scholarly journals Best Foot Forward: Neoadjuvant Systemic Therapy as Standard of Care in Triple-Negative and HER2-Positive Breast Cancer

Author(s):  
Priyanka Sharma ◽  
Roisin M. Connolly ◽  
Evanthia T. Roussos Torres ◽  
Alastair Thompson

Neoadjuvant systemic treatment of early-stage breast cancer has been used to improve resectability and reduce the extent of breast and axillary surgery. More recently, several other merits of neoadjuvant systemic treatment have emerged, including the ability to tailor clinically available adjuvant systemic therapy options based on pathologic response and to serve as a platform for early assessment of novel agents and response biomarkers and as an avenue for treatment optimization investigations (local and systemic therapy escalation and de-escalation trials guided by pathologic response). Attainment of a pathologic complete response (pCR) is associated with excellent long-term outcomes; conversely, the presence of residual disease is associated with a high risk of recurrence for patients with HER2-positive breast cancer and triple-negative breast cancer (TNBC). Treatment strategies in early-stage HER2-positive breast cancer include regimens incorporating trastuzumab, pertuzumab, ado-trastuzumab emtansine, and neratinib, resulting in high pCR rates and overall excellent long-term outcomes. Currently available cytotoxic regimens yield pCR for 35% to 55% of patients with TNBC, and immune checkpoint inhibition is showing early promise for this subtype. New drug and predictive biomarker evaluations in the neoadjuvant setting aim to develop optimal treatment strategies for the individual patient, with the ultimate goal of maximizing efficacy and minimizing toxicity. Research efforts involving novel agents are being undertaken to address the high risk of recurrence for patients with residual disease. Omission of breast surgery following neoadjuvant chemotherapy requires further development of imaging and biopsy techniques to accurately assess the extent of residual disease before clinical application.

2021 ◽  
Author(s):  
Jeffrey E. Johnson ◽  
Paula D Strassle ◽  
Guilherme C de Oliveira ◽  
Chris B. Agala ◽  
Philip M. Spanheimer ◽  
...  

Abstract Purpose To assess potential disparities in guideline-concordant care delivery among women with early stage triple-negative and HER2-positive breast cancer treated with breast conserving therapy. Methods Women ≥40 years old diagnosed with pT2N0M0 triple-negative or HER2-positive breast cancer treated with primary surgery and axillary staging between 2012 and 2017 were identified using the National Cancer Database (NCDB). The primary outcome was receipt of adjuvant systemic therapy and radiation concordant with current guidelines. Multivariable log binomial regression was used to assess the prevalence of optimal therapy use across patient and cancer characteristics. Kaplan-Meier curves were used to assess 5-year overall survival. Multivariable Cox proportional hazards regression was used to compare the impact of optimal therapy on 5-year mortality. Results 11,785 women were included with 7,843 receiving optimal therapy. Receipt of optimal therapy decreased with age even after adjusting for comorbidities and cancer characteristics; other sociodemographic factors were not associated with differences in receipt of optimal therapy. Among patients who did not receive adjuvant systemic therapy, most were not offered the treatment (49%) or refused (40%). Overall 5-year survival was higher among women who received optimal therapy (89% [95% CI 88.0-89.3] vs. 66% [95% CI 62.9-68.5]). Patients who received suboptimal therapy were over twice as likely to die within 5-years of their diagnosis (adjusted HR 2.44, 95% CI 2.12-2.82). Conclusion Age is the primary determinant of the likelihood of a woman to receive optimal adjuvant therapies in high-risk early stage breast cancer. Patients who did not receive optimal therapy had significantly diminished survival.


Author(s):  
Nuria Chic ◽  
Stephen J Luen ◽  
Paolo Nuciforo ◽  
Roberto Salgado ◽  
Debora Fumagalli ◽  
...  

Abstract In early-stage HER2-positive breast cancer, biomarkers that guide de-escalation and/or escalation of systemic therapy are needed. CelTIL score is a novel, combined biomarker based on stromal tumor-infiltrating lymphocytes and tumor cellularity and determined in tumor biopsies at week 2 of anti-HER2 therapy only. We evaluated the prognostic value of CelTIL in 196 patients with early-stage HER2-positive disease treated with standard trastuzumab-based chemotherapy in the NeoALTTO phase III trial. Using a pre-specified CelTIL cutoff, a better 5-year event-free survival and overall survival was observed between CelTIL-high and CelTIL-low score with a 76.4% (95% confidence interval [CI] = 68.0%–85.0%) versus 59.7% (95% CI = 50.0%–72.0%) (hazard ratio = 0.40; 95% CI = 0.17 to 0.94), and 86.4% (95% CI = 80.0%–94.0%) vs 73.5% (95% CI = 64.0%–84.0%) (hazard ratio = 0.43; 95% CI = 0.20 to 0.92), respectively. Statistical significance was maintained after adjusting for baseline TILs, hormone receptor status, pre-treatment tumor size and nodal status, type of surgery, treatment arm, and pathological complete response. Further studies to support CelTIL as an early read-out biomarker to help de-escalate/escalate systemic therapy in HER2-positive breast cancer seem warranted.


JAMA Oncology ◽  
2016 ◽  
Vol 2 (6) ◽  
pp. 751 ◽  
Author(s):  
Kristine R. Broglio ◽  
Melanie Quintana ◽  
Margaret Foster ◽  
Melissa Olinger ◽  
Anna McGlothlin ◽  
...  

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