TY - JOUR
T1 - Hormone-receptor expression and ovarian cancer survival
T2 - An Ovarian Tumor Tissue Analysis consortium study
AU - Sieh, Weiva
AU - Köbel, Martin
AU - Longacre, Teri A.
AU - Bowtell, David D.
AU - deFazio, Anna
AU - Goodman, Marc T.
AU - Høgdall, Estrid
AU - Deen, Suha
AU - Wentzensen, Nicolas
AU - Moysich, Kirsten B.
AU - Brenton, James D.
AU - Clarke, Blaise A.
AU - Menon, Usha
AU - Gilks, C. Blake
AU - Kim, Andre
AU - Madore, Jason
AU - Fereday, Sian
AU - George, Joshy
AU - Galletta, Laura
AU - Lurie, Galina
AU - Wilkens, Lynne R.
AU - Carney, Michael E.
AU - Thompson, Pamela J.
AU - Matsuno, Rayna K.
AU - Kjær, Susanne Krüger
AU - Jensen, Allan
AU - Høgdall, Claus
AU - Kalli, Kimberly R.
AU - Fridley, Brooke L.
AU - Keeney, Gary L.
AU - Vierkant, Robert A.
AU - Cunningham, Julie M.
AU - Brinton, Louise A.
AU - Yang, Hannah P.
AU - Sherman, Mark E.
AU - García-Closas, Montserrat
AU - Lissowska, Jolanta
AU - Odunsi, Kunle
AU - Morrison, Carl
AU - Lele, Shashikant
AU - Bshara, Wiam
AU - Sucheston, Lara
AU - Jimenez-Linan, Mercedes
AU - Driver, Kristy
AU - Alsop, Jennifer
AU - Mack, Marie
AU - McGuire, Valerie
AU - Rothstein, Joseph H.
AU - Rosen, Barry P.
AU - Bernardini, Marcus Q.
AU - Mackay, Helen
AU - Oza, Amit
AU - Wozniak, Eva L.
AU - Benjamin, Elizabeth
AU - Gentry-Maharaj, Aleksandra
AU - Gayther, Simon A.
AU - Tinker, Anna V.
AU - Prentice, Leah M.
AU - Chow, Christine
AU - Anglesio, Michael S.
AU - Johnatty, Sharon E.
AU - Chenevix-Trench, Georgia
AU - Whittemore, Alice S.
AU - Pharoah, Paul D.P.
AU - Goode, Ellen L.
AU - Huntsman, David G.
AU - Ramus, Susan J.
N1 - Funding Information:
This study was supported by the Carraresi Foundation through donations to the Vancouver General Hospital and University of British Columbia Hospital Foundation. AOC was supported by the US Department of Defense (DAMD17-01-1-0729), Cancer Council Victoria, Queensland Cancer Fund, Cancer Council New South Wales, Cancer Council South Australia, Cancer Foundation of Western Australia, Cancer Council Tasmania, Australian National Health and Medical Research Council (grants 400413 and 400281 ). HAW was funded by the US National Institutes of Health (NIH; grants R01CA58598, N01CN55424, N01PC67001 ). MAL was funded by the NIH ( R01CA61107 ), Danish Cancer Society ( 94 222 52 ), and the Mermaid I project. MAY+MAC was funded by the NIH (grants R01CA122443 and P50CA136393 ), Mayo Foundation, and the Fred C and Katherine B Andersen Foundation. The Polish Ovarian Cancer Study (POL) was funded by the NIH ( Z01CP010126 ). The Roswell Park Cancer Institute Ovarian Cancer Cohort (RPX) was funded by the Roswell Park Cancer Institute Alliance Foundation. The Study of Epidemiology and Risk Factors in Cancer Heredity (SEA) was funded by Cancer Research UK ( C490/A10119 C490/A10124 ), National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre, and the Cambridge Experimental Cancer Medicine Centre. STA was funded by the NIH ( U01CA71966, U01CA69417, R01CA16056, and K07CA143047 ). The UK Ovarian Cancer Population Study (UKO) was funded by Eve Appeal (Oak Foundation) and was supported by researchers at the NIHR University College London Hospitals Biomedical Research Centre. VAN was funded by the British Columbia Cancer Foundation, Vancouver General Hospital and University of British Columbia Hospital Foundation, and Sanofi-Aventis Canada. We thank all the women, study centres, and personnel who participated in this study. We gratefully acknowledge the contributions of the Australian Ovarian Cancer Study Group ; Karin Goodman, Ashley Pitzer, and the Mayo Clinic Medical Genome Facility; Fiona Blows and the SEARCH team; Ian Jacobs, Andy Ryan, Jeremy Ford, Nayaladzi Balogun; and the Cheryl Brown Ovarian Cancer Outcomes Unit.
