Positive response to neoadjuvant cyclophosphamide and doxorubicin in topoisomerase II nonamplified/HER2/neu negative/polysomy 17 absent breast cancer patients
Henry G Kaplan1, Judith A Malmgren2,3, Mary Atwood1, Lynn C Goldstein41Swedish Cancer Institute at Swedish Medical Center, Seattle, Washington, USA; 2HealthStat Consulting Inc., Seattle, Washington, USA; 3School of Public Health and Community Medicine, Department of Epidemiology, University of Washi...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2010-08-01
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| Series: | Cancer Management and Research |
| Online Access: | http://www.dovepress.com/positive-response-to-neoadjuvant-cyclophosphamide-and-doxorubicin-in-t-a5083 |
| _version_ | 1811245389350699008 |
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| author | Henry G Kaplan Judith A Malmgren Mary Atwood et al |
| author_facet | Henry G Kaplan Judith A Malmgren Mary Atwood et al |
| author_sort | Henry G Kaplan |
| collection | DOAJ |
| description | Henry G Kaplan1, Judith A Malmgren2,3, Mary Atwood1, Lynn C Goldstein41Swedish Cancer Institute at Swedish Medical Center, Seattle, Washington, USA; 2HealthStat Consulting Inc., Seattle, Washington, USA; 3School of Public Health and Community Medicine, Department of Epidemiology, University of Washington, Seattle, Washington, USA; 4PhenoPath Laboratories, Seattle, Washington, USAPurpose: Human epidermal growth factor receptor 2 (HER2)/neu, topoisomerase II alpha (TOP2A), and polysomy 17 may predict tumor responsiveness to doxorubicin (DOX) therapy.Methods: We identified neoadjuvant DOX/cyclophosphamide treated breast cancer patients in our registry from 1997 to 2008 with sufficient tissue for testing (n = 34). Fluorescence in situ hybridization (FISH) testing was done on deparaffinized tissue sections pretreated using vendor’s standard protocol modification, and incubated with US Food and Drug Administration approved Abbott Diagnostics Vysis PathVysion™ probe set, including Spectrum-Green-conjugated probe to a-satellite DNA located at the centromere of chromosome 17 (17p11.1–q11.1) and a Spectrum-Orange-conjugated probe to the TOP2A gene. Morphometric analysis was performed using a MetaSystems image analysis system. Manual counting was performed on all samples in which autofluorescence and/or artifact prevented the counting of sufficient numbers of cells. A ratio >2.0 was considered positive for TOP2A amplification. Polysomy 17 (PS17) presence was defined as signals of ≥2.5. Outcomes were pathological complete response (pCR), partial response (PR), and nonresponse (NR).Results: Of 34 patients tested, one was TOP2A amplified (hormone receptor negative/HER2 ­negative, partial responder). The subset of TOP2A nonamplified, HER2 negative, and PS17 absent (n = 23) patients had treatment response: pCR = 2 (9%), PR = 14 (61%), and NR = 7 (30%). Including the two PS17 present and HER2-positive patients (n = 33), 76% of TOP2A nonamplified patients had pCR or PR.Conclusions: We observed substantial treatment response in patients lacking three postulated predictors that would be difficult to attribute to cyclophosphamide alone. Patients who are HER2 negative and lack TOP2A amplification and PS17 should not be excluded from receiving DOX-containing regimens.Keywords: neoadjuvant chemotherapy, response rates, anthracycline therapy |
| first_indexed | 2024-04-12T14:39:14Z |
| format | Article |
| id | doaj.art-c86af2fada3b4d8a88b15e13ed6be130 |
| institution | Directory Open Access Journal |
| issn | 1179-1322 |
| language | English |
| last_indexed | 2024-04-12T14:39:14Z |
| publishDate | 2010-08-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Cancer Management and Research |
