Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

ePoster

8P - Characterization of immune microenvironment before and following anti-HER2 neoadjuvant therapy (NAT)

Date

24 May 2020

Session

ePoster

Presenters

Gaia Griguolo

Citation

Annals of Oncology (2020) 31 (suppl_2): S15-S41. 10.1016/annonc/annonc117

Authors

G. Griguolo1, G. Serna2, T. Pascual3, R. Fasani2, N. Chic4, L. Paré5, S. Pernas6, M. Muñoz4, A.M. Antunes De Melo e Oliveira7, M. Vidal4, A. Llombart Cussac8, J. Cortés9, P. Galván4, B. Bermejo10, N. Martínez11, R. López12, S. Morales13, P. Villagrasa5, A. Prat14, P. Nuciforo2

Author affiliations

  • 1 Department Of Surgery, Oncology And Gastroenterology, University of Padova, 35128 - Padova/IT
  • 2 Molecular Oncology Group, Vall d´Hebron Institute of Oncology, Barcelona/ES
  • 3 Hospital Clinic/idibaps, Solti Breast Cancer Research Group, Barcelona, Spain, Department of Genetics - University of North Carolina, Chapel Hill, ‎27599 - Chapel Hill/US
  • 4 Medical Oncology, Hospital Clinic/IDIBAPS, 08036 - Barcelona/ES
  • 5 Breast Cancer Research Group, SOLTI, 08008 - Barcelona/ES
  • 6 Medical Oncology, Institut Catala d'Oncologia, Hospitalet de Llobregat/ES
  • 7 Medical Oncology, Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology, Barcelona/ES
  • 8 Medical Oncology, Hospital Universitario Arnau de Vilanova, Universidad Catolica, 46015 - Valencia/ES
  • 9 Iob Institute Of Oncology, Quironsalud Group, Madrid & Barcelona;, Vall d'Hebron Institute of Oncology (VHIO), 08035 - Barcelona/ES
  • 10 Medical Oncology, Hospital Clínico Universitario de Valencia / INCLIVA / CIBERONC, Valencia/ES
  • 11 Medical Oncology, Hospital Universitario Ramón y Cajal, 28034 - Madrid/ES
  • 12 Medical Oncology, Hospital Clínico Universitario de Santiago / CIBERONC, Santiago de Compostela/ES
  • 13 Breast Cancer Unit, Hospital Universitario Arnau de Vilanova, 25198 - LLEIDA/ES
  • 14 Medical Oncology, Hospital Clinic/idibaps, SOLTI Breast Cancer Research Group, 08036 - Barcelona/ES
More

Abstract 8P

Background

Despite its recognized role in breast cancer (BC), the complexity of immune microenvironment remains largely unexplored. Multiplex immunohistochemistry (mIHC) holds opportunity to more comprehensively assess BC immunity, potentially providing information to improve immunotherapy.

Methods

In the neoadjuvant phase II SOLTI-1114 PAMELA trial (NCT01973660), 151 HER2+ BC patients received lapatinib and trastuzumab, plus hormonal therapy if HR+. Baseline (BSL, n=66) and day-15 (D15, n=54) biopsies from 76 patients were analyzed using a custom mIHC 6-plex panel, including immune subtyping (CD3, CD4, CD8, FOXP3), localization (keratin for tumor mask), and activity (Ki67 for proliferation). Immune cell density (cells/mm2) and localization were determined by digital image analysis and classified in: intratumor (A), proximal peritumor (B - < 10um; C - 10 to 30um from tumor) and distal peritumor stroma (D). Intrinsic subtyping was determined at the same timepoints using the PAM50 predictor (nCounter).

Results

Both at BSL and D15, no significant difference in immune subpopulation densities was observed according to PAM50 subtype. At both timepoints, fraction of proliferating (Ki67+) immune cells (all subpopulations) differed significantly according to subtype (basal-like tumors showing the highest and luminal tumors showing the lowest fraction of proliferating cells, p varying from <0.001 to 0.031). Tumors achieving a pCR showed numerically higher densities of CD3+, CD8+ and FOXP3+ cells. Association with pCR was stronger at D15 and for immune cells intratumor/more proximal to tumor (Table). Overall, at D15, tumors achieving pCR showed higher CD3+ density (p=0.03) and higher ratio in Ki67+CD8+/Ki67+FOXP3+ (p=0.03). Table: 8P

Odds ratios (95% CI) for pCR for 1000 cells/mm2 increases in immune cell density according to subpopulation, timepoint, and localization

Timepoint Baseline Day 15
Localization A B C D A B C D
Immune cell subpopulation CD3+ 1.37 (0.97-1.94) 1.31 (0.95-1.81) 1.35 (0.93-1.96) 1.02 (0.48-2.17) 1.38 (1.04-1.82) 1.25 (1.01-1.55) 1.31 (0.98-1.73) 1.79 (0.87-3.65)
CD8+ 1.51 (0.66-3.50) 1.33 (0.74-2.40) 1.39 (0.69-2.83) 1.00 (0.26-3.76) 1.61 (1.09-2.39) 1.42 (1.01-2.00) 1.59 (0.97-2.61) 2.87 (0.73-11.29)
FOXP3+ 1.12 (0.92-1.36) 1.28 (0.88-1.87) 1.43 (0.82-2.48) 0.26 (0.01-7.13) 1.10 (0.99-1.23) 1.19 (1.01-1.41) 1.31 (0.99-1.73) 4.61 (0.32-66.13)

Conclusions

In early HER2+ BC, immune cells show differential proliferation patterns according to tumor biology. Number of immune cells spatially interacting with tumor after priming by anti-HER2 therapy was associated with pCR.

Clinical trial identification

NCT01973660.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Vall d'Hebron Institute of Oncology (VHIO).

Disclosure

G. Griguolo: Travel/Accommodation/Expenses: Pfizer. A. Prat: Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), immediate family member being employed by Novartis: Novartis; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Roche; Honoraria (self): MSD Oncology; Honoraria (self): Lilly; Honoraria (self), Travel/Accommodation/Expenses: Daiichi Sankyo; Advisory/Consultancy: NanoString Technologies; Advisory/Consultancy: Amgen; Advisory/Consultancy: Bristol-Myers Squibb. P. Nuciforo: Advisory/Consultancy: Bayer; Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD Oncology; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis. All other authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings