Serum HER-2/neu and response to the aromatase inhibitor letrozole versus tamoxifen

Allan Lipton, H. Mouridsen, S. Ali, K. Leitzel, Laurence Demers, Harold Harvey, H. A. Chaudri-Ross, C. Brady, M. Dugan, W. Carney

Research output: Contribution to journalArticle

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Abstract

Letrozole (2.5 mg) has shown superior efficacy over tamoxifen (20 mg) in first-line treatment of postmenopausal women with advanced breast cancer, and reduced the risk of progression by 30% compared with tamoxifen (J Clin Oncol. 2001;19:2596-606). Elevated serum HER-2/neu is associated with lower efficacy and shorter survival in advanced breast cancer patients treated with hormonal therapy (Lipton et al. Proc Am Soc Clin Oncol. 2001;87). Retrospectively, pretreatment serum samples (562/907 patients) from the first-line trial were analyzed for HER-2/neu levels (Bayer Immuno l automated assay) relative to efficacy. With a cutoff of 15 ng/mL as the upper limit of normal. 29% of patients had an elevated serum HER-2/neu level. Objective response rate (ORR), clinical benefit rate (CBR), time to disease progression (TTP) and time to treatment failure (TTF) were analyzed in elevated vs. normal serum HER-2/neu groups, regardless of treatment and separately by treatment arm. The ORR (15% vs. 31%, P=.0001) and CBR (30% vs. 50%, P=.0001) were lower in patients with an elevated serum HER-2/neu level. Median TTP (5.7 vs. 9.5 mos, P=.0001) and TTF (4.2 vs. 9.2 mos, P=.0001) were significantly shorter for these patients. Multivariate analyses revealed elevated serum HER-2/neu as a negative predictor of ORR, CBR, TTP, and TTF after adjusting for other variables. In the elevated HER-2/neu group, there was no significant difference in ORR (17% vs. 13%, P=.45), CBR (33% vs. 26%, P=.31), median TTP (6.1 vs. 3.3 mos, P=.14) and TTF (6.0 vs. 3.2 mos, P=.10) for patients treated with letrozole and tamoxifen, respectively. For patients with normal serum HER-2/neu, ORR (38% vs. 25%, P=.008), CBR (56% vs. 45%, P=.03), median TTP (13.0 vs. 8.5 months, P=.002) and TTF (11.8 vs. 6.2 months, P=.003) were significantly better in patients treated with letrozole vs. tamoxifen. This study reconfirms serum HER-2/neu as a negative predictive factor for response to endocrine therapy in this advanced breast cancer population. Although results favored letrozole in patients with elevated serum HER-2/neu, there was no significant difference between tamoxifen and letrozole in any efficacy endpoint analyzed. However, patients with normal serum HER-2/neu levels receiving letrozole demonstrated a significantly higher ORR, CBR, and longer TTP and TTF than those receiving tamoxifen.

Original languageEnglish (US)
Number of pages1
JournalBreast Cancer Research and Treatment
Volume69
Issue number3
StatePublished - Jan 1 2001

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letrozole
Aromatase Inhibitors
Tamoxifen
Treatment Failure
Disease Progression
Serum
Breast Neoplasms
Therapeutics

