Marie Osdoit1, Christina Yau1, W Fraser Symmans2, Judy C Boughey3, Cheryl A Ewing1, Ron Balassanian4, Yunn-Yi Chen4, Gregor Krings4, Anne M Wallace5, Somaye Zare6, Oluwole Fadare6, Rachael Lancaster7, Shi Wei8, Constantine V Godellas9, Ping Tang10, Todd M Tuttle11, Molly Klein12, Sunati Sahoo13, Tina J Hieken3, Jodi M Carter14, Beiyun Chen14, Gretchen Ahrendt15, Julia Tchou16, Michael Feldman17, Eleni Tousimis18, Jay Zeck19, Nora Jaskowiak20, Husain Sattar21, Arpana M Naik22, Marie Catherine Lee23, Marilin Rosa24, Laila Khazai24, Mara H Rendi25, Julie E Lang26, Janice Lu27, Ossama Tawfik28, Smita M Asare29, Laura J Esserman1, Rita A Mukhtar1. 1. Department of Surgery, University of California San Francisco, San Francisco. 2. Department of Pathology, University of Texas MD Anderson Cancer Center, Houston. 3. Department of Surgery, Mayo Clinic, Rochester, Minnesota. 4. Department of Pathology, University of California San Francisco, San Francisco. 5. Department of Surgery, University of California San Diego, La Jolla. 6. Department of Pathology, University of California San Diego, La Jolla. 7. Department of Surgery, University of Alabama at Birmingham, Birmingham. 8. Department of Pathology, University of Alabama at Birmingham. 9. Department of Surgery, Loyola University Chicago Stritch School of Medicine, Chicago, Illinois. 10. Department of Pathology, Loyola University Chicago Stritch School of Medicine, Chicago, Illinois. 11. Department of Surgery, University of Minnesota, Minneapolis. 12. Laboratory Medicine and Pathology, Masonic Cancer Center, Minneapolis, Minnesota. 13. Department of Pathology, University of Texas Southwestern Medical Center, Dallas. 14. Laboratory Medicine and Pathology, May Clinic, Rochester, Minnesota. 15. Department of Surgery, University of Colorado Denver, Aurora. 16. Department of Surgery, University of Pennsylvania, Philadelphia. 17. Pathology & Laboratory Medicine, University of Pennsylvania, Philadelphia. 18. Department of Surgery, Georgetown University, Washington, DC. 19. Pathology and Laboratory Medicine, Georgetown University, Washington, DC. 20. Department of Surgery, University of Chicago, Illinois. 21. Department of Pathology, University of Chicago, Illinois. 22. Department of Surgery, Oregon Health & Science University, Portland. 23. Comprehensive Breast Program, Moffitt Cancer Center, Tampa, Florida. 24. Department of Pathology, Moffitt Cancer Center, Tampa, Florida. 25. Department of Pathology, University of Washington, Seattle. 26. Department of Surgery, University of Southern California, Los Angeles. 27. Department of Medicine, University of Southern California, Los Angeles. 28. Department of Pathology, University of Kansas, Kansas City. 29. Quantum Leap Healthcare Collaborative, San Francisco.
Abstract
Importance: Pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) in breast cancer strongly correlates with overall survival and has become the standard end point in neoadjuvant trials. However, there is controversy regarding whether the definition of pCR should exclude or permit the presence of residual ductal carcinoma in situ (DCIS). Objective: To examine the association of residual DCIS in surgical specimens after neoadjuvant chemotherapy for breast cancer with survival end points to inform standards for the assessment of pathologic complete response. Design, Setting, and Participants: The study team analyzed the association of residual DCIS after NAC with 3-year event-free survival (EFS), distant recurrence-free survival (DRFS), and local-regional recurrence (LRR) in the I-SPY2 trial, an adaptive neoadjuvant platform trial for patients with breast cancer at high risk of recurrence. This is a retrospective analysis of clinical specimens and data from the ongoing I-SPY2 adaptive platform trial of novel therapeutics on a background of standard of care for early breast cancer. I-SPY2 participants are adult women diagnosed with stage II/III breast cancer at high risk of recurrence. Interventions: Participants were randomized to receive taxane and anthracycline-based neoadjuvant therapy with or without 1 of 10 investigational agents, followed by definitive surgery. Main Outcomes and Measures: The presence of DCIS and EFS, DRFS, and LRR. Results: The study team identified 933 I-SPY2 participants (aged 24 to 77 years) with complete pathology and follow-up data. Median follow-up time was 3.9 years; 337 participants (36%) had no residual invasive disease (residual cancer burden 0, or pCR). Of the 337 participants with pCR, 70 (21%) had residual DCIS, which varied significantly by tumor-receptor subtype; residual DCIS was present in 8.5% of triple negative tumors, 15.6% of hormone-receptor positive tumors, and 36.6% of ERBB2-positive tumors. Among those participants with pCR, there was no significant difference in EFS, DRFS, or LRR based on presence or absence of residual DCIS. Conclusions and Relevance: The analysis supports the definition of pCR as the absence of invasive disease after NAC regardless of the presence or absence of DCIS. Trial Registration: ClinicalTrials.gov Identifier NCT01042379.
Importance: Pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) in breast cancer strongly correlates with overall survival and has become the standard end point in neoadjuvant trials. However, there is controversy regarding whether the definition of pCR should exclude or permit the presence of residual ductal carcinoma in situ (DCIS). Objective: To examine the association of residual DCIS in surgical specimens after neoadjuvant chemotherapy for breast cancer with survival end points to inform standards for the assessment of pathologic complete response. Design, Setting, and Participants: The study team analyzed the association of residual DCIS after NAC with 3-year event-free survival (EFS), distant recurrence-free survival (DRFS), and local-regional recurrence (LRR) in the I-SPY2 trial, an adaptive neoadjuvant platform trial for patients with breast cancer at high risk of recurrence. This is a retrospective analysis of clinical specimens and data from the ongoing I-SPY2 adaptive platform trial of novel therapeutics on a background of standard of care for early breast cancer. I-SPY2 participants are adult women diagnosed with stage II/III breast cancer at high risk of recurrence. Interventions: Participants were randomized to receive taxane and anthracycline-based neoadjuvant therapy with or without 1 of 10 investigational agents, followed by definitive surgery. Main Outcomes and Measures: The presence of DCIS and EFS, DRFS, and LRR. Results: The study team identified 933 I-SPY2 participants (aged 24 to 77 years) with complete pathology and follow-up data. Median follow-up time was 3.9 years; 337 participants (36%) had no residual invasive disease (residual cancer burden 0, or pCR). Of the 337 participants with pCR, 70 (21%) had residual DCIS, which varied significantly by tumor-receptor subtype; residual DCIS was present in 8.5% of triple negative tumors, 15.6% of hormone-receptor positive tumors, and 36.6% of ERBB2-positive tumors. Among those participants with pCR, there was no significant difference in EFS, DRFS, or LRR based on presence or absence of residual DCIS. Conclusions and Relevance: The analysis supports the definition of pCR as the absence of invasive disease after NAC regardless of the presence or absence of DCIS. Trial Registration: ClinicalTrials.gov Identifier NCT01042379.
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