Cyclin G, a recent addition to the cyclin family, was initially identified in screens for new src kinase family members and soon thereafter by differential screening for transcriptional targets of the tumor suppressor gene, p53. We have identified cyclin G as being overexpressed in breast and prostate cancer cells using differential display polymerase chain reaction screening. We demonstrate here that cyclin G is overexpressed in human breast and prostate cancer cells and in cancer cells in situ from tumor specimens. Cyclin G expression was tightly regulated throughout the cell cycle in normal breast cells, peaking at the S and G 2 /M phases of the cell cycle with lower levels in G 1 . The cell cycle-dependent expression was absent in breast cancer cells. Following DNA damage in normal p53؉/؉ cells, cyclin G is triggered to cluster in discrete nuclear DNA replication foci that contain replication-associated proteins such as proliferating cell nuclear antigen (PCNA). While p53؊/؊ cells displayed a faint cyclin G nuclear staining pattern, there was no increased expression and no change in distribution of the staining pattern after DNA damage. The specific subcellular localization of cyclin G at DNA replication foci provides an additional link between p53-mediated growth arrest and cell cycle regulation and suggests that cyclin G may act as an effector of p53-mediated events by functional association with replication foci protein(s).
Mammography and ultrasonography are traditional for preoperative estimation of breast cancer size; magnetic resonance imaging (MRI) is more recent but not as well studied. We compared ultrasonography, mammography, and MRI for preoperative imaging of primary breast cancer presenting as a mass in patients treated at our center over a 2-year period. Of the 61 breast cancers with all three imaging modalities performed, 52 were infiltrating ductal cancer, 5 were infiltrating lobular cancer, 2 were ductal carcinoma in situ, and 2 were other histologic types. When pathologic size was used to determine the accuracy of imaging assessments, the Pearson correlation coefficient was better for MRI (r = 0.80) than ultrasonography (r = 0.57) or mammography (r = 0.26). Mean tumor size was 2.1 cm by mammography, 1.73 cm by ultrasonography, 2.65 cm by MRI, and 2.76 cm by pathology. MRI-based tumor size was within 1 cm of pathologic size in 44 (72%) tumors, > 1 cm above pathologic size in 6 (10%) tumors, and > 1 cm below pathologic size in 11 (18%) tumors. We conclude that MRI is more accurate than either ultrasonography or mammography for assessment of the size of primary breast cancer presenting as a mass.
Background: The impact of length of time to surgery (TTS) on oncologic outcomes following neoadjuvant chemotherapy (NAC) in breast cancer patients is unclear. We investigated the relationship between TTS on residual cancer burden (RCB) score and oncologic outcomes. Methods: Patients with breast cancer receiving NAC from 2011 to 2017 were identified. The association of TTS with recurrence-free survival (RFS), overall and disease-specific survival (OS, DSS), and RCB score was examined with Kaplan-Meier and Cox proportional hazards analysis, adjusting for relevant clinicopathologic factors. Results: We identified 463 patients. Median TTS was 29 days (range 11-153). Median follow-up was 57 months (range, 2-93 months). Five-year local recurrencefree survival, locoregional RFS, OS, and DSS was 86%, 96%, 89%, and 91%, respectively. On multivariate analysis, TTS >6 weeks was independently associated with worse RFS (HR [hazard ratio] 3.45; p < .001) and DSS (HR 2.82; p < .05), while TTS >6 weeks was independently associated with a positive size of the effect on RCB score of 0.59 (p < .0001). Conclusion: Prolonged TTS is a modifiable risk factor for adverse oncologic outcomes following NAC for breast cancer, possibly mediated by increasing RCB score overtime after NAC. In the absence of contraindications, surgery should be performed within 6 weeks following NAC for optimal oncologic outcomes.
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