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Abstract: Clinical management of breast cancer is increasingly guided by assessment of tumor phenotypic parameters. One of these is estrogen receptor (ER) status, currently defined by ERα expression. However with the discovery of a second ER, ERβ and its variant isoforms, the definition of ER status is potentially more complex. In breast tumors there are two ERβ expression cohorts. One where ERβ is co-expressed with ERα and the other expressing ERβ alone. In the latter subgroup of currently defined ER negative patients ERβ has the potential to be a therapeutic target. Characterization of the nature and role of ERβ in ERα negative tumors is essentially unexplored but available data suggest that the role of ERβ may be different when co-expressed with ERα and when expressed alone. This review summarizes available data and explores the possibility that ERβ signaling may be a therapeutic target in these tumors. Evidence so far supports the idea that the role of ERβ in breast cancer is different in ERα negative compared to ERα positive tumors. However, cohort size and numbers of independent studies are small to date, and more studies are needed with better standardization of antibodies and protocols. Also, the ability to determine the role of ERβ in ERα negative breast cancer and therefore assess ERβ signaling pathways as therapeutic targets would be greatly facilitated by identification of specific downstream markers of ERβ activity in breast cancer. [Copyright &y& Elsevier]

The function of the mouse submaxillary gland/prolactin inducible protein (mSMGP/mPIP), the homologue of the human gross cystic disease fluid protein 15 (GCDFP-15)/prolactin inducible protein (hPIP) remains unknown. The human gene, normally expressed in apocrine glands of healthy individuals, is aberrantly expressed in human breast cancers where it is regulated by hormones including androgens, and in prostate cancers. We have previously reported that in the adult mouse and rat, gene expression is tissue-specific for the salivary and lacrimal glands, and is hormonally regulated. In this study, we examine the endogenous pattern of mouse SMGP/PIP (mSMGP/mPIP) gene expression in mid- and late-embryonic, and in early postnatal development. Gene expression was analyzed by RT-PCR followed by Southern blot analysis, and by in situ hybridization. Gene expression was detected in the submandibular gland as early as embryonic day 14 (E14), a period that coincides with the initiation of submandibular gland development in the embryo, suggesting that mSMGP/mPIP may have a functional role in the developing gland. Nearing the end of gestation, E18, mSMGP/mPIP transcripts were localized in the proacinar cells of the gland, and gene expression continued to be maintained following birth. In addition, during early postnatal development, mSMGP/mPIP gene expression was detected in the other two major salivary glands, the sublingual and parotid, as well as in the lacrimal gland and in reproductive tissues. In the prostate, gene expression was turned off by 10 weeks of age. The spatial and temporal pattern of the mSMGP/mPIP gene expression, in addition to our recent demonstration that mSMGP/mPIP is found in mouse saliva and can bind bacteria, suggest that this protein may have a protective role in the mouse. [Copyright &y& Elsevier]

Although it is generally accepted that human tissue biobanks are important to facilitate progress in health and medical research, many academic biobanks face sustainability challenges. We propose that biobank sustainability is challenged by a lack of available data describing the outputs and benefits that are produced by biobanks, as reflected by a dearth of publications that enumerate biobank outputs. We further propose that boosting the available information on biobank outputs and using a broader range of output metrics will permit economic analyses such as cost-consequence analyses of biobank activity. Output metrics and cost-consequence analyses can allow biobanks to achieve efficiencies, and improve the quality and/or quantity of their outputs. In turn, biobank output measures provide all stakeholders with explicit and accountable data on biobank value, which could contribute to the evolution of biobank operations to best match research needs, and mitigate some threats to biobank sustainability. [ABSTRACT FROM AUTHOR]

Purpose: Ipsilateral breast tumor recurrence (IBTR) can occur in 5–20% of women with early-stage breast cancer treated with breast-conserving therapy. Two entities of IBTR have been described: true recurrence (TR), suggested to be regrowth of disease at the tumor bed, and new primary (NP), distinct from the index lesion in histology and location. This study compared survival outcomes between two patient cohorts classified clinically as having either TR or NP. Methods and Materials: Between 1989 and 1999, 6,020 women were referred to the BC Cancer Agency with newly diagnosed pT1–2, N0–1, M0 invasive breast cancer, treated with breast-conserving surgery. Of these, 289 patients had pathologically confirmed IBTR. Retrospective analysis was performed, and a set of decision rules was applied to classify cases as TR or NP based on change in histology, grade, hormone receptor status, and tumor location. Of 289 patients, 129 (45%) were classified as having TR and 139 (48%) as having NP; 21 (7%) were unclassified. Results: The distributions of age at diagnosis, age at recurrence, and histopathologic factors were similar in the TR and NP cohorts (all p > 0.05). The mean time to recurrence was shorter in TR patients than in NP patients (4.8 years vs. 6.3 years, p = 0.001). Treatment of the IBTR did not differ between the two groups. In the TR and NP cohorts, breast cancer–specific survival was 55.7% vs. 61.3% (p = 0.93), and overall survival was 43.7% vs. 54.8% (p = 0.53). Conclusions: Time to recurrence is significantly shorter in patients with IBTR classified as true recurrence compared to new primary. Non–statistically significant trends for less favorable survival were observed for patients with TR. Further investigation of the hypothesis that TR and NP tumors are distinct entities with different survival prognoses will require standardized pathology review and molecular analyses. [ABSTRACT FROM AUTHOR]

Abstract: Human S100A7 (psoriasin) is considered a marker for specific stages of breast cancer. hS100A15 is almost identical to hS100A7 and difficult to discriminate. We developed specific probes to distinguish hS100A7 and hS100A15, and demonstrate their differential distribution in normal breast tissue. Further, hS100A7 and S100A15 transcripts are elevated in ER/PR negative breast cancers, but hS100A15 protein is detected in all cancer specimens while hS100A7 protein is sporadically expressed. The differential regulation, expression and distribution of hS100A7 and hS100A15 and their reported distinct functions are compelling reasons to discriminate among these proteins in normal breast and breast cancers. [Copyright &y& Elsevier]

Abstract: Estrogen receptor (ER)α activity is regulated by phosphorylation at several sites. Recently several antibodies specific for individual phosphorylated sites within ERα have became available. Validation and use of these antibodies suggests that several forms of phosphorylated ERα can be detected in multiple ER+ human breast tumor samples, thus providing relevance for investigating the regulation and function of phosphorylated ERα in human breast cancer. Generally, the phosphorylated ERα isoforms are associated with parameters that suggest that they are markers of an intact estrogen dependent signaling pathway and better clinical outcome with respect to tamoxifen therapy. Profiling of phosphorylated ERα may provide better biomarkers of endocrine therapy response over and above those currently available. [Copyright &y& Elsevier]