Outcomes with Adjuvant Olaparib in BRCA+ Breast Cancer
Background: Results from the phase III OlympiA trial had previously established that adjuvant olaparib is an effective treatment for BRCA-mutant, high-risk HER2-negative early breast cancer, and results from SABCS 2024 provided 6-year follow-up data for patients in the trial.
Key Findings: Dr Teplinsky noted the 6-year invasive disease-free survival (IDFS) results from the trial, which showed a continued benefit of olaparib in this setting, with the IDFS benefit increasing to 9.4% from the previously reported 8.4%, with a 6-year distant disease-free survival (DDFS) benefit of 7.8%, and overall survival (OS) improvement of 4.4% (HR=0.72). In addition, there was no increase in the incidence of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) in the trial, and the incidence of second primary malignancies was lower in olaparib arm.
“We get a lot of questions about MDS/AML risk with PARP inhibitors, and this data [from OlympiA] is reassuring.”
Implications: Dr Teplinsky noted that results from OlympiA continue to support olaparib as the current standard of care for patients with high-risk BRCA+ breast cancer and also reinforces importance of genetic testing in early breast cancer.
EMBER-3: Imlunestrant, a Next-Generation Oral SERD
Background: Dr Teplinsky also reported findings from the EMBER-3 trial for imlunestrant, an oral selective estrogen receptor degrader (SERD) which has brain penetrant activity. The study examined the efficacy of imlunestrant in patients with HR+/HER2- metastatic breast cancer.
Key Findings: Results reported at SABCS 2024 showed a 38% risk reduction in progression or death for patients on imlunestrant as compared to standard endocrine therapy for patients with ESR1-mutant tumors. In addition, a 43% reduction in the risk for progression or death was seen with imlunestrant + abemaciclib for all patients in the trial, regardless of ESR1 status. Notably, there was also a trend toward lower CNS progression rates with imlunestrant versus standard of care ET, although the overall number of events was small.
Implications: Dr Teplinsky noted that findings from EMBER could lead to a potential new option for HR+/HER2- metastatic breast cancer, particularly for ESR1-mutant tumors, although the treatment is still awaiting FDA approval.
“The combination of imlunestrant + abemaciclib is where we really see the strongest benefit.”
ZEST: ctDNA-Guided Intervention with Niraparib
Background: Circulating tumor DNA (ctDNA) monitoring is currently under investigation as a means to assess minimal residual disease for patients who have completed their treatment. The ZEST trial aimed to determine if ctDNA positivity post-treatment could guide therapy with niraparib (a PARP inhibitor), specifically, whether niraparib could improve disease free survival (DFS) in patients who had completed their treatment, with ctDNA+ status, but no evidence of radiographic recurrence.
Key Findings: Dr Teplinsky noted that, unfortunately, there was a very low rate of ctDNA positivity seen in the trial (~7.7%), which resulted in its early termination. In addition, 50% of those patients with ctDNA+ status already had metastatic disease at time of its detection. While there was a trend toward longer recurrence-free survival (RFS) for patients treated with niraparib, the study was underpowered to draw definitive conclusions.
Implications: While readout from this trial was much anticipated, Dr Teplinsky noted that the role of ctDNA monitoring in breast cancer remains unclear, and ongoing trials will be needed to define the clinical utility of ctDNA assessments.
“[ZEST] was one of the most anticipated trials, but unfortunately, it didn't have the power to answer its key questions.”
COMET: Active Surveillance for Low-Risk DCIS
Background: The final study highlighted by Dr Teplinsky was COMET, a trial investigating whether active surveillance was non-inferior to immediate surgery for patients with low-risk ductal carcinoma in situ (DCIS).
Key Findings: Results showed that, at 2 years, active surveillance was not inferior to immediate surgery, and no differences were observed with regard to invasive tumor size, nodal status, or grade. In addition, there were no significant differences observed for patient-reported outcomes including quality of life, anxiety, and depression.
Implications: While findings from COMET were promising and supportive of possibly delaying surgery for selected low risk DCIS patients, Dr Teplinsky cautioned that longer follow up is needed to establish the long-term safety of the approach.
“The short-term data [from COMET] is promising, but we need longer follow-up before changing practice.”
Conclusions & Key Takeaways
Dr. Teplinsky concluded her presentation with a summary of practice-changing findings from SABCS, as well as those areas requiring further research:
Dr Teplinsky noted the potentially practice-changing results from both the PATINA and EMBER-3 trials (although the regimens are awaiting FDA approval).
A study that Dr Teplinsky thought reinforces the current standard of care was the OlympiA trial with adjuvant olaparib.
A study that Dr Teplinsky thought answers a major question was BRCA BCY (regarding the benefit of risk-reducing surgery in young BRCA carriers).
A study which Dr Teplinsky thought needs more data was ZEST, examining the use of ctDNA to guide treatment in breast cancer.
Lastly, a study which Dr Teplinsky thought needs longer follow up was COMET, results from which imply that delaying DCIS surgery is safe for patients and did not compromise outcomes.
“This was an exciting SABCS. Some of these findings will change practice, while others raise more questions than they answer.”
Speaker Disclosure Information: Dr Teplinsky reported the following disclosures for this presentation:Advisory Board: Astra-Zeneca, Novartis, Immunogen, Pfizer; Honorarium/Travel: OncLive