Correlative studies of the Breast Cancer Index (HOXB13/IL17BR) and ER, PR, AR, AR/ER ratio and Ki67 for prediction of extended endocrine therapy benefit: a Trans-aTTom study
Abstract Background Multiple clinical trials demonstrate consistent but modest benefit of adjuvant extended endocrine therapy (EET) in HR + breast cancer patients. Predictive biomarkers to identify patients that benefit from EET are critical to balance modest reductions in risk against potential sid...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2022-12-01
|
| Series: | Breast Cancer Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13058-022-01589-x |
| _version_ | 1811198486487498752 |
|---|---|
| author | Dennis C. Sgroi Kai Treuner Yi Zhang Tammy Piper Ranelle Salunga Ikhlaaq Ahmed Lucy Doos Sarah Thornber Karen J. Taylor Elena Brachtel Sarah Pirrie Catherine A. Schnabel Daniel Rea John M. S. Bartlett |
| author_facet | Dennis C. Sgroi Kai Treuner Yi Zhang Tammy Piper Ranelle Salunga Ikhlaaq Ahmed Lucy Doos Sarah Thornber Karen J. Taylor Elena Brachtel Sarah Pirrie Catherine A. Schnabel Daniel Rea John M. S. Bartlett |
| author_sort | Dennis C. Sgroi |
| collection | DOAJ |
| description | Abstract Background Multiple clinical trials demonstrate consistent but modest benefit of adjuvant extended endocrine therapy (EET) in HR + breast cancer patients. Predictive biomarkers to identify patients that benefit from EET are critical to balance modest reductions in risk against potential side effects of EET. This study compares the performance of the Breast Cancer Index, BCI (HOXB13/IL17BR, H/I), with expression of estrogen (ER), progesterone (PR), and androgen receptors (AR), and Ki67, for prediction of EET benefit. Methods Node-positive (N+) patients from the Trans-aTTom study with available tissue specimen and BCI results (N = 789) were included. Expression of ER, PR, AR, and Ki67 was assessed by quantitative immunohistochemistry. BCI (H/I) gene expression analysis was conducted by quantitative RT-PCR. Statistical significance of the treatment by biomarker interaction was evaluated by likelihood ratio tests based on multivariate Cox proportional models, adjusting for age, tumor size, grade, and HER2 status. Pearson’s correlation coefficients were calculated to evaluate correlations between BCI (H/I) versus ER, PR, AR, Ki67 and AR/ER ratio. Results EET benefit, measured by the difference in risk of recurrence between patients treated with tamoxifen for 10 versus 5 years, is significantly associated with increasing values of BCI (H/I) (interaction P = 0.01). In contrast, expression of ER (P = 0.83), PR (P = 0.66), AR (P = 0.78), Ki67 (P = 0.87) and AR/ER ratio (P = 0.84) exhibited no significant relationship with EET benefit. BCI (H/I) showed a very weak negative correlation with ER (r = − 0.18), PR (r = − 0.25), and AR (r = − 0.14) expression, but no correlation with either Ki67 (r = 0.04) or AR/ER ratio (r = 0.02). Conclusion These findings are consistent with the growing body of evidence that BCI (H/I) is significantly predictive of response to EET and outcome. Results from this direct comparison demonstrate that expression of ER, PR, AR, Ki67 or AR/ER ratio are not predictive of benefit from EET. BCI (H/I) is the only clinically validated biomarker that predicts EET benefit. |
| first_indexed | 2024-04-12T01:32:33Z |
| format | Article |
| id | doaj.art-f73219a1ffd7495699a8f9ef0b2330f6 |
| institution | Directory Open Access Journal |
| issn | 1465-542X |
| language | English |
| last_indexed | 2024-04-12T01:32:33Z |
| publishDate | 2022-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Breast Cancer Research |
