PIK3CA mutation frequency ranges from 8% to
40% in breast cancer. PIK3CA mutations have been shown to be associated with
favorable clinicopathologic features including estrogen receptor positive
status. In this study, we investigated whether MRI features are correlated with
PIK3CA mutation status in patients with invasive breast cancer. Of the 54
patients, 20 (37%) had a PIK3CA mutation. PIK3CA mutated tumors were
significantly less likely to show intratumoral T2 high signal intensity
compared to wild type (P = .004). In
conclusion, intratumoral signal intensity on T2-weighted MR images is
significantly associated with PIK3CA mutation status.
Introduction: Phosphatidylinositol 3-kinase (PI3K) signaling pathway plays a crucial role in normal cellular processes involved in cell growth, proliferation, and survival[1]. Disruption of this pathway by gene loss, mutation, or amplification is one of the most common alterations in cancers. PIK3CA gene encodes p100α, the predominant isoform of the catalytic subunit of PI3K. The frequency of PIK3CA mutations in breast cancer ranges from 8% to 40%. PIK3CA mutations have been shown to be associated with favorable clinicopathologic features in breast cancer: older age at diagnosis, estrogen receptor (ER) positivity, human epidermal growth factor receptor 2 (HER2) negativity, lower tumor grade, lower tumor stage, and lymph node negativity[2]. To our knowledge, there is no reported study on correlation of breast MR imaging features with PIK3CA mutation status.
Purpose: To investigate whether the MR imaging features of invasive breast cancer are correlated with PIK3CA mutation status
Methods: In this institutional review board-approved HIPAA-compliant retrospective study, a total of 146 patients with invasive breast cancer who underwent PIK3CA mutation testing from December 1999 to May 2016 were identified. Patients who did not undergo MR imaging prior to breast cancer surgery and/or neoadjuvant chemotherapy (n = 53) and those who had genetic testing performed on soft tissues metastasized from breast cancer (n = 39) were excluded. Therefore, there were 54 patients with pretreatment MR imaging and PIK3CA mutation testing in breast cancer tissues. All MR images were independently reviewed by four breast imaging radiologists based on the Breast Imaging Reporting and Data System (BI-RADS) lexicon. In cases of multiple lesions, only the index lesion with the largest dimension was evaluated. In addition, intratumoral signal intensity and the presence of peritumoral edema were evaluated visually on T2-weighted images. Intratumoral signal intensity was evaluated to determine whether the signal intensity of the tumor was lower than, equivalent to, or higher than that of fibroglandular tissue. Peritumoral edema was determined when T2-weighted images showed a high signal posterior to the tumor mass in the prepectoral area or a fairly extensive high signal around the tumor mass. Each imaging finding was determined based on the descriptor assigned by the majority of readers. If there was a discrepancy in interpretation among the readers, a consensus was reached. In those cases, two readers reassessed the images together. To examine the correlation of MR imaging features with mutation status, we used the Χ2 test or the Fisher exact test for categorical variables and a t-test for continuous variables.
Results: Of the 54 patients, 20 (37%) had a PIK3CA mutation. The average age was significantly older in patients with PIK3CA mutation than those with wild type (53.1 years ± 11.8 vs 45.7 years ± 8.3; P = .009). There was no significant difference between the two groups in the distribution of stage (P = .60), tumor grade (P = .52), histologic tumor type (P = .26), or molecular subtype (P = .33). Breast cancers in the 54 patients were classified into molecular subtypes using surrogate markers as follows: 33 (61%), luminal A (ER-positive/HER2-negative; progesterone receptor [PR] may be positive or negative); 9 (17%), luminal B (ER-positive/HER2-positive; PR may be positive or negative), 6 (11%), HER2-enriched (ER-negative/PR-negative/HER2-positive); 6 (11%), triple-negative (ER-negative/PR-negative/HER2-negative). In terms of MR imaging features, PIK3CA mutated tumors were significantly less likely to show intratumoral T2 high signal intensity compared to wild type tumors (10% vs 36%; P = .004). This finding was also found in ER-positive (P = .049) or luminal A tumors (P = .011). However, there were no significant differences between PIK3CA mutation and wild type in the distribution of peritumoral edema and other BI-RADS descriptors for morphology and kinetics (P > .05).
Discussion/Conclusion: Intratumoral signal intensity on T2-weighted MR images is significantly associated with PIK3CA mutation status in patients with invasive breast cancer. Compared to wide type, PIK3CA mutated breast tumors are significantly less likely to show intratumoral high signal intensity, which may be related to intratumoral necrosis or cystic change.
[1] Paradiso A, Mangia A, Azzariti A, Tommasi S. Phosphatidylinositol 3-kinase in breast cancer: where from here? Clin Cancer Res 2007;13(20):5988-5990.
[2] Kalinsky K, Jacks LM, Heguy A, et al. PIK3CA mutation associates with improved outcome in breast cancer. Clin Cancer Res 2009;15(16):5049-5059.