| spelling | doaj.art-c86af2fada3b4d8a88b15e13ed6be1302022-12-22T03:28:57ZengDove Medical PressCancer Management and Research1179-13222010-08-012010default213218Positive response to neoadjuvant cyclophosphamide and doxorubicin in topoisomerase II nonamplified/HER2/neu negative/polysomy 17 absent breast cancer patientsHenry G KaplanJudith A MalmgrenMary Atwoodet alHenry G Kaplan1, Judith A Malmgren2,3, Mary Atwood1, Lynn C Goldstein41Swedish Cancer Institute at Swedish Medical Center, Seattle, Washington, USA; 2HealthStat Consulting Inc., Seattle, Washington, USA; 3School of Public Health and Community Medicine, Department of Epidemiology, University of Washington, Seattle, Washington, USA; 4PhenoPath Laboratories, Seattle, Washington, USAPurpose: Human epidermal growth factor receptor 2 (HER2)/neu, topoisomerase II alpha (TOP2A), and polysomy 17 may predict tumor responsiveness to doxorubicin (DOX) therapy.Methods: We identified neoadjuvant DOX/cyclophosphamide treated breast cancer patients in our registry from 1997 to 2008 with sufficient tissue for testing (n = 34). Fluorescence in situ hybridization (FISH) testing was done on deparaffinized tissue sections pretreated using vendor’s standard protocol modification, and incubated with US Food and Drug Administration approved Abbott Diagnostics Vysis PathVysion™ probe set, including Spectrum-Green-conjugated probe to a-satellite DNA located at the centromere of chromosome 17 (17p11.1–q11.1) and a Spectrum-Orange-conjugated probe to the TOP2A gene. Morphometric analysis was performed using a MetaSystems image analysis system. Manual counting was performed on all samples in which autofluorescence and/or artifact prevented the counting of sufficient numbers of cells. A ratio >2.0 was considered positive for TOP2A amplification. Polysomy 17 (PS17) presence was defined as signals of ≥2.5. Outcomes were pathological complete response (pCR), partial response (PR), and nonresponse (NR).Results: Of 34 patients tested, one was TOP2A amplified (hormone receptor negative/HER2 ­negative, partial responder). The subset of TOP2A nonamplified, HER2 negative, and PS17 absent (n = 23) patients had treatment response: pCR = 2 (9%), PR = 14 (61%), and NR = 7 (30%). Including the two PS17 present and HER2-positive patients (n = 33), 76% of TOP2A nonamplified patients had pCR or PR.Conclusions: We observed substantial treatment response in patients lacking three postulated predictors that would be difficult to attribute to cyclophosphamide alone. Patients who are HER2 negative and lack TOP2A amplification and PS17 should not be excluded from receiving DOX-containing regimens.Keywords: neoadjuvant chemotherapy, response rates, anthracycline therapyhttp://www.dovepress.com/positive-response-to-neoadjuvant-cyclophosphamide-and-doxorubicin-in-t-a5083 |
| spellingShingle | Henry G Kaplan Judith A Malmgren Mary Atwood et al Positive response to neoadjuvant cyclophosphamide and doxorubicin in topoisomerase II nonamplified/HER2/neu negative/polysomy 17 absent breast cancer patients Cancer Management and Research |
| title | Positive response to neoadjuvant cyclophosphamide and doxorubicin in topoisomerase II nonamplified/HER2/neu negative/polysomy 17 absent breast cancer patients |
| title_full | Positive response to neoadjuvant cyclophosphamide and doxorubicin in topoisomerase II nonamplified/HER2/neu negative/polysomy 17 absent breast cancer patients |
| title_fullStr | Positive response to neoadjuvant cyclophosphamide and doxorubicin in topoisomerase II nonamplified/HER2/neu negative/polysomy 17 absent breast cancer patients |
| title_full_unstemmed | Positive response to neoadjuvant cyclophosphamide and doxorubicin in topoisomerase II nonamplified/HER2/neu negative/polysomy 17 absent breast cancer patients |
| title_short | Positive response to neoadjuvant cyclophosphamide and doxorubicin in topoisomerase II nonamplified/HER2/neu negative/polysomy 17 absent breast cancer patients |
| title_sort | positive response to neoadjuvant cyclophosphamide and doxorubicin in topoisomerase ii nonamplified her2 neu negative polysomy 17 absent breast cancer patients |
| url | http://www.dovepress.com/positive-response-to-neoadjuvant-cyclophosphamide-and-doxorubicin-in-t-a5083 |
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