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Purpose: As we have published expertise in breast cancer xenograft models and clonal dynamics, our aim was to explore rates of engraftment based on type of tissue for attempted xenografting (primary vs relapsed/metastatic disease) and clinical breast biomarker subtype. Methods: Tissue from patients (pts) enrolled in a locally advanced/metastatic study and a breast tumour tissue repository (ie. resectable primaries) between Sept. 2008 and July 2015 underwent xenografting using NodScid/IL2rgKO (NSG) mice. Xenografts were passaged when tumour volume reached 1 cm3. Mice with no engraftment after 12 months (mos) were sacrificed. Pt charts were reviewed to determine biomarker status (hormone receptor [HR], HER2), date and type of tissue collection for xenografting. Prediction of successful engraftment based on tissue type and biomarker status was performed using nominal logistic regression. Results: A total of 70 tissue samples with known engraftment status were included in the analysis: 51 from primary breast tumour, 10 from relapsed disease (dz) with ≤ 1 line of therapy in the advanced setting and 9 from relapsed dz with > 1 line of therapy in the advanced setting. Tumours from pts treated with > 1 line of therapy were more likely to engraft compared to primary or recurrent dz with ≤ 1 line of therapy (89%, 35%, and 40% respectively; p=.008). HR- primary tumours were more likely to engraft compared to HR+ primary tumours: 71% of HR-/HER2- (triple negative) and 67% of HR-/HER2+ tumours versus 4% of HR+/HER2- and 38% of HR+/HER2+ tumours; p Conclusion: This preliminary study highlights potential differences in successful xenoengraftment based on biomarker status at diagnosis and type of tissue, primary vs relapsed tumour, the latter suggesting that the underlying biology of primary or first relapsed recurrent disease is distinct from more refractory disease, and warrants further exploration. This work is ongoing. (Funded by CBCRA, BCCF) Engraftment of primary tumour vs relapsed disease Primary tumour (N=52) N, (%)Recurrent disease and ≤ 1 line of Rx in advanced setting (N=10) N, (%)Recurrent disease and > 1 line of Rx in advanced setting (N=9) N, (%)Engraftment Yes18 (35)4 (40)8 (89)HR-/HER2-10 (55)1 (25)2 (25)HR-/HER2+4 (22)1 (25)1 (13)HR+/HER2+3 (17)00HR+/HER2-1 (6)2 (50)5 (62)Engraftment No33 (65)6 (60)1 (11)HR-/HER2-4 (12)00HR-/HER2+2 (6)1 (17)0HR+/HER2+5 (15)00HR+/HER2-22 (67)5 (83)1 (100) Citation Format: den Brok W-l, Chia S, Kalloger S, Bates C, Aparicio S, Mar C, Gelmon K, Eirew P. Rates of successful engraftment in breast cancer xenograft models based on tissue type: Primary vs relapsed disease [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-06-10.

Purpose: We have expertise in breast cancer xenograft models and have previously published data on clonal dynamics. Our aim was to explore clinical characteristics of those patients (pts) whose breast cancer tumours engrafted versus those that did not. Methods: Tissue from pts enrolled in a locally advanced/metastatic (MBC) study and a breast tumour tissue repository between Sept. 2008 and July 2014 underwent xenografting using NodScid/IL2rgKO (NSG) mice. Xenografts were passaged when tumour volume reached 1 cm3. Mice were sacrificed if no engraftment by 12 months (mos). Pt charts were reviewed to determine biomarker status (hormone receptor [HR], HER2), grade, LVI, time free from disease/progression, and pathologic complete response (pCR) for pts receiving neoadjuvant therapy. Results: A total of 64 pts had known xenograft status: 32 engrafters, 32 non-engrafters. Biomarker status did not predict likelihood of engraftment (p = .0695) and is shown in Table 1 along with site/timing of biopsy for tissue engraftment within biomarker groups. When HER2+ cases are excluded from analysis, the HR-/HER2- phenotype yields a 72% probability of engraftment compared to 39% for the HR+/HER2- group (p = .0418). For engrafters, 22/32 (68%) of pts had or went on to have relapsed or de novo MBC. For non-engrafters, 7/32 (22%) had or went on to have relapsed disease (p = .0004). Grade and LVI did not predict engraftment (p = .1806 and p = .8657 respectively). No grade 1 tumours engrafted (n = 3). There were 25 pts who received neoadjuvant chemotherapy: 14 engrafters, 11 non-engrafters. None of the engrafters achieved a pCR; 3 non-engrafters achieved a pCR. Median time to engraftment was 5 mos for pts with relapsed/advanced disease vs 9.8 mos for pts who did not relapse however, treatment was variable. Conclusion: This preliminary study highlights potential differences in clinical characteristics of engrafters vs non-engrafters in breast cancer xenograft models and warrants further exploration. (Funded by CBCRA, BCCF) TABLE 1.Biomarker status, tissue site/type in attempted xenografts.Engrafter (N = 32) N, (%)Non-engrafter (N = 32) N, (%)HR+/HER2-14 (44)22 (69)Tissue from:Primary tumour419Recurrence23Advanced dz on therapy80HR-/HER2-13 (40)5 (16)Tissue from:Primary tumour114Recurrence21Advanced dz on therapy00HER2+/HR+0 (0)2 (9)Tissue from:Primary tumour02Recurrence00Advanced dz on therapy00HER2+/HR-5 (16)3 (9)Tissue from:Primary tumour42Recurrence01Advanced dz on therapy10 Citation Format: Wendie D. den Brok, Stephen Chia, Cherie Bates, Steve Kalloger, Samuel Aparicio, Mar Mar, Karen Gelmon, Peter Eirew. Clinical characteristics of breast cancer xenograft models. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 638.