Genetic testing in a cohort of young patients with HER2-amplified breast cancer

Eccles, Diana; Li, N.; Handwerker, R.; Maishman, Tom; Copson, Ellen; Durcan, Lorraine; Gerty, Sue; Jones, Louise; Evans, D. Gareth; Haywood, Linda; Campbell, Ian

doi:10.1093/annonc/mdv592

Cited by 22 publications

(15 citation statements)

References 18 publications

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“…The strategy of adding oxaliplatin weekly to fluoropyrimidine-based chemotherapy was well studied. Except the CAO/ARO/AIO-04 trail, results from randomized phase III trials: STAR-01, ACCORD 12, NASPBR-04, and PETACC-6 showed that adding oxaliplatin to 5-FU/capecitabine-based preoperative CRT increased acute toxicity, but failed to improve the pCR rate and disease free or overall survival 10 - 13 , 17 . The CAO/ARO/AIO-04 trail with more than 1250 patients recruited reported a significant improvement of pCR rate (13% vs. 17%, P=0.04) and 3-years DFS (71.2% vs. 75.9%, P=0.03).…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, several large randomized phases III trials tested the efficacy of adding oxaliplatin to the multimodal neoadjuvant treatment for LARC. However, except the German CAO/ARO/AIO-04 study showing an improved disease free survival, integrating oxaliplatin into the combined modality strategies failed to show a survival benefit 10 - 13 . As a result, the strategy of simply adding oxaliplatin concomitant to conventional CRT remains unsatisfactory.…”

Section: Introductionmentioning

confidence: 99%

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Long-Term Outcome of Oxaliplatin and Capecitabine (XELOX) Concomitant with Neoadjuvant Radiotherapy and Extended to the Resting Period in High Risk Locally Advanced Rectal Cancer

Tang¹,

Wu²,

Bai³

et al. 2018

J. Cancer

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Purpose: This study aimed at investigating the long-term outcomes of oxaliplatin and capecitabine (XELOX) administered concurrently with preoperative radiation and extended to the resting period in patients with high-risk locally advanced rectal cancer (LARC).Methods: From January 2010 to December 2013, 45 patients were recruited. Study treatment consisted two cycles of XELOX regimen concomitant with preoperative radiation and then followed by an additional cycle of XELOX regimen between completion of neoadjuvant radiotherapy and surgery. Disease-free survival (DFS) time and overall survival (OS) time were analyzed.Results: The median follow-up was 51 months. Twelve (26.7%) patients developed local recurrence or distant metastasis, including 10 (22.2%) patients developing distant metastasis only, 1 (2.2%) patient local recurrence only, and 1 (2.2%) patient both local recurrence and distant metastasis. The estimated 3-year DFS and OS was 75.5% (95% CI, 63.0%-88.0%) and 88.6% (95% CI, 98.0%-79.2%), respectively. Receiving adjuvant chemotherapy was a significant predictor for DFS, with hazard ratio 0.24 (95% CI: 0.08-0.74).Conclusion: This intensified strategy with oxaliplatin and capecitabine (XELOX) administered concomitantly with neoadjuvant radiotherapy and then extended to the resting period in high-risk LARC patients is efficient. The long-term outcome is promising. Further study of this strategy is warranted.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Long-Term Outcome of Oxaliplatin and Capecitabine (XELOX) Concomitant with Neoadjuvant Radiotherapy and Extended to the Resting Period in High Risk Locally Advanced Rectal Cancer

Tang¹,

Wu²,

Bai³

et al. 2018

J. Cancer

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“…Eccles et al [39] also classified patients for TP53 screening taking into consideration HER2 status (score 3 +) from a large UK cohort study. Using this approach, 3% (9/304) of women were diagnosed with HER2-amplified BC ≤ 40 years of age.…”

Section: Discussionmentioning

confidence: 99%

Prevalence of germline TP53 variants among early-onset breast cancer patients from Polish population

et al. 2020

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Background The objective of this study was to determine spectrum and prevalence of germline mutations in TP53 gene among Polish women with early-onset breast cancer (BC), which has not been determined until now. Methods A cohort of 100 females with BC diagnosed ≤ 30 years of age and with a positive family history of cancer was used as a discovery cohort. 1880 women with BC ≤ 45 years old and a control group of 2000 healthy women were genotyped as a replication phase of this study. Results Four heterozygous pathogenic missense mutations were detected in a group of 100 patients with early-onset breast cancer. On the basis of software prediction and available literature data, all these variants were defined as pathogenic. None of these TP53 variants were detected among 1880 breast cancer patients and 2000 healthy controls. No large mutations were found among early-onset cases using MLPA reaction. Conclusion Germline pathogenic TP53 variants were found in 4% early-onset Polish BC patients. No founder mutations were identified in Polish population. To improve the treatment and surveillance screening, the search for germline TP53 pathogenic variants is recommended for all female BC cases diagnosed ≤ 30 years old.

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“…Amplification of HER2 has been reported as more common in women who carry a TP53 pathogenic variant compared with the population as a whole (Melhem-Bertrandt et al, 2012). In studies of patients with HER2+ breast tumors in the absence of LFS criteria, the TP53 frequency was higher, reported as 7.0% for women diagnosed before 31 years (Eccles et al, 2016), but only 0.5% when women were diagnosed before the age of 50 years (Rath et al, 2013).…”

Section: Tp53-targeted Studies: Frequency Of Tp53 Carriers In Nonconvmentioning

confidence: 99%

Current review ofTP53pathogenic germline variants in breast cancer patients outside Li-Fraumeni syndrome

2018

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Pathogenic germline variants in TP53 predispose carriers to the multi‐cancer Li‐Fraumeni syndrome (LFS). Widespread multigene panel testing is identifying TP53 pathogenic variants in breast cancer patients outside the strict clinical criteria recommended for LFS testing. We aimed to assess frequency and clinical implications of TP53 pathogenic variants in breast cancer cohorts ascertained outside LFS. Classification of TP53 germline variants reported in 59 breast cancer studies, and publicly available population control sets was reviewed and identified evidence for misclassification of variants. TP53 pathogenic variant frequency was determined for: breast cancer studies grouped by ascertainment characteristics; breast cancer cohorts undergoing panel testing; and population controls. Early age of breast cancer onset, regardless of family history or BRCA1/BRCA2 previous testing, had the highest pick‐up rate for TP53 carriers. Patients at risk of hereditary breast cancer unselected for features of LFS carried TP53 pathogenic variants at a frequency comparable to that of other non‐BRCA1/2 breast cancer predisposing genes, and ∼threefold more than reported in population controls. These results have implications for the implementation of TP53 testing in broader clinical settings, and suggest urgent need to investigate cancer risks associated with TP53 pathogenic variants in individuals outside the LFS spectrum.

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Genetic testing in a cohort of young patients with HER2-amplified breast cancer

Cited by 22 publications

References 18 publications

Long-Term Outcome of Oxaliplatin and Capecitabine (XELOX) Concomitant with Neoadjuvant Radiotherapy and Extended to the Resting Period in High Risk Locally Advanced Rectal Cancer

Long-Term Outcome of Oxaliplatin and Capecitabine (XELOX) Concomitant with Neoadjuvant Radiotherapy and Extended to the Resting Period in High Risk Locally Advanced Rectal Cancer

Prevalence of germline TP53 variants among early-onset breast cancer patients from Polish population

Current review ofTP53pathogenic germline variants in breast cancer patients outside Li-Fraumeni syndrome

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