Abstract P3-08-45: Pattern and biomarkers of recurrence in 305 triple negative breast cancer patients treated in a French comprehensive cancer center
Authors: Passildas-Jahanmohan Judith , Dhaou Mona Ouled , Kwiatkowski Fabrice , Finck Wilfrid , Poirier Camille , Mouret-Reynier Marie-Ange , Durando Xavier , Abrial Catherine , Penault-Llorca Frederique , Radosevic Nina 
Published: March 2020

Abstract
Background: Triple negative breast cancer (TNBC) is the most heterogeneous subtype of breast cancer. However, the initial treatment of this disease is still dichotomous: 1st-line surgery (Surg1) followed by adjuvant chemotherapy, or neoadjuvant chemotherapy (NACT) followed by surgery. After radiotherapy, most of the patients (pts) are only observed until recurrence. Our team has pointed earlier (SABCS 2017) that some TNBCs recur very rapidly, in less than 12 months (mo) after NACT. Pts with those tumors have a very poor prognosis (overall survival &lt; 6 mo). On the other side, a recent study has revealed a TNBC subgroup with late recurrences (&gt; 5 yrs post-diagnosis, Rueda et al, Nature 2019). Neither of those groups is currently recognized in clinical practice nor specifically managed. In this study, we analyzed pattern and potential clinico-pathological biomarkers of recurrence in a large TNBC patient cohort treated at a specialized cancer center in France, to get a better insight into the need and possibilities for specific prevention of recurrent TNBC. Pts and methods: The study retrospectively included 305 pts, treated between 2000 and 2015 in Centre Jean Perrin, Clermont-Ferrand (stage I-III: 135 pts by Surg1; 146 pts by NACT; stage IV: 24 pts). The following putative biomarkers were evaluated: breast tumor size, number of involved nodes, tumor histograde, presence of lympho-vascular invasion (LVI), tumor-infiltrating lymphocytes (TILs, according to PMIDs 25214542, 29024776), presence of epithelial-mesenchymal transition (expression of Zeb1 protein by immunohistochemistry) - all at the Surg1 and post-NACT residual tumor (RT), as well as pathological complete response to NACT (pCR). Median follow-up of the pts was 4.8 yrs. The biomarkers were evaluated by univariate and multivariate analysis. Results: Recurrence-free survival (RFS) rate was significantly higher in Surg1 than in NACT cohort (76% vs 62%, resp., p=0.016). Early recurrence rate (RR) (&lt; 12 mo post-Dg) was higher in the latter (5.6%) than in the former (2.4%), whereas the standard and the late RRs were comparable (RR 1-5 yrs post-Dg: 21.4% vs. 32.5%, p=0.05; &gt; 5 yrs: 7.0% vs 6.7%, Surg1 vs NACT, resp.) In Surg1 cohort, the independent recurrence biomarkers were pN (pN0 vs pN+, p=0.003) and LVI+ (LVI+ vs LVI-, p=0.005). In NACT cohort, the only independent recurrence biomarkers were post-NACT RT size (p=0.009) and number of the involved nodes (LN) (p&lt;10-7). When RT size and LN were combined, we obtained 5 post-NACT categories: RT≤1cm/LN=0, n=51; RT&gt;1cm≤2cm/LN=0, n=36; any RT/LN=1, n=18; RT≤2cm/LN≥2, n=11; RT&gt;2cm/LN≥2, n=16, with significantly different 5-year RFS rates (92%, 62%, 54%, 30%, 13%, p&lt;10-7). No predictive biomarker of early or late recurrences was identified, however, we observed a tendency of pts recurring early after NACT to have large RTs (&gt;2cm), with median TILs &lt;5%, in comparison with other non-pCR cases (p=0.10). Interestingly, both the post-NACT early recurring tumors (n=8) and the stage IV at Dg tumors (n=24) had very low TILs (&lt;5%), 8/8 (100%) in the former and 17/20 (85%) in the latter. Details of the TIL analysis will be presented at the meeting. Conclusion: Our results confirm that most TNBC recurrences occur 1-5 yrs post-Dg, however early (&lt; 1yr) and late (&gt; 5yrs) recurrences exist too, in up to 15% pts. The early recurrences are more frequent in the pts treated by NACT, and reflect high baseline metastatic capacity of the tumors. Big post-NACT RT size (&gt; 2 cm), TILs &lt; 5% and ≥ 2 LN+ are worth validation on larger cohorts as biomarkers of TNBC early and standard (1-5 yrs) recurrence. These 3 parameters, easily assessable in routine clinical practice, could help selecting pts with high risk of recurrence for specific therapies. To discover biomarkers of late TNBC recurrence, additional analyses are needed.
Citation Format: Judith Passildas-Jahanmohan, Mona Ouled Dhaou, Fabrice Kwiatkowski, Wilfrid Finck, Camille Poirier, Marie-Ange Mouret-Reynier, Xavier Durando, Catherine Abrial, Frederique Penault-Llorca, Nina Radosevic. Pattern and biomarkers of recurrence in 305 triple negative breast cancer patients treated in a French comprehensive cancer center [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-08-45.