Original p53 status predicts for pathological response in locally advanced breast cancer patients treated preoperatively with continuous infusion 5-fluorouracil and radiation therapy

Silvia C. Formenti, Gary Dunnington, Beatrice Uzieli, Heinz Lenz, S. Keren-Rosenberg, Howard Silberman, Darcy Spicer, Mary Denk, Gail Leichman, Susan Groshen, Kristy Watkins, Franco Muggia, Barbara Florentine, Michael Press, Kathleen Danenberg, Peter Danenberg

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Purpose/Objective: 1) To test feasibility of preoperative continuous infusion (c.i.) 5-Fluorouracil (5-FU) and radiation (RT) in locally advanced breast cancer. 2) To study clinical and pathological response rates of 5-FU and radiation. 3) To attempt preliminary correlations between biological probes and pathological response. Methods and Materials: Previously untreated, locally advanced breast cancer patients were eligible: only patients who presented with T3/T4 tumors that could not be resected with primary wound closure were eligible, while inflammatory breast cancer patients were excluded. The protocol consisted of preoperative c.k infusion 5-FU, 200 mg/m2/day with radiotherapy, 50 Gy at 2 Gy fractions to the breast and regional nodes: At mastectomy, pathological findings were classified based on persistence of invasive cancer: pathological complete response (pCR) = no residual invasive cells in the breast and axillary contents; pathological partial response (pPR) = presence of microscopic foci of invasive cells in either the breast or nodal specimens; no pathological response (pNR) = pathological persistence of tumor. For each patient pretreatment breast cancer biopsies were analyzed by immunohistochemistry for nuclear grade, ER/PR hormonal receptors, her2/neu and p53 overexpression. Results: Thirty-five women have completed the protocol and are available for analysis. 5-FU was interrupted during radiation in 10 of 35 patients because of oral mucositis in 8 patients, cellulitis in 1, and patient choice in another. Objective clinical response rate before mastectomy was 71% (25 of 35 patients): 4 CR, 21 PR. However, in all 35 patients tumor response was sufficient to make them resectable with primary wound closure. Accordingly, all patients underwent modified radical mastectomy: primary wound closure was achieved in all patients. At mastectomy there were 7 pCR (20%), 5 pPR (14%) and the remaining 23 patients (66%) had pathological persistence of cancer (pNR). Variables analyzed as potential predictors for pathological response (pPR and pCR) were: initial TNM clinical stage, clinical response, nuclear grade, hormonal receptor status, p53 overexpression, and Her2/neu overexpression in the pretreatment tumor biopsy. Only initial p53 status (lack of overexpression at immunohistochemistry) significantly correlated with achievement of a pathological response in this regimen (p = 0.010). Conclusion: The combination of e.i. 5-FU and radiation was well tolerated and generated objective clinical responses in 71% of the patients. With the limitation of the small sample size; the complete pathological response achieved (20%) compares favorably with that reported in other series of neoadjuvant therapy for similar stage breast cancer. These preliminary data suggest that initial p53 status predicts for pathological response (pPR and pCR) to the combination of e.i. 5-FU anti radiotherapy in locally advanced breast cancer.

Original languageEnglish (US)
Pages (from-to)1059-1068
Number of pages10
JournalInternational Journal of Radiation Oncology Biology Physics
Volume39
Issue number5
DOIs
StatePublished - Dec 1 1997
Externally publishedYes

Fingerprint

Fluorouracil
breast
radiation therapy
therapy
Radiotherapy
cancer
Breast Neoplasms
Mastectomy
Radiation
Neoplasms
Breast
tumors
closures
Wounds and Injuries
Immunohistochemistry
Inflammatory Breast Neoplasms
radiation
ErbB-2 Receptor
Modified Radical Mastectomy
Biopsy

Keywords

  • 5-Fluorouracil and radiation
  • Locally advanced breast cancer
  • P53
  • Pathological response

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Radiation

Cite this

Original p53 status predicts for pathological response in locally advanced breast cancer patients treated preoperatively with continuous infusion 5-fluorouracil and radiation therapy. / Formenti, Silvia C.; Dunnington, Gary; Uzieli, Beatrice; Lenz, Heinz; Keren-Rosenberg, S.; Silberman, Howard; Spicer, Darcy; Denk, Mary; Leichman, Gail; Groshen, Susan; Watkins, Kristy; Muggia, Franco; Florentine, Barbara; Press, Michael; Danenberg, Kathleen; Danenberg, Peter.

In: International Journal of Radiation Oncology Biology Physics, Vol. 39, No. 5, 01.12.1997, p. 1059-1068.