| spelling | doaj.art-f73219a1ffd7495699a8f9ef0b2330f62022-12-22T03:53:27ZengBMCBreast Cancer Research1465-542X2022-12-0124111010.1186/s13058-022-01589-xCorrelative studies of the Breast Cancer Index (HOXB13/IL17BR) and ER, PR, AR, AR/ER ratio and Ki67 for prediction of extended endocrine therapy benefit: a Trans-aTTom studyDennis C. Sgroi0Kai Treuner1Yi Zhang2Tammy Piper3Ranelle Salunga4Ikhlaaq Ahmed5Lucy Doos6Sarah Thornber7Karen J. Taylor8Elena Brachtel9Sarah Pirrie10Catherine A. Schnabel11Daniel Rea12John M. S. Bartlett13Molecular Pathology Research Unit, Department of Pathology, Harvard Medical School, Massachusetts General Hospital EastBiotheranostics, A Hologic CompanyBiotheranostics, A Hologic CompanyUniversity of EdinburghBiotheranostics, A Hologic CompanyCancer Research UK Clinical Trials Unit, University of BirminghamCancer Research UK Clinical Trials Unit, University of BirminghamCancer Research UK Clinical Trials Unit, University of BirminghamUniversity of EdinburghMolecular Pathology Research Unit, Department of Pathology, Harvard Medical School, Massachusetts General Hospital EastCancer Research UK Clinical Trials Unit, University of BirminghamBiotheranostics, A Hologic CompanyCancer Research UK Clinical Trials Unit, University of BirminghamUniversity of EdinburghAbstract Background Multiple clinical trials demonstrate consistent but modest benefit of adjuvant extended endocrine therapy (EET) in HR + breast cancer patients. Predictive biomarkers to identify patients that benefit from EET are critical to balance modest reductions in risk against potential side effects of EET. This study compares the performance of the Breast Cancer Index, BCI (HOXB13/IL17BR, H/I), with expression of estrogen (ER), progesterone (PR), and androgen receptors (AR), and Ki67, for prediction of EET benefit. Methods Node-positive (N+) patients from the Trans-aTTom study with available tissue specimen and BCI results (N = 789) were included. Expression of ER, PR, AR, and Ki67 was assessed by quantitative immunohistochemistry. BCI (H/I) gene expression analysis was conducted by quantitative RT-PCR. Statistical significance of the treatment by biomarker interaction was evaluated by likelihood ratio tests based on multivariate Cox proportional models, adjusting for age, tumor size, grade, and HER2 status. Pearson’s correlation coefficients were calculated to evaluate correlations between BCI (H/I) versus ER, PR, AR, Ki67 and AR/ER ratio. Results EET benefit, measured by the difference in risk of recurrence between patients treated with tamoxifen for 10 versus 5 years, is significantly associated with increasing values of BCI (H/I) (interaction P = 0.01). In contrast, expression of ER (P = 0.83), PR (P = 0.66), AR (P = 0.78), Ki67 (P = 0.87) and AR/ER ratio (P = 0.84) exhibited no significant relationship with EET benefit. BCI (H/I) showed a very weak negative correlation with ER (r = − 0.18), PR (r = − 0.25), and AR (r = − 0.14) expression, but no correlation with either Ki67 (r = 0.04) or AR/ER ratio (r = 0.02). Conclusion These findings are consistent with the growing body of evidence that BCI (H/I) is significantly predictive of response to EET and outcome. Results from this direct comparison demonstrate that expression of ER, PR, AR, Ki67 or AR/ER ratio are not predictive of benefit from EET. BCI (H/I) is the only clinically validated biomarker that predicts EET benefit.https://doi.org/10.1186/s13058-022-01589-xBreast Cancer IndexBCI (H/I)Breast cancerPredictive biomarkerExtended endocrine therapy |
| spellingShingle | Dennis C. Sgroi Kai Treuner Yi Zhang Tammy Piper Ranelle Salunga Ikhlaaq Ahmed Lucy Doos Sarah Thornber Karen J. Taylor Elena Brachtel Sarah Pirrie Catherine A. Schnabel Daniel Rea John M. S. Bartlett Correlative studies of the Breast Cancer Index (HOXB13/IL17BR) and ER, PR, AR, AR/ER ratio and Ki67 for prediction of extended endocrine therapy benefit: a Trans-aTTom study Breast Cancer Research Breast Cancer Index BCI (H/I) Breast cancer Predictive biomarker Extended endocrine therapy |
