Predicting response to primary chemotherapy

Gene expression profiling of paraffin-embedded core biopsy tissue

Lida Mina, Sharon E. Soule, Sunil Badve, Fredrick L. Baehner, Joffre Baker, Maureen Cronin, Drew Watson, Mei Lan Liu, George W. Sledge, Steve Shak, Kathy Miller

Research output: Contribution to journalArticle

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Abstract

Purpose: Primary chemotherapy provides an ideal opportunity to correlate gene expression with response to treatment. We used paraffin-embedded core biopsies from a completed phase II trial to identify genes that correlate with response to primary chemotherapy. Patients and Methods: Patients with newly diagnosed stage II or III breast cancer were treated with sequential doxorubicin 75 mg/M2 q2 wks × 3 and docetaxel 40 mg/M2 weekly × 6; treatment order was randomly assigned. Pretreatment core biopsy samples were interrogated for genes that might correlate with pathologic complete response (pCR). In addition to the individual genes, the correlation of the Oncotype DX Recurrence Score with pCR was examined. Results: Of 70 patients enrolled in the parent trial, core biopsies samples with sufficient RNA for gene analyses were available from 45 patients; 9 (20%) had inflammatory breast cancer (IBC). Six (14%) patients achieved a pCR. Twenty-two of the 274 candidate genes assessed correlated with pCR (p < 0.05). Genes correlating with pCR could be grouped into three large clusters: angiogenesis-related genes, proliferation related genes, and invasion-related genes. Expression of estrogen receptor (ER)-related genes and Recurrence Score did not correlate with pCR. In an exploratory analysis we compared gene expression in IBC to non-inflammatory breast cancer; twenty-four (9%) of the genes were differentially expressed (p < 0.05), 5 were upregulated and 19 were downregulated in IBC. Conclusion: Gene expression analysis on core biopsy samples is feasible and identifies candidate genes that correlate with pCR to primary chemotherapy. Gene expression in IBC differs significantly from noninflammatory breast cancer.

Original languageEnglish
Pages (from-to)197-208
Number of pages12
JournalBreast Cancer Research and Treatment
Volume103
Issue number2
DOIs
StatePublished - Jun 2007

Fingerprint

Gene Expression Profiling
Paraffin
Biopsy
Drug Therapy
Inflammatory Breast Neoplasms
Genes
Gene Expression
docetaxel
Breast Neoplasms
Recurrence
Estrogen Receptors
Doxorubicin
Down-Regulation
RNA

Keywords

  • Angiogenesis
  • Inflammatory breast cancer
  • Invasion
  • Proliferation

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Predicting response to primary chemotherapy : Gene expression profiling of paraffin-embedded core biopsy tissue. / Mina, Lida; Soule, Sharon E.; Badve, Sunil; Baehner, Fredrick L.; Baker, Joffre; Cronin, Maureen; Watson, Drew; Liu, Mei Lan; Sledge, George W.; Shak, Steve; Miller, Kathy.

In: Breast Cancer Research and Treatment, Vol. 103, No. 2, 06.2007, p. 197-208.

Research output: Contribution to journalArticle

Mina, Lida ; Soule, Sharon E. ; Badve, Sunil ; Baehner, Fredrick L. ; Baker, Joffre ; Cronin, Maureen ; Watson, Drew ; Liu, Mei Lan ; Sledge, George W. ; Shak, Steve ; Miller, Kathy. / Predicting response to primary chemotherapy : Gene expression profiling of paraffin-embedded core biopsy tissue. In: Breast Cancer Research and Treatment. 2007 ; Vol. 103, No. 2. pp. 197-208.
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abstract = "Purpose: Primary chemotherapy provides an ideal opportunity to correlate gene expression with response to treatment. We used paraffin-embedded core biopsies from a completed phase II trial to identify genes that correlate with response to primary chemotherapy. Patients and Methods: Patients with newly diagnosed stage II or III breast cancer were treated with sequential doxorubicin 75 mg/M2 q2 wks × 3 and docetaxel 40 mg/M2 weekly × 6; treatment order was randomly assigned. Pretreatment core biopsy samples were interrogated for genes that might correlate with pathologic complete response (pCR). In addition to the individual genes, the correlation of the Oncotype DX Recurrence Score with pCR was examined. Results: Of 70 patients enrolled in the parent trial, core biopsies samples with sufficient RNA for gene analyses were available from 45 patients; 9 (20{\%}) had inflammatory breast cancer (IBC). Six (14{\%}) patients achieved a pCR. Twenty-two of the 274 candidate genes assessed correlated with pCR (p < 0.05). Genes correlating with pCR could be grouped into three large clusters: angiogenesis-related genes, proliferation related genes, and invasion-related genes. Expression of estrogen receptor (ER)-related genes and Recurrence Score did not correlate with pCR. In an exploratory analysis we compared gene expression in IBC to non-inflammatory breast cancer; twenty-four (9{\%}) of the genes were differentially expressed (p < 0.05), 5 were upregulated and 19 were downregulated in IBC. Conclusion: Gene expression analysis on core biopsy samples is feasible and identifies candidate genes that correlate with pCR to primary chemotherapy. Gene expression in IBC differs significantly from noninflammatory breast cancer.",
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AU - Baker, Joffre

AU - Cronin, Maureen

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N2 - Purpose: Primary chemotherapy provides an ideal opportunity to correlate gene expression with response to treatment. We used paraffin-embedded core biopsies from a completed phase II trial to identify genes that correlate with response to primary chemotherapy. Patients and Methods: Patients with newly diagnosed stage II or III breast cancer were treated with sequential doxorubicin 75 mg/M2 q2 wks × 3 and docetaxel 40 mg/M2 weekly × 6; treatment order was randomly assigned. Pretreatment core biopsy samples were interrogated for genes that might correlate with pathologic complete response (pCR). In addition to the individual genes, the correlation of the Oncotype DX Recurrence Score with pCR was examined. Results: Of 70 patients enrolled in the parent trial, core biopsies samples with sufficient RNA for gene analyses were available from 45 patients; 9 (20%) had inflammatory breast cancer (IBC). Six (14%) patients achieved a pCR. Twenty-two of the 274 candidate genes assessed correlated with pCR (p < 0.05). Genes correlating with pCR could be grouped into three large clusters: angiogenesis-related genes, proliferation related genes, and invasion-related genes. Expression of estrogen receptor (ER)-related genes and Recurrence Score did not correlate with pCR. In an exploratory analysis we compared gene expression in IBC to non-inflammatory breast cancer; twenty-four (9%) of the genes were differentially expressed (p < 0.05), 5 were upregulated and 19 were downregulated in IBC. Conclusion: Gene expression analysis on core biopsy samples is feasible and identifies candidate genes that correlate with pCR to primary chemotherapy. Gene expression in IBC differs significantly from noninflammatory breast cancer.

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