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Prognostic role of PIK3CA mutations and their association with hormone receptor expression in breast cancer: a meta-analysis.

Pang B, Cheng S, Sun SP, An C, Liu ZY, Feng X, Liu GJ - Sci Rep (2014)

Bottom Line: PIK3CA mutations were not associated with OS (HR 1.06, 95%CI 0.67-1.67, p = 0.81) or RFS (HR 0.86, 95%CI 0.53-1.40, p = 0.55) in HR-positive BCa patients.In conclusion, PIK3CA mutations were significantly related to ER/PR expression and RFS in unsorted BCa patients.And PIK3CA mutations alone may have limited prognostic value for HR-positive BCa patients.

View Article: PubMed Central - PubMed

Affiliation: Clinical laboratory, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beixian Ge 5#, XiCheng District, Beijing 100053, China.

ABSTRACT
The phosphatidylinositol-4, 5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) gene is frequently mutated in breast cancer (BCa). Sex hormone receptors (HRs), including estrogen receptor (ER) and progesterone receptor (PR) play pivotal roles in BCa. In this study, we evaluated the association between PIK3CA mutations and ER/PR expression and the prognostic role of PIK3CA mutations in BCa patients, and in particular, HR-positive BCa. Thirty-two studies involving 5719 cases of BCa obtained from database searches were examined. PIK3CA gene mutations correlated significantly with ER/PR expression (p < 0.00001) and relapse-free survival (RFS) (hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.59-0.98, p = 0.03) but not overall survival (OS) (HR 1.14, 95%CI 0.72-1.82, p = 0.57) in unsorted BCa patients. PIK3CA mutations were not associated with OS (HR 1.06, 95%CI 0.67-1.67, p = 0.81) or RFS (HR 0.86, 95%CI 0.53-1.40, p = 0.55) in HR-positive BCa patients. In conclusion, PIK3CA mutations were significantly related to ER/PR expression and RFS in unsorted BCa patients. However, the clinical implications of PIK3CA mutations may vary according to different mutant exons. And PIK3CA mutations alone may have limited prognostic value for HR-positive BCa patients.

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Forest plot with OR evaluating the relationship between PIK3CA mutation and PR expression status.
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f3: Forest plot with OR evaluating the relationship between PIK3CA mutation and PR expression status.

Mentions: The relationship between PIK3CA gene mutations and ER expression was investigated in 4754 patients from 26 selected studies (Group A, the ER arm) using a fixed-effect model (Table 1). There was a significant association between PIK3CA gene mutations and ER expression in the patients in this group (odds ratio [OR] 1.92, 95%CI 1.65–2.23; P < 0.00001; Figure 2). Then we performed a separate analysis for PR expression in 3507 patients from 20 studies (Group A, the PR arm) using a fixed-effect model (Table 1), and found that PR expression was also significantly associated with PIK3CA mutations (OR 1.88, 95% CI 1.61–2.20; P < 0.00001) (Figure 3). Direct sequencing was the most frequently used method for detecting mutations in the selected studies. We introduced subgroups and found that direct sequencing and the other mutation detection methods produced similar results (p = 0.13).


Prognostic role of PIK3CA mutations and their association with hormone receptor expression in breast cancer: a meta-analysis.

Pang B, Cheng S, Sun SP, An C, Liu ZY, Feng X, Liu GJ - Sci Rep (2014)

Forest plot with OR evaluating the relationship between PIK3CA mutation and PR expression status.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4150110&req=5

f3: Forest plot with OR evaluating the relationship between PIK3CA mutation and PR expression status.
Mentions: The relationship between PIK3CA gene mutations and ER expression was investigated in 4754 patients from 26 selected studies (Group A, the ER arm) using a fixed-effect model (Table 1). There was a significant association between PIK3CA gene mutations and ER expression in the patients in this group (odds ratio [OR] 1.92, 95%CI 1.65–2.23; P < 0.00001; Figure 2). Then we performed a separate analysis for PR expression in 3507 patients from 20 studies (Group A, the PR arm) using a fixed-effect model (Table 1), and found that PR expression was also significantly associated with PIK3CA mutations (OR 1.88, 95% CI 1.61–2.20; P < 0.00001) (Figure 3). Direct sequencing was the most frequently used method for detecting mutations in the selected studies. We introduced subgroups and found that direct sequencing and the other mutation detection methods produced similar results (p = 0.13).

Bottom Line: PIK3CA mutations were not associated with OS (HR 1.06, 95%CI 0.67-1.67, p = 0.81) or RFS (HR 0.86, 95%CI 0.53-1.40, p = 0.55) in HR-positive BCa patients.In conclusion, PIK3CA mutations were significantly related to ER/PR expression and RFS in unsorted BCa patients.And PIK3CA mutations alone may have limited prognostic value for HR-positive BCa patients.

View Article: PubMed Central - PubMed

Affiliation: Clinical laboratory, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beixian Ge 5#, XiCheng District, Beijing 100053, China.

ABSTRACT
The phosphatidylinositol-4, 5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) gene is frequently mutated in breast cancer (BCa). Sex hormone receptors (HRs), including estrogen receptor (ER) and progesterone receptor (PR) play pivotal roles in BCa. In this study, we evaluated the association between PIK3CA mutations and ER/PR expression and the prognostic role of PIK3CA mutations in BCa patients, and in particular, HR-positive BCa. Thirty-two studies involving 5719 cases of BCa obtained from database searches were examined. PIK3CA gene mutations correlated significantly with ER/PR expression (p < 0.00001) and relapse-free survival (RFS) (hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.59-0.98, p = 0.03) but not overall survival (OS) (HR 1.14, 95%CI 0.72-1.82, p = 0.57) in unsorted BCa patients. PIK3CA mutations were not associated with OS (HR 1.06, 95%CI 0.67-1.67, p = 0.81) or RFS (HR 0.86, 95%CI 0.53-1.40, p = 0.55) in HR-positive BCa patients. In conclusion, PIK3CA mutations were significantly related to ER/PR expression and RFS in unsorted BCa patients. However, the clinical implications of PIK3CA mutations may vary according to different mutant exons. And PIK3CA mutations alone may have limited prognostic value for HR-positive BCa patients.

Show MeSH
Related in: MedlinePlus