Progesterone Receptor Quantification as a Strong Prognostic Determinant in Postmenopausal Breast Cancer Women under Tamoxifen Therapy

There is now an emerging body of evidence that shows there is a relationship between the survival of breast cancer patients and the expression level of steroid receptors. The aim of this study was to determine the relationship existing between estrogen receptors (ER) and progesterone receptors (PR) cytosolic content and the prognosis of postmenopausal breast cancer women under tamoxifen therapy. Two hundred and nineteen postmenopausal patients, without neoadjuvant chemotherapy and treated postoperatively with tamoxifen for at least 2 years, were followed up in our Cancer Center. We used flexible regression modeling and log likelihood methods for determining optimum cut-off values for steroid receptors, which allows the separation of patients into significantly different categories in term of survival. For PR, 3 categories were defined (category 1: PR < 10, category 2: 10 ≤ PR < 60 and category 3: PR ≥60 fmol/mg P). Univariate analysis at 8 years indicated that significant differences in event-free survival (EFS) were found for tumor size (T) (p = 0.005), lymph node status (N) (p = 0.003), histological Scarff, Bloom and Richardson grade (p = 0.003), ER values divided into 5 categories (p = 0.02) and PR values divided into 3 categories (p = 1 · 10−5). Eight-year EFS rate for the 3 PR categories, adjusted for N, were 39, 66 and 81%, respectively. Multivariate Cox analysis indicated that only T, N and PR values were significant variables for EFS. Patients with PR values ≥60 present significantly greater EFS rates than patients with PR < 60 (p < 0.001). Our results show that the PR level in ER positive postmenopausal women is a strong prognostic marker in postmenopausal breast cancer women under tamoxifen therapy.

[1]  D. Allred,et al.  Estrogen receptor status (ER) determined by immunohistochemistry (IHC) is superior to biochemical ligand-binding (LB) assay for evaluating breast cancer patients , 1997 .

[2]  J. Daurès,et al.  Changing estrogen and progesterone receptor patterns in breast carcinoma during the menstrual cycle and menopause , 1998, Cancer.

[3]  W. McGuire,et al.  Prognostic significance of progesterone receptor levels in estrogen receptor-positive patients with metastatic breast cancer treated with tamoxifen: results of a prospective Southwest Oncology Group study. , 1992, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[4]  W. McGuire,et al.  The value of estrogen and progesterone receptors in the treatment of breast cancer , 1980, Cancer.

[5]  G M Clark,et al.  Steroid receptors and other prognostic factors in primary breast cancer. , 1988, Seminars in oncology.

[6]  J. V. Von Roenn,et al.  Quantitative estrogen and progesterone receptor levels related to progression-free interval in advanced breast cancer patients treated with megestrol acetate or tamoxifen. , 1988, Seminars in oncology.

[7]  I. Christensen,et al.  Short recurrence-free survival associated with high oestrogen receptor levels in the natural history of postmenopausal, primary breast cancer. , 1993, European journal of cancer.

[8]  A. D. Schryver,et al.  Systemic treatment of early breast-cancer by hormonal, cytotoxic, or immune therapy: 133 randomized trials involving 31000 recurrences and 24000 deaths among 75000 women: 1 , 1992 .

[9]  J. Elwood,et al.  Oestrogen receptors in breast tumours: associations with age, menopausal status and epidemiological and clinical features in 735 patients. , 1980, British Journal of Cancer.

[10]  Earlybreastcancertrialistscol,et al.  Systemic treatment of early breast cancer by hormonal, cytotoxic, or immune therapy 133 randomised trials involving 31 000 recurrences and 24 000 deaths among 75 000 women , 1992, The Lancet.

[11]  R. Simon,et al.  Flexible regression models with cubic splines. , 1989, Statistics in medicine.

[12]  R. Rubens,et al.  Estrogen and progesterone receptors: Correlation of response rates, site and timing of receptor analysis , 1982, Breast cancer research and treatment.

[13]  A. Forsberg,et al.  Menopausal status and cut off levels of steroid receptor ligand binding assays in breast cancer. , 1989, Anticancer research.

[14]  Mike Clarke,et al.  Polychemotherapy for early breast cancer: an overview of the randomised trials , 1998, The Lancet.

[15]  G. Contesso,et al.  Is the negative prognostic value of high oestrogen receptor (ER) levels in postmenopausal breast cancer patients due to a modified ER gene product? , 1995, European journal of cancer.

[16]  O. H. Lowry,et al.  Protein measurement with the Folin phenol reagent. , 1951, The Journal of biological chemistry.

[17]  Mike Clarke,et al.  Tamoxifen for early breast cancer: an overview of the randomised trials , 1998, The Lancet.

[18]  Anthony Howell,et al.  Systemic treatment of early breast cancer by hormonal, cytotoxic, or immune therapy. 133 randomised trials involving 31,000 recurrences and 24,000 deaths among 75,000 women. Early Breast Cancer Trialists' Collaborative Group. , 1992 .

[19]  J. Raemaekers,et al.  Progesterone receptor activity and relapse-free survival in patients with primary breast cancer: The role of adjuvant chemotherapy , 1988, Breast Cancer Research and Treatment.

[20]  G. Leclercq,et al.  Estrogen receptors in human breast cancer. , 1973, European Journal of Cancer.

[21]  D. Coradini,et al.  Relationship between Steroid Receptors (As Continuous Variables) and Response to Adjuvant Treatments in Postmenopausal Women with Node-Positive Breast Cancer , 1999, The International journal of biological markers.

[22]  M. Lippman,et al.  The effects of androgens and antiandrogens on hormone-responsive human breast cancer in long-term tissue culture. , 1976, Cancer research.

[23]  W. McGuire,et al.  Measurement of steroid hormone receptors in breast cancer patients on tamoxifen , 2004, Breast Cancer Research and Treatment.

[24]  S. Korenman Comparative binding affinity of estrogens and its relation to estrogenic potency. , 1969, Steroids.

[25]  B. Rasmussen,et al.  BENEFICIAL EFFECT OF ADJUVANT TAMOXIFEN THERAPY IN PRIMARY BREAST CANCER PATIENTS WITH HIGH OESTROGEN RECEPTOR VALUES , 1985, The Lancet.

[26]  M. Fernö,et al.  Recurrence-free survival in breast cancer improved by adjuvant tamoxifen -especially for progesterone receptor positive tumors with a high proliferation , 2004, Breast Cancer Research and Treatment.

[27]  E. J. Gregory,et al.  Estrogen receptor as an independent prognostic factor for early recurrence in breast cancer. , 1977, Cancer research.

[28]  W. McGuire Estrogen receptors in human breast cancer. , 1973, The Journal of clinical investigation.