Evidence map›Paper›PMID 27177864›Full record

ArticleAnnals of oncology : official journal of the European Society for Medical Oncology2016

PIK3CA mutations are associated with reduced pathological complete response rates in primary HER2-positive breast cancer: pooled analysis of 967 patients from five prospective trials investigating lapatinib and trastuzumab.

S Loibl, I Majewski, V Guarneri, V Nekljudova, E Holmes, E Bria, C Denkert, C Schem, C Sotiriou, S Loi and 6 more

Erratum issuedOpen access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Annals of oncology : official journal of the European Society for Medical Oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 124 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
124citing papers in PubMed, 6 pooled it
11.0field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

124 citing papers in PubMed, 6 syntheses or guidelines pooled it, 226 citations in OpenAlex.

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64 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 10 institutions in 7 countries.

S LoiblGerman Breast Group, Neu-Isenburg, Germany sibylle.loibl@gbg.de.
I MajewskiThe Netherlands Cancer Institute, Amsterdam, The Netherlands.
V GuarneriDepartment of Surgery, Oncology and Gastroenterology, University of Padua, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy.
V NekljudovaGerman Breast Group, Neu-Isenburg, Germany.
E HolmesFrontier Science Scotland, Kincraig, UK.
E BriaDepartment of Medical Oncology, University of Verona, Verona, Italy.
C DenkertInstitute of Pathology, Charité Universitätsmedizin Berlin, and German Cancer Consortium (DKTK), Berlin.
C SchemDepartment of Obstetrics and Gynecology, University Hospital Kiel, Kiel, Germany.
C SotiriouInstitut Jules Bordet, Université Libre de Bruxelles, Brussel, Belgium.
S LoiPeter MacCallum Cancer Centre, East Melbourne, Australia.
M UntchDepartment of Obstetrics and Gynecology, Helios-Klinikum, Berlin-Buch, Germany.
P ConteDepartment of Surgery, Oncology and Gastroenterology, University of Padua, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy.
R BernardsThe Netherlands Cancer Institute, Amsterdam, The Netherlands.
M PiccartInstitut Jules Bordet, Université Libre de Bruxelles, Brussel, Belgium.
G von MinckwitzGerman Breast Group, Neu-Isenburg, Germany.
J BaselgaMemorial Sloan-Kettering Cancer Center, New York, USA.
German Breast group · DEThe Netherlands Cancer Institute · NLUniversité Libre de Bruxelles · BEUniversity of Padua · ITFrontier Agriculture (United Kingdom) · GBGerman Cancer Society · DEHelios Hospital Berlin-Buch · DEMemorial Sloan Kettering Cancer Center · USPeter MacCallum Cancer Centre · AUUniversity of Verona · IT

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4M
NCI NIH HHS P30 CA008748
6 · The paper itself

Abstract

backgroundThe predictive value of PIK3CA mutations in HER2 positive (HER2+) breast cancer treated with neoadjuvant anti-HER2 and chemotherapy has been reported, but the power for subgroup analyses was lacking. PATIENTS AND

methodsWe combined individual patient data from five clinical trials evaluating PIK3CA mutations and associations with pathological complete response (pCR), disease-free survival (DFS) and overall survival (OS). Patients received either trastuzumab (T), lapatinib (L) or the combination T/L in addition to a taxane-based chemotherapy. PIK3CA was genotyped in tumour biopsies taken before therapy.

resultsA total of 967 patients were included in this analysis; the median follow-up is 47 months. Overall, the pCR rate was significantly lower in the PIK3CA mutant compared with the wild-type group (16.2% versus 29.6%; P < 0.001). Within the hormone-receptor positive (HR+) subgroup, the PIK3CA mutant group had a pCR rate of only 7.6% compared with 24.2% in the wild-type group (P < 0.001). In contrast, in the HER2+/HR- group, there was no difference in pCR (27.2% versus 36.4%; P = 0.125) according to PIK3CA mutation status (interaction test P = 0.036). According to treatment arm, the pCR rate for mutant versus wild-type was 20.3% versus 27.1% for T (P = 0.343), 11.3% versus 16.9% for L (P = 0.369) and 16.7% versus 39.1% for T/L (P < 0.001). In the HR+ T/L group, the pCR rate was 5.5% versus 33.9% (interaction between HR and PIK3CA genotype P = 0.008). DFS and OS were not significantly different by mutation status, though the incidence rate of events was low. However, HR+/PIK3CA mutant patients seemed to have significantly worse DFS {hazard ratio (HR) 1.56 [95% confidence interval (CI) 1.00-2.45], P = 0.050; Pinteraction = 0.021}. T/L tended to improve DFS compared with T in the wild-type cohort, especially in the HR- group [HR 0.72, 95% CI (0.41-1.25), P = 0.242].

conclusionOverall PIK3CA mutant/HER2+ tumours had significantly lower pCR rates compared with wild-type tumours, however mainly confined to the HR+/PIK3CA mutant population. No definite conclusions can be drawn regarding survival.

Indexed as

AdultAgedAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBreast NeoplasmsChemotherapy, AdjuvantClass I Phosphatidylinositol 3-KinasesClinical Trials as TopicDisease-Free SurvivalErb-b2 Receptor Tyrosine KinasesFemaleGenotypeHumansLapatinibMiddle AgedAntibodies, Monoclonal, HumanizedBiomarkers, TumorClass I Phosphatidylinositol 3-KinasesERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesLapatinibPIK3CA protein, humanQuinazolinesTrastuzumabdouble anti-HER2 treatmentHER2+ breast cancerneoadjuvantpathological complete responsePIK3CAsurvival

Identifiers

PMID27177864
PMCPMC6279074
OpenAlexW2352525452

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.