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. 2019 May:114:167-174.
doi: 10.1016/j.ejrad.2019.03.017. Epub 2019 Mar 21.

Imaging features of triple-negative breast cancers according to androgen receptor status

Rosalind P Candelaria  1 , Beatriz E Adrada  2 , Wei Wei  3 , Alastair M Thompson  4 , Lumarie Santiago  5 , Deanna L Lane  6 , Monica L Huang  7 , Elsa M Arribas  8 , Gaiane M Rauch  9 , W Fraser Symmans  10 , Michael Z Gilcrease  11 , Lei Huo  12 , Bora Lim  13 , Naoto T Ueno  14 , Stacy L Moulder  15 , Wei Tse Yang  16
Affiliations

Imaging features of triple-negative breast cancers according to androgen receptor status

Rosalind P Candelaria et al. Eur J Radiol. 2019 May.

Abstract

Objective: Different molecular subtypes of triple-negative breast cancer (TNBC) have previously been identified through analysis of gene expression profiles. The luminal androgen receptor (LAR) subtype has been shown to have a lower rate of pathologic complete response to neoadjuvant chemotherapy than other TNBC subtypes. The purpose of this study was to determine if the imaging features of TNBCs differ by AR (androgen receptor) status, which is a surrogate immunohistochemical (IHC) marker for the chemoresistant LAR subtype of TNBC.

Materials and methods: This sub-study was part of a clinical trial in patients with stage I-III TNBC who were prospectively monitored for response while receiving neoadjuvant systemic therapy (NAST) at a single comprehensive cancer center. This interim imaging analysis included 144 patients with known AR status measured by IHC. AR-positive (AR+) tumors were defined as those in which at least 10% of tumor cells had positive nuclear AR staining. Two experienced, fellowship-trained breast radiologists who were blinded to the IHC results retrospectively reviewed and reached consensus on all imaging studies for the index lesion (i.e., mammogram, ultrasound, and breast magnetic resonance imaging). The index lesion for each patient was reviewed and described according to the fifth edition of the Breast Imaging Reporting and Data System lexicon. Logistic regression modeling was used to identify imaging features predictive of AR status. p ≤ 0.05 was considered statistically significant.

Results: Univariate logistic regression models for AR status showed that AR+ TNBC was significantly associated with heterogeneously dense breast composition on mammography (p = 0.02), mass with calcifications (p = 0.05), irregular mass shape on mammography (p = 0.03), and irregular mass shape on sonography (p = 0.003). Multivariate logistic regression models for AR status showed that AR+ TNBC was significantly associated with heterogeneously dense breast composition on mammography (p = 0.01), high mass density on mammography (p = 0.003), and irregular mass shape on sonography (p = 0.0004).

Conclusion: The imaging features of TNBCs differ by AR status. Multimodality breast imaging may help identify the LAR subtype of TNBC, which has been shown to be a subtype that is relatively resistant to neoadjuvant chemotherapy.

Keywords: Androgen receptor; MRI; Mammography; Triple-negative breast cancer; Ultrasound.

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Conflict of interest statement

Declaration of Interests

We wish to draw the attention of the Editor to the following facts which may be considered as potential conflicts of interest and to significant financial contributions to this work.

Rosalind P. Candelaria, MD – Nothing to disclose.

Beatriz E. Adrada, MD – Nothing to disclose.

Wei Wei, MS – Nothing to disclose.

Lumarie Santiago, MD – Nothing to disclose.

Deanna L. Lane, MD – Nothing to disclose.

Monica L. Huang, MD – Nothing to disclose.

Elsa M. Arribas, MD – Nothing to disclose.

Gaiane M. Rauch, MD, PhD – Nothing to disclose.

Michael Z. Gilcrease, MD, PhD – Nothing to disclose.

Lei Huo, MD, PhD – Nothing to disclose.

W. Fraser Symmans, MD – Delphi Diagnostics: intellectual property and founder shares; IONIS Pharmaceuticals: stock; Merck: advisory board honorarium; Almac Diagnostics: advisory board honorarium.

Alastair M. Thompson, MD – Pfizer: honorarium.

Bora Lim, MD – Pfizer: research funding

Naoto T. Ueno, MD, PhD – Pfizer: research funding; Epic Sciences: research funding

Stacy L. Moulder, MD – Oncothyreon: research funding and advisor; Seattle Genetics: research funding and advisor; Roche: research funding and advisor; Genentech: research funding and advisor; Novartis: research funding, advisor, and honorarium; Pfizer: research funding and advisor; EMD Serono: research funding and advisor; Bayer: advisor; Merck: advisor.

