PIK3CA exon 20 mutation is independently associated with a poor prognosis in breast cancer patients.
BACKGROUND
Prognostic factors that could select breast cancer patients with poor survival, and influence clinical trials of targeted therapy, are needed. However, the reported observations regarding the impact of PI3KCA mutation on breast cancers are controversial.


METHODS
We analyzed exons 4, 7, 9, and 20 of PI3KCA on a series of 158 patients. Clinicopathological characteristics were correlated with the mutation data.


RESULTS
Among 152 patients who were available for follow-up (median follow-up time, 6.57 years), 26% had PIK3CA mutations, more than half of which occurred in exon 20. The five-year survival rate of patients with exon 20 mutations (46%) was significantly lower than that of patients without (75%) (p = 0.0054). Multivariate analysis showed that PIK3CA exon 20 mutations and nodal involvement were independent risk factors for overall survival. The relative risk of death in patients with PIK3CA exon 20 mutations was 2.881 (95% CI, 1.406-5.900; p = 0.0038).


CONCLUSIONS
PIK3CA mutations are common in invasive ductal carcinomas of the breast. Our result suggests that PIK3CA exon 20 mutation is an independent risk factor for poor prognosis in breast cancer patients, indicating that differences in patient numbers with PIK3CA exon 20 mutations in study and control arms should be avoided in clinical trials of PI3K inhibitors.
Lai
Yuen-Liang
YL
Hospice Palliative Care Center, Mackay Memorial Hospital, 45 Minsheng Road, Danshui, Taipei, 251, Taiwan.
Mau
Bey-Liing
BL
Cheng
Wen-Hsuan
WH
Chen
Han-Ming
HM
Chiu
Hsi-Hsiung
HH
Tzen
Chin-Yuan
CY
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality; D018270:Carcinoma, Ductal, Breast / Q000235:genetics* / Q000401:mortality; D058534:Class I Phosphatidylinositol 3-Kinases; D005091:Exons; D005260:Female; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D011379:Prognosis; D012307:Risk Factors; D016019:Survival Analysis
D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human