Dataset Information

Loss of PTEN Expression, PIK3CA Mutations, and Breast Cancer Survival in the Nurses' Health Studies.

ABSTRACT:

Background

The relationships between PTEN loss and/or PIK3CA mutation and breast cancer prognosis remain controversial. We aim to examine the associations in large epidemiologic cohorts.

Methods

We followed women with invasive breast cancer from the Nurses' Health Studies with available data on tumor PTEN expression (n = 4,111) and PIK3CA mutation (n = 2,930). PTEN expression was evaluated by IHC and digitally scored (0%-100%). Pyrosequencing of six hotspot mutations of PIK3CA was performed.

Results

We found loss of PTEN expression (≤10%) occurred in 17% of cases, and PIK3CA mutations were detected in 11% of cases. After adjusting for clinical and lifestyle factors, PTEN loss was not associated with worse breast cancer-specific mortality among all samples [HR, 0.85; 95% confidence intervals (CI), 0.71-1.03] or among estrogen receptor (ER)-positive tumors (HR, 0.99; 95% CI, 0.79-1.24). However, among ER-negative tumors, PTEN loss was associated with lower breast cancer-specific mortality (HR, 0.68; 95% CI, 0.48-0.95). PIK3CA mutation was not strongly associated with breast cancer-specific mortality (HR, 0.89; 95% CI, 0.67-1.17). Compared with tumors without PTEN loss and without PIK3CA mutation, those with alterations (n = 540) were not at higher risk (HR, 1.07; 95% CI, 0.86-1.34). However, women with both PTEN loss and PIK3CA mutation (n = 38) were at an increased risk of breast cancer-specific mortality (HR, 1.65; 95% CI, 0.83-3.26).

Conclusions

In this large epidemiologic study, the PTEN-mortality association was more pronounced for ER-negative tumors, and the joint PTEN loss and PIK3CA mutation may be associated with worse prognosis.

Impact

Further studies with a larger sample of ER-negative tumors are needed to replicate our findings and elucidate underlying mechanisms.

SUBMITTER: Wang T

PROVIDER: S-EPMC9532372 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Publications

Loss of PTEN Expression, PIK3CA Mutations, and Breast Cancer Survival in the Nurses' Health Studies.

Wang Tengteng T Heng Yujing J YJ Baker Gabrielle M GM Bret-Mounet Vanessa C VC Quintana Liza M LM Frueh Lisa L Hankinson Susan E SE Holmes Michelle D MD Chen Wendy Y WY Willett Walter C WC Rosner Bernard B Tamimi Rulla M RM Eliassen A Heather AH

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20221001 10

<h4>Background</h4>The relationships between PTEN loss and/or PIK3CA mutation and breast cancer prognosis remain controversial. We aim to examine the associations in large epidemiologic cohorts.<h4>Methods</h4>We followed women with invasive breast cancer from the Nurses' Health Studies with available data on tumor PTEN expression (n = 4,111) and PIK3CA mutation (n = 2,930). PTEN expression was evaluated by IHC and digitally scored (0%-100%). Pyrosequencing of six hotspot mutations of PIK3CA was ...[more]

PMID: 35914729

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Project description:BackgroundThere is pressing needs to find the biomarker in the selection of neoadjuvant therapy in postmenopausal luminal breast cancer patients. We examined the hypothesis that PIK3CA mutations and low phosphatase and tensin homolog (PTEN) expression affect the response to neoadjuvant therapy and prognosis in postmenopausal luminal breast cancer patients.MethodsPostmenopausal patients with estrogen receptor-positive, human epidermal growth factor receptor 2-negative breast cancer, up to stage II, who underwent neoadjuvant chemotherapy (NAC; n = 60) or neoadjuvant endocrine therapy (NAE; n = 55) were selected. PIK3CA exon 9 and exon 20 mutations were screened by high resolution melting analysis and confirmed by Sanger sequence. PTEN expression was evaluated by immunohistochemistry. The relationships among PIK3CA mutations, PTEN expression, clinicopathological features, the pathological effect of neoadjuvant therapy, recurrence-free survival (RFS) and overall survival were analyzed.ResultsAmong 115 patients, PIK3CA mutations and low PTEN expression before treatment were detected in 35 patients (30.4%) and in 28 patients (24.3%), respectively. In the NAC group, tumor with PIK3CA mutations showed significantly poorer response than tumor with PIK3CA wild-type (p = 0.03). On the other hand, in the NAE group, there was no significant difference in pathological therapeutic effect between tumor with PIK3CA mutations and tumor with PIK3CA wild-type (p = 0.54). In the NAC group, the log-rank test showed no difference in RFS between patients with PIK3CA mutations and PIK3CA wild-type (p = 0.43), but patients with low PTEN expression showed significantly worse RFS compared to patients with high PTEN expression (5 year RFS 0.64 vs. 0.87, p = 0.01). In the Cox proportional hazards model for RFS, PTEN expression, progesterone receptor, and pathological therapeutic effect were predictive factors for time to recurrence (All p < 0.05).ConclusionsPIK3CA mutations are associated with resistance to NAC but do not affect the response to NAE. Low PTEN expression does not affect response to either NAC or NAE but correlates with shorter RFS in patients who received NAC. These biomarkers will be further evaluated for clinical use to treat postmenopausal luminal breast cancer patients.

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Dataset Information

Loss of PTEN Expression, PIK3CA Mutations, and Breast Cancer Survival in the Nurses' Health Studies.

Background

Methods

Results

Conclusions

Impact

Publications

Loss of PTEN Expression, PIK3CA Mutations, and Breast Cancer Survival in the Nurses' Health Studies.

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