Abstract
Background: In estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer, first-generation genomic signatures serve predominately as prognostic biomarkers and secondarily as predictors of response to chemotherapy. We compared both the prognostic and predictive value of histologic grades and genomic markers. Methods: We retrieved publicly available cDNA microarray data from 1373 primary ER+/HER2- breast cancers and developed a genomic signature simulated from Recurrence Online (http://www.recurrenceonline.com/) to calculate the recurrence score and risk using predefined sets of genes in the cDNA microarray. We then compared the prognostic and predictive information provided by histologic grade and genomic signature. Results: Based on genomic signatures, 55%, 28%, and 17% of breast cancers were classified as low, intermediate, and high risk, respectively, whereas the histologic grades were I, II, and III in 22%, 59%, and 19% of breast cancers, respectively. Univariate analysis in the untreated cohort revealed that both histologic grade (overall P = .007) and genomic signature (P <.001) could predict prognosis. Results were similar using the genomic signature, with pathologic complete response rates of 4.6%, 5.7%, and 16.5% for low-, intermediate-, and high-risk cancers, respectively. Neither biomarker was statistically significant in multivariate analysis for predictive response to neoadjuvant chemotherapy (NAC). Conclusion: Genomic signature was better at identifying low-risk cases compared to histologic grade alone, but both markers had similar predictive values for NAC response. Better predictive biomarkers for NAC response are still needed.
| Original language | English |
|---|---|
| Journal | Clinical Breast Cancer |
| DOIs | |
| Publication status | Accepted/In press - Jul 29 2015 |
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Keywords
- Breast cancer
- Chemotherapy response
- Genomic marker
- Grade
- Predictive marker
ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
Relative Prognostic and Predictive Value of Gene Signature and Histologic Grade in Estrogen Receptor-Positive, HER2-Negative Breast Cancer. / Iwamoto, Takayuki; Kelly, Catherine; Mizoo, Taeko; Nogami, Tomohiro; Motoki, Takayuki; Shien, Tadahiko; Taira, Naruto; Hayashi, Naoki; Niikura, Naoki; Fujiwara, Toshiyoshi; Doihara, Hiroyoshi; Matsuoka, Junji.
In: Clinical Breast Cancer, 29.07.2015.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Relative Prognostic and Predictive Value of Gene Signature and Histologic Grade in Estrogen Receptor-Positive, HER2-Negative Breast Cancer
AU - Iwamoto, Takayuki
AU - Kelly, Catherine
AU - Mizoo, Taeko
AU - Nogami, Tomohiro
AU - Motoki, Takayuki
AU - Shien, Tadahiko
AU - Taira, Naruto
AU - Hayashi, Naoki
AU - Niikura, Naoki
AU - Fujiwara, Toshiyoshi
AU - Doihara, Hiroyoshi
AU - Matsuoka, Junji
PY - 2015/7/29
Y1 - 2015/7/29
N2 - Background: In estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer, first-generation genomic signatures serve predominately as prognostic biomarkers and secondarily as predictors of response to chemotherapy. We compared both the prognostic and predictive value of histologic grades and genomic markers. Methods: We retrieved publicly available cDNA microarray data from 1373 primary ER+/HER2- breast cancers and developed a genomic signature simulated from Recurrence Online (http://www.recurrenceonline.com/) to calculate the recurrence score and risk using predefined sets of genes in the cDNA microarray. We then compared the prognostic and predictive information provided by histologic grade and genomic signature. Results: Based on genomic signatures, 55%, 28%, and 17% of breast cancers were classified as low, intermediate, and high risk, respectively, whereas the histologic grades were I, II, and III in 22%, 59%, and 19% of breast cancers, respectively. Univariate analysis in the untreated cohort revealed that both histologic grade (overall P = .007) and genomic signature (P <.001) could predict prognosis. Results were similar using the genomic signature, with pathologic complete response rates of 4.6%, 5.7%, and 16.5% for low-, intermediate-, and high-risk cancers, respectively. Neither biomarker was statistically significant in multivariate analysis for predictive response to neoadjuvant chemotherapy (NAC). Conclusion: Genomic signature was better at identifying low-risk cases compared to histologic grade alone, but both markers had similar predictive values for NAC response. Better predictive biomarkers for NAC response are still needed.
AB - Background: In estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer, first-generation genomic signatures serve predominately as prognostic biomarkers and secondarily as predictors of response to chemotherapy. We compared both the prognostic and predictive value of histologic grades and genomic markers. Methods: We retrieved publicly available cDNA microarray data from 1373 primary ER+/HER2- breast cancers and developed a genomic signature simulated from Recurrence Online (http://www.recurrenceonline.com/) to calculate the recurrence score and risk using predefined sets of genes in the cDNA microarray. We then compared the prognostic and predictive information provided by histologic grade and genomic signature. Results: Based on genomic signatures, 55%, 28%, and 17% of breast cancers were classified as low, intermediate, and high risk, respectively, whereas the histologic grades were I, II, and III in 22%, 59%, and 19% of breast cancers, respectively. Univariate analysis in the untreated cohort revealed that both histologic grade (overall P = .007) and genomic signature (P <.001) could predict prognosis. Results were similar using the genomic signature, with pathologic complete response rates of 4.6%, 5.7%, and 16.5% for low-, intermediate-, and high-risk cancers, respectively. Neither biomarker was statistically significant in multivariate analysis for predictive response to neoadjuvant chemotherapy (NAC). Conclusion: Genomic signature was better at identifying low-risk cases compared to histologic grade alone, but both markers had similar predictive values for NAC response. Better predictive biomarkers for NAC response are still needed.
KW - Breast cancer
KW - Chemotherapy response
KW - Genomic marker
KW - Grade
KW - Predictive marker
UR - http://www.scopus.com/inward/record.url?scp=84949528378&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84949528378&partnerID=8YFLogxK
U2 - 10.1016/j.clbc.2015.10.004
DO - 10.1016/j.clbc.2015.10.004
M3 - Article
C2 - 26631838
AN - SCOPUS:84960250675
JO - Clinical Breast Cancer
JF - Clinical Breast Cancer
SN - 1526-8209
ER -