Letrozole Is More Effective Neoadjuvant Endocrine Therapy Than Tamoxifen for ErbB-1– and/or ErbB-2–Positive, Estrogen Receptor–Positive Primary Breast Cancer: Evidence From a Phase III Randomized Trial

Ellis, Matthew J.; Coop, Andrew; Singh, Baljit; Mauriac, L.; Llombert-Cussac, Antonio; Jänicke, F.; Miller, William R.; Evans, Dean B.; Dugan, Margaret; Brady, C.; Quebe‐Fehling, Erhard; Borgs, Mieke

doi:10.1200/jco.2001.19.18.3808

Cited by 992 publications

(616 citation statements)

References 21 publications

Supporting

Mentioning

567

Contrasting

Unclassified

Order By: Relevance

“…12,20,[22][23][24][25] Briefly, a proportion score was assigned representing the estimated proportion of positive staining tumor cells (0 ¼ none; 1o1/100; 2 ¼ 1/100 to o1/10; 3 ¼ 1/10 to o1/3; 4 ¼ 1/3-2/3; 5 ¼ 42/3). Average estimated intensity of staining in positive cells was assigned an intensity score (0 ¼ none; 1 ¼ weak; 2 ¼ intermediate; 3 ¼ strong).…”

Section: Interpretation Of Immunostained Sections (Scoring System)mentioning

confidence: 99%

Progesterone receptor by immunohistochemistry and clinical outcome in breast cancer: a validation study

et al. 2004

View full text Add to dashboard Cite

Progesterone receptor is a surrogate marker of estrogen receptor activity in breast cancer and its utility in helping predict clinical outcome has been established using biochemical assays. However, most laboratories worldwide have switched to immunohistochemistry to assess progesterone receptor, but unfortunately no validated immunohistochemical assay exists for progesterone receptor. The purpose of this study was to develop and validate an immunohistochemical assay for progesterone receptor in breast cancer. The assay was based on monoclonal antibody 1294 (DakoCytomation) and slides were scored microscopically using the 'Allred score' on a scale of 0-8. The assay was compared to ligand-binding assay in 1235 breast cancers, and a subset (n ¼ 362) that received only hormonal therapy was used to define a cutoff for progesterone receptorpositive. Clinical utility was validated in an independent set of samples (n ¼ 423) from a clinical trial randomizing premenopausal breast cancer patients to tamoxifen þ oophorectomy vs observation following surgery. A cutoff of 42 (corresponding to 41% positive cells) dichotomized patients with significantly better or worse clinical outcome (P ¼ 0.0014). Progesterone receptor by immunohistochemistry provided significantly better results than progesterone receptor by ligand-binding assay in predicting clinical outcome. In the clinical trial, a positive result in univariate analyses was associated with significantly improved disease-free and overall survival both in untreated (hazard ratios/P ¼ 0.656/0.060 and 0.479/0.005, respectively) and hormonally treated patients (hazard ratios/P ¼ 0.529/0.017 and 0.451/0.007, respectively). Positive progesterone receptor remained significant for improved disease-free and overall survival (hazard ratios/P ¼ 0.666/0.038 and 0.549/0.007, respectively) in multivariate analyses including the standard variables of tumor size, nodal status, treatment, histological grade, and HER-2/neu status. Estrogen and progesterone receptors are codependent variables and progesterone receptor was a weaker predictor of response to endocrine therapy than estrogen receptor when both were included in multivariate analysis. This is the first comprehensive study assessing the clinical usefulness of progesterone receptor by immunohistochemistry in archival tissue in breast cancer. Progesterone receptor assessed by immunohistochemistry provides useful information about clinical outcome and it is better than progesterone receptor measured by ligand-binding assay.

show abstract

Section: Interpretation Of Immunostained Sections (Scoring System)mentioning

confidence: 99%

Progesterone receptor by immunohistochemistry and clinical outcome in breast cancer: a validation study

et al. 2004

View full text Add to dashboard Cite

show abstract

“…These aromatase inhibitors are less associated than tamoxifen with serious side effects, such as endometrial cancers and thromboembolic complications [107]. Letrozole is more effective as a neoadjuvant endocrine therapy than tamoxifen for ErbB-1-and/or ErbB-2-positive and ER-positive primary breast cancer [108]. This suggests that the growth-promoting effects of these receptor tyrosine kinases are estrogen-dependent.…”

Section: Aromatase Inhibitorsmentioning

confidence: 99%

Estrogens and their receptors in breast cancer progression: a dual role in cancer proliferation and invasion

