O1Utility of MRI in low and low to moderate density breasts with invasive lobular carcinoma Objective: To determine the feasibility of excluding MRI from the preoperative diagnostic pathway of invasive lobular carcinoma (ILC) in women with low and low to moderate density breasts on mammography. Methods: A total of 179 cases of ILC were diagnosed between 2009 and 2012. Forty-eight cases were identified as low and low to moderate density breasts. The study group includes 32 cases who underwent MRI. Parameters scrutinised include size and number of lesions on mammography, ultrasound and MRI, second-look ultrasound, type of surgery, further surgery and histology. Results: Twenty-nine cases had low to moderate density breasts and three had purely low density breasts. Average age of women was 64. Size of lesions ranged between 2 and 50 mm with an average of 20.14 mm. In 25/32 cases (78.12%) conventional imaging matched MRI. MRI identified additional disease in 7/32 (21.8%). This was predominantly in the form of satellites around the index lesion resulting in multifocality in 6/7. Four resulted appropriately in mastectomy. Two led to wider WLE appropriately. In one case, multicentric disease was correctly detected and subjected to mastectomy. Second-look ultrasound was recommended in 4/7 cases. All these cases had low to moderate density breasts on mammography and 6/7 cases measured more than 15 mm in size. Ultrasound matched MRI in one mammographically occult case and was subjected to appropriate WLE. In two cases there was much more disease than anticipated from conventional imaging and MRI (6.25%). Conclusion: Even in low and low to moderate density breasts where mammography has a higher exclusion value, MRI identified additional disease in 21.8% (7/32). O2Is ultrasound axillary staging less accurate in invasive lobular breast cancer than in ductal breast cancer? P Sankaye Objective: To identify whether axillary US is less accurate in invasive lobular breast cancer than in ductal breast cancer. Methods: Randomised cohorts of screening and symptomatic patients were retrospectively identified from histology records of 2010/11. Axillary US of 65 patients with primary breast cancers (BC) from each group of invasive lobular cancer (ILC) and invasive ductal cancer (IDC) were reviewed. Preoperative US-guided needle biopsy sampling was performed on abnormal lymph nodes (LN). Results: See Tables 1 and 2. Conclusion: The previous literature on this topic is inconclusive. Some authors have suggested axillary ultrasound in ILC may be less accurate than in IDC, with a higher false-negative axillary assessment rate. Another study concluded that axillary US accuracy rates in ILC were comparable with previous published studies of IDC, used FNA in all cases. We specifically compared accuracy rates of preoperative axillary staging between ILC and IDC in own institution, with 14G needle biopsy as the procedure of choice to sample abnormal nodes. We found that there is no statistical difference in accuracy in US axillary staging betwee...
Introduction: Magnetic resonance imaging (MRI) has been increasingly used to assess response to neoadjuvant chemotherapy (NAC). The aim of this retrospective study was to investigate the accuracy of MRI in predicting pathological complete response (pCR) and residual disease in patients treated with NAC. Methods: 152 patients with invasive breast cancer were treated with NAC (2005–2009). In our institute the response to neoadjuvant anthracycline (AC) based chemotherapy is monitored with MRI scanning before NAC and after 2 and 4 cycles. Taxane based chemotherapy was substituted for AC chemotherapy if MRI response was deemed inadequate. Response to NAC was measured using the modified response evaluation criteria in solid tumours (RECIST). Tumour extent and response on final MRI were correlated with the pathological findings on post-surgical specimens. pCR was defined as absence of invasive cancer. Sensitivity and specificity of MRI reporting was determined against response on histopathology. Potential predictive factors for response on MRI were assessed for significance. Results: In total, patients had 2(14.5%), 3(60.5%) or 4(25%) MRI scans. pCR was seen in 37(24.3%) patients. After 2 cycles of NAC, positive response (partial or complete) was seen on MRI in 76(50%) patients. Response was more likely in focal tumours versus multifocal tumours (chi square (χ2) 3.83, p = 0.05). In the non-responding group (n = 76), 74 had their treatment switched and a later response was detected in 50(67.6%) cases on MRI. In the 133 patients with 3 or more MRI scans, final MRI size was compared to tumour size on pathology. Median tumour extent on final MRI was 25.5mm (range 0–120) and median whole tumour