Association between HER2, TOP2A, and response to anthracycline-based preoperative chemotherapy in high-risk primary breast cancer.
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Association between HER2, TOP2A, and response to anthracycline-based preoperative chemotherapy in high-risk primary breast cancer. / Konecny, Gottfried E; Pauletti, Giovanni; Untch, Michael; Wang, He-Jing; Möbus, Volker; Kuhn, Walther; Thomssen, Christoph; Harbeck, Nadia; Wang, Ling; Apple, Sophia; Jänicke, Fritz; Slamon, Dennis J.
in: BREAST CANCER RES TR, Jahrgang 120, Nr. 2, 2, 2010, S. 481-489.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Association between HER2, TOP2A, and response to anthracycline-based preoperative chemotherapy in high-risk primary breast cancer.
AU - Konecny, Gottfried E
AU - Pauletti, Giovanni
AU - Untch, Michael
AU - Wang, He-Jing
AU - Möbus, Volker
AU - Kuhn, Walther
AU - Thomssen, Christoph
AU - Harbeck, Nadia
AU - Wang, Ling
AU - Apple, Sophia
AU - Jänicke, Fritz
AU - Slamon, Dennis J
PY - 2010
Y1 - 2010
N2 - In breast cancer, recent studies suggest that the value of HER2 for predicting response to anthracycline-based chemotherapy may be more likely related to the concomitant amplification of the TOP2A gene. Here, we study the association between HER2 or TOP2A status and response to anthracycline-based preoperative chemotherapy and explore the interaction between HER2 or TOP2A status and intense dose-dense (IDD) chemotherapy. HER2 and TOP2A gene alterations were quantified by fluorescence in situ hybridization in primary tumor core biopsies from 373 high-risk primary breast cancer patients (tumors >/=3 cm or inflammatory) that received an IDD or conventionally scheduled anthracycline-based preoperative chemotherapy. HER2 was amplified in 94/350 tumors (27%) of which 40/94 (46%) demonstrated TOP2A amplification, and 17/94 (18%) TOP2A deletions. TOP2A gene alterations were not found in HER2 non-amplified cases. HER2 amplification was associated with a significantly higher pathologic complete response (pCR) rate only when TOP2A was co-amplified (30% vs. 11%, P = 0.002), but not when deleted (13% vs. 11%, P = 0.755), or normal (14% vs. 11%, P = 0.578) compared to HER2 non-amplified tumors. In multivariate analysis, TOP2A amplification (odds ratio [OR] 3.04, P = 0.021), but not HER2 amplification (OR 1.74, P = 0.170) was associated with a significantly higher pCR rate. No interaction was observed between HER2 or TOP2A status and IDD chemotherapy. TOP2A gene amplification may define a subset of HER2-amplified breast cancers that are responsible for the markedly improved chemosensitivity seen in HER2-positive breast cancer. However, added benefit of IDD chemotherapy itself was not associated with HER2 or TOP2A status.
AB - In breast cancer, recent studies suggest that the value of HER2 for predicting response to anthracycline-based chemotherapy may be more likely related to the concomitant amplification of the TOP2A gene. Here, we study the association between HER2 or TOP2A status and response to anthracycline-based preoperative chemotherapy and explore the interaction between HER2 or TOP2A status and intense dose-dense (IDD) chemotherapy. HER2 and TOP2A gene alterations were quantified by fluorescence in situ hybridization in primary tumor core biopsies from 373 high-risk primary breast cancer patients (tumors >/=3 cm or inflammatory) that received an IDD or conventionally scheduled anthracycline-based preoperative chemotherapy. HER2 was amplified in 94/350 tumors (27%) of which 40/94 (46%) demonstrated TOP2A amplification, and 17/94 (18%) TOP2A deletions. TOP2A gene alterations were not found in HER2 non-amplified cases. HER2 amplification was associated with a significantly higher pathologic complete response (pCR) rate only when TOP2A was co-amplified (30% vs. 11%, P = 0.002), but not when deleted (13% vs. 11%, P = 0.755), or normal (14% vs. 11%, P = 0.578) compared to HER2 non-amplified tumors. In multivariate analysis, TOP2A amplification (odds ratio [OR] 3.04, P = 0.021), but not HER2 amplification (OR 1.74, P = 0.170) was associated with a significantly higher pCR rate. No interaction was observed between HER2 or TOP2A status and IDD chemotherapy. TOP2A gene amplification may define a subset of HER2-amplified breast cancers that are responsible for the markedly improved chemosensitivity seen in HER2-positive breast cancer. However, added benefit of IDD chemotherapy itself was not associated with HER2 or TOP2A status.
KW - Humans
KW - Female
KW - Disease-Free Survival
KW - Antineoplastic Agents therapeutic use
KW - Neoadjuvant Therapy
KW - Kaplan-Meier Estimate
KW - Gene Amplification
KW - In Situ Hybridization, Fluorescence
KW - Anthracyclines therapeutic use
KW - Antigens, Neoplasm genetics
KW - Breast Neoplasms drug therapy
KW - DNA Topoisomerases, Type II genetics
KW - DNA-Binding Proteins genetics
KW - Drug Resistance, Neoplasm genetics
KW - Receptor, erbB-2 genetics
KW - Humans
KW - Female
KW - Disease-Free Survival
KW - Antineoplastic Agents therapeutic use
KW - Neoadjuvant Therapy
KW - Kaplan-Meier Estimate
KW - Gene Amplification
KW - In Situ Hybridization, Fluorescence
KW - Anthracyclines therapeutic use
KW - Antigens, Neoplasm genetics
KW - Breast Neoplasms drug therapy
KW - DNA Topoisomerases, Type II genetics
KW - DNA-Binding Proteins genetics
KW - Drug Resistance, Neoplasm genetics
KW - Receptor, erbB-2 genetics
M3 - SCORING: Zeitschriftenaufsatz
VL - 120
SP - 481
EP - 489
JO - BREAST CANCER RES TR
JF - BREAST CANCER RES TR
SN - 0167-6806
IS - 2
M1 - 2
ER -
