bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P3-13-06: Osteocytic Connexin 43 Hemichannels in Prevention of Bone Metastasis
Authors: Zhou JZ , Jiang JX 
Published: August 2014

Abstract
Bone metastases are major, potentially fatal complications in patients with advanced cancers including breast, prostate and lung cancers. The gap junction-forming protein connexin 43 (Cx43) has been known to inhibit primary tumor cell growth. In addition to gap junctions, Cx43 also forms halves of gap junctions known as hemichannels which allow communication between the intracellular and extracellular environments. Cx43 hemichannels in osteocytes have been shown to open when induced by mechanical stimulation as well as by treatment with alendronate (AD), an efficacious and commonly used bisphosphonate drug. The opening of hemichannels is known to release small molecules important for bone formation and remodeling. To confirm the opening of Cx43 hemichannels in the presence of AD, we measured uptake of ethidium bromide (EtBr) in MLO-Y4 cells after the addition of AD. As expected, an increase in Cx43 hemichannels EtBr uptake was observed after AD treatment. To elucidate the effect(s) of osteocyte Cx43 hemichannels on cancer cell growth and migration, we treated MLO-Y4 osteocytes with AD. Conditioned media (CM) was collected after treatment and were used to incubate with metastatic MDA-MB-231 breast cancer cells and PC3 prostate cancer cells. Cell migration was measured using wound healing and transwell migration assays, and cell proliferation was measured using the soft agarose anchorage-independent growth assay. The CM collected from MLO-Y4 osteocytes treated with AD reduced cancer cell migration and proliferation in a dose-dependent manner. However, direct treatment with AD had no effect on the cell migration or proliferation of the MDA-MB-231 cells. These data validated that the decrease in migration and proliferation was not a result of direct action by AD on the cancer cells. In order to elucidate the direct functional involvement of Cx43 hemichannels in cell migration, we treated the MLO-Y4 cells with Cx43 (E2) antibody, a specific antibody which blocks hemichannel activity but not gap junction channels formed by Cx43. The inhibitory effect of the CM on the migration and proliferation of MDA-MB-231 and PC3 cells was diminished. Interestingly, the inhibitory effects of osteocytes on cancer cell migration were not observed when using osteoblasts. Together, these results suggest the functional importance of osteocytic Cx43 hemichannels in attenuating cancer cell migration and growth.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-13-06.
Abstract P3-14-02: Should patients with comedo ductal carcinoma in situ (DCIS) be managed as if they have locally invasive breast cancer?
Authors: Dillman Robert O , McClure Stephanie E , Heinemann Francis S 
Published: August 2014

Abstract
Withdrawn by Author
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-14-02.
Abstract P3-14-04: Symptomatic DCIS is a risk factor for invasion and should be managed accordingly
Authors: Dimopoulos N , Williams K , Kirwan CC , Johnson R , Howe M , Bundred NJ 
Published: August 2014

