way to predict which pf those given 1 yr of adjuvant her2+ therapy will recur

[Lani]

is being developed. Depressed #s of a subset of T cells in the immune system(Th1) is associated with that group of patients who recur --with that knowledge they can either add additional therapies on to prevent the recurrence or figure out how to improve the adjuvant regimen for that subgroup of patients or all her2 patients ( depending on the price/safety of the treatment) to prevent it ever becoming metastatic

This may also be able to be used to follow response to treatment of Stage IVs.

Many have hoped for a way to be monitored to determine early if treatment has worked or continues working (rather than waiting for a fracture, shortness of breath or a seizure.

If this proves out in larger #s of patienrs (95 here), this development can only improve how her2 bc is treated and perhaps avoid overtreatment as well.


Brief Report | December 30, 2015
Association of Depressed Anti-HER2 T-Helper Type 1 Response With Recurrence in Patients With Completely Treated HER2-Positive Breast CancerRole for Immune Monitoring ONLINE FIRST
Jashodeep Datta, MD1; Megan Fracol, MD1; Matthew T. McMillan, BA1; Erik Berk, PhD1; Shuwen Xu, MD1; Noah Goodman, MPH2; David A. Lewis, BA2; Angela DeMichele, MD, MSCE2,3; Brian J. Czerniecki, MD, PhD1,4
[+] Author Affiliations
JAMA Oncol. Published online December 30, 2015. doi:10.1001/jamaoncol.2015.5482

ABSTRACT

Importance There is a paucity of immune signatures identifying patients with human epidermal growth factor receptor 2 (HER2)-positive invasive breast cancer (IBC) at risk for treatment failure following trastuzumab and chemotherapy.

Objective To determine whether circulating anti-HER2 CD4-positive (CD4+) T-helper type 1 (Th1) immunity correlates with recurrence in patients with completely treated HER2-positive IBC.

Design, Setting, and Participants Hypothesis-generating exploratory translational analysis at a tertiary care referral center of patients with completely treated HER2-positive IBC with median (interquartile range) follow-up of 44 (31) months. Anti-HER2 Th1 responses were examined using peripheral blood mononuclear cells pulsed with 6 HER2-derived class II–promiscuous peptides via interferon-γ (IFN-γ) enzyme-linked immunospot assay.

Main Outcomes and Measures T-helper type 1 response metrics were anti-HER2 responsivity, repertoire (number of reactive peptides), and cumulative response across 6 peptides (spot-forming cells [SFCs]/106 cells). Anti-HER2 Th1 responses in treatment-naive patients (used as an immunologic baseline) were compared with those in patients completing trastuzumab and chemotherapy; in the latter group, analyses were stratified by recurrence status. Recurrence was defined as any locoregional or distant breast event, or both. Cox regression analysis estimated the instantaneous hazard of recurrence (ie, disease-free survival [DFS]) stratified by anti-HER2 Th1 responsivity.

Results In 95 women with HER2-positive IBC (median [range] age, 49 [24-85] years; 22 treatment-naive, 73 treated with trastuzumab and chemotherapy), depressed anti-HER2 Th1 responsivity (recurrence, 2 of 25 [8%], vs nonrecurrence, 40 of 48 [83%]; P < .001), mean (SD) repertoire (0.1 [0.1] vs 1.5 [0.2]; P < .001), and mean (SD) cumulative response (14.8 [2.0] vs 80.2 [11.0] SFCs/106 cells; P < .001) were observed in patients incurring recurrence (n = 25) compared with patients without recurrence (n = 48). After controlling for confounding, anti-HER2 Th1 responsivity remained independently associated with recurrence (P < .001). This immune disparity was mediated by anti-HER2 CD4+T-bet+IFN-γ+ (Th1)—not CD4+GATA-3+IFN-γ+ (Th2) or CD4+CD25+FoxP3+ (Treg)—phenotypes, and not attributable to immune incompetence. When stratifying trastuzumab plus chemotherapy-treated patients by Th1 responsivity, Th1-nonresponsive patients demonstrated a worse DFS (median, 47 vs 113 months; P < .001) compared with Th1-responsive patients (hazard ratio, 16.9 [95% CI, 3.9-71.4]; P < .001).

Conclusions and Relevance Depressed anti-HER2 Th1 response is a novel immune correlate to recurrence in patients with completely treated HER2-positive IBC. These data underscore a role for immune monitoring in patients with HER2-positive IBC to identify vulnerable populations at risk of treatment failure.