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Immune escape is a prerequisite for tumor growth. We previously described a decline in intratumor activated cytotoxic T cells and T cell receptor (TCR) clonotype diversity in invasive breast carcinomas compared to ductal carcinoma in situ (DCIS), implying a central role of decreasing T cell responses in tumor progression. To determine potential associations between peripheral immunity and breast tumor progression, here, we assessed the peripheral blood TCR clonotype of 485 breast cancer patients diagnosed with either DCIS or de novo stage IV disease at younger (<45) or older (≥45) age. TCR clonotype diversity was significantly lower in older compared to younger breast cancer patients regardless of tumor stage at diagnosis. In the younger age group, TCR-α clonotype diversity was lower in patients diagnosed with de novo stage IV breast cancer compared to those diagnosed with DCIS. In the older age group, DCIS patients with higher TCR-α clonotype diversity were more likely to have a recurrence compared to those with lower diversity. Whole blood transcriptome profiles were distinct depending on the TCR-α Chao1 diversity score. There were more CD8 + T cells and a more active immune environment in DCIS tumors of young patients with higher peripheral blood TCR-α Chao1 diversity than in those with lower diversity. These results provide insights into the role that host immunity plays in breast cancer development across different age groups., Competing Interests: Competing interests statement:K.P. serves on the Scientific Advisory Boards of Novartis, Ideaya Biosciences, and Scorpion Therapeutics, holds equity options in Scorpion Therapeutics and Ideaya Biosciences, and receives sponsored research funding through Dana-Farber from Novartis. F.M. is a cofounder of and has equity in Harbinger Health, has equity in Zephyr AI, and serves as a consultant for Harbinger Health, and Zephyr AI. She is also on the board of directors of Exscientia Plc. F.M. declares that none of these relationships are directly or indirectly related to the content of this manuscript. D.D. receives research funding from Canon, Inc. J.P. is currently an employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. J.P. contributed to this work prior to their employment at Merck Sharp & Dohme LLC. The opinions or perspectives expressed herein do not represent the opinions or perspectives of Merck Sharp & Dohme LLC.

The molecular underpinnings of HER2-low and HER2-0 (IHC 0) breast tumors remain poorly defined. Using genomic findings from 1039 patients with HER2-negative metastatic breast cancer undergoing next-generation sequencing from 7/2013-12/2020, we compare results between HER2-low (n = 487, 47%) and HER2-0 tumors (n = 552, 53%). A significantly higher number of ERBB2 alleles (median copy count: 2.05) are observed among HER2-low tumors compared to HER2-0 (median copy count: 1.79; P = 2.36e-6), with HER2-0 tumors harboring a higher rate of ERBB2 hemideletions (31.1% vs. 14.5%). No other genomic alteration reaches significance after accounting for multiple hypothesis testing, and no significant differences in tumor mutational burden are observed between HER2-low and HER2-0 tumors (median: 7.26 mutations/megabase vs. 7.60 mutations/megabase, p = 0.24). Here, we show that the genomic landscape of HER2-low and HER2-0 tumors does not differ significantly, apart from a higher ERBB2 copy count among HER2-low tumors, and a higher rate of ERBB2 hemideletions in HER2-0 tumors., (© 2023. The Author(s).)

This study was undertaken to assess the application of the British Paediatric Association's (BPA) published guidelines to the bacteriological screening of breast milk donated to a District General Hospital milk bank. Samples of donated milk were subjected to bacterial counts and provisional identification after both 24 and 48 h incubation on cysteine lactose electrolyte-deficient (CLED) and Columbia blood agar. 21.8% (76 out of 348) donations of milk failed to reach the BPA acceptable criteria. The organisms responsible for the rejection of these samples were all evident within 24 h incubation, and were not significantly confined to one medium. A large percentage of rejected samples originated from a small number of donor mothers; 63.2% came from one donor. In applying BPA guidelines, both CLED and Columbia blood agar were found to be equally effective in screening for unacceptable organisms in prepasteurization donated breast milk. The 24 h period allowed for bacteriological screening, prior to pasteurization of milk samples, was sufficient to allow the growth of all potentially pathogenic bacteria in this study. To prevent the donation of consistently contaminated milk, more active communication between the milk bank staff and the donor is recommended.

The accuracy of a lithium dosage prediction technique was studied retrospectively. The dosage-prediction technique evaluated is based on lithium body clearance. The medical records of 71 psychiatric patients (30 men, 41 women) were reviewed. Age, sex, height, weight, serum creatinine, and one-compartment intravenous dosage equations were used. The lithium dose that would produce steady-state concentrations equal to those actually attained clinically was calculated. Forty-five (64%) of the predictions were within one capsule/day of the actual dose. There were 42 episodes (59%) of underprediction and 10(14%) of overprediction by one or more capsules per day. Underprediction occurred significantly more often in women than in men (31/41 versus 11/30). Predictions differed from actual doses by three or more capsules per day in 10 cases, nine of which were underpredictions. These patients did not differ significantly from the rest of the study group in age, sex, weight, serum creatinine, creatinine clearance, concurrent medical problems, or other medications. This lithium dosage prediction technique may be reliable, rapid, and inexpensive, but further refinement and prospective evaluation are necessary.