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Background This study is to evaluate the associations between long-term survival and stage I breast cancer by examining the hormonal receptor (HR) and human epidermal growth factor receptor-2 (HER2) status. Materials and methods A total of 1595 breast cancer patients who were seen from 1990 to 2008 with surgery as first treatment and pathology stage I (T1N0) were included in this study. HR and HER2 status were used to approximate breast cancer subtypes. Additionally, ten-year relapse-free survival (RFS) rate and failure patterns of each subtype were evaluated. Multivariate analyses were performed in each subtype to identify the risk factors of recurrence. Results Luminal-like (HR positive and HER2 negative) stage I patients showed a 10-year RFS rate of 89.5%, HER2 positive 92.9%, triple negative 91.1%, and unclassified subtype 86.2% (p = 0.089), respectively. The 10-year overall survival was 94.1% in luminal-like subtype, 90.1% in HER2, 94.5% in triple negative, and 85.3% in unclassified subtype. The independent recurrence risk factors in luminal-like subtype were ≤40 years of age (hazard ratio [HR] 2.2, 95% confidence interval [CI], 1.1–4.4), nuclear grade III (HR 2.7, CI, 1.4–5.3), and tumor >1.5 cm (HR 1.8, CI 1.0–3.4), and in unclassified subtype ≤40 years of age, tumor >1.5 cm, and adjuvant hormonal therapy. No risk factors were identified in HER2 or triple negative subtype. Conclusions The factors associated with poor prognosis of stage I breast cancer vary by subtype. No risk factors were identified in HER2 subtype or triple negative patients. Tumor size >1.5 cm, age ≤40 years and nuclear grade 3 are the risk factors associated with poor prognosis in luminal-like subtype.

We previously identified 34 genes of interest (GOI) in 2006 to aid the oncologists to determine whether post-mastectomy radiotherapy (PMRT) is indicated for certain patients with breast cancer. At this time, an independent cohort of 135 patients having DNA microarray study available from the primary tumor tissue samples was chosen. Inclusion criteria were 1) mastectomy as the first treatment, 2) pathology stages I-III, 3) any locoregional recurrence (LRR) and 4) no PMRT. After inter-platform data integration of Affymetrix U95 and U133 Plus 2.0 arrays and quantile normalization, in this paper we used 18 of 34 GOI to divide the mastectomy patients into high and low risk groups. The 5-year rate of freedom from LRR in the high-risk group was 30%. In contrast, in the low-risk group it was 99% (p, Highlights • No molecular markers are available to determine post-mastectomy radiotherapy for breast cancer patients. • Statistically about 2-8% N0 and 20% of N1 mastectomy patients would develop local/regional recurrence (LRR). • An 18-gene classifier is capable of identifying patients at risk for LRR after mastectomy. There is no consensus whether to give post-mastectomy radiotherapy to all N1 patients according to the St. Gallen consensus meeting in 2015. Currently about one half of N1 mastectomy patients have been given adjuvant radiotherapy in the United States. From a separate patient population, we now have developed an 18-gene classifier included in our previously published 34-gene panel. This diminished multigene set of classifier is capable of differentiating post-mastectomy breast cancer patients into the low- and high-risk groups. This new classifier has the potential to spare low-risk N1 patients from radiotherapy and at the same time help identify high-risk N0 patients for radiotherapy.

Gastrin-releasing peptide (GRP) is a putative itch-specific neurotransmitter, but definite evidence in the dorsal root ganglion (DRG) and spinal cord is lacking. We generated and validated a Grp-Cre knock-in (GrpCre-KI) mouse line whereby Grp neurons are genetically labeled. Cre-dependent marking analysis revealed exclusive innervation of the upper epidermis of the skin by GRP fibers. Importantly, optical stimulation of Grp fibers expressing channel rhodopsin (ChR2) in the skin evoked itch but not pain-related scratching behaviors, while conditional deletion of Grp in sensory neurons attenuated non-histaminergic itch. In contrast, intersectional genetic ablation of spinal Grp neurons did not affect itch nor pain transmission. Our study demonstrates a role of GRP in sensory neurons in itch and suggests that GRP sensory neurons are dedicated to itch transmission. GrpCre-KI mice provide a long-sought avenue for investigating peripheral coding mechanism of itch and further interrogation of itch-nerve fibers in the skin under chronic pruritus.HighlightsValidated expression of a Grp-Cre knock-in line in sensory neurons that innervate the skinOpto-activation of Grp sensory neurons evokes itch behaviorConditional deletion of Grp in sensory neurons reduces non-histaminergic itch behaviorIntersectional ablation of Grp spinal neurons does not affect itch or pain behaviors

Purpose This study is designed to validate a previously developed locoregional recurrence risk (LRR) scoring system and further define which groups of patients with breast cancer would benefit from postmastectomy radiation therapy (PMRT). Methods and Materials An LRR risk scoring system was developed previously at our institution using breast cancer patients initially treated with modified radical mastectomy between 1990 and 2001. The LRR score comprised 4 factors: patient age, lymphovascular invasion, estrogen receptor negativity, and number of involved lymph nodes. We sought to validate the original study by examining a new dataset of 1545 patients treated between 2002 and 2007. Results The 1545 patients were scored according to the previously developed criteria: 920 (59.6%) were low risk (score 0-1), 493 (31.9%) intermediate risk (score 2-3), and 132 (8.5%) were high risk (score ≥4). The 5-year locoregional control rates with and without PMRT in low-risk, intermediate-risk, and high-risk groups were 98% versus 97% ( P =.41), 97% versus 91% ( P =.0005), and 89% versus 50% ( P =.0002) respectively. Conclusions This analysis of an additional 1545 patients treated between 2002 and 2007 validates our previously reported LRR scoring system and suggests appropriate patients for whom PMRT will be beneficial. Independent validation of this scoring system by other institutions is recommended.