| title | Correlative studies of the Breast Cancer Index (HOXB13/IL17BR) and ER, PR, AR, AR/ER ratio and Ki67 for prediction of extended endocrine therapy benefit: a Trans-aTTom study |
| title_full | Correlative studies of the Breast Cancer Index (HOXB13/IL17BR) and ER, PR, AR, AR/ER ratio and Ki67 for prediction of extended endocrine therapy benefit: a Trans-aTTom study |
| title_fullStr | Correlative studies of the Breast Cancer Index (HOXB13/IL17BR) and ER, PR, AR, AR/ER ratio and Ki67 for prediction of extended endocrine therapy benefit: a Trans-aTTom study |
| title_full_unstemmed | Correlative studies of the Breast Cancer Index (HOXB13/IL17BR) and ER, PR, AR, AR/ER ratio and Ki67 for prediction of extended endocrine therapy benefit: a Trans-aTTom study |
| title_short | Correlative studies of the Breast Cancer Index (HOXB13/IL17BR) and ER, PR, AR, AR/ER ratio and Ki67 for prediction of extended endocrine therapy benefit: a Trans-aTTom study |
| title_sort | correlative studies of the breast cancer index hoxb13 il17br and er pr ar ar er ratio and ki67 for prediction of extended endocrine therapy benefit a trans attom study |
| topic | Breast Cancer Index BCI (H/I) Breast cancer Predictive biomarker Extended endocrine therapy |
| url | https://doi.org/10.1186/s13058-022-01589-x |
| work_keys_str_mv | AT denniscsgroi correlativestudiesofthebreastcancerindexhoxb13il17branderprararerratioandki67forpredictionofextendedendocrinetherapybenefitatransattomstudy AT kaitreuner correlativestudiesofthebreastcancerindexhoxb13il17branderprararerratioandki67forpredictionofextendedendocrinetherapybenefitatransattomstudy AT yizhang correlativestudiesofthebreastcancerindexhoxb13il17branderprararerratioandki67forpredictionofextendedendocrinetherapybenefitatransattomstudy AT tammypiper correlativestudiesofthebreastcancerindexhoxb13il17branderprararerratioandki67forpredictionofextendedendocrinetherapybenefitatransattomstudy AT ranellesalunga correlativestudiesofthebreastcancerindexhoxb13il17branderprararerratioandki67forpredictionofextendedendocrinetherapybenefitatransattomstudy AT ikhlaaqahmed correlativestudiesofthebreastcancerindexhoxb13il17branderprararerratioandki67forpredictionofextendedendocrinetherapybenefitatransattomstudy AT lucydoos correlativestudiesofthebreastcancerindexhoxb13il17branderprararerratioandki67forpredictionofextendedendocrinetherapybenefitatransattomstudy AT sarahthornber correlativestudiesofthebreastcancerindexhoxb13il17branderprararerratioandki67forpredictionofextendedendocrinetherapybenefitatransattomstudy AT karenjtaylor correlativestudiesofthebreastcancerindexhoxb13il17branderprararerratioandki67forpredictionofextendedendocrinetherapybenefitatransattomstudy AT elenabrachtel correlativestudiesofthebreastcancerindexhoxb13il17branderprararerratioandki67forpredictionofextendedendocrinetherapybenefitatransattomstudy AT sarahpirrie correlativestudiesofthebreastcancerindexhoxb13il17branderprararerratioandki67forpredictionofextendedendocrinetherapybenefitatransattomstudy AT catherineaschnabel correlativestudiesofthebreastcancerindexhoxb13il17branderprararerratioandki67forpredictionofextendedendocrinetherapybenefitatransattomstudy AT danielrea correlativestudiesofthebreastcancerindexhoxb13il17branderprararerratioandki67forpredictionofextendedendocrinetherapybenefitatransattomstudy AT johnmsbartlett correlativestudiesofthebreastcancerindexhoxb13il17branderprararerratioandki67forpredictionofextendedendocrinetherapybenefitatransattomstudy |