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Intratumor Heterogeneity of the Estrogen Receptor and the Long-term Risk of Fatal Breast Cancer
Karolinska Inst, Sweden.
Univ Calif San Francisco, CA USA; Buck Inst Res Aging, CA USA.
Karolinska Inst, Sweden.
Univ Calif San Francisco, CA USA.
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2018 (English)In: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 110, no 7, p. 726-733, article id djx270Article in journal (Refereed) Published
Abstract [en]

Background: Breast cancer patients with estrogen receptor (ER)-positive disease have a continuous long-term risk for fatal breast cancer, but the biological factors influencing this risk are unknown. We aimed to determine whether high intratumor heterogeneity of ER predicts an increased long-term risk (25 years) of fatal breast cancer. Methods: The STO-3 trial enrolled 1780 postmenopausal lymph node-negative breast cancer patients randomly assigned to receive adjuvant tamoxifen vs not. The fraction of cancer cells for each ER intensity level was scored by breast cancer pathologists, and intratumor heterogeneity of ER was calculated using Raos quadratic entropy and categorized into high and low heterogeneity using a predefined cutoff at the second tertile (67%). Long-term breast cancer-specific survival analyses by intra-tumor heterogeneity of ER were performed using Kaplan-Meier and multivariable Cox proportional hazard modeling adjusting for patient and tumor characteristics. Results: A statistically significant difference in long-term survival by high vs low intratumor heterogeneity of ER was seen for all ER-positive patients (P amp;lt; .001) and for patients with luminal A subtype tumors (P = .01). In multivariable analyses, patients with high intratumor heterogeneity of ER had a twofold increased long-term risk as compared with patients with low intratumor heterogeneity (ER-positive: hazard ratio (HR] = 1.98, 95% confidence interval (CI] = 1.31 to 3.00; luminal A subtype tumors: HR = 2.43, 95% CI -1.18 to 4.99). Conclusions: Patients with high intratumor heterogeneity of ER had an increased long-term risk of fatal breast cancer. Interestingly, a similar long-term risk increase was seen in patients with luminal A subtype tumors. Our findings suggest that intratumor heterogeneity of ER is an independent long-term prognosticator with potential to change clinical management, especially for patients with luminal A tumors.

Place, publisher, year, edition, pages
OXFORD UNIV PRESS INC , 2018. Vol. 110, no 7, p. 726-733, article id djx270
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:liu:diva-151805DOI: 10.1093/jnci/djx270ISI: 000445380200009PubMedID: 29361175OAI: oai:DiVA.org:liu-151805DiVA, id: diva2:1253268
Note

Funding Agencies|Swedish Research Council [521-2014-2057, 2014-2271]; FORTE [2014-1962, 2016-00081]; Swedish Cancer Society [CAN2016/684]; Stiftelsen Gosta Miltons Donationsfond (The Gosta Milton Donation Fund); California Breast Cancer Research Program BCRP award [180B-0065]; Cancerforeningen i Stockholm (Stockholm Cancer Society)

Available from: 2018-10-04 Created: 2018-10-04 Last updated: 2018-10-04

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Nordenskjöld, BoStål, Olle
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Division of Surgery, Orthopedics and OncologyFaculty of Medicine and Health SciencesDepartment of Oncology
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