Platet

Cathiard

Gleizes

et al. 2004

Critical Reviews in Oncology/Hematology

318

236

View full text Add to dashboard Cite

Estrogens play an important role in regulating the growth and differentiation of normal, premalignant and malignant cell types, especially breast epithelial cells, through interaction with two nuclear estrogen receptors (ER and ERIn this review, we present a brief overview of the actions of estrogens in the different steps of breast carcinogenesis, including cancer progression to metastasis, and of their clinical consequences in the prevention, prognosis and treatment of the disease. The requirement of estrogen receptors, mainly of the alpha subtype, in normal mammary gland differentiation and growth has been evidenced by estrogen receptor deficiency in animals. The promotion of breast cancer carcinogenesis by prolonged exposure to estrogens is well-documented and this has logically led to the use of antiestrogens as potentially chemopreventive agents. In breast cancer progression, however, the exact roles of estrogen receptors have been less well established but they may possibly be dual. Estrogens are mitogenic in ER-positive cells and antiestrogens are an efficient adjuvant therapy for these tumors. On the other hand, the fact that estrogens and their receptors protect against cancer cell invasiveness through distinct mechanisms in experimental models may explain why the presence of ER is associated with well-differentiated and less invasive tumors.2

show abstract

“…It is suggested that reduced circulating estrogens after menopause could be the cause of the increase of ER-positive/PgR-negative or ER-positive/low-PgR tumors in postmenopausal women [15]. On the other hand, PgR does not fully reflect estrogen dependence: many PgR-negative tumors respond to endocrine therapy, such as tamoxifen or aromatase inhibitors [11,[16][17][18].…”

Section: Introductionmentioning

confidence: 99%

Differential expression of progesterone receptor, FOXA1, GATA3, and p53 between pre- and postmenopausal women with estrogen receptor-positive breast cancer

Hosoda

Yamamoto

Nakano

et al. 2014

Breast Cancer Res Treat

View full text Add to dashboard Cite

Estrogen receptor (ER) is essential for estrogen-dependent growth, and its level of expression is considered a crucial determinant of response to endocrine therapy and prognosis in ER-positive breast cancer. On the other hand, the clinical role of progesterone receptor (PgR) in ER-positive breast cancer remains controversial, although testing of PgR by immunohistochemistry (IHC) has become routine. Recent studies indicated that plasma estradiol levels were related to expression levels of estrogen-responsive genes in ER-positive breast cancer tissues in both preand postmenopausal women. In this study, we analyzed expression levels of estrogen-responsive genes (PgR and TFF1), a progesterone-responsive gene (RANKL), ER-related genes (FOXA1 and GATA3), HER2, Ki67 and p53 in ER-positive, HER2-negative breast cancer tissues by IHC.Correlations between expression levels of these molecular markers and clinicopathological factors, including prognosis, were compared between pre-and postmenopausal women. Serum levels of estrone, estradiol, progesterone and testosterone were also measured. Expression levels of PgR, TFF1, RANKL and GATA3 were significantly higher in premenopausal women than in postmenopausal women. Serum estradiol levels were positively correlated with Ki67 labeling index (LI) in premenopausal women, but not in postmenopausal women. High expression of FOXA1 and GATA3 was significantly associated with improved disease-free survival in premenopausal women, but not in postmenopausal women, whereas high expression of PgR and low expression of p53 was significantly correlated with improved disease-free survival in postmenopausal women, but not in premenopausal women. Moreover, the best cutoff points of 3 Ki67 LI for disease-free survival were 30% for premenopausal women and 14% for postmenopausal women. Expression levels of ER, TFF1 and RANKL were not associated with disease-free survival in either pre-or postmenopausal women. Our results suggest that the mechanisms of development and estrogen-dependent growth of ER-positive breast cancer might differ according to menopausal status.

show abstract

Letrozole Is More Effective Neoadjuvant Endocrine Therapy Than Tamoxifen for ErbB-1– and/or ErbB-2–Positive, Estrogen Receptor–Positive Primary Breast Cancer: Evidence From a Phase III Randomized Trial

Cited by 992 publications

References 21 publications

Progesterone receptor by immunohistochemistry and clinical outcome in breast cancer: a validation study

Progesterone receptor by immunohistochemistry and clinical outcome in breast cancer: a validation study

Estrogens and their receptors in breast cancer progression: a dual role in cancer proliferation and invasion

Differential expression of progesterone receptor, FOXA1, GATA3, and p53 between pre- and postmenopausal women with estrogen receptor-positive breast cancer

Contact Info

Product

Resources

About