Abstract
Background: The National ABS Guidelines indicate axillary surgery is unwarranted in DCIS but should be offered to patients undergoing mastectomy. Up to 30% of pre-operatively diagnosed DCIS lesions harbour occult invasive cancers at mastectomy.
Methods: To determine if DCIS mode of presentation, size (or other clinical factors such as Grade or HER2 status) predict invasion or nodal involvement, 380 patients undergoing surgery with a DCIS pre-operative (B5) diagnosis were studied. In total 162 patients underwent mastectomy +/− axillary staging for DCIS and 216 conservation surgery between 2008–2011 in one unit.
HER2, oestrogen receptor (ER) and progesterone receptor (PR) expression within primary DCIS were established using immunohistochemistry. HER2 was scored 0 (absent) to 3 (maximum). Scores ≥2 were taken as positive if amplified on FISH testing. ER and PR scored positive if ≥5% of cells stained.
Results: In total 216 had Breast Conservation and 162 Mastectomy with 127 undergoing sentinel lymph node biopsy (111) or subsequent axillary surgery (16).
Of 162 patients undergoing mastectomy for DCIS, 121 (75%) underwent axillary staging, with 9 (7%) having involved nodes.
Screening mammography detected 117 (72%) but 45 (28%) presented symptomatically with a breast mass. Median age at diagnosis was 57.8 years (range 29–94). Women less than 35 years of age had tumours sized greater than 4 cm in 72.3% compared to 59% in older women (p &lt; 0.05).
In total 50 (31%) women with DCIS had occult invasive disease, with an additional 9 (6%) having microinvasion. Young age (p 0.003), - symptomatic presentation (p &lt; 0.001), presence of a palpable mass (p &lt;0.001), ultrasound visibility (p &lt;0.01) and Her2 negativity (p &lt; 0.05) were associated with invasion, however size of DCIS, grade, oestrogen and progesterone receptor status were not.
Sentinel node involvement was associated with symptomatic presentation (p = 0.03) and presence of a palpable mass (p = 0.04) but not DCIS size, grade, age or receptor status.
Conclusion: Symptomatic DCIS presents more frequently with an occult invasive component and nodal invasion. In symptomatic DCIS presenting with a mass lesion.
Ultrasound of the axilla and breasts should be a requisite preoperative assessment for all women. Moreover, sentinel node biopsy should be considered in patients with DCIS and a mass lesion.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-14-04.
Abstract P3-14-05: Recurrence in Patients Diagnosed with Ductal Carcinoma in Situ: Predictors and Prognostic Significance
Authors: Sue GR , Killelea B , Horowitz NR , Lannin DR , Chagpar AB 
Published: August 2014

Abstract
Background: While patients diagnosed with ductal carcinoma in situ (DCIS) enjoy a favorable prognosis, recurrence after definitive management does occur in a subset of these patients. Factors influencing the development of recurrence, and the ultimate impact of this event on overall survival, remain poorly understood. We sought to determine clinicopathologic factors affecting recurrence and the prognostic role this plays in patients with DCIS.
Methods: A retrospective chart review of 205 consecutive patients who presented to an academic breast center with DCIS from 2000 to 2003 was conducted under an IRB-approved protocol. Non-parametric statistical analyses comparing patients who recurred to those who did not were then performed using SPSS Statistical Software.
Results: With a median follow-up of 8.5 years, 14 (6.8%) of the 205 patients who presented with DCIS between 2000–2003 had an invasive or in situ recurrence. The median age of all patients at the time of diagnosis of their initial DCIS was 55.5 years (range; 35.8–88.9). 51 (24.9%) had possible (albeit not definitive) microinvasion on their initial specimen. The majority were grade 2 (91; 44.4%), and 99 (48.3%) had comedo histology. The median size of DCIS on the initial excision was 10 mm (range; 0.1–80). All patients underwent definitive surgery to negative margins. The mean time to recurrence was 4.7 years (range; 1.1–10.6). On bivariate analysis, histologic grade of DCIS was the only factor that was significantly correlated with the risk of recurrence. Patients with grade 3 DCIS were more likely to develop a recurrence compared to those with grade 2 or grade 1 DCIS (12.3% vs. 3.3% vs. 0%, respectively, p = 0.032). Patient age, race, extent of DCIS, and histologic subtype were not associated with recurrence (see table below). 5-year actuarial overall survival was no different between those who developed a recurrence and those who did not (92.9 vs. 95.7%, p = 0.171).

Conclusions: Approximately 7% of patients diagnosed with DCIS will recur within 10 years. Patients with high grade DCIS are more likely to recur, and this seems to be more predictive of recurrence than other clinicopathologic markers. Irrespective of whether or not patients with DCIS recur, overall survival is not significantly different between these two groups, and patients with DCIS enjoy an outstanding prognosis regardless.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-14-05.
Abstract P4-01-05: Utility of Preoperative Routine MRI and PET/CT in Breast Cancer Staging vs. Surgical Staging
Authors: Higaki K , Kochi M , Ito M , Otani S 
Published: August 2014

