bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase II study of lapatinib in recurrent or metastatic EGFR and/or ErbB2 expressing adenoid cystic (ACC) and non-ACC malignant tumors of the salivary glands (MSGT)
Authors: Agulnik M. , Cohen E. E. , Cohen R. B. , Chen E. X. , Hotte S. J. , Winquist E. , Laurie S. , Hayes D. N. , Dancey J. E. , Siu L. L. 
Published: March 2020

5566 Background: The limited therapeutic index of chemotherapy in recurrent or metastatic MSGT provides a strong rationale for the evaluation of molecularly targeted agents in this disease. Lapatinib is a dual inhibitor of EGFR and ErbB2 tyrosine kinase activity. Expression of ErbB2 and EGFR has been associated with biological aggressiveness and poor prognosis in MSGT, respectively. We conducted a phase II study to determine the antitumor activity of lapatinib in MSGT. Methods: The main study has a two-stage design in which patients (pts) with progressive, recurrent or metastatic ACC, and immunohistochemically expressing at least 1+ EGFR and/or 2+ ErbB2, were treated with lapatinib 1500 mg PO daily. Each cycle consists of 4 weeks of continuous dosing. Pts with non-ACC MSGT of other histologies, meeting identical eligibility criteria, were treated in this trial as a single-stage, separate cohort. Results: Of 57 pts screened for this study, 29/33 (88%) ACC and 22/24 (92%) non-ACC pts expressed EGFR and/or ErbB2. Thirty-eight pts have been accrued to the study to date (20 ACC/18 non-ACC). The remaining 13 pts who were screened positive either declined entry or were ineligible for other reasons. Baseline data on 34 pts are: M:F = 25:9, median age 56 (range 38–80), PS 0:1:2 = 16:17:1, prior radiation:chemotherapy = 30:18. After 92 cycles of therapy, the most frequent adverse events experienced (as % of cycles) were diarrhea (54%), pain (52%), fatigue (52%), lymphopenia (39%), anemia (38%), hyperglycemia (38%) and dyspnea (34%). No grade 4 adverse events have occurred and only 8 pts experienced a grade 3 adverse event, primarily pain and dyspnea. No significant cardiac toxicity has been observed. Among 14 ACC pts evaluable for response so far: 9 have SD (range 2–9 cycles), 3 PD, and 2 died prior to cycle 2. For 12 evaluable non-ACC pts: 8 have SD (range 2–9 cycles), and 4 PD. No pts have had an objective response. Conclusions: Although there are no objective responses to date, lapatinib is well tolerated, with tumor stabilization achieved by 64% of pts and 24/38 pts remain on treatment at present. Trial accrual of ACC pts into the first stage has been completed, the second stage will open if an objective response is seen. No significant financial relationships to disclose.
Radiosensitization with a COX2 inhibitor with chemoradiation for head and neck cancer
Authors: Prellop P. , Peters G. , Carroll W. , Nabell L. , Spencer S. , Ove R. 
Published: March 2020

5582 Background: Cyclo-oxygenase 2 (COX2) inhibitors have shown promise as radio- and chemosensitizers. We conducted a phase IB/II study to evaluate the toxicity and efficacy of celecoxib, a selective COX2 inhibitor, administered concurrently with carboplatin, paclitaxel, and radiation for locally advanced or recurrent head and neck cancer. Methods: Patients with stage III/IV or recurrent squamous cell carcinoma of the oropharynx, oral cavity, hypopharynx, or larynx were eligible. Primary endpoints were toxicity, local control and survival. Patients were treated with weekly carboplatin (AUC = 2.0), paclitaxel (30 mg/m2) and concurrent radiation (70 Gy). Celecoxib (400 mg bid) was started 1 week prior to the initiation of radiotherapy and was given for a total of 2 years. In 12/04, the study closed due to concerns of cardiotoxicity with COX-2 inhibitors. Celecoxib was discontinued in all patients. The study restarted in 5/06 with the modification that celecoxib would be given only during radiation. Results: Between 12/02 and 1/06, a total of 28 patients were enrolled: 89% were male, median age was 56.5, 3 with recurrent cancer and 25 treated definitively. Five patients have been treated on the modified study. Grade 3/4 toxicities include: mucositis (35% G3), dermatitis (18% G3; 7% G4), febrile neutropenia (21% G3; 3% G4), dysphagia (57% G3), nausea/vomiting (29% G3). Thirty percent did not complete prescribed chemotherapy due to myelosuppression. Acturarial 2 year outcomes in the 20 evaluable, definitively treated patients: 65% survival, 76% local control. Conclusions: Compared to published data using carbo/taxol and RT, an unexpectantly high incident of febrile neutropenia was observed but no increase in radiation dermatitis or mucositis. Two year survival data is comparable to published data. No significant financial relationships to disclose.
Effect of the third generation selective estrogen receptor modulator arzoxifene on mammographic breast density
Authors: Kimler B. F. , Ursin G. , Fabian C. J. , Anderson J. R. , Chamberlain C. , Mayo M. S. , O’Shaughnessy J. A. , Lynch H. T. , Johnson K. A. , Browne D. 
Published: March 2020

