Association of Residual Ductal Carcinoma in Situ with Breast Cancer Recurrence in the Neoadjuvant I-SPY2 Trial

Marie Osdoit, Christina Yau, W. Fraser Symmans, Judy C. Boughey, Cheryl A. Ewing, Ron Balassanian, Yunn Yi Chen, Gregor Krings, Anne M. Wallace, Somaye Zare, Oluwole Fadare, Rachael Lancaster, Shi Wei, Constantine V. Godellas, Ping Tang, Todd M. Tuttle, Molly Klein, Sunati Sahoo, Tina J. Hieken, Jodi M. CarterBeiyun Chen, Gretchen Ahrendt, Julia Tchou, Michael Feldman, Eleni Tousimis, Jay Zeck, Nora Jaskowiak, Husain Sattar, Arpana M. Naik, Marie Catherine Lee, Marilin Rosa, Laila Khazai, Mara H. Rendi, Julie E. Lang, Janice Lu, Ossama Tawfik, Smita M. Asare, Laura J. Esserman, Rita A. Mukhtar

Research output: Contribution to journalArticlepeer-review


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: Identifier NCT01042379..

Original languageEnglish (US)
Pages (from-to)1034-1041
Number of pages8
JournalJAMA surgery
Issue number11
StatePublished - Nov 9 2022

ASJC Scopus subject areas

  • Surgery


Dive into the research topics of 'Association of Residual Ductal Carcinoma in Situ with Breast Cancer Recurrence in the Neoadjuvant I-SPY2 Trial'. Together they form a unique fingerprint.

Cite this