The pathogenesis of breast cancers that do not express estrogen receptors or Her-2/neu receptors (ERx/HER2x phenotype) is incompletely understood. We had observed markedly elevated gene expression of gamma-aminobutyric acid type A (GABA A ) receptor subunit p (GABAp, GABRP) in some breast cancers with ERx/HER2x phenotype. In this study, transcriptional profiles (TxPs) were obtained from 82 primary invasive breast cancers by oligonucleotide microarrays. Real-time reverse transcription-polymerase chain reaction (RT-PCR) was used to measure GABAp gene expression in a separate cohort of 121 invasive breast cancers. GABAp gene expression values from TxP and RT-PCR were standardized and compared with clinicopathologic characteristics in the 203 patients. GABAp gene expression was increased in 16% of breast cancers (13/82 TxP, 20/ 121 RT-PCR), particularly in breast cancers with ERx/HER2x phenotype (60%), and breast cancers with basal-like genomic profile (60%). The profile of genes coexpressed with GABAp in these tumors was consistent with an immature cell type. In multivariate linear regression analysis, the level of GABAp gene expression was associated with ERx/HER2x phenotype (P<0.0001), younger age at diagnosis (P = 0.0003), and shorter lifetime duration of breastfeeding (£ 6 months) in all women (P = 0.017) and specifically in parous women (P = 0.013). GABAp gene expression was also associated with combinations of high grade with ERx/HER2x phenotype (P = 0.002), and with Hispanic ethnicity (P = 0.036). GABAp gene expression is increased in breast cancers of immature (undifferentiated) cell type and is significantly associated with shorter lifetime history of breastfeeding and with high-grade breast cancer in Hispanic women.
We assessed the correlation between dynamic MRI results and clinical outcomes in patients with malignant gliomas. Rapid serial MRIs were obtained after bolus injection of gadolinium that resulted in an initial fast uptake followed by a slow uptake of contrast. The maximum rate of uptake and delayed rate of uptake were correlated with survival and prognostic covariates such as age and histology. In 121 subjects, higher maximum uptake rates, 3.6 signal intensity units per second or greater, were associated with shorter survival (p = 0.0066). The correlation of delayed rate of uptake with survival was less significant. After adjusting for age, histology, and Karnofsky performance score, the maximum rate of uptake remained more significantly correlated with survival than the delayed rate of uptake. Thirty-one patients had surgery within 1 month of dynamic MRI, and those with glioblastoma multiforme or anaplastic gliomas had higher maximum rates of uptake than those with pure necrosis or mixed tumor and necrosis (p = 0.022). No correlation between delayed rate of uptake and histology was seen in this group of patients. Our results suggest that the maximum rate of uptake in dynamic MRI can be a prognostic measure for patients with malignant gliomas. Further prospective study is needed to assess the utility of this technique for evaluating brain tumors.
10519 Objective. Triple-negative breast cancer is defined as a subtype of invasive breast cancer which lacks estrogen and progesterone receptor expression as well as HER2/neu expression and is highly similar to the basal-like subtype defined by gene expression profiling. Method. 1,143 patients treated at MD Anderson Cancer Center in neoadjuvant trials were included in a retrospective comparative analysis between triple-negative tumors and non-triple-negative tumors for response to neoadjuvant chemotherapy as well as long- term survival. Results. 827/1,143 (72%) patients had received taxanes, either as a single-agent (n=60) or in combination with anthracycline (n=767), whereas the remainder patients received an anthracycline-only chemotherapy. Overall 258/1,143 (23%) tumors were triple- negative. Complete pathological response (pCR) was achieved in 63/257 (25%) patients with triple-negative tumors compared to 99/888 (11%) in patients with non-triple-negative tumors (odds ratio [OR] 1.14, 95%CI: 1.09–1.20, p=.0082). Triple-negative status correlated significantly with high nuclear grade (p<.0001), whereas no significant correlation with any established clinicopathologic parameter was observed. However, 5-year overall survival (5yrOS) was 66% in the triple-negative group compared to 83% in the non-triple-negative control group (OR 2.1, 95%CI: 1.6–2.8, p<.0001). In multivariate analyses, triple-negative status (hazard ratio [HR] 2.0, 95%CI: 1.4–2.8, p<.0001), high nuclear grade, increased tumor size (HR 1.5, 95%CI: 1.3–1.8, p<.0001), positive nodal status (HR 1.4, 95%CI: 1.2–1.7, p=.0002) and high nuclear grade (HR 1.7, 95%CI: 1.1- 2.4, p=.0089) were significantly associated with decreased 5yrOS. When survival was analyzed according to both response rate and triple negative status, achievement of pCR was a stronger predictor of survival compared to triple-negative status. Conclusion. Triple- negative expression status among patients with breast cancer constitutes an independent unfavorable prognostic factor with regards to overall survival unless achieving pCR after neoadjuvant chemotherapy. No significant financial relationships to disclose.
