Early onset HER2‐positive breast cancer is associated with germline <i>TP53</i> mutations

Melhem-Bertrandt, Amal; Bojadzieva, Jasmina; Ready, Kaylene; Obeid, Elias; Liu, Diane D.; Gutierrez‐Barrera, Angelica M.; Litton, Jennifer K.; Olopade, Olufunmilayo I.; Hortobágyi, Gabriel N.; Strong, Louise C.; Arun, Banu K.

doi:10.1002/cncr.26377

Cited by 130 publications

(98 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…32,58 The connection of PR positive and a slower histological progress in breast cancer observed in this study might also be a result of a negative association between PR and Her-2 positive in breast cancers 56 caused by the loss of PR protein due to Her-2 overexpression through the PI3K/Akt signaling pathway. 59 Relationship of Her-2, PR, ER, Ki-67 and p53 in signaling transduction pathways In this study, it was found that Her-2 overexpression was negatively connected with PR and ER expression and positively connected with Ki-67 positive and p53 positive, which was consistent with previous reports 30,32,37,44,46,49,53,59,60 This suggests that there might be some relationship among Her-2 and these genes in signal transduction pathways. Through MAPK and PI3K signaling pathways, Her-2 prevents apoptosis and promotes cell proliferation.…”

Section: Discussionsupporting

confidence: 92%

“…28,29 It was found that Her-2 and Tp53 genes were both present on chromosome 17 and there was a strong association between Her-2 overexpression and p53 mutations in breast cancer. 30,31 ER and PR were negatively correlated with Her-2 overexpression. 32,33 The association between Her-2 and Ki-67 in breast cancer patients 5,6,31,34,35 makes Ki-67 an emerging biomarker for breast cancer.…”

Section: Introductionmentioning

confidence: 91%

See 1 more Smart Citation

Comparative study of Her-2, p53, Ki-67 expression and clinicopathological characteristics of breast cancer in a cohort of northern China female patients

Zhang

et al. 2017

Bioengineered

View full text Add to dashboard Cite

The objective was to study the relationship among Her-2, Ki-67, p53 expression and the clinicopathologic characteristics of breast cancer in the patients of northern China. Expression of Her-2, Ki-67, p53 and clinical characteristics of 260 breast cancer patients were retrospectively studied. Her-2 overexpression led to higher incidence rates of infiltrating ductal carcinoma and axillary lymph node metastasis, bigger diameters of the primary tumors, later pTNM staging, and a lower incidence rate of ductal carcinoma in situ (p < 0.05). High expression of ER and PR led to fewer patients classified histologically in higher grade (p D 0.001), while high expression of Ki-67 and p53 caused more patients classified histologically in higher grade (p D 0.001). In patients histologically classified in grade 1 and 2, the expression of Ki-67 and p53 was significantly (p D 0.001) higher, and the expression of ER and PR was significantly lower, in Her-2 positive patients than Her-2 negative patients. Breast cancer with Her-2 overexpression was more likely to recur and metastasize than Her-2 negative breast cancer. Higher coincidence of high expression of p53 and Ki-67 with Her-2 overexpression and more progressed tumors suggested that in addition to p53, Ki-67 might also be a prognostic biomarker of breast cancer.

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 91%

Comparative study of Her-2, p53, Ki-67 expression and clinicopathological characteristics of breast cancer in a cohort of northern China female patients

Zhang

et al. 2017

Bioengineered

View full text Add to dashboard Cite

show abstract

“…Una característica interesante del cáncer de mama asociado a mutaciones en el gen TP53 es que su fenotipo es positivo para los receptores hormonales y para el gen Her2 (16)(17)(18). En el estudio de Mascari, et al, 84 % de los tumores de mama asociados al síndrome de Li Fraumeni fueron positivos para los receptores hormonales de estrógenos y progesterona, y 63 % de los tumores invasivos lo fueron para el gen Her2/neu (16).…”

Section: Síndrome De Li-fraumeni Y Cáncer De Senounclassified

“…En el estudio de Mascari, et al, 84 % de los tumores de mama asociados al síndrome de Li Fraumeni fueron positivos para los receptores hormonales de estrógenos y progesterona, y 63 % de los tumores invasivos lo fueron para el gen Her2/neu (16). En otro estudio presentado en el 2012 por Melhem-Bertrand, et al, en el que se estudiaron mujeres con estudio genético del gen TP53 ante la sospecha del síndrome de Li-Fraumeni, 67 % de los casos de cáncer de mama con mutaciones en dicho gen fueron positivos también para el gen Her2, comparado con 25 % de las pacientes de control con cáncer de mama cuyo resultado fue negativo para las mutaciones en el gen TP53 (18).…”

Section: Síndrome De Li-fraumeni Y Cáncer De Senounclassified

“…Los tumores filoides malignos de mama pueden estar asociados al síndrome de Li-Fraumeni, como en el caso de esta paciente; sin embargo, estos no son tan frecuentes como los tumores de estirpe epitelial (18)(19)(20). Hasta el momento, son pocos los casos reportados de cáncer de mama masculino asociados al síndrome de Li-Fraumeni.…”

