Risk and prognostic factors for endometrial carcinoma after diagnosis of breast or Lynch-associated cancers-A population-based analysis.

Sharon E Johnatty,Colin J R Stewart,Penelope M Webb,Martin K Oehler,Deborah Smith,Alison Brand,Amanda B Spurdle,Yee Leung,Daniel Buchanan

doi:10.1002/cam4.1890

Abstract

We hypothesized that endometrial carcinoma (EC) patients with a prior cancer diagnosis, after accounting for EC arising after tamoxifen‐treated prior breast carcinoma, are more likely to have an underlying genetic basis. We used information from a population‐based study to compare measured risk factors, tumor characteristics, survival, and known mismatch repair (MMR) pathogenic variant status for EC subgroups according to prior diagnosis of cancer (none, breast cancer tamoxifen‐treated or not, Lynch Syndrome (LS)‐associated cancer). Family history of any cancer was increased for EC cases with prior breast cancer, both tamoxifen treated (P = 0.005) and untreated (P = 0.01). EC cases with prior LS‐associated cancer more often reported family history of LS‐associated cancer (P = 0.04) and breast cancer (P = 0.05). EC patients with a germline pathogenic MMR gene variant were more likely to report a prior cancer than cases with a MMR proficient tumor (P = 0.0001), but more than half (54.5%) of MMR carriers reported no prior cancer. Women developing EC after tamoxifen treatment for breast cancer were significantly more likely to develop EC of malignant mixed mullerian tumor subtype (13.2% vs 2.6%, P = 1.3 × 10−6), present with stage IV disease (8.8% vs 1.2%, P = 1.6 × 10−6), and have poorer survival (HRadj 1.96; P = 0.001). While report of prior cancer is an indicator of MMR pathogenic variant status, molecular analysis of all ECs at diagnosis is warranted to detect all patients with LS. Results also indicate the importance of longer‐term monitoring of women treated with tamoxifen for symptoms of EC, and the need for studies assessing the biological mechanism underlying the poorer prognosis of this subset of EC patients.

Highlights

Endometrial carcinoma (EC) is the fifth most common cancer in women in developed countries, accounting for 4.8% of new cancers and 2.1% of cancer deaths
The risk estimates for EC following a prior breast or Lynch Syndrome (LS)‐associated cancer associated with the risk factors highlighted above were necessarily imprecise given the smaller sample sizes
They were generally in the same direction as those reported for EC with no prior cancer, with elevated risk associated with increasing Body mass index (BMI), and decreased risk associated with OC use, increasing parity, later age at menarche, and postmenopausal HRT use

Summary

| INTRODUCTION

Endometrial carcinoma (EC) is the fifth most common cancer in women in developed countries, accounting for 4.8% of new cancers and 2.1% of cancer deaths. We considered the possibility that classical epidemiological risk factors for EC (such as obesity) may be less important for EC patients with prior cancer report (and suspected genetic basis). To investigate these questions, we detailed prior cancer report and tamoxifen use for women with EC and controls participating in the population‐based Australian National Endometrial Cancer Study (ANECS). We compared epidemiological risk factors, reported family history, tumor characteristics, survival, and known MMR gene pathogenic variant status for EC subgroups according to cancer types diagnosed prior to recruitment, and for women without EC and no reported personal history of cancer

| METHODS

| RESULTS

| DISCUSSION