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Lipton, Allan ; Mouridsen, H. ; Ali, S. ; Leitzel, K. ; Demers, Laurence ; Harvey, Harold ; Chaudri-Ross, H. A. ; Brady, C. ; Dugan, M. ; Carney, W. / Serum HER-2/neu and response to the aromatase inhibitor letrozole versus tamoxifen. In: Breast Cancer Research and Treatment. 2001 ; Vol. 69, No. 3.
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title = "Serum HER-2/neu and response to the aromatase inhibitor letrozole versus tamoxifen",
abstract = "Letrozole (2.5 mg) has shown superior efficacy over tamoxifen (20 mg) in first-line treatment of postmenopausal women with advanced breast cancer, and reduced the risk of progression by 30{\%} compared with tamoxifen (J Clin Oncol. 2001;19:2596-606). Elevated serum HER-2/neu is associated with lower efficacy and shorter survival in advanced breast cancer patients treated with hormonal therapy (Lipton et al. Proc Am Soc Clin Oncol. 2001;87). Retrospectively, pretreatment serum samples (562/907 patients) from the first-line trial were analyzed for HER-2/neu levels (Bayer Immuno l automated assay) relative to efficacy. With a cutoff of 15 ng/mL as the upper limit of normal. 29{\%} of patients had an elevated serum HER-2/neu level. Objective response rate (ORR), clinical benefit rate (CBR), time to disease progression (TTP) and time to treatment failure (TTF) were analyzed in elevated vs. normal serum HER-2/neu groups, regardless of treatment and separately by treatment arm. The ORR (15{\%} vs. 31{\%}, P=.0001) and CBR (30{\%} vs. 50{\%}, P=.0001) were lower in patients with an elevated serum HER-2/neu level. Median TTP (5.7 vs. 9.5 mos, P=.0001) and TTF (4.2 vs. 9.2 mos, P=.0001) were significantly shorter for these patients. Multivariate analyses revealed elevated serum HER-2/neu as a negative predictor of ORR, CBR, TTP, and TTF after adjusting for other variables. In the elevated HER-2/neu group, there was no significant difference in ORR (17{\%} vs. 13{\%}, P=.45), CBR (33{\%} vs. 26{\%}, P=.31), median TTP (6.1 vs. 3.3 mos, P=.14) and TTF (6.0 vs. 3.2 mos, P=.10) for patients treated with letrozole and tamoxifen, respectively. For patients with normal serum HER-2/neu, ORR (38{\%} vs. 25{\%}, P=.008), CBR (56{\%} vs. 45{\%}, P=.03), median TTP (13.0 vs. 8.5 months, P=.002) and TTF (11.8 vs. 6.2 months, P=.003) were significantly better in patients treated with letrozole vs. tamoxifen. This study reconfirms serum HER-2/neu as a negative predictive factor for response to endocrine therapy in this advanced breast cancer population. Although results favored letrozole in patients with elevated serum HER-2/neu, there was no significant difference between tamoxifen and letrozole in any efficacy endpoint analyzed. However, patients with normal serum HER-2/neu levels receiving letrozole demonstrated a significantly higher ORR, CBR, and longer TTP and TTF than those receiving tamoxifen.",
author = "Allan Lipton and H. Mouridsen and S. Ali and K. Leitzel and Laurence Demers and Harold Harvey and Chaudri-Ross, {H. A.} and C. Brady and M. Dugan and W. Carney",
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Lipton, A, Mouridsen, H, Ali, S, Leitzel, K, Demers, L, Harvey, H, Chaudri-Ross, HA, Brady, C, Dugan, M & Carney, W 2001, 'Serum HER-2/neu and response to the aromatase inhibitor letrozole versus tamoxifen', Breast Cancer Research and Treatment, vol. 69, no. 3.

Serum HER-2/neu and response to the aromatase inhibitor letrozole versus tamoxifen. / Lipton, Allan; Mouridsen, H.; Ali, S.; Leitzel, K.; Demers, Laurence; Harvey, Harold; Chaudri-Ross, H. A.; Brady, C.; Dugan, M.; Carney, W.

In: Breast Cancer Research and Treatment, Vol. 69, No. 3, 01.01.2001.

Research output: Contribution to journalArticle

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AU - Mouridsen, H.

AU - Ali, S.

AU - Leitzel, K.

AU - Demers, Laurence

AU - Harvey, Harold

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AU - Brady, C.

AU - Dugan, M.

AU - Carney, W.

