Abstract
PurposePrediction of response to primary endocrine therapy (PET) in older women is based on measurement of oestrogen receptor (ER), progesterone receptor (PgR) and human epidermal growth factor (HER)-2. This study uses a unique method for construction of core needle biopsy (CNB) tissue microarray (TMA), to correlate expression of a panel of 17 biomarkers with clinical outcome, in patients receiving PET.MethodsOver 37 years (1973–2010), 1758 older (≥ 70 years) women with operable primary breast cancer were managed in a single institution. Of these, 693 had sufficient good-quality CNB to construct TMA, of which 334 had ER-positive tumours treated by PET with a minimum of 6-month follow-up. A panel of biomarkers was measured by immunohistochemistry (ER, PgR, HER2, Ki-67, p53, CK5/6, CK 7/8, EGFR, BCL-2, MUC1, VEGF, LKB1, BRCA1, HER3, HER4, PTEN and AIB1). Expression of each biomarker was dichotomised into ‘low’ or ‘high’ based on breast cancer-specific survival (BCSS).ResultsFrom the panel of biomarkers, multivariate analysis showed:High ER (p = 0.003) and PgR (p = 0.002) were associated with clinical benefit of PET at 6 months, as opposed to progressive disease.High ER (p = 0.0023), PgR (p < 0.001) and BCL-2 (p = 0.043) and low LKB1 (p = 0.022) were associated with longer time to progression.High PgR (p < 0.001) and low MUC1 (p = 0.021) were associated with better BCSS.Expression of other biomarkers did not show any significant correlation.ConclusionsIn addition to ER and PgR; MUC1, BCL-2 and LKB1 are important in determining the outcome of PET in this cohort.
Highlights
Surgery has better locoregional control of primary breast cancer compared to primary endocrine therapy (PET) in older women [1]
Bioinformatics principles and technologies [37] could help to analyse a large database comparing biomarker expression with clinical outcome, into a format which could be used clinically to help inform patients when making the decision between primary surgery and PET. This present study is unique in the examination of a large panel of biomarkers and their application to primary treatment of operable breast cancer in older women
The study adds to the evidence base that breast cancer in older women is generally less aggressive than in their younger counterparts
Summary
Surgery has better locoregional control of primary breast cancer compared to primary endocrine therapy (PET) in older women [1]. The 2012 joint guidance from the International Society of Geriatric Oncology and European Society of Breast Cancer Specialists [2] recommend that PET should only be offered to patients with oestrogen receptor (ER)-positive tumours with a life expectancy of 2–3 years despite optimisation of medical conditions. Around 40% of older women with primary breast cancer in the UK are treated by PET [3,4,5]. Breast Cancer Research and Treatment (2021) 185:647–655 subjective and dependent on interpretation of frailty and impact of comorbidity on quality of life. Patients report good satisfaction and low treatment morbidity with PET [2]. Surgery and PET have been shown to have similar survival outcomes for up to 5 years [6]; PET appears to be an attractive treatment option in some patients
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