562 Background: Arzoxifene (ARZ) is currently being studied for treatment of breast cancer patients in a Phase II trial because of tamoxifen-like efficacy but lack of uterine agonist effect. We conducted a Phase II chemoprevention trial in women at high risk for development of breast cancer on the basis of personal or family history. Methods: Potential subjects had multiple biomarkers assessed, including random periareolar fine needle aspiration (RPFNA) with breast epithelial cells processed for cytomorphology and immunocytochemistry. Women who exhibited cytologic hyperplasia ± atypia were eligible for enrollment. Subjects were stratified on the basis of atypia, estrogen receptor expression, menopause status, germline BrCa1/2 mutation status, and accrual site. Subjects were randomized (double-blind) between placebo and ARZ (LY353381.HCI, 20 mg daily) for 6 mo, with an option to continue on study for another 6 mo while receiving open-label ARZ. Assessments conducted at baseline, 6 mo, and 12 mo included mammographic breast density. Mammograms were digitized to image files which were cropped to remove labels and dates, and then identified by a study subject ID number and a random coding for baseline, 6 or 12 mo. This allowed the reader (GU) to view the three files for a subject, but to remain blinded as to the sequence of the films or the study agent. The files were assessed for mammographic density using the Madena computer-assisted system. Results: Of 199 subjects enrolled on the study, 52% were pre-menopausal; with 101 women randomized to placebo and 98 to ARZ. At baseline, mean values were comparable for placebo and ARZ groups for breast area (∼244 cm2), total dense area (∼100 cm2), and the percent of the breast at increased density (41.3% vs 46.2%). After 6 mo, there were minimal changes in total breast area (P=0.13); but statistically significant decreases (P<0.001) for the comparison of placebo vs ARZ (2-sided T-test) for change in both dense area (+3.8 vs −12.9 cm2) and percent breast density (+0.8% vs −4.6%). Conclusions: The 3rd generation SERM arzoxifene administered for 6 mo produces statistically significant decreases in mammographic breast density relative to placebo in women at high risk for development of breast cancer. No significant financial relationships to disclose.
Analysis of fracture risk factors from the ’Arimidex’, Tamoxifen, Alone or in Combination (ATAC) trial: 5-year data
Authors: Howell A. 
Published: March 2020

563 Background: The Completed Treatment Analysis of the ATAC trial at 68 months’ median follow-up confirmed that initial adjuvant treatment with anastrozole has significant efficacy and tolerability advantages compared with tamoxifen (ATAC Trialists’ Group. Lancet 2005; 365: 60–2). In the ATAC trial, the rate of all fracture types for anastrozole was higher than with tamoxifen. To better understand the impact of fracture risk factors on actual fracture rates, we undertook an analysis of the risk factors for all reported fractures in the ATAC trial up to 5 years. Methods: The analysis followed a time-to-event approach, using the Cox model with forward selection of prognostic covariates, together with the likelihood ratio test at the 5% significance level. Considered risk factors were age, body mass index (by tertile), previous hormone replacement therapy, concomitant medications (vitamin D, calcium, thiazides, statins, corticosteroids, thyroid hormones, bisphosphonates, antiepileptics, anxiolytics), geographical region (very high, high, or moderate and low hip fracture risk areas) (Kanis et al. J Bone Miner Res 2002; 17: 1237–44), smoking, and trial therapy (anastrozole or tamoxifen). Hazard ratios and associated 95% confidence intervals were obtained from the final model, which contained all statistically significant factors. Results: Of 6186 women, 524 (8.5%) had a fracture. Statistically significant predictors of fracture were age, region, and trial therapy ( Table ). A significant decrease in fracture risk was also observed in statin users although this decrease may not have been due to statin use, but rather to related factors. Conclusions: It is essential that individuals at high risk of fracture be identified so that they can receive appropriate evaluation and treatment. Profiling of risk as described here could enable the development of risk scores that would allow the identification and close observation of patients at high risk of fracture prior to commencing adjuvant therapy. [Table: see text] [Table: see text]
Confirmation of double-peaked time distribution of mortality for breast cancer in a population-based study
Authors: Wong N. S. , Gao F. , Tan S. B. , Machin D. , Ng E. H. 
Published: March 2020

