Tumor-infiltrating lymphocytes and molecular response after neoadjuvant therapy for HR+/HER2- breast cancer: results from two prospective trials.
PURPOSE
The aim was to evaluate the role of tumor-infiltrating lymphocytes (TIL) in predicting molecular response after preoperative endocrine or cytotoxic treatment for HR+/HER2- patients who do not achieve a pathological complete response.


METHODS
Stromal (Str) TIL were centrally evaluated on samples from diagnostic core-biopsies of HR+/HER2- patients included in two prospective randomized trials: the LETLOB trial (neoadjuvant endocrine-based treatment) and the GIOB trial (neoadjuvant chemotherapy-based treatment). Pre- and post-treatment Ki67 was centrally assessed.


RESULTS
StrTIL were evaluable in 111 cases (n = 73 from the LETLOB trial and n = 38 from the GIOB trial). Median StrTIL was 2%. Patients with high StrTIL (StrTIL ≥10%, n = 28) had more frequently breast cancer of ductal histology (p = 0.02), high grade (p = 0.049), and high Ki67 (p = 0.02). After neoadjuvant endocrine treatment (LETLOB cohort), a significant Ki67 suppression (p < 0.01) from pre- to post-treatment was observed in both the low and high StrTIL groups. High StrTIL patients achieve more frequently a relative Ki67 suppression ≥50% from baseline as compared to low StrTIL patients (55 vs. 35%, p non significant). After neoadjuvant chemotherapy (GIOB cohort), a significant Ki67 suppression was observed only for low StrTIL patients (Wilcoxon p = 0.001) and not in the high StrTIL group (p = 0.612). In this cohort, the rate of patients achieving a relative Ki67 suppression ≥50% from baseline was significantly higher in the low vs high StrTIL group (64% vs 10%, p = 0.003). Geometric mean Ki67 suppression was evaluated in each cohort according to StrTIL: the lowest value (-41%) was observed for high StrTIL cases treated with chemotherapy.


CONCLUSIONS
This hypothesis-generating study suggests that in HR+/HER2- breast cancer StrTIL at baseline may influence the achievement of a molecular response after neoadjuvant treatment. Further evaluation in large studies is needed, and interaction with the type of treatment warrants to be explored.
['Dieci|M V|MV|', 'Frassoldati|A|A|', 'Generali|D|D|', 'Bisagni|G|G|', 'Piacentini|F|F|', 'Cavanna|L|L|', 'Cagossi|K|K|', 'Puglisi|F|F|', 'Michelotti|A|A|', 'Berardi|R|R|', 'Banna|G|G|', 'Goubar|A|A|', 'Ficarra|G|G|', 'Griguolo|G|G|', 'Conte|Pierfranco|P|', 'Guarneri|V|V|']
D000328:Adult D000368:Aged D000369:Aged, 80 and over D000971:Antineoplastic Combined Chemotherapy Protocols D014408:Biomarkers, Tumor D001943:Breast Neoplasms D017024:Chemotherapy, Adjuvant D005260:Female D006801:Humans D000077341:Lapatinib D000077289:Letrozole D016246:Lymphocytes, Tumor-Infiltrating D008875:Middle Aged D020360:Neoadjuvant Therapy D009570:Nitriles D011446:Prospective Studies D011799:Quinazolines D018719:Receptor, ErbB-2 D011956:Receptors, Cell Surface D016896:Treatment Outcome D014230:Triazoles
Tumor-infiltrating lymphocytes Neoadjuvant Ki67 Chemotherapy Endocrine therapy