NIHR Cambridge Dementia Biomedical Research Unit

1015 Background: Neo-tAnGo was an NCRI UK neoadjuvant breast cancer study testing the addition of gemcitabine to anthracycline and taxane-based treatment and also the sequencing of chemotherapy. In a translational substudy, sequential fresh tissue was analysed for PAM 50 subgroups. Methods: Neo-tAnGo recruited 831 patients. 162 patients were consented for Neo-tAnGo Science, for 3 additional fresh tissue samples to be taken at diagnosis (diag), mid-chemotherapy (CT) and end-CT. Standard methodology was used for PAM 50 subtyping. Results: Fresh tissue samples at diag were received from 123 patients (pts). 45 pts (37%) had 2 additional samples provided (at mid- and end-CT). 57 pts (46%) had 1 additional sample provided (34 at mid-CT, 23 at end-CT). PAM 50 subtyping at diag was as follows: 31 (25%) BASAL; 30 (24%) HER2; 39 (32%) LUM B; 13 (11%) LUM A; 10 (8%) NORMAL-like. Pathological complete response rates (pCR: no disease in breast or axillary nodes, n = 121 pts) differed between PAM 50 subtype at diag (p = 0.04): BASAL 11/31 (35%); HER2 8/30 (27%); LUM B 3/37 (8%); LUM A 1/13 (8%); NORMAL-like 3/10 (30%). Of the 94 pts who were not PAM50 NORMAL-like at diag and had 2+ samples, 42 (45%) ‘shifted to NORMAL-like’. This was associated with slightly higher pCR rates (24% vs 15% who didn’t ‘shift to NORMAL-like’, p = 0.44) and borderline significantly higher rates of pCR or minimal residual disease (MRD: <10% residual scattered tumour cells) (48% vs. 27% who didn’t ‘shift to NORMAL-like’, p = 0.06). In the 102 pts with 2+ samples, 58 pts (57%) showed a shift to a better prognosis PAM 50 subtype after CT (Group (Gp) 1), 37 (36%) showed no change (Gp 2) and 7 (7%) a shift to a worse prognosis subtype (Gp 3). pCR rates were 26% Gp1, 14% Gp2 and 0% Gp3 (p = 0.05). pCR/MRD rates were 48% Gp1, 22% Gp2 and 0% Gp3 (p = 0.001). Conclusions: PAM 50 subtype at diagnosis correlates with pCR to neoadjuvant chemotherapy. Shift to a better prognosis PAM 50 group during neoadjuvant chemotherapy was demonstrated in 57% of pts and was significantly correlated with higher pCR and pCR/MRD rates. Clinical trial information: 78234870.