593 Background: Double-peaked time distributions of mortality hazard function have been reported for breast cancer patients from Western populations treated with mastectomy alone and is thought to reflect accelerated tumor growth at metastatic sites mediated by angiogenesis after primary tumor removal. Similar data is not available for Asian populations. We sought to investigate if differences exist in the pattern of mortality hazard function between Western breast cancer patients and Asian patients in Singapore treated with mastectomy alone which may suggest underlying differences in tumor biology between the two populations. Methods: We performed a retrospective cohort study of 3809 female unilateral breast cancer patients registered in the Singapore Breast Cancer Registry between October 1994 to June 1999. Data regarding patient demographics, tumor characteristics and death data were available. Overall survival curves were calculated using the Kaplan-Meier method and compared by the log-rank test. Death-specific hazard rate was calculated as the conditional probability of dying in a time interval, given that the patient was alive at the beginning of the interval. The life table method was used to calculate the yearly hazard rates. All tests were two-sided and significant at the 5% level. Results: In this cohort, 1169 patients (45.9%) had mastectomy alone without further adjuvant therapy. Demographics were: median age 55; 87.4% Chinese; 62.9% postmenopausal; 51.6% hormone receptor positive; 70.3% node negative; 22.8% high histological grade; 76.9% stage I or II. A double-peaked mortality hazard pattern, with a first major mortality rise reaching the maximum at the 2nd - 4th year after diagnosis and a second small mortality rise near the 9th year was observed. Analyses by subgroups showed a similar pattern in node positive or high grade tumors but not in node negative or well to moderately differentiated tumors. A double peaked pattern was seen regardless of menopausal status. The double-peaked pattern observed in our patients was quantitatively and qualitatively similar to that reported by Western series. Conclusions: Our study confirms a double-peaked process in Asian patients and gives further support to the tumor dormancy hypothesis. No significant financial relationships to disclose.
Local-regional relapse and distant metastasis in conservatively managed triple negative early stage breast cancer
Authors: Haffty B. G. , Yang Q. , Reiss M. , Kearney T. , Hait W. , Toppmeyer D. 
Published: March 2020

594 Background: Triple negative (TN) basal-like breast cancers (Negative for ER,PR,HER2/neu) represent an aggressive phenotype, with unique clinical and pathologic features. The purpose of this study was to determine the prognostic significance of this classification with respect to local-regional relapse and distant metastasis in a cohort of conservatively managed breast cancer patients. Methods: A large data base of conservatively managed breast cancer patients with long term follow-up, in which all three immunhistochemical markers, ER,PR and HER2/neu were available was reviewed. Patients were classified as TN if they tested negative for all three markers. Of 442 patients in the data base with all three markers available, 100 were classified as TN. All clinical, pathologic, outcomes and molecular marker data were entered into a computerized database. Results: As of September 2005, with a median follow-up of 7 years, of the 442 patients in the study there have been 50 in-breast relapses, 10 nodal relapses, 68 distant relapses and 62 deaths. Compared with the other subtypes, the TN cohort had a poorer overall survival (67% vs 75%, p = .096), poorer distant metastasis-free rate (61% vs 75%, p = .002), poorer cause-specific survival (67% vs 78%, p = .03), and poorer nodal relapse-free rate (93% vs 99%, p = .021). In a multivariate Cox regression analysis, TN subtype was an independent predictor of distant metastasis (HR=2.6, CI 1.53–4.35, p = .004) and cause- specific survival (HR= 2.36, CI 1.28–4.38, p= .006). There was no significant difference in local (in-breast) control between the TN and other subtypes. BRCA testing was performed on 85 patients in this cohort, of whom 8 had deleterious mutations in BRCA1 and 6 had deleterious mutations in BRCA2. Of 8 BRCA1 mutant patients 7 were classified as TN, while only 1 of 6 BRCA2 patients were TN (p < .001). Conclusions: Patients classified as TN have a poor prognosis with respect to overall, disease free and cause specific survival. However there was no evidence that these patients are at higher risk for local relapse following conservative surgery and radiation. BRCA1 mutant patients develop predominantly TN tumors. No significant financial relationships to disclose.
Bimodal breast cancer incidence patterns provide support for a dualistic model of mammary carcinogenesis
Authors: Anderson W. F. , Pfeiffer R. M. , Dores G. M. , Sherman M. E. 
Published: March 2020