PY - 2013/8
Y1 - 2013/8
N2 - Background: Few biomarkers of ovarian cancer prognosis have been established, partly because subtype-specific associations might be obscured in studies combining all histopathological subtypes. We examined whether tumour expression of the progesterone receptor (PR) and oestrogen receptor (ER) was associated with subtype-specific survival. Methods: 12 studies participating in the Ovarian Tumor Tissue Analysis consortium contributed tissue microarray sections and clinical data to our study. Participants included in our analysis had been diagnosed with invasive serous, mucinous, endometrioid, or clear-cell carcinomas of the ovary. For a patient to be eligible, tissue microarrays, clinical follow-up data, age at diagnosis, and tumour grade and stage had to be available. Clinical data were obtained from medical records, cancer registries, death certificates, pathology reports, and review of histological slides. PR and ER statuses were assessed by central immunohistochemistry analysis done by masked pathologists. PR and ER staining was defined as negative (<1% tumour cell nuclei), weak (1 to <50%), or strong (≥50%). Associations with disease-specific survival were assessed. Findings: 2933 women with invasive epithelial ovarian cancer were included: 1742 with high-grade serous carcinoma, 110 with low-grade serous carcinoma, 207 with mucinous carcinoma, 484 with endometrioid carcinoma, and 390 with clear-cell carcinoma. PR expression was associated with improved disease-specific survival in endometrioid carcinoma (log-rank p<0·0001) and high-grade serous carcinoma (log-rank p=0·0006), and ER expression was associated with improved disease-specific survival in endometrioid carcinoma (log-rank p<0·0001). We recorded no significant associations for mucinous, clear-cell, or low-grade serous carcinoma. Positive hormone-receptor expression (weak or strong staining for PR or ER, or both) was associated with significantly improved disease-specific survival in endometrioid carcinoma compared with negative hormone-receptor expression, independent of study site, age, stage, and grade (hazard ratio 0·33, 95% CI 0·21-0·51; p<0·0001). Strong PR expression was independently associated with improved disease-specific survival in high-grade serous carcinoma (0·71, 0·55-0·91; p=0·0080), but weak PR expression was not (1·02, 0·89-1·18; p=0·74). Interpretation: PR and ER are prognostic biomarkers for endometrioid and high-grade serous ovarian cancers. Clinical trials, stratified by subtype and biomarker status, are needed to establish whether hormone-receptor status predicts response to endocrine treatment, and whether it could guide personalised treatment for ovarian cancer. Funding: Carraresi Foundation and others.
AB - Background: Few biomarkers of ovarian cancer prognosis have been established, partly because subtype-specific associations might be obscured in studies combining all histopathological subtypes. We examined whether tumour expression of the progesterone receptor (PR) and oestrogen receptor (ER) was associated with subtype-specific survival. Methods: 12 studies participating in the Ovarian Tumor Tissue Analysis consortium contributed tissue microarray sections and clinical data to our study. Participants included in our analysis had been diagnosed with invasive serous, mucinous, endometrioid, or clear-cell carcinomas of the ovary. For a patient to be eligible, tissue microarrays, clinical follow-up data, age at diagnosis, and tumour grade and stage had to be available. Clinical data were obtained from medical records, cancer registries, death certificates, pathology reports, and review of histological slides. PR and ER statuses were assessed by central immunohistochemistry analysis done by masked pathologists. PR and ER staining was defined as negative (<1% tumour cell nuclei), weak (1 to <50%), or strong (≥50%). Associations with disease-specific survival were assessed. Findings: 2933 women with invasive epithelial ovarian cancer were included: 1742 with high-grade serous carcinoma, 110 with low-grade serous carcinoma, 207 with mucinous carcinoma, 484 with endometrioid carcinoma, and 390 with clear-cell carcinoma. PR expression was associated with improved disease-specific survival in endometrioid carcinoma (log-rank p<0·0001) and high-grade serous carcinoma (log-rank p=0·0006), and ER expression was associated with improved disease-specific survival in endometrioid carcinoma (log-rank p<0·0001). We recorded no significant associations for mucinous, clear-cell, or low-grade serous carcinoma. Positive hormone-receptor expression (weak or strong staining for PR or ER, or both) was associated with significantly improved disease-specific survival in endometrioid carcinoma compared with negative hormone-receptor expression, independent of study site, age, stage, and grade (hazard ratio 0·33, 95% CI 0·21-0·51; p<0·0001). Strong PR expression was independently associated with improved disease-specific survival in high-grade serous carcinoma (0·71, 0·55-0·91; p=0·0080), but weak PR expression was not (1·02, 0·89-1·18; p=0·74). Interpretation: PR and ER are prognostic biomarkers for endometrioid and high-grade serous ovarian cancers. Clinical trials, stratified by subtype and biomarker status, are needed to establish whether hormone-receptor status predicts response to endocrine treatment, and whether it could guide personalised treatment for ovarian cancer. Funding: Carraresi Foundation and others.
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U2 - 10.1016/S1470-2045(13)70253-5
DO - 10.1016/S1470-2045(13)70253-5
M3 - Article
C2 - 23845225
AN - SCOPUS:84880845489
SN - 1470-2045
VL - 14
SP - 853
EP - 862
JO - The Lancet Oncology
JF - The Lancet Oncology
IS - 9
ER -