Research output: Contribution to journalArticle

Formenti, SC, Dunnington, G, Uzieli, B, Lenz, H, Keren-Rosenberg, S, Silberman, H, Spicer, D, Denk, M, Leichman, G, Groshen, S, Watkins, K, Muggia, F, Florentine, B, Press, M, Danenberg, K & Danenberg, P 1997, 'Original p53 status predicts for pathological response in locally advanced breast cancer patients treated preoperatively with continuous infusion 5-fluorouracil and radiation therapy', International Journal of Radiation Oncology Biology Physics, vol. 39, no. 5, pp. 1059-1068. https://doi.org/10.1016/S0360-3016(97)00506-3
Formenti, Silvia C. ; Dunnington, Gary ; Uzieli, Beatrice ; Lenz, Heinz ; Keren-Rosenberg, S. ; Silberman, Howard ; Spicer, Darcy ; Denk, Mary ; Leichman, Gail ; Groshen, Susan ; Watkins, Kristy ; Muggia, Franco ; Florentine, Barbara ; Press, Michael ; Danenberg, Kathleen ; Danenberg, Peter. / Original p53 status predicts for pathological response in locally advanced breast cancer patients treated preoperatively with continuous infusion 5-fluorouracil and radiation therapy. In: International Journal of Radiation Oncology Biology Physics. 1997 ; Vol. 39, No. 5. pp. 1059-1068.
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abstract = "Purpose/Objective: 1) To test feasibility of preoperative continuous infusion (c.i.) 5-Fluorouracil (5-FU) and radiation (RT) in locally advanced breast cancer. 2) To study clinical and pathological response rates of 5-FU and radiation. 3) To attempt preliminary correlations between biological probes and pathological response. Methods and Materials: Previously untreated, locally advanced breast cancer patients were eligible: only patients who presented with T3/T4 tumors that could not be resected with primary wound closure were eligible, while inflammatory breast cancer patients were excluded. The protocol consisted of preoperative c.k infusion 5-FU, 200 mg/m2/day with radiotherapy, 50 Gy at 2 Gy fractions to the breast and regional nodes: At mastectomy, pathological findings were classified based on persistence of invasive cancer: pathological complete response (pCR) = no residual invasive cells in the breast and axillary contents; pathological partial response (pPR) = presence of microscopic foci of invasive cells in either the breast or nodal specimens; no pathological response (pNR) = pathological persistence of tumor. For each patient pretreatment breast cancer biopsies were analyzed by immunohistochemistry for nuclear grade, ER/PR hormonal receptors, her2/neu and p53 overexpression. Results: Thirty-five women have completed the protocol and are available for analysis. 5-FU was interrupted during radiation in 10 of 35 patients because of oral mucositis in 8 patients, cellulitis in 1, and patient choice in another. Objective clinical response rate before mastectomy was 71{\%} (25 of 35 patients): 4 CR, 21 PR. However, in all 35 patients tumor response was sufficient to make them resectable with primary wound closure. Accordingly, all patients underwent modified radical mastectomy: primary wound closure was achieved in all patients. At mastectomy there were 7 pCR (20{\%}), 5 pPR (14{\%}) and the remaining 23 patients (66{\%}) had pathological persistence of cancer (pNR). Variables analyzed as potential predictors for pathological response (pPR and pCR) were: initial TNM clinical stage, clinical response, nuclear grade, hormonal receptor status, p53 overexpression, and Her2/neu overexpression in the pretreatment tumor biopsy. Only initial p53 status (lack of overexpression at immunohistochemistry) significantly correlated with achievement of a pathological response in this regimen (p = 0.010). Conclusion: The combination of e.i. 5-FU and radiation was well tolerated and generated objective clinical responses in 71{\%} of the patients. With the limitation of the small sample size; the complete pathological response achieved (20{\%}) compares favorably with that reported in other series of neoadjuvant therapy for similar stage breast cancer. These preliminary data suggest that initial p53 status predicts for pathological response (pPR and pCR) to the combination of e.i. 5-FU anti radiotherapy in locally advanced breast cancer.",
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T1 - Original p53 status predicts for pathological response in locally advanced breast cancer patients treated preoperatively with continuous infusion 5-fluorouracil and radiation therapy

AU - Formenti, Silvia C.

AU - Dunnington, Gary

AU - Uzieli, Beatrice

AU - Lenz, Heinz

AU - Keren-Rosenberg, S.