size on pathology was 22.5mm (range 0–120). MRI response was apparent in 115 (75.7%) cases (sensitivity = 92.3%, specificity = 56.3% and PPV = 93.9%). In a 2-tailed analysis MRI response showed strong correlation with actual pathological response (spearman's = 0.501, p < 0.0001). MRI correctly diagnosed pCR in 15 of 37(40.5%) patients with pCR. Linear regression shows that overall tumour extent on MRI was highly predictive of whole tumour size on pathology (coefficient = 0.459, p < 0.0001). However, MRI overestimated residual disease in 24(18%) cases (median size difference of 39mm, range 12–120mm) and underestimated minimal residual disease in 12(9%) cases. In univariate analysis, time of response to NAC was a predictor of pCR (p = 0.013), with greater number of early responders having pCR than late responders. Complete response on MRI was a significant predictor of pCR (p < 0.0001), with a greater proportion of patients having pCR compared to those not showing complete response on MRI. Both complete response on final MRI (p = 0.276) and pCR (p = 0.069) show favourable disease-free survival (DFS), however neither reaches statistical significance on Kaplan-Meier curve (Median follow up of 43 months, range 13–78). Conclusions: Early responders and tumours achieving complete response on MRI are significant predictors of histopathological response. Serial MRI is predictive of response to NAC and possibly also a predictor of DFS. In this series MRI overestimated residual disease in nearly 1 in 5 patients. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-01-14.
Objective: To determine the feasibility of excluding MRI from the preoperative diagnostic pathway of invasive lobular carcinoma (ILC) in women with low and low to moderate density breasts on mammography. Methods: A total of 179 cases of ILC were diagnosed between 2009 and 2012. Forty-eight cases were identified as low and low to moderate density breasts. The study group includes 32 cases who underwent MRI. Parameters scrutinised include size and number of lesions on mammography, ultrasound and MRI, second-look ultrasound, type of surgery, further surgery and histology. Results: Twenty-nine cases had low to moderate density breasts and three had purely low density breasts. Average age of women was 64. Size of lesions ranged between 2 and 50 mm with an average of 20.14 mm. In 25/32 cases (78.12%) conventional imaging matched MRI. MRI identified additional disease in 7/32 (21.8%). This was predominantly in the form of satellites around the index lesion resulting in multifocality in 6/7. Four resulted appropriately in mastectomy. Two led to wider WLE appropriately. In one case, multicentric disease was correctly detected and subjected to mastectomy. Second-look ultrasound was recommended in 4/7 cases. All these cases had low to moderate density breasts on mammography and 6/7 cases measured more than 15 mm in size. Ultrasound matched MRI in one mammographically occult case and was subjected to appropriate WLE. In two cases there was much more disease than anticipated from conventional imaging and MRI (6.25%). Conclusion: Even in low and low to moderate density breasts where mammography has a higher exclusion value, MRI identified additional disease in 21.8% (7/32). O2 Is ultrasound axillary staging less accurate in invasive lobular breast cancer than in ductal breast cancer?
Twenty-five years after its first description the p53 protein has been shown to play a key role in both cancer and ageing. The p53 protein is activated by many different stress pathways, including oncogene action and DNA damage. The elucidation of the p53 response, which is aberrant in most cancers (including breast, lung, stomach and colorectal cancer), has provided many new targets for drug development and p53 gene therapy is now approved in China. In tumours where p53 is mutant small molecules may be able to restore its function. In many tumours the wild-type p53 gene remains intact but its function is compromised by loss of upstream signalling pathways or downstream effectors. A key regulator is Mdm2, an E3 ubiquitin ligase, that binds and ubiquitinates p53 and directs its degradation via the proteosome. Small potent peptides that can block the p53 Mdm2 interaction and activate the p53 response have been described. Growing selections of lead small molecules that mimic the action of these peptides have also been recently discovered. Cell-based screens have revealed that inhibitors of nuclear export and inhibitors of transcription (one of which is in clinical trial) can also activate the p53 response therapeutically. The pharmaceutical regulation of the p53 pathway offers great hope for improved treatment of human cancer.
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