Abstract
Background: Staging of breast cancer is one of the most important factors in determining treatment options. The aim of this study is to assess the utility of routine magnetic resonance imaging (MRI) and positron emission tomography and computed tomography (PET/CT) in preoperative breast cancer staging.
Patients and methods: We examined 616 consecutive patients, who were newly-diagnosed with operable primary breast cancer less than 3 cm, at our institution between 2009 and 2011. They all underwent MRI and PET/CT to assign the clinical stage by TNM classification. Tumor size was measured by contrast MRI examinations and node status and metastases were evaluated on PET/CT. We examined their clinical and pathological T and N status retrospectively to assess the utility and concordance rate of preoperative imaging studies. Patients with tumors more than 3 cm were excluded from this study, since preoperative systemic therapy is the standard therapeutic strategy for those patients.
Results: The concordance rate of T status was 79.9% in clinical T1 patients (366/458) and 55.6% in clinical T2 patients (88/158). The concordance rate of N status was 83.8% in clinical N0 patients (495/591) and 60.0% in clinical N1 patients (15/25). As a result, the concordance rate of clinical stage was 66.5% in clinical stage I patients (296/445) and 55.0% in clinical stage II patients (94/171). In addition, 43 patients were diagnosed as contrary breast cancer by MRI (7.5%) and 31 contrary breast cancer (5.4%) and 12 other malignant disease (1.9%) were found by PET/CT.
Conclusions: MRI and PET/CT are valuable tools to provide information on tumor size, lymph node involvement, distant metastases and other occult primary disease. Preoperative routine MRI and PET/CT studies have a substantial impact on patients with operable primary breast cancer.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-01-05.
Abstract P4-01-08: Effect of bilateral salpingo-oophrectomy on breast MRI fibroglandular volume and background parenchymal enhancement for BRCA 1/2 mutation carriers.
Authors: De Leo MJ , Domchek S , Kontos D , Conant E , Weinstein S 
Published: August 2014

Abstract
PURPOSE: Bilateral salpingo-oophrectomy (BSO) reduces breast cancer risk in women with BRCA1/2 mutations by approximately 50%. Annual screening for these high-risk women includes breast MRI and mammography. It is unknown whether BSO affects fibroglandular volume (FG) and background enhancement (BG) on breast MRI in this population. The purpose of this study is to assess the difference in FG and BG in BRCA1/2 mutation carriers before and after BSO on breast MRI.
METHOD AND MATERIALS: We compared FG and BG on contrast-enhanced breast MRI before and after BSO. Two readers blinded to both clinical and imaging history scored FG according to the BI-RADS criteria from 1–4: fatty, scattered, heterogeneously dense, or extremely dense. BG was graded based on the MRI BI-RADS scale from 1–4: minimal, mild, moderate, and marked. Average BIRADS scores of each reader were used to calculate mean FG and BG (±SD) before and after BSO, and compared using a paired t-test for significance.
RESULTS: We examined 60 women with BRCA1/2 mutations who underwent breast MRI before and after BSO from 2001–2011 at our institution. Five patients were excluded from the final analysis as they underwent mastectomy or bilateral radiation therapy before post-BSO MRI. Mean time to post-BSO MRI was 8.3 months ± 7 months. Mean pre- and post-operative FG were 2.64±0.78 and 2.58±0.75, respectively (p = 0.622). Mean pre- and post-operative BG were 2.46±0.93 and 1.87±0.81, respectively (p = 0.0001). Breast cancer was detected in 8 women at a median time of 3.4 years following BSO. In these 8 women, mean pre- and post-operative FG were 3.10±0.57 and 2.55±0.69, respectively. Mean pre- and post-operative BG were 3.20±0.67 and 2.35±0.71, respectively.
CONCLUSION: In this population of 55 BRCA1/2 mutation carriers who underwent breast MRI before and after BSO, there was a significant reduction in BG following BSO. There was no difference in FG on MRI following BSO. For the 8 patients in this cohort who were diagnosed with breast cancer after BSO, there was a trend toward higher FG and BG both before and after BSO, in comparison to the patients who were not diagnosed with breast cancer, suggesting that rates of higher FG and BG may be associated with increased risk for developing breast cancer.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-01-08.
Abstract P4-01-11: Clinical Findings and Outcomes from MRI Staging of Breast Cancer in a Diverse Population
Authors: Raghavendra A , Ji L , Ricker C , Tang S , Church TD , Larsen L , Sheth P , Sposto R , Sener S , Tripathy D 
Published: August 2014