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N2 - Letrozole (2.5 mg) has shown superior efficacy over tamoxifen (20 mg) in first-line treatment of postmenopausal women with advanced breast cancer, and reduced the risk of progression by 30% compared with tamoxifen (J Clin Oncol. 2001;19:2596-606). Elevated serum HER-2/neu is associated with lower efficacy and shorter survival in advanced breast cancer patients treated with hormonal therapy (Lipton et al. Proc Am Soc Clin Oncol. 2001;87). Retrospectively, pretreatment serum samples (562/907 patients) from the first-line trial were analyzed for HER-2/neu levels (Bayer Immuno l automated assay) relative to efficacy. With a cutoff of 15 ng/mL as the upper limit of normal. 29% of patients had an elevated serum HER-2/neu level. Objective response rate (ORR), clinical benefit rate (CBR), time to disease progression (TTP) and time to treatment failure (TTF) were analyzed in elevated vs. normal serum HER-2/neu groups, regardless of treatment and separately by treatment arm. The ORR (15% vs. 31%, P=.0001) and CBR (30% vs. 50%, P=.0001) were lower in patients with an elevated serum HER-2/neu level. Median TTP (5.7 vs. 9.5 mos, P=.0001) and TTF (4.2 vs. 9.2 mos, P=.0001) were significantly shorter for these patients. Multivariate analyses revealed elevated serum HER-2/neu as a negative predictor of ORR, CBR, TTP, and TTF after adjusting for other variables. In the elevated HER-2/neu group, there was no significant difference in ORR (17% vs. 13%, P=.45), CBR (33% vs. 26%, P=.31), median TTP (6.1 vs. 3.3 mos, P=.14) and TTF (6.0 vs. 3.2 mos, P=.10) for patients treated with letrozole and tamoxifen, respectively. For patients with normal serum HER-2/neu, ORR (38% vs. 25%, P=.008), CBR (56% vs. 45%, P=.03), median TTP (13.0 vs. 8.5 months, P=.002) and TTF (11.8 vs. 6.2 months, P=.003) were significantly better in patients treated with letrozole vs. tamoxifen. This study reconfirms serum HER-2/neu as a negative predictive factor for response to endocrine therapy in this advanced breast cancer population. Although results favored letrozole in patients with elevated serum HER-2/neu, there was no significant difference between tamoxifen and letrozole in any efficacy endpoint analyzed. However, patients with normal serum HER-2/neu levels receiving letrozole demonstrated a significantly higher ORR, CBR, and longer TTP and TTF than those receiving tamoxifen.

AB - Letrozole (2.5 mg) has shown superior efficacy over tamoxifen (20 mg) in first-line treatment of postmenopausal women with advanced breast cancer, and reduced the risk of progression by 30% compared with tamoxifen (J Clin Oncol. 2001;19:2596-606). Elevated serum HER-2/neu is associated with lower efficacy and shorter survival in advanced breast cancer patients treated with hormonal therapy (Lipton et al. Proc Am Soc Clin Oncol. 2001;87). Retrospectively, pretreatment serum samples (562/907 patients) from the first-line trial were analyzed for HER-2/neu levels (Bayer Immuno l automated assay) relative to efficacy. With a cutoff of 15 ng/mL as the upper limit of normal. 29% of patients had an elevated serum HER-2/neu level. Objective response rate (ORR), clinical benefit rate (CBR), time to disease progression (TTP) and time to treatment failure (TTF) were analyzed in elevated vs. normal serum HER-2/neu groups, regardless of treatment and separately by treatment arm. The ORR (15% vs. 31%, P=.0001) and CBR (30% vs. 50%, P=.0001) were lower in patients with an elevated serum HER-2/neu level. Median TTP (5.7 vs. 9.5 mos, P=.0001) and TTF (4.2 vs. 9.2 mos, P=.0001) were significantly shorter for these patients. Multivariate analyses revealed elevated serum HER-2/neu as a negative predictor of ORR, CBR, TTP, and TTF after adjusting for other variables. In the elevated HER-2/neu group, there was no significant difference in ORR (17% vs. 13%, P=.45), CBR (33% vs. 26%, P=.31), median TTP (6.1 vs. 3.3 mos, P=.14) and TTF (6.0 vs. 3.2 mos, P=.10) for patients treated with letrozole and tamoxifen, respectively. For patients with normal serum HER-2/neu, ORR (38% vs. 25%, P=.008), CBR (56% vs. 45%, P=.03), median TTP (13.0 vs. 8.5 months, P=.002) and TTF (11.8 vs. 6.2 months, P=.003) were significantly better in patients treated with letrozole vs. tamoxifen. This study reconfirms serum HER-2/neu as a negative predictive factor for response to endocrine therapy in this advanced breast cancer population. Although results favored letrozole in patients with elevated serum HER-2/neu, there was no significant difference between tamoxifen and letrozole in any efficacy endpoint analyzed. However, patients with normal serum HER-2/neu levels receiving letrozole demonstrated a significantly higher ORR, CBR, and longer TTP and TTF than those receiving tamoxifen.

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