Wei Tse Yang, MD – Wolters Kluewer: consultant; GE Healthcare: consultant; Seno Medical Instruments: advisory committee member; Elsevier: royalties.

Declarations of interest:

• Rosalind P. Candelaria, MD – Nothing to disclose.

• Beatriz E. Adrada, MD – Nothing to disclose.

• Wei Wei, MS – Nothing to disclose.

• Lumarie Santiago, MD – Nothing to disclose.

• Deanna L. Lane, MD – Nothing to disclose.

• Monica L. Huang, MD – Nothing to disclose.

• Elsa M. Arribas, MD – Nothing to disclose.

• Gaiane M. Rauch, MD, PhD – Nothing to disclose.

• Michael Z. Gilcrease, MD, PhD – Nothing to disclose.

• Lei Huo, MD, PhD – Nothing to disclose.

• W. Fraser Symmans, MD – Delphi Diagnostics: intellectual property and founder shares; IONIS Pharmaceuticals: stock; Merck: advisory board honorarium; Almac Diagnostics: advisory board honorarium.

• Alastair M. Thompson, MD – Pfizer: honorarium.

• Bora Lim, MD – Pfizer: research funding.

• Naoto T. Ueno, MD, PhD – Pfizer: research funding; Epic Sciences: research funding.

• Stacy L. Moulder, MD – Oncothyreon: research funding and advisor; Seattle Genetics: research funding and advisor; Roche: research funding and advisor; Genentech: research funding and advisor; Novartis: research funding, advisor, and honorarium; Pfizer: research funding and advisor; EMD Serono: research funding and advisor; Bayer: advisor; Merck: advisor.

• Wei Tse Yang, MD – Wolters Kluewer: consultant; GE Healthcare: consultant; Seno Medical Instruments: advisory committee member; Elsevier: royalties.

Figures

Figure 1.
Figure 1.
74-year-old woman with AR+ TNBC. (a) Right lateromedial magnification mammogram shows an irregular mass with associated coarse heterogeneous calcifications. (b) Breast ultrasound of the same mass shows irregular shape, angular margins, and a heterogeneous echo pattern. (c) Sagittal subtraction MR image of the same mass shows irregular shape and irregular margins.
Figure 1.
Figure 1.
74-year-old woman with AR+ TNBC. (a) Right lateromedial magnification mammogram shows an irregular mass with associated coarse heterogeneous calcifications. (b) Breast ultrasound of the same mass shows irregular shape, angular margins, and a heterogeneous echo pattern. (c) Sagittal subtraction MR image of the same mass shows irregular shape and irregular margins.
Figure 1.
Figure 1.
74-year-old woman with AR+ TNBC. (a) Right lateromedial magnification mammogram shows an irregular mass with associated coarse heterogeneous calcifications. (b) Breast ultrasound of the same mass shows irregular shape, angular margins, and a heterogeneous echo pattern. (c) Sagittal subtraction MR image of the same mass shows irregular shape and irregular margins.
Figure 2.
Figure 2.
38-year-old woman with AR– TNBC. (a) Left lateromedial mammogram shows an oval mass (white circle) without calcifications and with circumscribed margins. (b) Breast ultrasound of the same mass shows oval shape, circumscribed margins, and hypoechoic echo pattern. (c) Axial subtraction MR image of the same mass shows oval shape, circumscribed margins, and heterogeneous internal enhancement.
Figure 2.
Figure 2.
38-year-old woman with AR– TNBC. (a) Left lateromedial mammogram shows an oval mass (white circle) without calcifications and with circumscribed margins. (b) Breast ultrasound of the same mass shows oval shape, circumscribed margins, and hypoechoic echo pattern. (c) Axial subtraction MR image of the same mass shows oval shape, circumscribed margins, and heterogeneous internal enhancement.
Figure 2.
Figure 2.
38-year-old woman with AR– TNBC. (a) Left lateromedial mammogram shows an oval mass (white circle) without calcifications and with circumscribed margins. (b) Breast ultrasound of the same mass shows oval shape, circumscribed margins, and hypoechoic echo pattern. (c) Axial subtraction MR image of the same mass shows oval shape, circumscribed margins, and heterogeneous internal enhancement.
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