Abstract
Background: Staging breast MRI can detect occult breast cancers in 1–10% of newly diagnosed patients. The performance of MRI, impact of patient factors, and resulting surgical management in underserved and diverse populations has not been well studied.
Methods We performed a retrospective analysis of consecutive patients with newly diagnosed in situ or invasive breast cancer (2006–2011) who had a preoperative staging MRI seen at our Centers that cares for an underserved and minority population. IRB approval was obtained to extract demographic and clinicopathological data, imaging studies and surgical treatment. Non-index lesions (NIL) were defined as those in breast or axillary nodes not known to be malignant or presenting with clinical, mammographic or ultrasound findings, in a different quadrant and given an MRI BIRADS score of 4 or 5. Occult cancers (OC) were those lesions found by biopsy or surgery to be invasive or in situ cancer. Logistic regression was used to examine the association between the probability of a NIL or OC and patients characteristics. Statistical computation was performed using STATA.
Results: Among 678 patients, 144 (21%) had a total of 171 NIL identified by MRI; 67 (9.8%) were ipsilateral, 44 (6.5%) contralateral and 24(3.5%)axillary nodes. 57 patients (8.4%) had a total of 62 OCs detected −34 (5%) ipsilateral, 8(1.2%) contralateral, and 9(1.3%) axillary nodes of which 49 (7.2%) were invasive and 8 (1.2%) in situ. 40% of patients with NILs were confirmed as OCs.

Analyses showed that age was marginally significantly associated with the probability of having OC(OR = 1.5 for each 10 years increase, p = 0.080). Patients with no BRCA mutation had significantly higher chance of having NILs tested with MRI (p = 0.003), but the probability of having OC did not significantly differ between those tested. Ipsilateral compared to contralateral NILs had a 4-fold higher chance of being OCs(p &lt; 0.001). For NILs (n = 157), 59 (37.6%) underwent biopsy, 11 (7%) biopsy followed by lumpectomy, 10(6.4%) had lumpectomy, 24 (15.3%) mastectomy, 15 (9.6%) biopsy followed by mastectomy and (15)9.6% node dissection. Amongst OCs (n = 62) 6 (3.8%) underwent biopsy, 6 (3.8%) biopsy followed by lumpectomy, 6 (3.8%) lumpectomy, 20(12.7%) mastectomy, 12 (7.6%) had biopsy followed by mastectomy and 10 (6.4 %) node dissection.
Conclusions: In this diverse population, staging MRI detected NILs and OC in 21% and 8.4% of patients, respectively. Laterality and age seemed to be associated with chance of having OC. Interestingly, none of the OCs detected were among the known 32 mutation carriers. MRI staging appears to identify OC to an equal extent in a largely Hispanic and younger underserved population as reported in the literature for populations of mostly insured patients.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-01-11.
Abstract P4-01-15: Impact of Preoperative MRI on the Surgical Treatment of Breast Cancer: A SEER-Medicare Analysis
Authors: Thorsen CM , Weiss JE , Kerlikowske K , Ozanne EM , Buist DS , Hubbard RA , Tosteson AN , Henderson LM , Virnig BA , Goodrich ME , Onega TL 
Published: August 2014

