The impact of tumor progesterone receptor status on optimal adjuvant endocrine therapy for postmenopausal patients with early‐stage breast cancer

Abstract

BACKGROUNDEmerging data suggest that treatment outcomes with aromatase inhibitors (AIs) and/or tamoxifen may differ for tumors that express both the estrogen receptor (ER) and the progesterone receptor (PR) (ER+/PR+) compared with those that lack PR expression (ER+/PR−). However, the optimal sequencing of AIs and tamoxifen as adjuvant therapy is not known and may differ for biologic subsets of cancers.METHODSMarkov models were used to simulate disease‐free survival (DFS) separately among postmenopausal women with ER+/PR+ cancers and women with ER+/PR− cancers. By using risk estimates reported from randomized clinical trials, treatment with 5 years of an AI alone with sequential treatment consisting of tamoxifen with crossover to an AI at 2 years was compared.RESULTSFor women with ER+/PR+ cancers, sequential therapy with tamoxifen followed by crossover to an AI at 2 years yielded modest improvements in 10‐year DFS estimates compared with planned AI monotherapy (84.3% vs. 82.2% and 68.8% vs. 64.8% for lymph node‐negative and lymph node‐positive patients, respectively). However, for women with ER+/PR− cancers, upfront treatment with an AI yielded improved outcomes with 10‐year DFS rates of 90.5% and 80.1% for the lymph node‐negative and node‐positive groups, respectively, compared with 88.2% and 76.1%, respectively, for sequential treatment with tamoxifen followed by an AI.CONCLUSIONSModeling estimates suggested that the optimal endocrine treatment strategy may differ based on the biologic features of breast cancer tumors. Patients with ER+/PR+ tumors achieved optimal 10‐year DFS estimates with tamoxifen followed by a crossover to AI therapy, whereas patients with ER+/PR− tumors fared best when they initiated treatment with AI. Cancer 2006. © 2006 American Cancer Society.

Differential Regulation of Breast Cancer-Associated Genes by Progesterone Receptor Isoforms PRA and PRB in a New Bi-Inducible Breast Cancer Cell Line

“…PR isoforms are considered as prognostic markers of breast cancer development and metastasis independently of the progestational status [48], [57]. P4 exerts antiproliferative effects in mammary PR+ cells [40] and few proliferating mammary epithelial cells (MEC) express PR [58], [59].…”

Progesterone receptor B (PRB) promoter hypermethylation in sporadic breast cancer

“…Tumours that lack PR expression are more likely to be of a higher grade, display greater aneuploidy, be HER 2 positive, have lower levels of ER expression and have a lower response rate to tamoxifen in the metastatic setting than other ER positive tumours. For reasons of intrinsic tumour biology it appears that tumours lacking PR may be particularly sensitive to oestrogen deprivation associated with AI treatment [19].…”

Linkage of progestin and epidermal growth factor signaling: Phosphorylation of progesterone receptors mediates transcriptional hypersensitivity and increased ligand-independent breast cancer cell growth

“…PRs are independent markers of breast cancer prognosis, irrespective of progestational status (60)(61)(62). Further, ER+/PR+ tumors clearly metastasize (63).…”