Association of Somatic Driver Alterations With Prognosis in Postmenopausal, Hormone Receptor–Positive, HER2-Negative Early Breast Cancer

Luen, Stephen J.; Asher, Rebecca; Lee, Chee Khoon; Savas, Peter; Kammler, Roswitha; Dell’Orto, Patrizia; Biasi, Olivia; Demanse, David; JeBailey, Lellean; Dolan, S. Ranieri; Hackl, Wolfgang; Thuerlimann, Beat; Viale, Giuseppe; Colleoni, Marco; Regan, Meredith M.; Loi, Sherene

doi:10.1001/jamaoncol.2018.1778

Cited by 37 publications

(41 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Structural variations (SV), which alter chromosomal structure and the DNA copy number, are increasingly recognized as major contributors to genome variability [62] . Copy number changes at 11q13 region are associated with several cancer phenotypes such as primary melanoma [63] , breast cancer [64] , [65] , [66] , [67] , [68] , [69] , [70] , head and neck cancers [71] , [72] , [73] , bladder, lung, oral squamous cell, liver and esophageal cancers [ 57 , 74 ], cervical cancer [61] , endocrine tumors (ETs) of pancreas and duodenum [75] , ovarian cancer [74] and prostate cancer [76] . In certain disease conditions, the 11q13 copy number changes span several mega bases (Mb) of DNA [ 77 , 78 ].…”

Section: Fads and Elovl Biochemical Functionsmentioning

confidence: 99%

Polyunsaturated fatty acid biosynthesis pathway and genetics. implications for interindividual variability in prothrombotic, inflammatory conditions such as COVID-19✰,✰✰,★,★★

Kothapalli¹,

Park²,

Brenna

2020

Prostaglandins, Leukotrienes and Essential Fatty Acids

View full text Add to dashboard Cite

show abstract

Section: Fads and Elovl Biochemical Functionsmentioning

confidence: 99%

Polyunsaturated fatty acid biosynthesis pathway and genetics. implications for interindividual variability in prothrombotic, inflammatory conditions such as COVID-19✰,✰✰,★,★★

Kothapalli¹,

Park²,

Brenna

2020

Prostaglandins, Leukotrienes and Essential Fatty Acids

View full text Add to dashboard Cite

show abstract

“…FGFR1 amplification has been associated with poor prognosis in hormone receptor-positive, lymph node-positive breast cancers [ 9 ]. HER2 amplification [ 10 ] or PIK3CA and ESR1 mutations [ 11 – 13 ] have been linked to response to therapy. However, a heterogeneous spectrum of driver alterations characterizes the molecular portrait of invasive breast tumors and their clinical implications remain to be fully elucidated.…”

Section: Introductionmentioning

confidence: 99%

Inter-tumor genomic heterogeneity of breast cancers: comprehensive genomic profile of primary early breast cancers and relapses

et al. 2020

Self Cite

View full text Add to dashboard Cite

Background The breast cancer genome dynamically evolves during malignant progression and recurrence. We investigated the genomic profiles of primary early-stage breast cancers and matched relapses to elucidate the molecular underpinnings of the metastatic process, focusing on potentially actionable alterations in the recurrences. Methods A mono-institutional cohort of 128 patients with breast cancers (n = 68 luminal B HER2, n = 6 luminal B HER2+, n = 1 HER2+ non-luminal, n = 56 triple negative) and at least one recurrence in a timeframe of 17 years was evaluated. Next-generation sequencing comprehensive genomic profiling was performed on 289 formalin-fixed paraffin-embedded (FFPE) samples, including primary tumors and matched relapses. Correlations of genomic aberrations with clinicopathologic factors and time to breast cancer relapse were analyzed. Results Genomic data were available for 188 of 289 FFPE samples that achieved the sequencing quality parameters (failure rate 34.9%), including 106 primary tumors and 82 relapses. All primary and relapse samples harbored at least one genomic alteration, with a median number of six alterations per sample (range 1–16). The most frequent somatic genomic alterations were mutations of TP53 (primary tumors = 49%, relapses = 49%) and PIK3CA (primary tumors = 33%, relapses = 30%). Distinctive genomic alterations of primary tumors were significantly associated with molecular subtypes. TP53, PIK3R1, and NF1 somatic alterations were more frequently detected in triple negative tumors (p value < 0.05); CCND1, FGF3, and FGFR1 copy number gains were recurrently identified in luminal cases (p value < 0.05). Moreover, TP53 mutations and MYC amplification were significantly and independently associated with a shorter time to relapse (p value < 0.05). Molecular subtype changes between primary tumors and relapses were seen in 10 of 128 (7.8%) cases. Most driver genomic alterations (55.8%) were shared between primary tumors and matched recurrences. However, in 39 of 61 cases (63.9%), additional private alterations were detected in the relapse samples only, including 12 patients with potentially actionable aberrations. Conclusions Specific genomic aberrations of primary breast cancers were associated with time to relapse. Primary tumors and matched recurrences showed a core of shared driver genomic aberrations but private actionable alterations have been identified in the relapses.

