Biomarkers expression in benign breast diseases and risk of subsequent breast cancer: a case-control study.

Margarita Posso,Mar Sánchez,Laia Serrano,Sònia Servitja,Joana Ferrer,Josep M Corominas,Laia Domingo,Isabel Torá‐Rocamora,María Sala,María Vernet‐Tomas,Anabel Romero,María Jesús Quintana,Carmen Vidal,Carmen Natal,Marta Román,Xavier Castells,Marisa Baré,Francina Saladié

doi:10.1002/cam4.1080

Abstract

Women with benign breast diseases (BBD) have a high risk of breast cancer. However, no biomarkers have been clearly established to predict cancer in these women. Our aim was to explore whether estrogen receptor (ER), progesterone receptor (PR), and Ki67 expression stratify risk of breast cancer in screened women with BBD. We conducted a nested case–control study. Women with breast cancer and prior BBDs (86 cases) were matched to women with prior BBDs who were free from breast cancer (172 controls). The matching factors were age at BBD diagnosis, type of BBD, and follow‐up time since BBD diagnosis. ER, PR, and Ki67 expression were obtained from BBDs’ specimens. Conditional logistic regression was used to estimate odds ratios (ORs), and 95% confidence intervals (CIs) of breast cancer risk according to ER, PR, and Ki67 expression. Women with >90% of ER expression had a higher risk of breast cancer (OR = 2.63; 95% CI: 1.26–5.51) than women with ≤70% of ER expression. Similarly, women with >80% of PR expression had a higher risk of breast cancer (OR = 2.22; 95% CI: 1.15–4.27) than women with ≤40% of PR expression. Women with proliferative disease and ≥1% of Ki67 expression had a nonsignificantly increased risk of breast cancer (OR = 1.16; 95% CI: 0.46–2.90) than women with <1% of Ki67 expression. A high expression of ER and PR in BBD is associated with an increased risk of subsequent breast cancer. In proliferative disease, high Ki67 expression may also have an increased risk. This information is helpful to better characterize BBD and is one more step toward personalizing the clinical management of these women.

Highlights

Benign breast diseases (BBD) are associated with an increased risk of subsequent breast cancer [1, 2]
Receptors (PR) stratifies the risk of subsequent cancer in women with benign breast diseases (BBD). We found both that women with high expression of estrogen receptor (ER) or progesterone receptor (PR) in BBD had an increased risk of subsequent breast cancer
Our results may be useful to improve the clinical management of women with BBD identified in the screening context since they are mostly nonproliferative diseases

Summary

Introduction

Benign breast diseases (BBD) are associated with an increased risk of subsequent breast cancer [1, 2]. The type of histological abnormality of BBD stratifies this risk. Proliferative disease with and without atypia could be associated with a two-to fourfold increased risk of developing breast cancer, nonproliferative diseases have a minimal increased risk of breast cancer [1]. The introduction of mammographic screening has led to a rise in the detection of BBD [2,3,4]. We have previously described that approximately 1.8% of screened women were found to have a BBD in our Spanish cohort [6]. It is possible that intensive screening can enhance the benefits for women with BBD, the majority of these women are still following routine screening recommendations [2, 4]

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Conclusion