Outcome and mutational landscape of patients with PIK3CA-mutated metastatic breast cancer (mBC)

Mosele, Maria Fernanda; Lusque, Amélie; Dien, Alicia Tran; Droin, Nathalie; Tourneau, Christophe Le; Lacroix, Ludovic; Bièche, Ivan; Massard, Christophe; Bertucci, François; André, Fabrice

doi:10.1093/annonc/mdz100

Cited by 8 publications

(6 citation statements)

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“…PIK3CA is mutated in up to 40% of human breast cancers and most alterations occur within the kinase (H1047R) and helical domains (E542K and E545K) of p110α resulting in hyperactivation of PI3K [31,32]. The prognostic impact of PI3CA mutations is still unclear: while in early ER-positive/HER2-negative breast cancer, an association with an increased diseasefree survival has been reported, they seem to decrease prognosis in the advanced setting [33][34][35]. Importantly, the rate of PIK3CA mutations is not increased in MBC as compared to primary breast cancer and the concordance between matched primary and metastatic tissue samples is high [36].…”

Section: Receptor Tyrosine Kinasesmentioning

confidence: 99%

Endocrine-Resistant Breast Cancer: Mechanisms and Treatment

Hartkopf

Grischke

Brucker³

2020

Breast Care

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Background: Endocrine treatment is one of the most effective therapies for estrogen receptor-positive breast cancer. However, most tumors will develop resistance to endocrine therapy as the cancer progresses. This review focuses on the mechanisms and markers of endocrine-resistant breast cancer. In addition, current and future strategies to overcome endocrine resistance are discussed. Summary: Several molecular mechanisms of endocrine resistance have been identified, including alterations in the ESR1 gene or in the PIK-3CA/mTOR pathway. Meanwhile, CDK4/6, mTOR, and PI3K inhibition have shown to improve the efficacy of endocrine treatment and new promising approaches are being developed. Key Message: Overcoming primary or acquired resistance to endocrine treatment remains a major challenge. Since the molecular mechanisms of endocrine resistance are manifold, optimal combination and sequencing strategies will have to be developed in the future.

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Section: Receptor Tyrosine Kinasesmentioning

confidence: 99%

Endocrine-Resistant Breast Cancer: Mechanisms and Treatment

Hartkopf

Grischke

Brucker³

2020

Breast Care

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“…The influence of these molecular aberrations on outcomes is still unclear. Whereas PIK3CA mutation in early hormone receptor positive (HR+)/HER2- breast cancer is associated with a better recurrence-free survival [26] and a better disease-free survival (DFS) [27], recent molecular profiling data from MBC patients seem to indicate that in advanced HR+/HER2- breast cancer, a PIK3CA mutation would lead to a certain resistance to chemotherapy and a poor outcome [28]. In the case of HER2-positive breast cancer, PIK3CA mutations seem to be associated with worse prognosis, either in the advanced and in the early setting [29, 30] .…”

Section: Introductionmentioning

confidence: 99%

Efficacy of PI3K inhibitors in advanced breast cancer

et al. 2019

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The phosphoinositide 3 (PI3)-kinase/Akt signaling pathway has always been a focus of interest in breast cancer due to its role in cell growth, cell proliferation, cell migration and deregulated apoptosis. Its activation has been linked to endocrine resistance and worse prognosis in certain subgroups of breast cancer. In addition, deregulation of the PI3K/Akt pathway including PIK3CA activating mutation is frequently present in breast cancer. Multiple efforts have been carried out to target this pathway, initially with pan-PI3K inhibitors with some hint of activity but hampered by their limiting side-effects. A recent large randomized trial in patients with endocrine-resistant PIK3CA-mutant hormone receptor (HR)-positive tumors led to the approval of the first PI3K inhibitor, alpelisib, in combination with fulvestrant. The specificity of alpelisib against the p110α catalytic isoform provided additional efficacy and a better toxicity profile. In this review, we summarize the main research with PI3K inhibitors in breast cancer and we provide some insight of potential future combinations of this treatment in breast cancer patients.

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“…The impact of these mutations on the outcome of BC is still not clear. It has been reported in some studies that early hormone receptor positive (HR+ive) /HER2-ive breast cancer with PIK3CA mutation is associated with a better recurrence-free survival [ 41 ] and a better disease-free survival (DFS) [ 42 ] whereas recent molecular profiling data from metastatic BC patients indicate that in advanced HR+/HER2- BC, a PIK3CA mutation would lead to a certain resistance to chemotherapy and a poor outcome [ 43 ]. Another important finding from preclinical study shows that PI3K/AKT/mTOR pathway plays a potential role in secondary endocrine resistance in HR+BC [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

Landscape of clinically actionable mutations in breast cancer ‘A cohort study’

Ghosh

Naik

Lingaraju

et al. 2021

Translational Oncology

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Breast cancer (BC) is a heterogeneous disease. Numerous chemotherapeutic agents are available for early stage or advanced/metastatic breast cancer to provide maximum benefit with minimum side effects. However, the clinical outcome of patients with the same clinical and pathological characteristics and treated with similar treatments may show major differences and a vast majority of patients still develop treatment resistance and eventually succumb to disease. It remains an unmet need to identify specific molecular defects, new biomarkers to enable clinicians to adopt individualized treatment for every patient in terms of endocrine, chemotherapy or targeted therapy which will improve clinical outcomes in BC. Our study aimed to identify frequent hotspot mutation profile in BC by targeted deep sequencing in cancer-related genes using Illumina Truseq amplicon/Swift Accel-Amplicon panel and MiSeq technology in an IRB-approved prospective study in a CLIA compliant laboratory. All the cases had pathology review for stage, histological type, hormonal status and Ki-67. Data was processed using Strand NGS™. Mutations identified in the tumor were assessed for ‘actionability’ i.e. response to therapy and impact on prognosis.

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Outcome and mutational landscape of patients with PIK3CA-mutated metastatic breast cancer (mBC)

Cited by 8 publications

References 0 publications

Endocrine-Resistant Breast Cancer: Mechanisms and Treatment

Endocrine-Resistant Breast Cancer: Mechanisms and Treatment

Efficacy of PI3K inhibitors in advanced breast cancer

Landscape of clinically actionable mutations in breast cancer ‘A cohort study’

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