Abstract
Background: Preoperative magnetic resonance imaging (MRI) use has increased for women with invasive breast cancer and ductal carcinoma in situ (DCIS). Prior studies have disputed whether preoperative MRI is associated with increased rates of mastectomy. We evaluated the rates of mastectomy versus breast conserving surgery (BCS) and their association with preoperative MRI in older women.
Methods: We identified women in SEER-Medicare 66 years or older diagnosed with DCIS or invasive breast cancer between 2002 and 2007 treated within 6 months of diagnosis with mastectomy or breast conserving surgery (BCS) with or without radiotherapy (RT). Preoperative MRI was defined as MRI occurring before a woman's first surgery after her initial diagnosis. We looked for surgical treatment (BCS or mastectomy) and radiotherapy, age at diagnosis, year of diagnosis and cancer type, overall and separately by receipt of MRI. We examined the association of surgical treatment with MRI using multivariable logistic regression adjusting for age at diagnosis, year of diagnosis, cancer type and radiotherapy.
Results: Among the 70,758 women identified, 5,126 (7.2%) had a preoperative MRI. The overall use of MRI increased from 1.2% in 2002 to 18.0% in 2007 (p &lt; 0.0001). Women with MRI were more likely to undergo mastectomy than those without MRI (331 per 1000 vs. 314 per 1000; respectively, p &lt; 0.0001) and more likely to undergo BCS RT (432 per 1000 vs. 354 per 1000; respectively, p &lt; 0.0001).
Conclusion: The use of preoperative MRI has increased in recent years and is significantly associated with increased rates of BCS RT and mastectomy. Limitations of this study include that it is an observational analysis and that selection bias may exist for MRI and aggressive treatment that is not related to what is observed on MRI. Further studies are needed to understand how patient characteristics and information obtained from MRI influence treatment choices.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-01-15.
Abstract P4-01-17: Ductolobular breast carcinoma and the role of preoperative magnetic resonance imaging
Authors: Postma EL , El Sharouni MA , Verkooijen HM , Witkamp AJ , van den Bosch MA , van Hillegersberg R , van Diest PJ 
Published: August 2014

Abstract
Introduction: Lobular carcinoma is the second most frequently diagnosed type of invasive breast cancer (about 10%) after the ductal NOS type (80%). In patients with lobular carcinoma, magnetic resonance imaging (MRI) plays an important role in the pre-operative work up, since mammography and ultrasound often underestimate the tumor extent and have a high false negative rate for additional foci in the ipsi- or contra lateral breast when compared to MRI. As the histological spectrum of invasive breast cancers is however a continuum with gradual transitions between types, mixed type invasive carcinomas with both ductal and lobular histologic features occur and are usually denoted ductolobular cancer. In our institution, MRI is part of the routine pre-operative work up in patients with ductolobular breast cancer, but the value of MRI in the pre-operative work up of ductolobular carcinoma has yet to be determined.
Purpose: We set out to determine the probability of detecting additional, clinically relevant, findings on MRI in patients diagnosed with ductolobular carcinoma.
Methods: We retrospectively searched the pathology database for all patients diagnosed with histologically proven ductolobular breast cancer at our institution between 2008-Sept 2012. Findings on mammography and ultrasound were compared with the findings on the pre-operative MRI. Additional findings on MRI (larger tumor size, additional ipsi- and contralateral lesions) were verified by pathology evaluation.
Results: Out of the 121 patients diagnosed with ductolobular cancer, 91 (75%) underwent MRI for pre-operative work-up. With MRI, 67 additional findings were detected in 56 (62%) patients. In 23 patients a contralateral additional lesion was seen, of which 12 turned out malignant. Ipsilateral lesions were seen in 28 patients, 20 of which were malignant at histology. In 16 patients, more extensive disease was seen on MRI compared to conventional imaging (mean difference was 18 mm, range 6–67 mm). MRI correlated better with the histological extent of these tumors (r = 0.97) than conventional imaging (r = 0.79). Of all MRI detected additional findings, 69% (46/67) was proven malignant after histology assessment. On patient-level, MRI led to the detection of one or more malignant finding(s) in 41/91 (45%) patients.
Conclusion: For patients diagnosed with invasive ductolobular breast cancer, the probability of detecting clinically relevant additional findings on MRI is high. Preoperative MRI should therefore be part of the routine work up of this breast cancer type.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-01-17.