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Published in: Journal of Cancer Research and Clinical Oncology 7/2007

01-07-2007 | Original Paper

HER-2/neu status and response to CMF: retrospective study in a series of operable breast cancer treated with primary CMF chemotherapy

Authors: Catalina Falo, Abelardo Moreno, Mar Varela, Belen Lloveras, Agnès Figueras, Agustín Escobedo

Published in: Journal of Cancer Research and Clinical Oncology | Issue 7/2007

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Abstract

Purpose

Primary chemotherapy brings the opportunity for an early and accurate assessment of response and offers an ideal model to search for new predictors of response. HER-2/neu is one of the most studied genes for this purpose.

Patients and methods

Her-2/neu was tested in a non-randomized series of 300 patients with operable breast carcinomas treated with primary CMF. Response was assessed by mammography. Disease-free survival (DFS) and overall survival (OS) were calculated after a mean follow-up of 116 months. Statistical analysis was performed to study the association between HER-2/neu status and response to CMF.

Results

Overexpression/amplification was found in 23.66% cases. Univariate analysis showed that response was similar in HER-2/neu positive and negative tumors (51.38 vs. 47.36%, P = 0.6). Triple negative tumors (ER, PR and HER-2/neu negative) presented the highest response rate (64.9%). By multivariate analysis, response was significantly correlated to higher nuclear grade and negative estrogen receptor status (P = 0.02 and 0.007, respectively). Patients with HER-2/neu positive tumors presented shorter survival rates (P = 0.06). Patients with response to CMF showed a better survival over non-responders independent of Her-2/neu status. Patients with the combination of response to CMF and Her-2/neu negative tumors presented the best outcome. On the other hand, the association of no response to CMF and positive Her-2/neu score was statistically related to poor DFS and OS.

