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PAM50 for prediction of response to neoadjuvant chemotherapy for ER-positive breast cancer

  • Preclinical study
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Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Purpose

There is an urgent need for the development of a predictor of response to chemotherapy for ER-positive breast cancer which is less chemosensitive than for ER-negative breast cancer in order to avoid unnecessary chemotherapy. In the present study, intrinsic subtyping by PAM50 was evaluated for its ability to predict a response to chemotherapy.

Patients and Methods

For this study, 124 patients with ER-positive breast cancer treated with neoadjuvant sequential paclitaxel and FEC (NAC) were evaluated. Tumor biopsy specimens obtained before NAC were subjected to intrinsic subtyping (IS) by gene expression (GE) using PAM50 (PAM50-IS) or immunohistochemistry (IHC-IS).

Results

Of the PAM50-ISs (Luminal A, Luminal B, HER2-enriched, and Basal-like), GE-Luminal A showed the lowest pCR rate (1.9%), and multivariate analysis revealed that GE-Luminal A was a significant (P = 0.031) predictor of non-pCR independently of other clinicopathological parameters, including Ki67, and tumor-infiltrating lymphocytes. Of the IHC-ISs, on the other hand, IHC-Luminal A was not significantly associated with pCR. We also found that breast tumors with low ER levels (1–9%), like ER-negative tumors, were mostly GE-HER2-enriched and GE-Basal-like, and more sensitive to NAC than those with high ER levels (≥ 10%).

Conclusions

GE-Luminal A intrinsically subtyped by PAM50 was the least sensitive to NAC and very unlikely to attain pCR. IHC-Luminal A identified by IHC, on the other hand, was not significantly predictive of pCR. In addition, PAM50 revealed that tumors with low ER (1–9%) were more like ER-negative tumors than ER-positive tumors, and most such cases should therefore would better be treated with chemotherapy.

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Abbreviations

ER:

Estrogen receptor

PR:

Progesterone receptor

HER2:

Human epidermal growth factor receptor 2

DMFS:

Distant metastasis-free survival

pCR:

Pathological complete response

IHC:

Immunohistochemistry

FISH:

Fluorescence in situ hybridization

HG:

Histological grade

NAC:

Neoadjuvant chemotherapy

GE:

Gene expression

IS:

Intrinsic subtype

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Acknowledgements

This study was supported, in part, by the Knowledge Cluster Initiative of the Ministry of Education, Culture, Sports, Science and Technology.

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Authors and Affiliations

  1. Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, 2-2-E10 Yamadaoka, Suita-shi, 565-0871, Osaka, Japan

    Ako Matsushita Ohara, Yasuto Naoi, Kenzo Shimazu, Naofumi Kagara, Masafumi Shimoda, Tomonori Tanei, Tomohiro Miyake, Seung Jin Kim & Shinzaburo Noguchi

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  1. Ako Matsushita Ohara
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  2. Yasuto Naoi
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  3. Kenzo Shimazu
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  4. Naofumi Kagara
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Correspondence to Yasuto Naoi.

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Conflict of interest

Dr. Shinzaburo Noguchi has been an advisor for Taiho, AstraZeneca and Novartis, and has received research funding for other studies from Sysmex, AstraZeneca, Novartis, Chugai, Daiichi-Sankyo, Kyowa-Kirin, Takeda, Pfizer, Ono, Taiho, and Eisai, and honoraria from AstraZeneca, Novartis, Pfizer, Chugai, Takeda, Sysmex, Nippon Kayaku, and Ono. Dr. Yasuto Naoi has received research funding from Sysmex and AstraZeneca. Dr. Naofumi Kagara has received honoraria from AstraZeneca and Novartis. Dr. Masafumi Shimoda has received research funding from Novartis and AstraZeneca, and honoraria from Chugai, Eisai, Novartis, and Takeda. Dr. Kenzo Shimazu has received honoraria from AstraZeneca, Chugai, and Sysmex. Dr. Seung Jin Kim received honoraria from AstraZeneca, Chugai, Eisai, Kyowa-Kirin, Novartis, Pfizer, Shimadzu, Taiho, and Takeda.

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This study complies with the current relevant laws of and guidelines for Japan.

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10549_2018_5020_MOESM1_ESM.docx

Supplementary Fig.1. Comparison of DMFS between ER-negative, ER-low, and ER-high breast cancers. Patients (n = 32) with ER-negative (0%) tumors were treated with neoadjuvant chemotherapy and those with ER-low (1–9%) tumors (n = 16) or ER-high (> 10%) tumors (n = 108) were treated with neoadjuvant chemotherapy plus adjuvant hormonal therapy. (DOCX 17 KB)

Supplementary material 2 (PPTX 58 KB)

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Ohara, A.M., Naoi, Y., Shimazu, K. et al. PAM50 for prediction of response to neoadjuvant chemotherapy for ER-positive breast cancer. Breast Cancer Res Treat 173, 533–543 (2019). https://doi.org/10.1007/s10549-018-5020-7

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