Changes in Gene Expression Associated With Response to Neoadjuvant Chemotherapy in Breast Cancer

Hannemann, Juliane; Oosterkamp, Hendrika M.; Bosch, C.; Velds, Arno; Wessels, Lodewyk; Loo, C.; Rutgers, Emiel J. T.; Rodenhuis, S.; Vijver, Marc J. van de

doi:10.1200/jco.2005.09.077

Cited by 154 publications

(106 citation statements)

References 26 publications

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“…Besides this, there is no delay of administration of chemotherapy and there is no need of two surgical procedures [27]. [28,29]. However, these profiles are not validated for clinical practice.…”

Section: Discussionmentioning

confidence: 99%

Preoperative chemotherapy is safe in early breast cancer, even after 10 years of follow-up; clinical and translational results from the EORTC trial 10902

Nes

Putter

Julien³

et al. 2008

Breast Cancer Res Treat

102

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International audienceThe Preoperative Chemotherapy in Primary Operable Breast Cancer (POCOB) study was designed to compare preoperative with postoperative chemotherapy in patients with early breast cancer concerning breast conserving therapy (BCT) procedures, disease free survival (DFS) and overall survival (OS). Patients ( = 698) with early breast cancer were enrolled between 1991 and 1999 and randomized between preoperative versus postoperative chemotherapy (four cycles of fluorouracil, epirubicin, and cyclophosphamide). Endpoints were BCT procedures, DFS, OS, and tumor response to preoperative chemotherapy. In addition, tumor tissue was collected for translational research and the following markers were examined: ER, PgR, HER2, p21, p53, and bcl-2 expression. With a median follow-up of 10 years, there was no statistically significant difference between the two treatment arms for OS (HR = 1.09; 95%CI 0.83–1.42; = 0.54), DFS (HR = 1.12; 95%CI 0.90–1.39; = 0.30), or locoregional recurrences (LRR, HR = 1.16; 95%CI 0.77–1.74). Preoperative chemotherapy was associated with an increase in BCT rates. BCT in part feasible due to tumor downsizing after preoperative chemotherapy was not correlated with higher LRR or worse OS compared to BCT which was feasible without downsizing of the tumor. Using available tumor material, only tumor stage, nodal stage, and grade were independent prognostic factors for overall survival. Preoperative chemotherapy does not result in a difference in OS or DFS compared to postoperative chemotherapy in patients with early breast cancer. Moreover, it increases BCT rates with no significant increase of LRR. This implies that preoperative chemotherapy is a safe procedure for patients with early breast cancer, even after a follow-up period of 10 years

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Section: Discussionmentioning

confidence: 99%

Preoperative chemotherapy is safe in early breast cancer, even after 10 years of follow-up; clinical and translational results from the EORTC trial 10902

Nes

Putter

Julien³

et al. 2008

Breast Cancer Res Treat

102

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“…Gene 'signatures' or predictors have been devised for several chemotherapy regimens, including paclitaxel followed by fluorouracil, AC, AC/doxorubicindocetaxel and taxane only chemotherapy (Chang et al, 2003(Chang et al, , 2005bAyers et al, 2004;Hannemann et al, 2005;Cleator et al, 2006). Although these results are promising, the exceedingly small sample size and limitations with the current technology and analysis methods have so far precluded definitive conclusions (Brenton et al, 2005;Reis-Filho et al, 2006b).…”

Section: Discussionmentioning

confidence: 99%

“…The use of expression arrays to derive molecular profiles that are predictive of clinical outcome has received great attention in the last 5 years (van't Veer et al, 2005;Reis-Filho et al, 2006b), especially in the neoadjuvant setting (Davidson and Morrow, 2005). Predictive signatures for different neoadjuvant chemotherapy regimens have been reported by some investigators but with less success by others (Chang et al, 2003;Ayers et al, 2004;Cleator and Ashworth, 2004;Chang et al, 2005a;Hannemann et al, 2005;Iwao-Koizumi et al, 2005;Modlich et al, 2005;Rouzier et al, 2005;Dressman et al, 2006;Reis-Filho et al, 2006b). Although some of these results are promising, issues related to the instability of mRNA, experimental design and data analysis have led many to call into question the validity of current approaches (Ransohoff, 2004;Brenton et al, 2005;Ioannidis, 2005;Reis-Filho et al, 2006b).…”

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confidence: 99%

Microarray-based comparative genomic hybridisation of breast cancer patients receiving neoadjuvant chemotherapy

et al. 2006

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We analysed the molecular genetic profiles of breast cancer samples before and after neoadjuvant chemotherapy with combination doxorubicin and cyclophosphamide (AC). DNA was obtained from microdissected frozen breast core biopsies from 44 patients before chemotherapy. Additional samples were obtained before the second course of chemotherapy (D21) and after the completion of the treatment (surgical specimens) in 17 and 21 patients, respectively. Microarray-based comparative genome hybridisation was performed using a platform containing B5800 bacterial artificial chromosome clones (genome-wide resolution: 0.9 Mb). Analysis of the 44 pretreatment biopsies revealed that losses of 4p, 4q, 5q, 12q13.11 -12q13.12, 17p11.2 and 17q11.2; and gains of 1p, 2p, 7q, 9p, 11q, 19p and 19q were significantly associated with oestrogen receptor negativity. 16q21 -q22.1 losses were associated with lobular and 8q24 gains with ductal types. Losses of 5q33.3 -q4 and 18p11.31 and gains of 6p25.1 -p25.2 and Xp11.4 were associated with HER2 amplification. No correlations between DNA copy number changes and clinical response to AC were found. Microarray-based comparative genome hybridisation analysis of matched pretreatment and D21 biopsies failed to identify statistically significant differences, whereas a comparison between matched pretreatment and surgical samples revealed a statistically significant acquired copy number gain on 11p15.2 -11p15.5. The modest chemotherapy-driven genomic changes, despite profound loss of cell numbers, suggest that there is little therapeutic selection of resistant non-modal cell lineages.

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“…Patients received neoadjuvant chemotherapy in one of two clinical studies ongoing or received treatment according to the standard arm of these trials [8]. Patients with invasive breast cancer greater than 3 cm and/or involved lymph nodes were eligible for these studies.…”

Section: Patientsmentioning

confidence: 99%

The 70-gene signature as a response predictor for neoadjuvant chemotherapy in breast cancer

Straver

Glas

Hannemann

et al. 2009

Breast Cancer Res Treat

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226

118

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Changes in Gene Expression Associated With Response to Neoadjuvant Chemotherapy in Breast Cancer

Cited by 154 publications

References 26 publications

Preoperative chemotherapy is safe in early breast cancer, even after 10 years of follow-up; clinical and translational results from the EORTC trial 10902

Preoperative chemotherapy is safe in early breast cancer, even after 10 years of follow-up; clinical and translational results from the EORTC trial 10902

Microarray-based comparative genomic hybridisation of breast cancer patients receiving neoadjuvant chemotherapy

The 70-gene signature as a response predictor for neoadjuvant chemotherapy in breast cancer

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