Biology of Oestrogen-Receptor Positive Primary Breast Cancer in Older Women with Utilisation of Core Needle Biopsy Samples and Correlation with Clinical Outcome.

Ruth M Parks,Mohammad Albanghali,Andrew R Green,Ian O Ellis,Kwok-Leung Cheung,Binafsha M Syed

doi:10.3390/cancers12082067

Ruth M Parks, Mohammad Albanghali + Show 4 more

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https://doi.org/10.3390/cancers12082067

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The majority of biological profiling studies use surgical excision (SE) samples, excluding patients receiving nonsurgical and neoadjuvant therapy. We propose using core needle biopsy (CNB) for biological profiling in older women. Over 37 years (1973–2010), 1 758 older (≥70 years) women with operable primary breast cancer attended a dedicated clinic. Of these, 693 had sufficient quality CNB to construct tissue microarray (TMA). The pattern of biomarkers was analysed in oestrogen receptor (ER)-positive cases, using immunohistochemistry and partitional clustering analysis. The biomarkers measured were: progesterone receptor (PgR), Ki67, Epidermal Growth Factor Receptor (EGFR), Human Epidermal Growth Factor Receptor (HER)-2, HER3, HER4, p53, cytokeratins CK5/6 and CK7/8, Mucin (MUC)1, liver kinase B1 (LKB1), Breast Cancer Associated gene (BRCA) 1, B-Cell Lymphoma (BCL)-2, phosphate and tensin homolog (PTEN), vascular endothelial growth factor (VEGF), and Amplified in breast cancer 1 (AIB1). CNB TMA construction was possible in 536 ER-positive cases. Multivariate analysis showed progesterone receptor (PgR) (p = 0.015), Ki67 (p = 0.001), and mucin (MUC)1 (p = 0.033) as independent predictors for breast-cancer-specific survival (BCSS). Cluster analysis revealed three biological clusters, which were consistent with luminal A, luminal B, and low-ER luminal. The low-ER luminal cluster had lower BCSS compared to luminal A and B. The presence of the low-ER luminal cluster unique to older women, identified in a previous study in SE TMAs in the same cohort, is confirmed. This present study is novel in its use of core needle biopsy tissue microarrays to profile the biology of breast cancer in older women.

Highlights

The biology of breast cancer in older women differs compared to younger equivalents; older women are more likely to have cancers that are oestrogen receptor (ER)-positive [1,2,3] and demonstrate less aggressive features [4,5,6,7]
A UK national audit found that 40% of breast cancer patients aged >70 years and 55% aged >80 years were treated by primary endocrine therapy (PET) [8]
Preservation of core needle biopsy (CNB) tissue leads to faster penetration of the tissue by a fixative agent when compared to surgical excision (SE), resulting in less chance of enzyme degradation and, better preservation of biological features [9,10]

Summary

Introduction

The biology of breast cancer in older women differs compared to younger equivalents; older women are more likely to have cancers that are oestrogen receptor (ER)-positive [1,2,3] and demonstrate less aggressive features [4,5,6,7]. The majority of studies to date that have profiled the biology of breast cancer have used surgical excision (SE) specimens to do so. This creates potential bias in having not included the large group of patients who have PET and, cannot provide any insight when considering neoadjuvant therapy. This present study has, chosen to focus on ER-positive breast cancer. As an alternative to SE profiling, core needle biopsy (CNB), which is usually obtained at diagnosis in breast cancer patients, should be considered for the study of tumour biology. Preservation of CNB tissue leads to faster penetration of the tissue by a fixative agent when compared to SE, resulting in less chance of enzyme degradation and, better preservation of biological features [9,10]

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