AU - Silberman, Howard

AU - Spicer, Darcy

AU - Denk, Mary

AU - Leichman, Gail

AU - Groshen, Susan

AU - Watkins, Kristy

AU - Muggia, Franco

AU - Florentine, Barbara

AU - Press, Michael

AU - Danenberg, Kathleen

AU - Danenberg, Peter

PY - 1997/12/1

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N2 - Purpose/Objective: 1) To test feasibility of preoperative continuous infusion (c.i.) 5-Fluorouracil (5-FU) and radiation (RT) in locally advanced breast cancer. 2) To study clinical and pathological response rates of 5-FU and radiation. 3) To attempt preliminary correlations between biological probes and pathological response. Methods and Materials: Previously untreated, locally advanced breast cancer patients were eligible: only patients who presented with T3/T4 tumors that could not be resected with primary wound closure were eligible, while inflammatory breast cancer patients were excluded. The protocol consisted of preoperative c.k infusion 5-FU, 200 mg/m2/day with radiotherapy, 50 Gy at 2 Gy fractions to the breast and regional nodes: At mastectomy, pathological findings were classified based on persistence of invasive cancer: pathological complete response (pCR) = no residual invasive cells in the breast and axillary contents; pathological partial response (pPR) = presence of microscopic foci of invasive cells in either the breast or nodal specimens; no pathological response (pNR) = pathological persistence of tumor. For each patient pretreatment breast cancer biopsies were analyzed by immunohistochemistry for nuclear grade, ER/PR hormonal receptors, her2/neu and p53 overexpression. Results: Thirty-five women have completed the protocol and are available for analysis. 5-FU was interrupted during radiation in 10 of 35 patients because of oral mucositis in 8 patients, cellulitis in 1, and patient choice in another. Objective clinical response rate before mastectomy was 71% (25 of 35 patients): 4 CR, 21 PR. However, in all 35 patients tumor response was sufficient to make them resectable with primary wound closure. Accordingly, all patients underwent modified radical mastectomy: primary wound closure was achieved in all patients. At mastectomy there were 7 pCR (20%), 5 pPR (14%) and the remaining 23 patients (66%) had pathological persistence of cancer (pNR). Variables analyzed as potential predictors for pathological response (pPR and pCR) were: initial TNM clinical stage, clinical response, nuclear grade, hormonal receptor status, p53 overexpression, and Her2/neu overexpression in the pretreatment tumor biopsy. Only initial p53 status (lack of overexpression at immunohistochemistry) significantly correlated with achievement of a pathological response in this regimen (p = 0.010). Conclusion: The combination of e.i. 5-FU and radiation was well tolerated and generated objective clinical responses in 71% of the patients. With the limitation of the small sample size; the complete pathological response achieved (20%) compares favorably with that reported in other series of neoadjuvant therapy for similar stage breast cancer. These preliminary data suggest that initial p53 status predicts for pathological response (pPR and pCR) to the combination of e.i. 5-FU anti radiotherapy in locally advanced breast cancer.

AB - Purpose/Objective: 1) To test feasibility of preoperative continuous infusion (c.i.) 5-Fluorouracil (5-FU) and radiation (RT) in locally advanced breast cancer. 2) To study clinical and pathological response rates of 5-FU and radiation. 3) To attempt preliminary correlations between biological probes and pathological response. Methods and Materials: Previously untreated, locally advanced breast cancer patients were eligible: only patients who presented with T3/T4 tumors that could not be resected with primary wound closure were eligible, while inflammatory breast cancer patients were excluded. The protocol consisted of preoperative c.k infusion 5-FU, 200 mg/m2/day with radiotherapy, 50 Gy at 2 Gy fractions to the breast and regional nodes: At mastectomy, pathological findings were classified based on persistence of invasive cancer: pathological complete response (pCR) = no residual invasive cells in the breast and axillary contents; pathological partial response (pPR) = presence of microscopic foci of invasive cells in either the breast or nodal specimens; no pathological response (pNR) = pathological persistence of tumor. For each patient pretreatment breast cancer biopsies were analyzed by immunohistochemistry for nuclear grade, ER/PR hormonal receptors, her2/neu and p53 overexpression. Results: Thirty-five women have completed the protocol and are available for analysis. 5-FU was interrupted during radiation in 10 of 35 patients because of oral mucositis in 8 patients, cellulitis in 1, and patient choice in another. Objective clinical response rate before mastectomy was 71% (25 of 35 patients): 4 CR, 21 PR. However, in all 35 patients tumor response was sufficient to make them resectable with primary wound closure. Accordingly, all patients underwent modified radical mastectomy: primary wound closure was achieved in all patients. At mastectomy there were 7 pCR (20%), 5 pPR (14%) and the remaining 23 patients (66%) had pathological persistence of cancer (pNR). Variables analyzed as potential predictors for pathological response (pPR and pCR) were: initial TNM clinical stage, clinical response, nuclear grade, hormonal receptor status, p53 overexpression, and Her2/neu overexpression in the pretreatment tumor biopsy. Only initial p53 status (lack of overexpression at immunohistochemistry) significantly correlated with achievement of a pathological response in this regimen (p = 0.010). Conclusion: The combination of e.i. 5-FU and radiation was well tolerated and generated objective clinical responses in 71% of the patients. With the limitation of the small sample size; the complete pathological response achieved (20%) compares favorably with that reported in other series of neoadjuvant therapy for similar stage breast cancer. These preliminary data suggest that initial p53 status predicts for pathological response (pPR and pCR) to the combination of e.i. 5-FU anti radiotherapy in locally advanced breast cancer.

KW - 5-Fluorouracil and radiation

KW - Locally advanced breast cancer

KW - P53

KW - Pathological response

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