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The Long-HER Study: Clinical and Molecular Analysis of Patients with HER2+ Advanced Breast Cancer Who Become Long-Term Survivors with Trastuzumab-Based Therapy
by
Manso, Luis
, Berges-Soria, Julia
, Catalán, Gustavo
, Ciruelos, Eva M.
, Gallego, José V. Álvarez
, López-Vacas, Rocío
, Santaballa, Ana
, López, Isabel Álvarez
, López, José Miramón
, Margeli, Mireia
, Farre, Xavier González
, Mendiola, Cesar
, Zamora, Pilar
, Bofill, Francisco J. Salvador
, Crespo, Carmen
, Lao, Juan
, Borrego, Manuel Ruiz
, Espinosa, Enrique
, Vara, Juan A. Fresno
, Gámez-Pozo, Angelo
, Calero, Juan L. Bayo
, Pérez Carrión, Ramón M.
, Afonso, Ruth
in
Breast cancer
/ Cancer research
/ Care and treatment
/ Prognosis
/ Trastuzumab
2014
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The Long-HER Study: Clinical and Molecular Analysis of Patients with HER2+ Advanced Breast Cancer Who Become Long-Term Survivors with Trastuzumab-Based Therapy
by
Manso, Luis
, Berges-Soria, Julia
, Catalán, Gustavo
, Ciruelos, Eva M.
, Gallego, José V. Álvarez
, López-Vacas, Rocío
, Santaballa, Ana
, López, Isabel Álvarez
, López, José Miramón
, Margeli, Mireia
, Farre, Xavier González
, Mendiola, Cesar
, Zamora, Pilar
, Bofill, Francisco J. Salvador
, Crespo, Carmen
, Lao, Juan
, Borrego, Manuel Ruiz
, Espinosa, Enrique
, Vara, Juan A. Fresno
, Gámez-Pozo, Angelo
, Calero, Juan L. Bayo
, Pérez Carrión, Ramón M.
, Afonso, Ruth
in
Breast cancer
/ Cancer research
/ Care and treatment
/ Prognosis
/ Trastuzumab
2014
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The Long-HER Study: Clinical and Molecular Analysis of Patients with HER2+ Advanced Breast Cancer Who Become Long-Term Survivors with Trastuzumab-Based Therapy
by
Manso, Luis
, Berges-Soria, Julia
, Catalán, Gustavo
, Ciruelos, Eva M.
, Gallego, José V. Álvarez
, López-Vacas, Rocío
, Santaballa, Ana
, López, Isabel Álvarez
, López, José Miramón
, Margeli, Mireia
, Farre, Xavier González
, Mendiola, Cesar
, Zamora, Pilar
, Bofill, Francisco J. Salvador
, Crespo, Carmen
, Lao, Juan
, Borrego, Manuel Ruiz
, Espinosa, Enrique
, Vara, Juan A. Fresno
, Gámez-Pozo, Angelo
, Calero, Juan L. Bayo
, Pérez Carrión, Ramón M.
, Afonso, Ruth
in
Breast cancer
/ Cancer research
/ Care and treatment
/ Prognosis
/ Trastuzumab
2014
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The Long-HER Study: Clinical and Molecular Analysis of Patients with HER2+ Advanced Breast Cancer Who Become Long-Term Survivors with Trastuzumab-Based Therapy
Journal Article
The Long-HER Study: Clinical and Molecular Analysis of Patients with HER2+ Advanced Breast Cancer Who Become Long-Term Survivors with Trastuzumab-Based Therapy
2014
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Overview
Trastuzumab improves survival outcomes in patients with HER2+ metastatic breast cancer. The Long-Her study was designed to identify clinical and molecular markers that could differentiate long-term survivors from patients having early progression after trastuzumab treatment. Data were collected from women with HER2-positive metastatic breast cancer treated with trastuzumab that experienced a response or stable disease during at least 3 years. Patients having a progression in the first year of therapy with trastuzumab were used as a control. Genes related with trastuzumab resistance were identified and investigated for network and gene functional interrelation. Models predicting poor response to trastuzumab were constructed and evaluated. Finally, a mutational status analysis of selected genes was performed in HER2 positive breast cancer samples. 103 patients were registered in the Long-HER study, of whom 71 had obtained a durable complete response. Median age was 58 years. Metastatic disease was diagnosed after a median of 24.7 months since primary diagnosis. Metastases were present in the liver (25%), lungs (25%), bones (23%) and soft tissues (23%), with 20% of patients having multiple locations of metastases. Median duration of response was 55 months. The molecular analysis included 35 patients from the group with complete response and 18 patients in a control poor-response group. Absence of trastuzumab as part of adjuvant therapy was the only clinical factor associated with long-term survival. Gene ontology analysis demonstrated that PI3K pathway was associated with poor response to trastuzumab-based therapy: tumours in the control group usually had four or five alterations in this pathway, whereas tumours in the Long-HER group had two alterations at most. Trastuzumab may provide a substantial long-term survival benefit in a selected group of patients. Whole genome expression analysis comparing long-term survivors vs. a control group predicted early progression after trastuzumab-based therapy. Multiple alterations in genes related to the PI3K-mTOR pathway seem to be required to confer resistance to this therapy.
Publisher
Public Library of Science
Subject
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