Abstract PD1-1: Tumor infiltrating lymphocytes and correlation with outcome in the Cher-LOB study
Authors: Dieci Maria Vittoria , Bisagni Giancarlo , Cagossi Katia , Bottini Alberto , Sarti Samanta , Piacentini Federico , Conte Pierfranco , Guarneri Valentina 
Published: May 2015

Background: Tumor infiltrating lymphocytes (TIL) are emerging as a strong prognostic and predictive factor for breast cancer, especially for the HER2-positive and triple negative subtypes (Loi S, Ann Oncol 2014; Dieci MV, Ann Oncol 2014). Here we report the results of the TIL biomarker analysis performed in the CherLOB study.

Methods: The phase II neoadjuvant CherLOB study (Guarneri, J Clin Oncol 2012) randomized 121 HER2-positive, stage II-IIIA breast cancer patients to anthracyclines/taxane-based chemotherapy plus trastuzumab (arm A), lapatinib (arm B), or both (arm C). Primary endpoint was pathological complete response (pCR). Hematoxylin and eosin-stained slides from both pre-treatment biopsies and post-treatment surgical samples were centralized and evaluated for the % of intratumoral (It) and stromal (Str) TIL as previously described (Denkert C, J Clin Oncol 2010). Samples were classified as lymphocyte-predominant (LP) if ItTIL and/or StrTIL &gt;=60% and as non-LP if ItTIL and StrTIL &lt;60%.

Results: Pre-treatment TIL evaluation was available for 105 of the 118 CherLOB patients who were assessable for pathological response. Both ItTIL and StrTIL as continuous variables (per 10% increase) were associated with a higher probability of achieving a pCR (adjusted OR: 2.64, 95%CI 1.46-4.79, p=0.001 and 1.32 95%CI 1.08-1.6, p=0.006 for ItTIL and StrTIL, respectively). pCR rates were significantly higher in LP compared to non-LP cases (59% vs 27%, p=0.011). According to treatment, TIL effect was more evident in patients treated with HER2 double-blockade (arm C). According to estrogen receptor (ER) status, no difference in pCR rates between LP and non-LP cases was observed in the ER-positive population, whereas pCR rate was more than doubled for ER-negative LP compared to ER-negative non-LP patients (Table 1).

Table 1  n totpCR rate %poverallLP1759  non-LP88270.011Arm ALP540  non-LP27260.52Arm BLP650  non-LP28210.15Arm CLP683  non-LP33330.022ER+LP633  non-LP59250.67ER-LP1173  non-LP29310.02

Overall, 71 of the 121 CherLOB patients had residual disease at surgery: for 54 of them, paired pre-treatment and post-treatment TIL were available. No significant changes in ItTIL and StrTIL levels were observed before and after treatment. However, six cases presented a LP phenotype on the residual disease; all but one of them started from a non-LP pre-treatment phenotype and received lapatinib as part of the neoadjuvant treatment (4 arm B, 1 arm C).

Conclusions: In this analysis, TIL predicted the achievement of pCR for early HER2-positive patients undergoing neoadjuvant chemotherapy plus anti-HER2 agents. TIL predictive effect seems limited to ER-negative patients. Combinations of chemotherapy plus anti-HER2 agents containing lapatinib may be able to convert a non-LP into a LP tumor. Updating of follow-up is ongoing, correlations between TIL and survival will be presented at the meeting.

Citation Format: Maria Vittoria Dieci, Giancarlo Bisagni, Katia Cagossi, Alberto Bottini, Samanta Sarti, Federico Piacentini, Pierfranco Conte, Valentina Guarneri. Tumor infiltrating lymphocytes and correlation with outcome in the Cher-LOB study [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr PD1-1.