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Tumor characteristics and outcome by androgen receptor expression in triple-negative breast cancer patients treated with neo-adjuvant chemotherapy

  • Epidemiology
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Abstract

Purpose

To assess clinical pathological characteristics and outcome of triple-negative breast cancers (TNBC) by androgen receptor (AR) protein expression.

Methods

We retrospectively evaluated AR by immunohistochemistry on core-needle biopsy, (CNB) and residual disease (RD) in a consecutive institutional series of TNBC patients treated with neo-adjuvant chemotherapy (NACT) between 2000 and 2017. We investigated univariate associations between AR-expression on CNB (using different cut-offs), clinical pathological variables, and pathologic complete response (pCR). Next, we used multiple correspondence analysis (MCA) to investigate the relationships between AR on CNB and standard clinical and pathological variables, including stromal tumor infiltrating lymphocytes (sTILs). Finally, we investigated the prognostic value of AR-expression on CNB and RD using the Fine and Gray model.

Results

We included 71 patients; median follow-up was 6.7 years. Considering the ≥ 1% cut-off, AR was present in 32% on the CNB and 14% on RD. AR-low (1-34% positive tumor cells) patients were associated with younger (premenopausal) age and AR-high (≥ 34% positive tumor cells) with older (postmenopausal) age. AR on CNB did not correlate with other features nor was it predictive for pCR or prognostic for metastatic outcome, regardless of the used cut-off. The MCA suggested that body mass index (BMI) affects the predictive role of AR-low and -high for pCR differently. AR-loss on RD was prognostic for a better 5-year distant disease-free survival (DDFS) as compared to RD with retained AR-expression (61.6% (95% CI 44.26–79.14) and 25.0% (95% CI 3.94–87.21), respectively; p = 0.01).

Conclusion

Low and high AR-expression on CNB of TNBC were correlated with age and menopausal status but qualitative AR was not predictive for pCR. AR-loss on RD was prognostic for DDFS in TNBC patients treated with NACT.

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Abbreviations

AR:

Androgen receptor

BCSS:

Breast cancer-specific survival

CNB:

Core-needle biopsy

Cos2:

Squared cosine

DAB:

3,3′-Diaminobenzidin tetrahydrochloride

DDFS:

Distant disease-free survival

ER:

Estrogen receptor

FFPE:

Formalin-fixed paraffin embedded

FISH:

Fluorescent in situ hybridization

HER2:

Human epidermal growth factor receptor 2

IHC:

Immunohistochemistry

LPBC:

Lymphocyte-predominant breast cancer

MCA:

Multiple correspondence analysis

NACT:

Neo-adjuvant chemotherapy

pCR:

Pathological complete response

PR:

Progesterone receptor

RCB:

Residual cancer burden

RD:

Residual disease

sTILs:

Stromal tumor-infiltrating lymphocytes

TNBC:

Triple-negative breast cancer

UHL:

University Hospitals Leuven

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Acknowledgements

We would like to thank Funds of Friends for Cancer Research Leuven for supporting this research. The authors would also like to thank Sarah Cumps, Eef Allegaert and Kathleen Van den Eynde from the Department of Imaging and Pathology, Translational Cell & Tissue Research of the KU Leuven, for their technical support.

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Authors and Affiliations

  1. Department of Oncology, KU Leuven, 3000, Leuven, Belgium

    Lynn Jongen, Hans Wildiers, Kevin Punie, Ann Smeets, Ignace Vergote & Patrick Neven

  2. Department of Imaging and Pathology, Laboratory of Translational Cell & Tissue Research and University Hospitals Leuven, KU Leuven, 3000, Leuven, Belgium

    Giuseppe Floris

  3. Department of General Medical Oncology, University Hospitals Leuven, KU Leuven, 3000, Leuven, Belgium

    Hans Wildiers & Kevin Punie

  4. Department of Cellular and Molecular Medicine, KU Leuven, 3000, Leuven, Belgium

    Frank Claessens

  5. Department of Oncology, Laboratory for Translational Breast Cancer Research, KU Leuven, 3000, Leuven, Belgium

    François Richard & Christine Desmedt

  6. Interuniversity Centre for Biostatistics and Statistical Bioinformatics, 3000, Leuven, Belgium

    Annouschka Laenen

  7. Department of Gynecology and Obstetrics, University Hospitals Leuven, KU Leuven, 3000, Leuven, Belgium

    Jan Ardui, Patrick Berteloot, Ignace Vergote & Patrick Neven

  8. Department of Surgical Oncology, University Hospitals Leuven, KU Leuven, 3000, Leuven, Belgium

    Ann Smeets

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  1. Lynn Jongen
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Correspondence to Patrick Neven.

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Conflict of interest

Hans Wildiers received travel support from Roche and Pfizer, and his institution received consulting fees and honoraria from Roche, Astra Zeneca, Amgen, Lilly, Novartis, Abbvie, Vifor Pharma, Pfizer, Celldex therapeutics, Janssen-CILAG, TRM Oncology, PUMA Biotechnology, ORION corporation and an unrestricted research grant from Roche. Christine Desmedt received speakers fee from Roche Diagnostics for her institution. Kevin Punie received travel support from Astra Zeneca, Novartis, Pfize, Pharma Mar and Roche. His institution received research funding from Sanofi, honoraria for consulting or advisory roles from Astra Zeneca, Novartis, Pfizer, Roche and Vifor Pharma and speaker fees from Novartis and Pfizer. Ann Smeets received for her institution a grant from MSD for medication for a window of opportunity trial. Patrick Neven received speaker’s fees, consulting fees, and research support from Roche (all provided to his institute). Patrick Neven is on the advisory board of Novartis, AstraZeneca, Lilly, and Pfizer (all consulting fees are provided to his institute). Ignace Vergote is on the advisory board of: Advaxis, Inc., Eisai Inc., MSD Belgium, Roche NV, Genmab A/S, Genmab US, F. Hoffmann-La Roche Ltd, Pharmamar, Millennium Pharmaceuticals, Clovis Oncology Inc., AstraZeneca NV, Tesaro Bio GmbH, Tesaro Inc, Oncoinvent AS, and Immunogen Inc. Ignace Vergote has contracted research (via KU Leuven) of: Oncoinvent AS, and Genmab A/S – Genmab B.V. Ignace Vergote receives corporate sponsored research grants by Amgen and Roche. Ignace Vergote received travel support by: Takeda Oncology, Pharma Mar, Genmab, Roche, Astrazeneca, and Tesaro. All other authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional committee (UHL, Belgium) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The study was approved by the Ethics Committee of the UHL in Belgium before the study started.

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Jongen, L., Floris, G., Wildiers, H. et al. Tumor characteristics and outcome by androgen receptor expression in triple-negative breast cancer patients treated with neo-adjuvant chemotherapy. Breast Cancer Res Treat 176, 699–708 (2019). https://doi.org/10.1007/s10549-019-05252-6

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