Section: Síndrome De Li-fraumeni Y Cáncer De Senounclassified

See 1 more Smart Citation

Síndrome de Li-Fraumeni

Ossa

Molina

Cock-Rada³

2016

biomedica

View full text Add to dashboard Cite

Contribución de los autores:Carlos Andrés Ossa: médico tratante, coordinación del estudio clínico y paraclínico del paciente Gustavo Molina: médico tratante Alicia María Cock-Rada: valoración oncogenética e interpretación de los resultados moleculares Todos los autores participaron en la escritura del manuscrito y en la búsqueda de bibliografía. El síndrome de Li-Fraumeni se caracteriza por la aparición de tumores en múltiples órganos, generalmente a temprana edad. Esta condición hereditaria es causada por mutaciones germinales en el gen TP53, que codifica el gen supresor tumoral p53. Se presenta el caso de una paciente de 31 años con diagnóstico clínico y molecular de síndrome de Li-Fraumeni, que presentó dos tumores sincrónicos a los 31 años: un leiomiosarcoma de antebrazo y un tumor filoides de mama. Tenía el antecedente de un hijo con diagnóstico de carcinoma cortical suprarrenal a los tres años, que falleció a los cinco años debido a la enfermedad. Además, su abuela y su bisabuela maternas habían fallecido de cáncer gástrico a los 56 y 60 años, respectivamente, y la madre y una hermana de su abuelo materno presentaron cáncer de mama pasados los 60 y los 40 años de edad, respectivamente. Después de una asesoría genética, se ordenó hacer la secuenciación completa y el análisis de duplicaciones y deleciones en el gen TP53. El estudio molecular en una muestra de ADN proveniente de linfocitos de sangre periférica reveló la mutación germinal c.527G>T (p.Cys176Phe) en el exón 5 del gen, mutación deletérea descrita anteriormente en tejidos tumorales. Hasta donde se sabe, este es el primer caso que se publica en Colombia de síndrome de Li-Fraumeni con diagnóstico molecular confirmado. El diagnóstico y el manejo del síndrome de Li-Fraumeni deben estar a cargo de un equipo multidisciplinario, y debe contarse con asesoría genética para el paciente y sus familiares. Síndrome de Li-FraumeniPalabras clave: síndrome de Li-Fraumeni, gen TP53, asesoramiento genético, síndromes neoplásicos hereditarios, tumor filoides, Colombia. doi: http://dx.doi.org/10.7705/biomedica.v36i3.2793 Li-Fraumeni syndromeThe Li-Fraumeni syndrome is characterized clinically by the appearance of tumors in multiple organs generally at an early age. This hereditary condition is caused by germinal mutations in the TP53 gene, which codifies for the tumoural suppressor gene p53. We present the case of a patient aged 31 with clinical and molecular diagnosis of Li-Fraumeni syndrome who presented two synchronous tumors: a leiomyosarcoma on the forearm and a phyllodes breast tumour. She had a family history of cancer, including a son diagnosed with a cortical adrenal carcinoma when he was three years old, who died at five from the disease. Furthermore, her maternal grandmother and great-grandmother died of stomach cancer at 56 and 60 years old, respectively, while her other greatgrandmother and a great aunt presented with breast cancer at the ages of 60 and 40, respectively. After genetic counseling, complete sequencing and analysis of duplications and delet...

show abstract

GermlineTP53Mutations in Patients With Early-Onset Colorectal Cancer in the Colon Cancer Family Registry

et al. 2015

View full text Add to dashboard Cite

IMPORTANCE Li-Fraumeni syndrome, usually characterized by germline TP53 mutations, is associated with markedly elevated lifetime risks of multiple cancers, and has been linked to an increased risk of early-onset colorectal cancer. OBJECTIVE To examine the frequency of germline TP53 alterations in patients with early-onset colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS This was a multicenter cross-sectional cohort study of individuals recruited to the Colon Cancer Family Registry (CCFR) from 1998 through 2007 (genetic testing data updated as of January 2015). Both population-based and clinic-based patients in the United States, Canada, Australia, and New Zealand were recruited to the CCFR. Demographic information, clinical history, and family history data were obtained at enrollment. Biospecimens were collected from consenting probands and families, including microsatellite instability and DNA mismatch repair immunohistochemistry results. A total of a 510 individuals diagnosed as having colorectal cancer at age 40 years or younger and lacking a known hereditary cancer syndrome were identified from the CCFR as being potentially eligible. Fifty-three participants were excluded owing to subsequent identification of germline mutations in DNA mismatch repair genes (n = 47) or biallelic MUTYH mutations (n = 6). INTERVENTIONS Germline sequencing of the TP53 gene was performed. Identified TP53 alterations were assessed for pathogenicity using literature and international mutation database searches and in silico prediction models. MAIN OUTCOMES AND MEASURES Frequency of nonsynonymous germline TP53 alterations. RESULTS Among 457 eligible participants (314, population-based; 143, clinic-based; median age at diagnosis, 36 years [range, 15–40 years]), 6 (1.3%; 95%CI, 0.5%–2.8%) carried germline missense TP53 alterations, none of whom met clinical criteria for Li-Fraumeni syndrome. Four of the identified TP53 alterations have been previously described in the literature in probands with clinical features of Li-Fraumeni syndrome, and 2 were novel alterations. CONCLUSIONS AND RELEVANCE In a large cohort of patients with early-onset colorectal cancer, germline TP53 mutations were detected at a frequency comparable with the published prevalence of germline APC mutations in colorectal cancer. With the increasing use of multigene next-generation sequencing panels in hereditary cancer risk assessment, clinicians will be faced with the challenge of interpreting the biologic and clinical significance of germline TP53 mutations in families whose phenotypes are atypical for Li-Fraumeni syndrome.

show abstract

Early onset HER2‐positive breast cancer is associated with germline TP53 mutations

Cited by 130 publications

References 22 publications

Comparative study of Her-2, p53, Ki-67 expression and clinicopathological characteristics of breast cancer in a cohort of northern China female patients

Comparative study of Her-2, p53, Ki-67 expression and clinicopathological characteristics of breast cancer in a cohort of northern China female patients

Síndrome de Li-Fraumeni

GermlineTP53Mutations in Patients With Early-Onset Colorectal Cancer in the Colon Cancer Family Registry

Contact Info

Product

Resources

About