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Prognostic utility of HOXB13:IL17BR and Molecular Grade Index in early-stage breast cancer patients from the Stockholm trial
Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences.
bioTheranostics, San Diego, CA, USA.
bioTheranostics, San Diego, CA, USA.
Massachusetts General Hospital, USA.
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2011 (English)In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 104, no 11, 1762-1769 p.Article in journal (Refereed) Published
Abstract [en]

Background: A dichotomous index combining two gene expression assays, HOXB13:IL17BR (H:I) and molecular grade index (MGI), was developed to assess risk of recurrence in breast cancer patients. The study objective was to demonstrate the prognostic utility of the combined index in early-stage breast cancer.

Methods: In a blinded retrospective analysis of 588 ER-positive tamoxifen-treated and untreated breast cancer patients from the randomized prospective Stockholm trial, H:I and MGI were measured using real-time RT-PCR. Association with patient outcome was evaluated by Kaplan-Meier analysis and Cox proportional hazard regression. A continuous risk index was developed using Cox modeling.

Results: The dichotomous H:I+MGI was significantly associated with distant recurrence and breast cancer death. The >50% of tamoxifen-treated patients categorized as low-risk had <3% 10-year distant recurrence risk. A continuous risk model (Breast Cancer Index (BCI)) was developed with the tamoxifen-treated group and the prognostic performance tested in the untreated group was 53% of patients categorized as low-risk with an 8.3% 10-year distant recurrence risk.

Conclusion: Retrospective analysis of this randomized, prospective trial cohort validated the prognostic utility of H:I+MGI and was used to develop and test a continuous risk model that enables prediction of distant recurrence risk at the patient level.

Place, publisher, year, edition, pages
Nature Publishing Group , 2011. Vol. 104, no 11, 1762-1769 p.
Keyword [en]
Breast Cancer Index, recurrence, risk assessment, gene expression profiling, prognosis
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-68122DOI: 10.1038/bjc.2011.145ISI: 000290953200016OAI: diva2:416457
32nd Annual CTRC-AACR San Antonio Breast Cancer Symposium. December 10, San Diego
Original Publication: Piiha-Lotta Jerevall, Xiai-Jun Ma, Hongying Li, Ranelle Salunga, Nicole C. Kesty, Mark G. Erlander, Dennis Sgroi, Birgitta Holmlund, Lambert Skoog, Tommy Fornander, Bo Nordenskjöld and Olle Stål, Prognostic utility of HOXB13:IL17BR and Molecular Grade Index in early-stage breast cancer patients from the Stockholm trial, 2011, British Journal of Cancer, (104), 11, 1762-1769. Copyright: Nature Publishing Group Available from: 2011-05-11 Created: 2011-05-11 Last updated: 2012-01-17Bibliographically approved
In thesis
1. Homeobox B13 in breast cancer: Prediction of tamoxifen benefit
Open this publication in new window or tab >>Homeobox B13 in breast cancer: Prediction of tamoxifen benefit
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

A major issue in the management of breast cancer is to identify patients who are less likely to be cured after primary treatment and would benefit from adjuvant chemotherapy. Of great importance is also identification of patients with only local disease who traditionally would be given chemotherapy but would survive without. In this thesis we have validated the utility of the two-gene ratio HOXB13:IL17BR, which previously has been demonstrated to predict disease-free survival in tamoxifen-treated breast cancer patients. We have also studied the prognostic and predictive utility of a single gene as a biomarker in breast cancer medicine.

We could confirm that HOXB13:IL17BR may classify patients with different treatment benefit; only patients with a low value showed benefit from prolonged duration of tamoxifen therapy, whereas for the group with high ratios, the long-term recurrence rate did not improve with longer treatment duration.

The combination of HOXB13:IL17BR and the molecular grade index (MGI), another prognostic marker, has been shown to outperform either alone in predicting risk of breast cancer recurrence. We validated the prognostic utility of HOXB13:IL17BR+MGI in a large randomized patient cohort and found that this risk classification identified more than 50% of the tamoxifen-treated lymph node-negative patients as having a less than 3% risk of distant recurrence and breast cancer death. Furthermore, we developed and tested a continuous risk model of HOXB13:IL17BR+MGI called Breast Cancer Index (BCI), for estimation of recurrence risk at the individual level. Our study shows that BCI has the ability to identify more than 50% of patients with a low risk of recurrence more accurately than using traditional risk assessment. These results suggest that BCI may help clinicians to make better informed treatment decisions and spare toxic chemotherapy for a large group of breast cancer patients.

The protein expression of HOXB13 was also shown to be a valuable predictor in postmenopausal patients. High expression was associated with worse outcome after tamoxifen therapy. In a premenopausal cohort, patients with hormone receptor-positive tumors showed benefit from tamoxifen regardless of HOXB13 expression. Further analysis indicated that estrogen receptor β (ERβ) modified the performance of HOXB13 as a predictor of treatment effect and should be taken into account when identifying patients less likely to respond to the therapy given.

In conclusion, BCI identifies patients with a very low risk of distant recurrence. It may be utilized in the management of breast cancer patients to optimize the use of chemotherapy. HOXB13 protein expression may be used as a marker for tamoxifen benefit, but its performance in premenopausal patients might be modified by ERβ.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2011. 69 p.
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1243
National Category
Medical and Health Sciences
urn:nbn:se:liu:diva-68137 (URN)978-91-7393-184-7 (ISBN)
Public defence
2011-06-01, Berzeliussalen, Hälsouniversitetet, Campus US, Linköpings universitet, Linköping, 13:00 (Swedish)
Available from: 2011-05-12 Created: 2011-05-12 Last updated: 2011-05-12Bibliographically approved

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