Circulating PIK3CA mutation detection at diagnosis in non-metastatic inflammatory breast cancer patients

Allouchery, V.; Perdrix, A.; Calbrix, Céline; Berghian, Anca; Lequesne, Justine; Fontanilles, Maxime; Leheurteur, Marianne; Étancelin, Pascaline; Sarafan-Vasseur, Nasrin; Fiore, Frédéric Di; Clatot, Florian

doi:10.1038/s41598-021-02643-y

Cited by 6 publications

(5 citation statements)

References 49 publications

(49 reference statements)

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“…A study reported by Arteaga's group characterized the molecular profiling of the residual disease of patients with TNBC [43]. The investigators showed an enrichment of basal-like TNBC samples with MCL1 amplifications, PTEN deletions-mutations and JAK2 amplifications; enrichments occurred in genes constituting cell-cycle regulators and PI3K/ mTOR pathway, confirmed consistently in other studies [44][45][46][47]. Potential actionability of the genomic alterations was suggested, to select postneoadjuvant treatments.…”

Section: Molecular and Immunological Characteristic Of The Residual D...supporting

confidence: 54%

Postneoadjuvant treatment for triple-negative breast cancer

Trapani

Ferraro

Giugliano

et al. 2022

Current Opinion in Oncology

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Purpose of reviewTriple-negative breast cancer (TNBC) has been conventionally associated with poor prognosis, as a result of limited therapeutic options. In the early setting, prognosis is informed by clinical–pathological factors; for patients receiving neoadjuvant treatments, pathological complete response (pCR) is the strongest factor. In this review, we mapped the landscape of clinical trials in the postneoadjuvant space, and identified three patterns of clinical trial design.Recent findingsFor patients at higher risk, effective postneoadjuvant treatments are of paramount importance to address a high clinical need. Postneoadjuvant risk-adapted treatments have demonstrated to improve survival in patients at high of recurrence.SummaryPatients at high risk have indication for adjuvant treatment intensification, informed by baseline clinical, pathological or molecular factors (type 1 approach), on the presence, extent and molecular characteristics of the residual disease at the time of surgery (type 2) or on risk factors assessed in the postsurgical setting (type 3), for example, circulating tumour DNA. Most of the past trials were based on type 2 approaches, for example, with capecitabine and Olaparib. Few trials were based on a type 1 approach, notably pembrolizumab for early TNBC. The clinical validity of type 3 approaches is under investigation in several ongoing trials.

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Section: Molecular and Immunological Characteristic Of The Residual D...supporting

confidence: 54%

Postneoadjuvant treatment for triple-negative breast cancer

Trapani

Ferraro

Giugliano

et al. 2022

Current Opinion in Oncology

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“…A high expression of PI3K is correlated with a larger tumor size, lymph node metastases, advanced tumor stage in TNBC [ 37 ], and unfavorable outcomes in various solid tumors [ 38 , 39 , 40 , 41 ]. The PI3K/mTOR pathway is also strongly activated in IBC tumors [ 42 ], and the PI3K/Akt and PI3K/mTOR pathways are crucial for IBC invasion [ 43 , 44 ]. In addition, PIK3CA is the second most commonly mutated gene after TP53 in both TNBC (16%) and IBC (29.5%) [ 11 , 45 , 46 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of Kinase Targets for Enhancing the Antitumor Activity of Eribulin in Triple-Negative Breast Cell Lines

et al. 2023

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Background: Triple-negative breast cancer (TNBC) is the most aggressive molecular subtype of breast cancer, and current treatments are only partially effective in disease control. More effective combination approaches are needed to improve the survival of TNBC patients. Eribulin mesylate, a non-taxane microtubule dynamics inhibitor, is approved by the U.S. Food and Drug Administration to treat metastatic breast cancer after at least two previous chemotherapeutic regimens. However, eribulin as a single agent has limited therapeutic efficacy against TNBC. Methods: High-throughput kinome library RNAi screening, Ingenuity Pathway Analysis, and STRING analysis were performed to identify target kinases for combination with eribulin. The identified combinations were validated using in vivo and ex vivo proliferation assays. Results: We identified 135 potential kinase targets whose inhibition enhanced the antiproliferation effect of eribulin in TNBC cells, with the PI3K/Akt/mTOR and the MAPK/JNK pathways emerging as the top candidates. Indeed, copanlisib (pan-class I PI3K inhibitor), everolimus (mTOR inhibitor), trametinib (MEK inhibitor), and JNK-IN-8 (pan-JNK inhibitor) produced strong synergistic antiproliferative effects when combined with eribulin, and the PI3K and mTOR inhibitors had the most potent effects in vitro. Conclusions: Our data suggest a new strategy of combining eribulin with PI3K or mTOR inhibitors to treat TNBC.

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“…Plasma-derived DNA is the most popular source of cell free DNA (cfDNA) for tumor follow-up and even for cancer diagnosis (Allouchery et al, 2021). One of its advantages is its simple collection.…”

Section: Discussionmentioning

confidence: 99%

Increased DNA content in stomach fluids: diagnostic implications of a possible new gastric cancer marker

Cadoná

Pelosof

Zitron

et al. 2023

Preprint

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Objective: To investigate the diagnostic and prognostic role of gastric fluid DNA (gfDNA) in gasric cancer (GC) patients and controls submitted to upper digestive endoscopy. Design: The concentration of gfDNA was evaluated in 941 samples, including subjects with normal gastric mucosa (n = 10), peptic diseases (n = 596), pre-neoplastic conditions (n = 99), and cancer (n = 236). gfDNA levels were evaluated according to age, gender, BMI, gastric fluids pH, use of proton-pump inhibitors, GC tumor subtypes, histological grades, clinical stages, and disease progression/outcome. Results: In the non-cancer group, we observed that gfDNA levels are increased in women as compared to men (p=7.44e-4). Remarkably, gfDNA levels are increased in GC patients as compared to non-GC (normal + peptic diseases, p=5.67e-13) and in GC versus pre-neoplastic disease (p=1.53e-6). Similar differences were also seen when more advanced tumors (T3) were compared to early stages (T2 and below) (p=5.97-4). Moreover, our results suggest the prognostic value of gfDNA as GC-patients with higher gfDNA concentrations (<1.28ng/microliter) had increased infiltration of immune cells in the tumor (p=1.06e-3), which parallels with better disease-free survival (p= 0.014). Conclusion: These findings highlight the significance of collecting and studying stomach fluids from gastric cancer patients and reveals the potential impact of this approach as well as its diagnostic and prognostic value for disease management.

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Circulating PIK3CA mutation detection at diagnosis in non-metastatic inflammatory breast cancer patients

Cited by 6 publications

References 49 publications

Postneoadjuvant treatment for triple-negative breast cancer

Postneoadjuvant treatment for triple-negative breast cancer

Identification of Kinase Targets for Enhancing the Antitumor Activity of Eribulin in Triple-Negative Breast Cell Lines

Increased DNA content in stomach fluids: diagnostic implications of a possible new gastric cancer marker

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