Julie Lang, MD, is chief of Breast Surgery at the Lerner Research Institute and co-leader of the Breast Cancer Program at Cleveland Clinic.

Julie Lang, MD

"[Approximately] 40% of patients had immune-related adverse [effects] that were noteworthy, and surgeons should be aware of these."

Julie Lang, MD, chief of Breast Surgery at the Lerner Research Institute and co-leader of the Breast Cancer Program at Cleveland Clinic, discusses findings from a real-world, retrospective study evaluating the safety of the perioperative treatment regimen from the phase 3 KEYNOTE-522 trial (NCT03036488)—neoadjuvant pembrolizumab (Keytruda) in combination with chemotherapy, followed by adjuvant pembrolizumab—and the implications of these findings for surgical planning in patients with early-stage triple-negative breast cancer (TNBC).

The analysis focused on immune-related adverse effects (irAEs) associated with the regimen, particularly endocrinopathies, which were observed in approximately 40% of patients. These included thyroid dysfunction, adrenal insufficiency such as Addison’s disease, and abnormalities in glucose regulation. Lang emphasizes that such toxicities are clinically significant and may require modifications to perioperative management. The findings underscore the importance of multidisciplinary coordination, particularly with endocrinology, for appropriate preoperative risk assessment.

Early in the adoption of the KEYNOTE-522 regimen, standardized protocols for monitoring thyroid function, cortisol, and glucose were not uniformly implemented. This led to missed or delayed recognition of irAEs, prompting changes in institutional practices. Lang notes that routine endocrine evaluation—including testing of thyroid-stimulating hormone and cortisol—is now advised for all patients receiving pembrolizumab-based neoadjuvant therapy.

Importantly, some endocrinopathies appear to persist beyond the treatment period, raising concerns about the long-term implications for patient health and survivorship. Lang highlights the need for ongoing collaboration with endocrinology colleagues to determine the chronicity of these toxicities and whether they represent permanent sequela of immune checkpoint inhibition.

Overall, Lang concludes that although the KEYNOTE-522 regimen improves pathologic complete response rates in early-stage TNBC, it also introduces a spectrum of irAEs that may influence surgical planning and long-term management.

Videos

Julie Lang, MD, discusses real-world safety data from for the KEYNOTE-522 regimen in early triple-negative breast cancer.

Dr Lang on Real-World Safety Data for Perioperative Pembrolizumab in Early TNBC

Dr Lang on Real-World Outcomes With the KEYNOTE-522 Regimen in Early-Stage TNBC

“We [noted that] 80% of patients could have been eligible for breast-conserving surgery, yet a small fraction [ultimately] went forward with [breast-conserving surgery] and [many] instead opted for mastectomy. [This finding presents] an opportunity to reconsider practice for our patients.”

Julie Lang, MD, chief, Breast Surgery, Lerner Research Institute; co-leader, Breast Cancer Program, Cleveland Clinic, discusses findings from a real-world, retrospective study evaluating the effect of the neoadjuvant KEYNOTE-522 trial (NCT03036488) regimen (pembrolizumab [Keytruda] plus chemotherapy) on pathologic complete response (pCR) rates and subsequent surgical decision-making in patients with early-stage triple-negative breast cancer (TNBC).

The study retrospectively analyzed 240 patients with TNBC treated between 2019 and 2022, comparing outcomes between those who received the KEYNOTE-522 regimen (n = 86) and those who received standard chemotherapy (n = 154). Results demonstrated a significantly higher pCR rate in the KEYNOTE-522 cohort compared with the control group, at 59.3% vs 33.1%, respectively (

However, the rate of breast conservation therapy did not differ between groups, at 32.1% vs 33.1% in the investigational and control arms, respectively (

 = .47), highlighting a gap between clinical response and surgical decision-making. Notably, axillary lymph node dissection was required significantly less often in the KEYNOTE-522 cohort compared with the control group, at 25.6% vs 39.6%, respectively (

 = .03), indicating that neoadjuvant pembrolizumab may reduce the need for extensive nodal surgery.

Lang notes that approximately 80% of patients were candidates for breast conservation, yet many still opted for mastectomy. These findings highlight a discrepancy between clinical tumor response and surgical decision-making, suggesting that factors beyond tumor biology, such as patient preference and physician recommendation, may influence surgical choices. Given the observed real-world pCR rates of approximately 60%, Lang explains that there is an opportunity to reassess the role of neoadjuvant therapy in guiding surgical planning and to better counsel patients on their eligibility for breast conservation.

Julie Lang, MD, discusses real-world outcomes of the neoadjuvant KEYNOTE-522 regimen in patients with early-stage triple-negative breast cancer.

Julie Lang, MD, chief of Breast Surgery, co-leader of the Breast Cancer Program, General Surgery, the Cleveland Clinic Main Campus, discusses potential applications for the Parsortix® PC1 system in metastatic breast cancer.

The Parsortix PC1 system is an in vitro diagnostic device intended to enrich circulating tumor cells (CTCs) from peripheral blood from patients with metastatic breast cancer. In May 2022, the FDA granted class II clearance for Parsortix as a diagnostic for metastatic breast cancer, making it the first device approved for the use of detecting cancer by harvesting cells from a patient blood sample.

The approval was based on findings from a prospective clinical trial (NCT03427450) conducted at The University of Texas MD Anderson Cancer Center, the University of Southern California, the Northwestern Medical Center, and the University of Rochester, which evaluated blood samples taken from patients with breast cancer and healthy female volunteers with no history of cancer. Findings presented at the 2022 San Antonio Breast Cancer Symposium showed that harvested cells can be evaluated using standard orthogonal methodologies, such as gene expression and fluorescence in situ hybridization, to identify and characterize CTCs.

Although investigators were excited about the trial’s findings and the FDA approval, additional studies could include better cytology methods so that a higher proportion of CTCs adhere to the cytology slides used in the device, Lang notes. Based on cell line proof-of-principle studies done in parallel to the clinical trial, 37% to 51% of the CTCs were harvested by Parsortix, meaning the test could have increased sensitivity with more refined cytology methods, Lang says.

Lang explains that sequencing studies to detect mutations could also be performed, and other studies could include single-cell sequencing to examine tumor biology and better understand resistance in metastatic breast cancer cells.

Individual hospitals will need to decide how to apply Parsortix and what subsequent studies may be beneficial in their patient populations, Lang concludes.

Julie Lang, MD, discusses potential applications for the Parsortix® PC1 system in metastatic breast cancer.

Julie Lang, MD

Articles

Dr Lang on Real-World Safety Data for Perioperative Pembrolizumab in Early TNBC

Dr Lang on Real-World Outcomes With the KEYNOTE-522 Regimen in Early-Stage TNBC

Dr. Lang on the Potential Applications for the Parsortix® PC1 System in Breast Cancer