Prospective Biomarker Analysis of the Randomized CHER-LOB Study Evaluating the Dual Anti-HER2 Treatment With Trastuzumab and Lapatinib Plus Chemotherapy as Neoadjuvant Therapy for HER2-Positive Breast Cancer.

BACKGROUND: The CHER-LOB randomized phase II study showed that the combination of lapatinib and trastuzumab plus chemotherapy increases the pathologic complete remission (pCR) rate compared with chemotherapy plus either trastuzumab or lapatinib. A biomarker program was prospectively planned to identify potential predictors of sensitivity to different treatments and to evaluate treatment effect on tumor biomarkers. MATERIALS AND METHODS: Overall, 121 breast cancer patients positive for human epidermal growth factor 2 (HER2) were randomly assigned to neoadjuvant chemotherapy plus trastuzumab, lapatinib, or both trastuzumab and lapatinib. Pre- and post-treatment samples were centrally evaluated for HER2, p95-HER2, phosphorylated AKT (pAKT), phosphatase and tensin homolog, Ki67, apoptosis, and PIK3CA mutations. Fresh-frozen tissue samples were collected for genomic analyses. RESULTS: A mutation in PIK3CA exon 20 or 9 was documented in 20% of cases. Overall, the pCR rates were similar in PIK3CA wild-type and PIK3CA-mutated patients (33.3% vs. 22.7%; p = .323). For patients receiving trastuzumab plus lapatinib, the probability of pCR was higher in PIK3CA wild-type tumors (48.4% vs. 12.5%; p = .06). Ki67, pAKT, and apoptosis measured on the residual disease were significantly reduced from baseline. The degree of Ki67 inhibition was significantly higher in patients receiving the dual anti-HER2 blockade. The integrated analysis of gene expression and copy number data demonstrated that a 50-gene signature specifically predicted the lapatinib-induced pCR. CONCLUSION: PIK3CA mutations seem to identify patients who are less likely to benefit from dual anti-HER2 inhibition. p95-HER2 and markers of phosphoinositide 3-kinase pathway deregulation are not confirmed as markers of different sensitivity to trastuzumab or lapatinib. IMPLICATIONS FOR PRACTICE: HER2 is currently the only validated marker to select breast cancer patients for anti-HER2 treatment; however, it is becoming evident that HER2-positive breast cancer is a heterogeneous disease. In addition, more and more new anti-HER2 treatments are becoming available. There is a need to identify markers of sensitivity to different treatments to move in the direction of treatment personalization. This study identified PIK3CA mutations as a potential predictive marker of resistance to dual anti-HER2 treatment that should be further studied in breast cancer

Branching fraction and CP asymmetries of B0→KS0KS0KS0

We present measurements of the branching fraction and time-dependent CP-violating asymmetries in B0→K0SK0SK0S decays based on 227×106 Υ(4S)→BB decays collected with the BABAR detector at the PEP-II asymmetric-energy B factory at SLAC. We obtain a branching fraction of (6.9+0.9−0.8±0.6)×10−6, and CP asymmetries C=−0.34+0.28−0.25±0.05 and S=−0.71+0.38−0.32±0.04, where the first uncertainties are statistical and the second systematic

Branching fraction and CP asymmetries of B0→KS0KS0KS0

We present measurements of the branching fraction and time-dependent CP-violating asymmetries in B0→K0SK0SK0S decays based on 227×106 Υ(4S)→BB decays collected with the BABAR detector at the PEP-II asymmetric-energy B factory at SLAC. We obtain a branching fraction of (6.9+0.9−0.8±0.6)×10−6, and CP asymmetries C=−0.34+0.28−0.25±0.05 and S=−0.71+0.38−0.32±0.04, where the first uncertainties are statistical and the second systematic

Improved Measurement of the Cabibbo-Kobayashi-Maskawa Angle α Using B0(B¯)→ρ+ρ- Decays

We present results from an analysis of B0(B̅ 0)→ρ+ρ- using 232×106 Υ(4S)→BB̅ decays collected with the BABAR detector at the PEP-II asymmetric-energy B factory at SLAC. We measure the longitudinal polarization fraction fL=0.978±0.014(stat)+0.021/-0.029(syst) and the CP-violating parameters SL=-0.33±0.24(stat)+0.08/-0.14(syst) and CL=-0.03±0.18(stat)±0.09(syst). Using an isospin analysis of B→ρρ decays, we determine the unitarity triangle parameter α. The solution compatible with the standard model is α=(100±13)°

Improved measurement of the Cabibbo-Kobayashi-Maskawa angle α using B0(B)→p+p- decays

We present results from an analysis of B0(B¯¯¯0)→ρ+ρ− using 232×106 Υ(4S)→BB¯¯¯ decays collected with the BABAR detector at the PEP-II asymmetric-energy B factory at SLAC. We measure the longitudinal polarization fraction fL=0.978±0.014(stat)+0.021−0.029(syst) and the CP-violating parameters SL=−0.33±0.24(stat)+0.08−0.14(syst) and CL=−0.03±0.18(stat)±0.09(syst). Using an isospin analysis of B→ρρ decays, we determine the unitarity triangle parameter α. The solution compatible with the standard model is α=(100±13)°

Measurement of the CP violating asymmetry amplitude sin 2beta

We present results on time-dependent CP-violating asymmetries in neutral B decays to several CP eigenstates. The measurements use a data sample of about 88 million Y(4S) --> B Bbar decays collected between 1999 and 2002 with the BABAR detector at the PEP-II asymmetric-energy B Factory at SLAC. We study events in which one neutral B meson is fully reconstructed in a final state containing a charmonium meson and the other B meson is determined to be either a B0 or B0bar from its decay products. The amplitude of the CP-violating asymmetry, which in the Standard Model is proportional to sin2beta, is derived from the decay-time distributions in such events. We measure sin2beta = 0.741 +/- 0.067 (stat) +/- 0.034 (syst) and |lambda| = 0.948 +/- 0.051 (stat) +/- 0.030 (syst). The magnitude of lambda is consistent with unity, in agreement with the Standard Model expectation of no direct CP violation in these modes.Comment: 7 pages, 2 postscript figures, submitted to PR

Measurement of branching fractions and charge asymmetries for exclusive B decays to charmonium

We report measurements of branching fractions and charge asymmetries of exclusive decays of neutral and charged B mesons into two-body final states containing a charmonium state and a light strange meson. The charmonium mesons considered are J/ψ, ψ(2S) and χc1, and the light meson is either K or K∗. We use a sample of about 124×106 BB¯¯¯ pairs collected with the BABAR detector at the PEP-II storage ring at the Stanford Linear Accelerator Center

Search for strange-pentaquark production in e+e− annihilation at √s=10.58 GeV

We search for strange pentaquark states that have been previously reported by other experiments -- the Θ(1540)+, Ξ5(1860)−−, and Ξ5(1860)0 -- in 123 fb−1 of data recorded with the BaBar detector at the PEP-II e+e− storage ring. We find no evidence for these states and set 95% confidence level upper limits on the number of Θ(1540)+ and Ξ5(1860)−− pentaquarks produced per e+e− annihilation event that are about eight and four times lower than the rates measured for ordinary baryons of similar mass