595 Background: Although breast cancers are extremely heterogeneous with respect to clinical presentation, histopathological appearance, and molecular alterations; breast cancer is often viewed as a single biologic entity with common etiology and unified pathogenesis. Accumulating data has challenged this view, demonstrating that the stratification of tumors by gene expression profiles, immunohistochemical (IHC) staining patterns, and other techniques may permit the categorization of breast cancers into two main pathways of mammary carcinogenesis. Based upon cellular origin and/or estrogen receptor (ER) expression there are 1) tumors from stem cells committed to luminal differentiation and ER expression and 2) neoplasms from stem cells programmed to display basal differentiation and lacking ER expression. If confirmed, these observations may form the basis for revised conceptual frameworks. Methods:: We applied age-at-diagnosis density plots and a two component statistical mixture model to breast cancer cases overall (n=270,124) in the SEER program. These age distributions were reevaluated after stratification by histopathologic type, race, and ER. Results: A bimodal distribution provided a better fit for the age distribution patterns than a single distribution for breast cancers overall and for all histologic types, except medullary carcinoma. However, the proportion of early-onset and late-onset tumors varied: ductal and tubular carcinomas demonstrated relatively equal proportions; lobular, papillary and mucinous tumors were associated with late-onset populations; and inflammatory and medullary tumors were more related to early-onset disease. Medullary carcinomas were exceptional in showing a single distribution irrespective of race and/or ER status. Of note, medullary breast carcinomas are rare tumors that are associated with germline mutations in BRCA1. Conclusion: Most histopathologic types of breast carcinomas demonstrated a bimodal mixture of early- and late-onset cancer populations, possibly representing two major age-related causal pathways. These population-based results seem consistent with emerging molecular data, showing two main classes of breast cancer based upon cellular origin and ER expression. No significant financial relationships to disclose.
Race as a risk factor for developing osteonecrosis of the jaw after long term bisphosphonate therapy in patients with metastatic breast cancer
Authors: Aiti T. , McDunn S. , Hussein L. , Ashkenazi I. , Jajeh A. , Wang Y. , Zaren H. A. 
Published: March 2020

596 Background: Association between osteonecrosis of the jaw (ONJ) and bisphosphonate treatment has been increasingly reported in the literature. Methods: This is a retrospective review of a single institution’s experience with patients diagnosed with bone metastasis secondary to breast cancer, who developed ONJ while treated with bisphosphonates (Zoledronic acid - Zometa; Pamidronate - Aredia), between 1.1.2001 and 10.30.2005. Presentation, age, race, and outcome were reviewed. Logistic Regression was used to test for statistical significance. Results: 161 patients with bone metastasis secondary to breast cancer treated with bisphosphonates were reviewed (82 African American, 29 Caucasians, 26 Hispanic, 15 Asian and 9 others.). ONJ developed in 6 (3.7%) patients, 5 of which were Caucasians. Logistic regression adjusting for dose shows that the odds ratio for developing ONJ comparing Caucasians with non-Caucasians is 45.7 (p=0.016). Age did not impact occurrence of ONJ. All 6 patients developed ONJ after a minimum of 31 months of treatment. Two patients had a history of previous tooth extraction. In four other patients, ONJ appeared spontaneously. One patient, who presented with an abscess, developed sepsis which resulted in the patient’s death. Two patients were treated with debridement and antibiotics and their lesions healed. Three other patients ended up suffering from a chronically exposed bone. Conclusion: ONJ is a serious complication of bisphosphonate therapy and it affected a significant proportion of our patients. Our data suggests that Caucasians may be more susceptible. Since sample size is small, determining if race is a risk factor for the development of ONJ, while on bisphosphonate therapy, will require further investigation. No significant financial relationships to disclose.
Initial biopsy procedure for breast cancer diagnosis influences number of surgical procedures and cost of care
Authors: Al-Refaie W. B. , Cormier J. N. , Xing Y. , Hunt K. K. , Fearmonti G. , Ghandi R. , Kuerer H. M. , Meric-Bernstam F. , Bedrosian I. , Lucci A. 
Published: March 2020

