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Negative expression of estrogen receptor (ER) predicts response to chemotherapy in breast cancers (BCs). ER negative cancers are those with less than 1 % of nuclear staining. Tumors with 1-10 % staining are sub-classified as "low-positive" (ER-low). HER2 negative tumors with ER low staining are considered biologically and clinically equivalent to ER negative tumors. This study investigates whether ER low expression in HER2-positive (HER2+) BCs has different clinical behavior than ER negative HER2-positive tumors. We used a sample of 171 patients with HER2+ BCs to compare risk of residual cancer after neoadjuvant chemotherapy by different ER expression strength. Patients were classified into 3 groups: ER-negative (ER1 %); ER-low (ER10 %, any intensity or33 % staining, weak intensity); and ER-high (ER = 10-33 %, moderate to strong intensity or33 %, any intensity). The risk of residual cancer in patients with ER-low tumors was similar to the risk in patients with ER-negative tumors (RR = 0.76, 95 % CI: 0.30-1.93). Conversely, patients with ER-high tumors had twice the risk of residual cancer than patients with ER-negative tumors (RR = 2.20, 95 % CI: 1.46-3.31). These findings persisted after adjusting for tumor grade, clinical tumor and lymph node stage, chemotherapy regimen, and progesterone receptor status. In this cohort of patients with HER2+ BCs, ER-low tumors had a similar pathologic response to chemotherapy as ER-negative tumors suggesting similar clinical behavior. Future research should address biological explanations to these similarities between ER negative and ER low breast cancers such as HER2 enriched phenomenon.

This abstract is being presented as a short talk in the scientific program. A full abstract is printed in the Proffered Abstracts section (PR15) of the Conference Proceedings. Citation Format: Madeleine J. Oudin, Oliver Jonas, Tatiana Kosciuk, Liliane Broye, Jeff Wyckoff, Joelle Klazen, John Lamar, Sreeja Asokan, Charlie Whittaker, Robert Langer, Michael Cima, Kari Wisinski, Richard Hynes, Douglas Lauffenburger, Patricia Keely, James Bear, Frank Gertler. Haptotaxis and direct remodeling of the extracellular matrix by tumor cells is important for metastasis. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr B41.