Conclusions

CMF indication is independent of Her-2/neu status.
Literature
go back to reference Allred DC, Clark GM, Tandon AK et al (1992) HER-2/neu in node-negative breast cancer: prognostic significance of overexpression influenced by the presence of in situ carcinoma. J Clin Oncol 10:599–605PubMed Allred DC, Clark GM, Tandon AK et al (1992) HER-2/neu in node-negative breast cancer: prognostic significance of overexpression influenced by the presence of in situ carcinoma. J Clin Oncol 10:599–605PubMed
go back to reference Bargmann CI, Hung MC, Weinberg (1986) The neu oncogene encodes an epidermal growth factor receptor-related protein. Nature 319:226–230PubMedCrossRef Bargmann CI, Hung MC, Weinberg (1986) The neu oncogene encodes an epidermal growth factor receptor-related protein. Nature 319:226–230PubMedCrossRef
go back to reference Baselga J, Seidman AD, Rosen PP et al (1997) HER2 overexpression and paclitaxel sensitivity in breast cancer: therapeutic implications. Oncology 11:43–48PubMed Baselga J, Seidman AD, Rosen PP et al (1997) HER2 overexpression and paclitaxel sensitivity in breast cancer: therapeutic implications. Oncology 11:43–48PubMed
go back to reference Bonadonna G, Valagussa P, Brambilla C et al (1998) Primary chemotherapy in operable breast cancer: eight-year experience at the Milan Cancer Institute. J Clin Oncol 16:93–100PubMed Bonadonna G, Valagussa P, Brambilla C et al (1998) Primary chemotherapy in operable breast cancer: eight-year experience at the Milan Cancer Institute. J Clin Oncol 16:93–100PubMed
go back to reference Buchholz TA, Huang EH, Berry D et al (2004) HER2/neu positive disease does not increase risk of locorregional recurrence for patients treated with neoadjuvant doxorrubicin-based chemotherapy, mastectomy, and radiotherapy. Int J Radiat Oncol Biol Phys 59:1337–1342PubMedCrossRef Buchholz TA, Huang EH, Berry D et al (2004) HER2/neu positive disease does not increase risk of locorregional recurrence for patients treated with neoadjuvant doxorrubicin-based chemotherapy, mastectomy, and radiotherapy. Int J Radiat Oncol Biol Phys 59:1337–1342PubMedCrossRef
go back to reference Falo C, Moreno A, Lloveras B et al (2003) Algorithm for the diagnosis of HER-2/neu status in breast infiltrating carcinomas. Am J Clinical Oncol 26:465–470CrossRef Falo C, Moreno A, Lloveras B et al (2003) Algorithm for the diagnosis of HER-2/neu status in breast infiltrating carcinomas. Am J Clinical Oncol 26:465–470CrossRef
go back to reference Falo C, Moreno A, Benito E et al (2005) Primary chemotherapy with cyclophosphamide, methotrexate, and 5-fluorouracil in operable breast carcinoma. Cancer 12:657–663CrossRef Falo C, Moreno A, Benito E et al (2005) Primary chemotherapy with cyclophosphamide, methotrexate, and 5-fluorouracil in operable breast carcinoma. Cancer 12:657–663CrossRef
go back to reference Fisher B, Bryant J, Wolmark N et al (1998) Effect of preoperative chemotherapy on the outcome of women with operable breast cancer. J Clin Oncol 16:2672–2685PubMed Fisher B, Bryant J, Wolmark N et al (1998) Effect of preoperative chemotherapy on the outcome of women with operable breast cancer. J Clin Oncol 16:2672–2685PubMed
go back to reference Goldhirsch A, Glick JH, Gelber RD et al (2005) Meeting Highlights: International Expert consensus on the primary therapy of early breast cancer 2005. Ann of Oncol 16:1569–1583CrossRef Goldhirsch A, Glick JH, Gelber RD et al (2005) Meeting Highlights: International Expert consensus on the primary therapy of early breast cancer 2005. Ann of Oncol 16:1569–1583CrossRef
go back to reference Gusterson BA, Gelber RD, Goldhirsch A et al (1992) Prognostic importance of c-erbB-2 expression in breast cancer. J Clin Oncol 10:1049–1056PubMed Gusterson BA, Gelber RD, Goldhirsch A et al (1992) Prognostic importance of c-erbB-2 expression in breast cancer. J Clin Oncol 10:1049–1056PubMed
go back to reference Haffty BG, Brown F, Carter D et al (1996) Evaluation of HER-2/neu oncoprotein expression as a prognostic indicator of local recurrence in conservatively treated breast cancer: a case-control study. Int J Radiat Oncol Biol Phys 35:751–757PubMedCrossRef Haffty BG, Brown F, Carter D et al (1996) Evaluation of HER-2/neu oncoprotein expression as a prognostic indicator of local recurrence in conservatively treated breast cancer: a case-control study. Int J Radiat Oncol Biol Phys 35:751–757PubMedCrossRef
go back to reference Konecny GE, Thomssen Ch, Lück HJ et al (2004) HER-2/neu gene amplification and response to paclitaxel in patients with metastatic breast cancer. J Natl Cancer Inst 96:1141–1151PubMedCrossRef Konecny GE, Thomssen Ch, Lück HJ et al (2004) HER-2/neu gene amplification and response to paclitaxel in patients with metastatic breast cancer. J Natl Cancer Inst 96:1141–1151PubMedCrossRef
go back to reference Martin M, Pienkowski T, Mackey J et al (2005) Adjuvant docetaxel for node-positive breast cancer. N Engl J Med 352:2302–2313PubMedCrossRef Martin M, Pienkowski T, Mackey J et al (2005) Adjuvant docetaxel for node-positive breast cancer. N Engl J Med 352:2302–2313PubMedCrossRef
go back to reference Ménard S, Valagussa P, Pilotti S et al (2001) Response to cyclophosphamide, methrotrexate and fluorouracil in lymph node-positive breast cancer according to HER-2 overexpression and other tumor biologic variables. J Clin Oncol 19:329–335PubMed Ménard S, Valagussa P, Pilotti S et al (2001) Response to cyclophosphamide, methrotrexate and fluorouracil in lymph node-positive breast cancer according to HER-2 overexpression and other tumor biologic variables. J Clin Oncol 19:329–335PubMed
go back to reference Miles DW, Harris WH, Gillett CE et al (1999) Effect of c-erbB(2) and estrogen receptor status on survival of women with primary breast cancer treated with adjuvant cyclophosphamide/methotrexate/fluorouracil. Int J Cancer 84:354–359PubMedCrossRef Miles DW, Harris WH, Gillett CE et al (1999) Effect of c-erbB(2) and estrogen receptor status on survival of women with primary breast cancer treated with adjuvant cyclophosphamide/methotrexate/fluorouracil. Int J Cancer 84:354–359PubMedCrossRef
