Prognostic Significance of Single Progesterone Receptor Positivity

Single progesterone receptor positive (PgRþ), especially in form of ER /PgRþ/HER2 , is a nonnegligible phenomenon. Little is known about the characteristics and the role of single PgR positive in this phenotype. Therefore, we explore the significance of single PgR positivity by comparing ER /PgRþ/HER2 breast cancers with triple negative breast cancers (TNBCs). Three thousand nine hundred sixty-six cases of primary invasive breast carcinoma operated consecutively from January 2005 to May 2008 in Cancer Hospital, Chinese Academy of Medical Sciences were examined. Two hundred forty (6%) cases were identified as ER / PgRþ/HER2 breast cancers and 348 (8.8%) cases as TNBCs. Clinicopathological characteristics and survivals were analyzed respectively and then compared between 2 subtypes. Compared with patients with TNBCs, ER /PgRþ/HER2 tumor tended to have lower tumor grade (Grade 3: 45.7% vs. 37.5%, P1⁄4 0.051) and smaller tumor size (P1⁄4 0.036). However, no differences were found between ER /PgRþ/HER2 and TNBC patients in relapse-free survival (RFS) and OS. The 5-year RFS rates were 80.7% and 77.4%, respectively (P1⁄4 0.330) and the 5-year OS rates were 88.0% and 85.2%, respectively (P1⁄4 0.290). ER /PgRþ/HER2 patients receiving adjuvant endocrine treatment had better RFS (P1⁄4 0.016) and overall survival (OS) (P< 0.0001) than patients receiv, MD, PhD, Fei M uan, MD, ing Li, BcS, and Yang Luo, MD TNBC, suggesting that it should also be regarded as biologically distinctive group and single PgR positive itself is not a good prognostic factor. However, adjuvant endocrine therapy could still benefit this group of patients. Further investigations should be done to elucidate the underlying mechanism. (Medicine 94(46):e2066) Abbreviations: AJCC/UICC = American Joint Committee on Cancer/International Union Against Cancer, ASCO/CAP = American Society of Clinical Oncology/College of American Pathologists, BCS = breast conserving surgery, BMI = bone mass index, ER = estrogen receptor, HER2 = human epidermal growth factor receptor 2, IDC = invasive ductal carcinoma, MRM = modified radical mastectomy, NA = not applicable, OS = overall survival, PgR = progesterone receptor, RFS = relapse-free survival, SD = standard deviation, TNBCs = triple negative breast cancers. INTRODUCTION B reast cancer shows distinctly diverse clinicopathological characteristics, different therapeutic responsiveness, and variable outcomes in different subtypes based on gene expression signature. However, gene profiling is still limited in current practice. Therefore, immunohistochemical surrogate markers have been developed including estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2). Among them, ER and HER2 have secured their positions as prognostic factors, however, there is still lack of agreement on the role of PgR in breast cancer. PgR belongs to a large superfamily of ligand-activated nuclear receptors. The binding of progesterone to PgR induces conformational changes that lead to the formation of homoor heterodimers, increased receptor phosphorylation, interaction with target gene promoters by binding to progesterone response elements, and to specific coactivators and general transcription factors. Further researches also showed that PgR is a protein in which synthesis is positively regulated by ER. The presence of a functional ER is required for PgR synthesis in the cell. Therefore, the presence of PgR may indicate a more functionally intact ER pathway. A recent published paper demonstrated that in IHC-defined luminal A tumors, more than 20% of PRpositive tumor cells predicted significantly better survival. This t Gallen guideline to use PgR cut off of inal A-like with Luminal B-like breast mplication of PgR in ER negative breast www.md-journal.com | 1 cancer is still unknown. Previously, single PgR positivity was believed to be a rare phenomenon and may be false positive in IHC examination. There once was a debate on whether it is time to stop PgR testing in breast cancer management. However, more and more researches supported that it was not insignificant, accounting for 3.4% to 7% of total cases. In addition, some even found that PgR status was a strong prognostic factor for survivals. Although previous literatures suggested that ER /PgRþ tumors might have biologic characteristics somewhere in between ERþ/PgRþ and ERþ/ PgR , HER2 was not taken into consideration at that time. Thus, up until now, very little was known about the clinical– pathological characteristics and outcomes of ER /PgRþ/ HER2 phenotype. Triple negative breast cancer (TNBC) is a distinct subtype of breast cancer, which is characterized as ER negative, PR negative, and HER2 negative, featuring rapid progression and poor prognosis. To illustrate the true significance of single PgR positivity, we compared a group of ER /PgRþ/HER2 patients with TNBC patients. To our knowledge, this is the first study to investigate the differences and similarities between ER /PgRþ/HER2 and TNBC patients. Also this is the largest series of ER /PgRþ/HER2 tumors ever explored to evaluate the efficacy of adjuvant endocrine therapy exclusively in this group of patients.