Background: Image-guided percutaneous needle biopsy of the breast is a common procedure. In breast cancer patients (pts) undergoing core biopsies and surgical resection on the same day, the rate of tumor cell displacement along the needle track has been reported to be up to 50%. However, the clinical significance of this finding in triple negative breast cancer (TNBC) patients (pts) undergoing serial biopsies while receiving neoadjuvant chemotherapy (NACT) is unknown. Here we report the incidence of needle-track seeding (NTS) in a cohort of TNBC pts enrolled on a molecular triaging protocol involving serial biopsies of the index breast lesion. Methods: We reviewed the clinical records of 144 consecutive TNBC pts enrolled on a molecular triaging protocol at MD Anderson Cancer Center. Per protocol, all pts underwent a pre-treatment research biopsy and were initiated on anthracycline based NACT (AC). Pts with inadequate response to front-line NACT were encouraged to undergo additional biopsies of the index breast lesion prior to switching therapies. Serial breast ultrasound (US) was performed to monitor therapeutic response and incidental evidence of needle-track seeding noted on US was documented. Results: Clinicopathological characteristics of the pts are summarized in Table 1. 89% (128/144) of pts had a diagnostic breast biopsy done at another center prior to presenting at MDACC. To date, we have performed 209 US guided biopsies of index breast lesions in 144 pts. 92% (193/209) of these biopsies were done mainly for research purposes. 1.4% (2/144) of pts were found to have evidence of NTS on follow up US. The first pt had a T1N0 (1.9cm), grade 3, invasive ductal carcinoma (IDC) at diagnosis. She underwent a diagnostic biopsy followed by a research biopsy before initiating AC. She was found to have NTS as well as progression of disease (PD) on follow up US after 2 cycles of AC. The second pt had a T2N0 (3cm), grade 3 IDC at diagnosis. She underwent a diagnostic biopsy at another center, followed by a research biopsy before initiating AC. Like the first pt, she was found to have NTS and PD on follow up US after 2 cycles of AC. Both pts are currently on neoadjuvant clinical trials of novel agents. Conclusion: The rate of NTS detected on US in TNBC pts undergoing serial biopsies of index breast lesions while receiving NACT is low and further studies are needed to determine the impact of serial biopsies on long term outcomes in TNBC. Table 1: Patient CharacteristicsCharacteristicN=144Age - Median (years, interquartile range)55 (46-62)Tumor Size Mean (cm, standard deviation)3.4 (2.2)T1 – n(%)35 (24)T2 – n(%)89 (62)T3 – n(%)19 (13)T4 – n(%)1 (1)Clinical Nodal Status Negative – n(%)74 (51)Positive – n(%)70 (49)Grade 1 – n(%)1 (1)2 – n(%)17 (12)3 – n(%)124 (86)Unknown – n(%)2 (1)Histologic Subtype Invasive ductal carcinoma – n(%)121 (84)Invasive lobular carcinoma – n(%)2 (1)Mixed ductal and lobular carcinoma – n(%)3 (2)Metaplastic carcinoma – n(%)13 (9)Not specified – n(%)5 (3)Laterality Right – n(%)72 (50)Left – n(%)72 (50) Citation Format: Yam C, Santiago L, Candelaria RP, Adrada BE, Rauch GM, Hess KR, Litton JK, Piwnica-Worms H, Mittendorf EA, Ueno NT, Lim B, Murthy RK, Damodaran S, Helgason T, Huo L, Thompson AM, Gilcrease MZ, Symmans WF, Moulder SL, Yang W. Risk of needle-track seeding with serial ultrasound guided biopsies in triple negative breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-03-05.
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Pseudoprogression (psPD) refers to an increase in size or appearance of new areas of MRI contrast enhancement soon after completing chemoradiation, timely diagnosis of which has been a challenge. Given that tissue sampling of the MRI changes would be expected to accurately distinguish psPD from true progression when MRI changes are first seen, we examined the utility of surgery in diagnosing psPD and influencing patient outcome. We retrospectively reviewed data from adults with GBM who had MRI changes suggestive of progression within 3 months of chemoRT; of these, 34 underwent surgical resection. Three subsets-tumor, psPD or mixed-were identified based on histology and immunohistochemistry in the surgical group and by imaging characteristics in the nonsurgical group. A cohort of patients with stable disease post-chemoRT served as control. PFS and OS were determined using the Kaplan-Meier method and log rank analysis. Concordance for psPD between radiological interpretation and subsequent histological diagnosis was seen in only 32 % of cases (11/34) 95 %CI 19-49 %. A large proportion of patients had a histologically "mixed" pattern with tumor and treatment effect. No significant differences in PFS or OS were seen among the three subtypes. Surgical sampling and histologic review of MRI changes after chemoRT may not serve as a gold standard to distinguish psPD from true progression in GBM patients. Refinement of the histological criteria, careful intraoperative selection of regions of interest and advanced imaging modalities are needed for early differentiation of PsPD from progression to guide clinical management.
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