go back to reference Moreno A, Lloveras B, Figueras A et al (1997) Ductal carcinoma in situ of the breast: correlation between histologic classifications and biologic markers. Mod Pathol 10(11):1088–1092PubMed Moreno A, Lloveras B, Figueras A et al (1997) Ductal carcinoma in situ of the breast: correlation between histologic classifications and biologic markers. Mod Pathol 10(11):1088–1092PubMed
go back to reference Moreno A, Escobedo A, Benito E, Serra JM, Guma A, Riu F (2002) Pathologic changes related to CMF primary chemotherapy in breast cancer. Pathological evaluation of response predicts clinical outcome. Breast Cancer Res Treat 75(2):119–125PubMedCrossRef Moreno A, Escobedo A, Benito E, Serra JM, Guma A, Riu F (2002) Pathologic changes related to CMF primary chemotherapy in breast cancer. Pathological evaluation of response predicts clinical outcome. Breast Cancer Res Treat 75(2):119–125PubMedCrossRef
go back to reference Muss HB, Thor AD, Berry DA et al (1994) C-erbB-2 expression and response to adjuvant therapy in women with node-positive early breast cancer. N Engl J Med 330:1260–1266PubMedCrossRef Muss HB, Thor AD, Berry DA et al (1994) C-erbB-2 expression and response to adjuvant therapy in women with node-positive early breast cancer. N Engl J Med 330:1260–1266PubMedCrossRef
go back to reference Paik S, Hazan R, Fisher ER et al (1990) Pathologic findings from the National Surgical Adjuvant Breast and Bowel Project: prognostic significance of c-erbB-2 protein overexpression in primary breast cancer. J Clin Oncol 8:103–112PubMed Paik S, Hazan R, Fisher ER et al (1990) Pathologic findings from the National Surgical Adjuvant Breast and Bowel Project: prognostic significance of c-erbB-2 protein overexpression in primary breast cancer. J Clin Oncol 8:103–112PubMed
go back to reference Paik S, Bryant J, Tan-Chiu E et al (2000) HER2 and choice of adjuvant chemotherapy for invasive breast cancer: National Surgical Adjuvant Breast And Bowel Project Protocol B-15. J Natl Cancer Inst 92:1991–1998PubMedCrossRef Paik S, Bryant J, Tan-Chiu E et al (2000) HER2 and choice of adjuvant chemotherapy for invasive breast cancer: National Surgical Adjuvant Breast And Bowel Project Protocol B-15. J Natl Cancer Inst 92:1991–1998PubMedCrossRef
go back to reference Reed W, Hannisdal E, Boehler PJ et al (2000) The prognostic value of p53 and c-erbB-2 immunostaining is overrated for patients with lymph node negative breast carcinoma: a multivariate analysis of prognostic factors in 613 patients with a follow-up of 14–30 years. Cancer 88:804–813PubMedCrossRef Reed W, Hannisdal E, Boehler PJ et al (2000) The prognostic value of p53 and c-erbB-2 immunostaining is overrated for patients with lymph node negative breast carcinoma: a multivariate analysis of prognostic factors in 613 patients with a follow-up of 14–30 years. Cancer 88:804–813PubMedCrossRef
go back to reference Slamon DJ, Clark GM, Wong SG et al (1987) Human breast cancer. Correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235:177–182PubMedCrossRef Slamon DJ, Clark GM, Wong SG et al (1987) Human breast cancer. Correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235:177–182PubMedCrossRef
go back to reference Sorlie T, Perou CM, Tibshirani R et al (2001) Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA 98:10869–10874PubMedCrossRef Sorlie T, Perou CM, Tibshirani R et al (2001) Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA 98:10869–10874PubMedCrossRef
go back to reference Van de Vijver MJ, Peterse JL, Mooi WJ et al (1988) Neu-protein overexpression in breast cancer. Association with comedo-type ductal carcinoma in situ and limited prognostic value in stage II breast cancer. N Engl J Med 319:1239–1245PubMedCrossRef Van de Vijver MJ, Peterse JL, Mooi WJ et al (1988) Neu-protein overexpression in breast cancer. Association with comedo-type ductal carcinoma in situ and limited prognostic value in stage II breast cancer. N Engl J Med 319:1239–1245PubMedCrossRef
go back to reference van’t Veer LJ, Dai H, van de Vijver MJ et al (2002) Gene expression profiling predicts clinical outcome of breast cancer. Nature (Lond) 415:530–536CrossRef van’t Veer LJ, Dai H, van de Vijver MJ et al (2002) Gene expression profiling predicts clinical outcome of breast cancer. Nature (Lond) 415:530–536CrossRef
go back to reference Wright C, Nicholson S, Angus B et al (1992) Relationship between c-erB-2 protein product expression and response to endocrine therapy in advanced breast cancer. Br J Cancer 65:118–121PubMed Wright C, Nicholson S, Angus B et al (1992) Relationship between c-erB-2 protein product expression and response to endocrine therapy in advanced breast cancer. Br J Cancer 65:118–121PubMed
go back to reference Yang W, Klos Ks, Zhou X et al (2003) ErbB2 overexpression in human breast carcinoma is correlated with p21Cip1 up-regulation and tyrosine-15 hyperphosphorilation of p34Cdc2: poor responsiveness to chemotherapy with cyclophosphamide, methotrexate, and 5-fluorouracil is associated with ErbB2 overexpression and with p21Cip1 overexpression. Cancer 98:1123–1130PubMedCrossRef Yang W, Klos Ks, Zhou X et al (2003) ErbB2 overexpression in human breast carcinoma is correlated with p21Cip1 up-regulation and tyrosine-15 hyperphosphorilation of p34Cdc2: poor responsiveness to chemotherapy with cyclophosphamide, methotrexate, and 5-fluorouracil is associated with ErbB2 overexpression and with p21Cip1 overexpression. Cancer 98:1123–1130PubMedCrossRef
Metadata
Title
HER-2/neu status and response to CMF: retrospective study in a series of operable breast cancer treated with primary CMF chemotherapy
Authors
Catalina Falo
Abelardo Moreno
Mar Varela
Belen Lloveras
Agnès Figueras
Agustín Escobedo
Publication date
01-07-2007
Publisher
Springer-Verlag
Published in
Journal of Cancer Research and Clinical Oncology / Issue 7/2007
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-006-0176-7

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