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PI3K mutations in breast cancer: prognostic and therapeutic implications.

Mukohara T - Breast Cancer (Dove Med Press) (2015)

Bottom Line: The PI3K pathway is the most frequently enhanced oncogenic pathway in breast cancer.Since the first discovery of PIK3CA mutations in solid malignancies in 2004, numerous studies have revealed the prognostic and therapeutic implications of these mutations.Given that PIK3CA-mutant breast cancer appears to have a distinct tumor biology, development of more individualized targeted therapies based on the PIK3CA genotype is awaited.

View Article: PubMed Central - PubMed

Affiliation: Cancer Center and Division of Medical Oncology/Hematology, Kobe University Hospital, Kobe, Japan.

ABSTRACT
The PI3K pathway is the most frequently enhanced oncogenic pathway in breast cancer. Among mechanisms of PI3K enhancement, PIK3CA mutations are most frequently (∼30%) observed, along with protein loss of PTEN. Since the first discovery of PIK3CA mutations in solid malignancies in 2004, numerous studies have revealed the prognostic and therapeutic implications of these mutations. Although many issues remain unconfirmed, some have been carved in stone by the level of consistency they have shown among studies: 1) PIK3CA mutations are most likely to be observed in ER-positive/HER2-negative tumors, and are associated with other good prognostic characters; 2) PIK3CA mutations can coexist with other PI3K-enhancing mechanisms, such as HER2 amplification and PTEN protein loss; 3) PIK3CA mutations are potentially a good prognostic marker; 4) PIK3CA may predict a poorer tumor response to trastuzumab-based therapies, but its impact on disease-free survival and overall survival is uncertain; and 5) based on reports of early clinical trials, PIK3CA mutations do not guarantee a dramatic response to PI3K inhibitors. Collectively, there is currently no sufficient evidence to recommend routine genotyping of PIK3CA in clinical practice. Given that PIK3CA-mutant breast cancer appears to have a distinct tumor biology, development of more individualized targeted therapies based on the PIK3CA genotype is awaited.

No MeSH data available.


Related in: MedlinePlus

Difference between prognostic and predictive biomarkers.
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f3-bctt-7-111: Difference between prognostic and predictive biomarkers.

Mentions: A number of studies have evaluated the clinical relevance of PI3K mutations, some of which asked if they have prognostic or predictive value, or both. Prognostic and predictive factors are often confused. The original definition of a prognostic biomarker is a marker that provides information on the likely course of the cancer disease in an untreated individual. In contrast, predictive biomarkers are defined as markers that can be used to identify subpopulations of patients who are most likely to respond to a given therapy. Distinguishing these terms thus requires the use of biomarker-positive and -negative subgroups and treated and untreated subgroups (Figure 3). However, if time-independent end points such as response rate (RR) and pathologic complete response (p-CR) rate are considered, a cohort in which all patients are treated with a given therapy will provide a predictive biomarker, because p-CR rate as an example in untreated patients would have been 0, regardless of the biomarker status.


PI3K mutations in breast cancer: prognostic and therapeutic implications.

Mukohara T - Breast Cancer (Dove Med Press) (2015)

Difference between prognostic and predictive biomarkers.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4440424&req=5

f3-bctt-7-111: Difference between prognostic and predictive biomarkers.
Mentions: A number of studies have evaluated the clinical relevance of PI3K mutations, some of which asked if they have prognostic or predictive value, or both. Prognostic and predictive factors are often confused. The original definition of a prognostic biomarker is a marker that provides information on the likely course of the cancer disease in an untreated individual. In contrast, predictive biomarkers are defined as markers that can be used to identify subpopulations of patients who are most likely to respond to a given therapy. Distinguishing these terms thus requires the use of biomarker-positive and -negative subgroups and treated and untreated subgroups (Figure 3). However, if time-independent end points such as response rate (RR) and pathologic complete response (p-CR) rate are considered, a cohort in which all patients are treated with a given therapy will provide a predictive biomarker, because p-CR rate as an example in untreated patients would have been 0, regardless of the biomarker status.

Bottom Line: The PI3K pathway is the most frequently enhanced oncogenic pathway in breast cancer.Since the first discovery of PIK3CA mutations in solid malignancies in 2004, numerous studies have revealed the prognostic and therapeutic implications of these mutations.Given that PIK3CA-mutant breast cancer appears to have a distinct tumor biology, development of more individualized targeted therapies based on the PIK3CA genotype is awaited.

View Article: PubMed Central - PubMed

Affiliation: Cancer Center and Division of Medical Oncology/Hematology, Kobe University Hospital, Kobe, Japan.

ABSTRACT
The PI3K pathway is the most frequently enhanced oncogenic pathway in breast cancer. Among mechanisms of PI3K enhancement, PIK3CA mutations are most frequently (∼30%) observed, along with protein loss of PTEN. Since the first discovery of PIK3CA mutations in solid malignancies in 2004, numerous studies have revealed the prognostic and therapeutic implications of these mutations. Although many issues remain unconfirmed, some have been carved in stone by the level of consistency they have shown among studies: 1) PIK3CA mutations are most likely to be observed in ER-positive/HER2-negative tumors, and are associated with other good prognostic characters; 2) PIK3CA mutations can coexist with other PI3K-enhancing mechanisms, such as HER2 amplification and PTEN protein loss; 3) PIK3CA mutations are potentially a good prognostic marker; 4) PIK3CA may predict a poorer tumor response to trastuzumab-based therapies, but its impact on disease-free survival and overall survival is uncertain; and 5) based on reports of early clinical trials, PIK3CA mutations do not guarantee a dramatic response to PI3K inhibitors. Collectively, there is currently no sufficient evidence to recommend routine genotyping of PIK3CA in clinical practice. Given that PIK3CA-mutant breast cancer appears to have a distinct tumor biology, development of more individualized targeted therapies based on the PIK3CA genotype is awaited.

No MeSH data available.


Related in: MedlinePlus