show abstract

“…Given the variation in these results, it has become increasingly important to understand how the effect of mutations in PIK3CA may be modified by other factors, including medication use. Although several studies have now demonstrated that the presence of PIK3CA mutations modifies the effect of cancer therapies such as trastuzamab and letrozole [10,11], the effect of other medications, including aspirin and other non-steroidal anti-inflammatory drugs (NSAIDS), remains understudied. Aspirin/NSAIDs inhibit the activity of the enzymes cyclooxygenase (COX) 1 and COX-2, which results in a reduction in the synthesis of prostaglandins, which are involved in cell proliferation, apoptosis, migration, and invasion [12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Different associations of tumor PIK3CA mutations and clinical outcomes according to aspirin use among women with metastatic hormone receptor positive breast cancer

McCarthy

Kumar

et al. 2020

BMC Cancer

View full text Add to dashboard Cite

Introduction: The relationships among PIK3CA mutations, medication use and tumor progression remains poorly understood. Aspirin use post-diagnosis may modify components of the PI3K pathway, including AKT and mTOR, and has been associated with lower risk of breast cancer recurrence and mortality. We assessed time to metastasis (TTM) and survival with respect to aspirin use and tumor PIK3CA mutations among women with metastatic breast cancer.Methods: Patients with hormone receptor positive, HER2 negative (HR+/HER2-) metastatic breast cancer treated in 2009-2016 who received tumor genotyping were included. Aspirin use between primary and metastatic diagnosis was extracted from electronic medical records. TTM and survival were estimated using Cox proportional hazards regression. Results: Among 267 women with metastatic breast cancer, women with PIK3CA mutated tumors had longer TTM than women with PIK3CA wildtype tumors (7.1 vs. 4.7 years, p = 0.008). There was a significant interaction between PIK3CA mutations and aspirin use on TTM (p = 0.006) and survival (p = 0.026). PIK3CA mutations were associated with longer TTM among aspirin non-users (HR = 0.60 95% CI:0.44-0.82 p = 0.001) but not among aspirin users (HR = 1.57 0.86-2.84 p = 0.139). Similarly, PIK3CA mutations were associated with reduced mortality among aspirin non-users (HR = 0.70 95% CI:0.48-1.02 p = 0.066) but not among aspirin users (HR = 1.75 95% CI:0.88-3.49 p = 0.110).

show abstract

Association of Somatic Driver Alterations With Prognosis in Postmenopausal, Hormone Receptor–Positive, HER2-Negative Early Breast Cancer

Abstract: ClinicalTrials.gov Identifier: NCT00004205.

Cited by 37 publications

References 45 publications

Polyunsaturated fatty acid biosynthesis pathway and genetics. implications for interindividual variability in prothrombotic, inflammatory conditions such as COVID-19✰,✰✰,★,★★

Polyunsaturated fatty acid biosynthesis pathway and genetics. implications for interindividual variability in prothrombotic, inflammatory conditions such as COVID-19✰,✰✰,★,★★

Inter-tumor genomic heterogeneity of breast cancers: comprehensive genomic profile of primary early breast cancers and relapses

Different associations of tumor PIK3CA mutations and clinical outcomes according to aspirin use among women with metastatic hormone receptor positive breast cancer

Contact Info

Product

Resources

About