598 Background: Excisional biopsy (ExB) and percutaneous needle biopsy (PB) are both accurate methods for diagnosing breast cancer. However, comprehensive breast cancer staging requires surgical assessment of the primary tumor and regional nodes. This study was designed to examine surgical and financial implications for breast cancer patients undergoing either ExB or PB. Methods: We evaluated 2,459 women with invasive breast cancer enrolled in a comprehensive database from 2000 to 2005. Clinical and treatment factors were compared for patients who had ExB versus PB. Total costs, facility fees (operating rooms, radiology suites, and pathology processing), and professional fees were estimated. A multivariate logistic regression was performed to determine factors associated with biopsy type. Results: PB was utilized in 1817 (74%) patients and ExB in 642 (26%). Of ExB patients, 86% were performed prior to referral. Patients undergoing ExB required a greater number of surgical procedures for margin control and lymph node assessment compared to PB (median 2.0 vs. 1.0, respectively). ExB exacted a cost increase 1.7 times that of PB, with a difference of >$3400 at our institution. After adjusting for age, tumor size and year of diagnosis, ExB was significantly associated with an increased number of surgical procedures required for definitive treatment compared to PB (OR = 166.7, p < 0.001). Conclusions: Excisional biopsy for breast cancer diagnosis results in an increased need for return trips to the operating room and higher cost of care. Percutaneous biopsy should be considered as the preferred approach in the diagnosis of breast cancer. No significant financial relationships to disclose.
Comparative analysis of MRI vs mammography in evaluation of size, number of lesions and nodal status of breast cancer
Authors: Saha S. , Chitneni S. , Sehgal R. , Arora M. , Desouza B. , David S. , Singh T. 
Published: March 2020

600 Background: Breast MRI is thought to be better in evaluating patients (pts) with BrCa. Our study was to compare MRI vs mam to predict leisons and LNS in BrCa. Methods: A retrospective study of 100 consecutive pts with pathologically proven BrCa was done. All had preoperative MRI and mam. Findings were compared to the final pathologic size, used as gold standard. MRI and was done at same center and single surgeon did all surgeries. Results: Of 100 pts,MRI reported 124 lesions. MRI reported size in 107 and mam reported size in 63 lesions. In MRI detected sizes 8% had same size as pathological size, 66% were overestimated by a mean of 0.64cm and 26% were underestimated by a mean of 0.48cm. For mam lesions, 10% had same size, 34% were overestimated by a mean of 1.10cm, 57% were underestimated by a mean of 0.78 cm. Total of 25 additional lesions were found in 23 pts in same and 6 leisons in 6 pts in contralateral breast by MRI. MRI also detected enlarged axillary and intramammary LN in 15% pts, 40% were true positives(+ve) and 60% were false +ve. One pt had metastatic LN in the contralateral axilla detected by MRI and confirmed by lymphoscintogram and pathology. 3% pts had neo-adjuvant chemotherapy Conclusion: In our study mam underestimated the breast lesion size in pts significantly more than MRI, but MRI overestimated BrCa lesion size in more number of pts. The mean difference in size on MRI when compared to the pathological size is less than 1 cm, while mam overestimated by a mean of greater than 1cm. This might be particularly important for T1 and T2 lesions, where size is the most important criterion for the T-stage classification. The identification of additional lesions and enlarged LN on MRI further validates the utility of MRI. [Table: see text] No significant financial relationships to disclose.