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, Deborah Smith, Daniel Buchanan, Yee Leung, Martin K. Oehler, Alison Brand, Penelope M. Webb, Amanda B. Spurdle

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)6411-6422
Number of pages12
JournalCancer Medicine
Volume7
Issue number12
DOIs
Publication statusPublished - 1 Dec 2018

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Endometrial Neoplasms
Breast
DNA Mismatch Repair
Hereditary Nonpolyposis Colorectal Neoplasms
Tamoxifen
Population
Neoplasms
Breast Neoplasms
Malignant Mixed Tumor
Survival

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Johnatty, Sharon E. ; Stewart, Colin J.R. ; Smith, Deborah ; Buchanan, Daniel ; Leung, Yee ; Oehler, Martin K. ; Brand, Alison ; Webb, Penelope M. ; Spurdle, Amanda B. / Risk and prognostic factors for endometrial carcinoma after diagnosis of breast or Lynch-associated cancers—A population-based analysis. In: Cancer Medicine. 2018 ; Vol. 7, No. 12. pp. 6411-6422.
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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.",
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Risk and prognostic factors for endometrial carcinoma after diagnosis of breast or Lynch-associated cancers—A population-based analysis. / Johnatty, Sharon E.; Stewart, Colin J.R.; Smith, Deborah; Buchanan, Daniel; Leung, Yee; Oehler, Martin K.; Brand, Alison; Webb, Penelope M.; Spurdle, Amanda B.

In: Cancer Medicine, Vol. 7, No. 12, 01.12.2018, p. 6411-6422.

Research output: Contribution to journalArticle

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T1 - Risk and prognostic factors for endometrial carcinoma after diagnosis of breast or Lynch-associated cancers—A population-based analysis

AU - Johnatty, Sharon E.

AU - Stewart, Colin J.R.

AU - Smith, Deborah

AU - Buchanan, Daniel

AU - Leung, Yee

AU - Oehler, Martin K.

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