Relationship between quantitative estrogen and progesterone receptor expression and human epidermal growth factor receptor 2 (HER-2) status with recurrence in the Arimidex, Tamoxifen, Alone or in Combination trial

Mitch Dowsett, Craig Allred, Jill Knox, Emma Quinn, Janine Salter, Chris Wale, Jack Cuzick, Joan Houghton, Norman Williams, Elizabeth Mallon, Hugh Bishop, Ian Ellis, Denis Larsimont, Hironobu Sasano, Pauline Carder, Antonio Llombart Cussac, Fiona Knox, Valerie Speirs, John Forbes, Aman Buzdar

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Abstract

PURPOSE: To determine the relationship between quantitative estrogen-receptor (ER) and progesterone-receptor (PgR) expression and human epidermal growth factor 2 (HER-2) status with time to recurrence (TTR) in postmenopausal women with hormone receptor-positive primary breast cancer treated with anastrozole or tamoxifen as adjuvant therapy.

PATIENTS AND METHODS: Formalin-fixed, paraffin-embedded tumor blocks were retrospectively collected from patients in the monotherapy arms of the Arimidex, Tamoxifen Alone or in Combination (ATAC) trial and centrally tested for ER, PgR and HER-2. ER and PgR were scored using continuous scales and HER-2 was scored as 0 to 3+ with 2+ cases being analyzed by fluorescence in situ hybridization.

RESULTS: Blocks were collected from 2,006 of 5,880 eligible patients. Tissue was assessable and ER and/or PgR positivity confirmed centrally in 1,782 cases. In these, TTR was longer for anastrozole than for tamoxifen by a similar extent to that in the overall trial. None of the three biomarkers identified a set of patients with differential benefit from anastrozole over tamoxifen. Patients with low ER, low PgR, and high HER-2 expression had a poorer prognosis with either drug. Only 2.6% of patients in the highest quartile of PgR experienced recurrence after 5 years, compared with 13.2% in the lowest quartile.

CONCLUSION: Quantitative expression of ER and PgR and HER-2 status did not identify patients with differential relative benefit from anastrozole over tamoxifen: TTR was longer for anastrozole than for tamoxifen in all molecular subgroups. Low ER or PgR or high HER-2 expression are associated with a high risk of recurrence with either anastrozole or tamoxifen.

Original languageEnglish
Pages (from-to)1059-65
Number of pages7
JournalJournal of Clinical Oncology
Volume26
Issue number7
DOIs
Publication statusPublished - 1 Mar 2008

Keywords

  • Antineoplastic Combined Chemotherapy Protocols
  • Breast Neoplasms
  • Chemotherapy, Adjuvant
  • Double-Blind Method
  • Female
  • Humans
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Nitriles
  • Postmenopause
  • Prognosis
  • Receptor, ErbB-2
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Retrospective Studies
  • Survival Rate
  • Tamoxifen
  • Time Factors
  • Tissue Array Analysis
  • Treatment Outcome
  • Triazoles
  • Journal Article
  • Randomized Controlled Trial

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    Dowsett, M., Allred, C., Knox, J., Quinn, E., Salter, J., Wale, C., Cuzick, J., Houghton, J., Williams, N., Mallon, E., Bishop, H., Ellis, I., Larsimont, D., Sasano, H., Carder, P., Cussac, A. L., Knox, F., Speirs, V., Forbes, J., & Buzdar, A. (2008). Relationship between quantitative estrogen and progesterone receptor expression and human epidermal growth factor receptor 2 (HER-2) status with recurrence in the Arimidex, Tamoxifen, Alone or in Combination trial. Journal of Clinical Oncology, 26(7), 1059-65. https://doi.org/10.1200/JCO.2007.12.9437