Tumori Journal Abstract Book - October 2020 - 111

E - Breast Cancer	
HER2 score2+/ISH+ and HER2 score2+/ISH- groups
may suggests a paradigm shift in the current classification
of HER2 status, consistently with emerging data on "HER2
low" BC landscape.

E22
Circulating tumor DNA-based
longitudinal evaluation of ESR1
epigenetic status in Hormone
Receptor positive HER2 negative
metastatic breast cancer
Gerratana L.1, Basile D.2, Franzoni A.3, Allegri L.4, Viotto D.5, Corvaja
C.6, Bortot L.6, Bertoli E.2, Buriolla S.2, Targato G.6, Da Ros L.1, Russo
S.7, Di Nardo P.1, Alberti M.2, Mazzeo R.2, Bonotto M.7, Belletti B.5,
Baldassarre G.5, Damante G.3, Puglisi F.8
1

Dipartimento di Oncologia Medica, Centro di Riferimento Oncologico di Aviano
IRCCS, Aviano; 2Dipartimento di Area Medica, Università degli Studi di Udine Dipartimento di Oncologia Medica, Centro di Riferimento Oncologico di Aviano
IRCCS, Udine; 3Istituto di Genetica Medica, Azienda Sanitaria Universitaria
Friuli Centrale, Udine; 4Dipartimento di Area Medica, Università degli Studi di
Udine, Udine; 5SOC Oncologia Molecolare e Modelli Preclinici di Progressione
Tumorale, Centro di Riferimento Oncologico di Aviano IRCCS, Aviano;
6
Dipartimento di Area Medica, Università degli Studi di Udine - Dipartimento di
Oncologia, Azienda Sanitaria Universitaria Friuli Centrale, Udine; 7Dipartimento
di Oncologia, Azienda Sanitaria Universitaria Friuli Centrale, Udine;
8
Dipartimento di Area Medica, Università degli Studi di Udine - Dipartimento di
Oncologia Medica, Centro di Riferimento Oncologico di Aviano IRCCS, Aviano

Background: Although endocrine therapy (ET) is the
mainstay of treatment for Hormone Receptor positive
HER2 negative Metastatic Breast Cancer (Luminal MBC),
secondary resistances ultimately emerge mainly due to
gene alterations. Epigenetic-mediated events are less
known and potentially involved in alternative adaptive
mechanisms. The aim of this study was to test the feasibility of ESR1 epigenetic characterization through circulating
tumor DNA (ctDNA) and its potential application for early
sensitivity assessment.
Methods: The multicenter pragmatic study prospectively
enrolled 49 women with Luminal MBC. Patients (pts)
where characterized through ctDNA using Next Generation
Sequencing and methylation specific droplet digital PCR
(MSddPCR) before treatment start (BL) and after 3 months
concomitantly with CT scan restaging (E1). ESR1 epigenetic status was defined by assessing the methylation of its
main promoters (prom A and B). Associations were tested
through Mann-Whitney U test, matched pairs variations
through Wilcoxon test and survival was analyzed by Cox
regression.
Results: The ET backbone was mainly based on aromatase
inhibitors (71%) in association with CDK4/6 inhibitors
(94%). Bone metastases were the most represented (65%),
ESR1 and PIK3CA were mutated (mut) in 7 (14%) and 11
(23%) pts respectively. Notably, both genes were mut in 1
patient. The median methylation for promA was 38.5%

111
(inter quartile rage, IQR 33 - 43) and 33% (IQR 21.8 - 46)
for promB, with no significant differences in the overall
population (P = 0.1127). Significantly lower promA at
baseline was observed in pts with liver metastases
(P=0.0212) and in pts with ESR1 mut (median 41, IQR 33
- 46; median 25, IQR 18.5 - 34.5 respectively in ESR1
wild-type and mut; P = 0.0091). No significant impact on
PFS was observed for promA and promB dichotomized at
the median, while a ⩾200% increase in promB or in either
promA or B at E1 resulted in a significantly worse prognosis (respectively HR 4.42, P = 0.010 and HR 3.61, P =
0.017). A significant increase at E1 was observed for promB
among pts with PIK3CA mut (P = 0.0173). A trend was
observed for promB in ESR1 wild-type pts and for promA
in the ESR1 mut subgroup.
Conclusions: The study proofed the concept of an epigenetic characterization based on ctDNA apt to be integrated
in the current clinical workflow to give useful insights on
early treatment sensitivity. Although exploratory, these
results support the emerging new strategy of dynamic epigenetic profiling.

E23
TISSUE IMMUNE PROFILE CAN PREDICT
RESPONSE TO NEOADJUVANT THERAPY
IN TNBC
Scagnoli S.1, Cerbelli B.2, Mezi S.2, Pisegna S.2, De Luca A.2, Amabile
M.2, Roberto M.3, Strigari L.4, Fortunato L.5, Costarelli L.5, Della
Rocca C.2, Marchetti P.2, D'Amati G.2, Botticelli A.2
1

Università di Roma "Sapienza", Roma; 2Università di Roma "Sapienza"
- Policlinico Umberto I, Roma; 3Università di Roma "Sapienza" - Policlinico
Sant'Andrea, Roma; 4Università di Bologna - Policlinico Sant'Orsola Malpighi
di Bologna, Bologna; 5Azienda Ospedaliera San Giovanni Addolorata, Roma

Background: Pathological complete response (pCR) after
neoadjuvant chemotherapy (NACT) can predict better survival outcomes in patients with early triple negative breast
cancer (TNBC). However, only about 40% of patients will
achieve a pCR. Therefore, the identification of new biomarkers is an urgent need. Tumor infiltrating lymphocyties
(TILs), PD-L1 and CD73 are immune-related biomarkers
that can be evaluated in cancer cells and tumor microenvironment.. We investigated if the combination of these biomarkers in a Tissue Immune Profile (TIP), can predict
pCR better than a single biomarkers.
Methods: TILs, CD73 expression by cancer cells and
PD-L1 expression by immune cells have been evaluated
on pre-NACT biopsies. TILs ⩾ 50% were defined as highTILs (H-TILs). We defined CD73 low (CD73 ⩽40%) and
CD73 high (CD73 >40%) using the median value of
expression in our population as cut-off. PD-L1 =1% was
considered positive. We defined TIP positive (TIP+) as
the concomitant presence of TILS⩾50%, PD-L1⩾1% and
Tumori Journal Abstract Book - October 2020

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