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

Dowsett, Mitch;Allred, Craig;Knox, Jill;Quinn, Emma;Buzdar, Aman;et.al.
(2008) Journal of Clinical Oncology — Vol. 26, n° 7, p. 1059-1065 (2008)

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  • Dowsett, Mitch
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  • Allred, Craig
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  • Knox, Jill
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  • Quinn, Emma
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  • Buzdar, Aman
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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.
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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), 1059-1065. https://doi.org/10.1200/JCO.2007.12.9437 (Original work published 2008)