bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adjuvant trastuzumab (T) therapy in HER2+ breast cancer after ASCO 2005: Patients’ attitudes and immediate economic burden
Authors: Benn S. M. , Jha G. , Ratliff T. W. , Spiers K. , Baskin R. , Yunus F. , Osarogiagbon R. , Boston B. , Minhas S. , Jahanzeb M. 
Published: March 2020

10565 Background: Data from 3 large randomized trials documenting the efficacy of T in the adjuvant setting were reported at ASCO 2005, and subsequently published in NEJM 2005; 353: (16) pp 1659–72 and 1673–1684 . We decided to offer T, and attempted to assess patients’ characteristics that influence its acceptance, in a subgroup of HER2 + patients that had already completed adjuvant chemotherapy at our institution within 12 months prior to these reported results. Methods: Using Electronic Medical Records (OpTx, Canada), we identified HER2+ breast cancer patients who had completed adjuvant therapy within the prior 12 months and administered an informational synopsis about the study results. They then completed a questionnaire, including their demographic information, that established their understanding of the data and documented their decision to receive or to not receive adjuvant T as an afterthought. Results: We identified 1442 breast cancer patients in Optx that were seen at UTCI for initial or follow up visits between May 2004 and May 2005. Those with 3 or fewer visits within the last year and those who received no chemotherapy (n = 770) were excluded. Of the remaining 672 patients, only 104 (15%) had documented HER2+ disease. Fourteen HER2+ patients had metastatic disease, while 84 patients, though HER2+, had either completed adjuvant chemotherapy greater than 12 months prior or were currently receiving adjuvant therapy or T, and/or had other reasons to not be suitable for T. Six patients qualified for this study; 5 decided to receive adjuvant T and 1 chose not to because she perceived the additional benefit to be minimal. Conclusions: While our sample size was too small in the end to draw conclusions about patients’ attitudes towards new data on adjuvant T, we were struck by the small number of patients who could be offered T as an afterthought despite our large patient volume. The magnitude of the perceived economic burden and its imminence after the release of these data may have been overestimated. [Table: see text]
Nitric oxide and asymmetric dimethylarginine (ADMA) in malignancy associated thrombosis and their modulation by anticoagulants
Authors: Fareed J. , Hoppensteadt D. A. , Demir M. , Iqbal O. , Jeske W. , Tobu M. , Bick R. 
Published: March 2020

10573 Background: Cancer associated thrombotic complications are primarily due to endothelial dysfunction and upregulation of inflammatory processes. Nitric oxide (NO) represents one of the major endothelial derived vasoactive mediators. Asymmetric dimethylarginine (ADMA) is an endogenous competitive inhibitor of NO synthase which inhibits NO production at pathophysiologic levels. Plasma ADMA levels are upregulated in atherosclerosis, hypertension, end stage renal disease, chronic heart failure and microangiopathy. Methods: To test the hypothesis that endothelial dysfunction in cancer patients may result in increased ADMA levels, plasma samples were retrospectively analyzed from an open label, multidose, active comparator designed study in which all patients (n = 110) were initially treated with low molecular weight heparin, enoxaparin (E) at 1–1.5 mg/kg sc for 5 days and further subdivided into group E which continued to receive E and warfarin (W) group which was given oral anticoagulants for a period of up to 12 weeks. Baseline blood samples (BL), 5 days post E (IPE) and 4–6 week samples from the E and W were analyzed for ADMA and NO levels by ELISA methods. Results: Both the ADMA and NO levels were markedly elevated in cancer patients. The E treated group showed a marked decrease in the ADMA levels which persisted throughout the treatment period. However, in the W converted group the ADMA levels rebounded to an increased level indicating that E differentially regulated ADMA in these patients. The down regulation pattern of NO was similar for both E and W. Conclusions: These results suggest that patients with cancer and thrombosis exhibit simultaneous upregulation of ADMA and NO. While E and W show a differential regulation of ADMA both result in downregulation of NO. The fact that E regulates ADMA is highly suggestive of its role in iNOS regulation which may be involved in the inflammatory response in cancer patients. [Table: see text] No significant financial relationships to disclose.
Preoperative dose-dense sequential chemotherapy of epirubicin/cyclophosphamide followed by docetaxel/capecitabine in patients with early breast cancer
Authors: Iacobelli S. , Cianchetti E. , Ficorella C. , Angelucci D. , Grossi S. , Ricevuto E. , Castrilli G. , Zilli M. , Tinari N. , Natoli C. 
Published: March 2020

10598 Background: The use of preoperative chemotherapy for breast cancer has been shown to result in similar disease-free and overall survival as postoperative adjuvant chemotherapy. Additionally, the rate of pathologic complete response (pCR) in the breast after preoperative chemotherapy has been shown to correlate with survival. The objective of this study was to evaluate the activity and safety of a dose-dense and sequential chemotherapy of epirubicin/cyclophosphamide (EC) followed by docetaxel/capecitabine (DXe) given preoperatively in patients with early breast cancer not candidate to breast-conserving surgery. Methods: Forty-one women with histologically/cytologically confirmed primary breast cancer (T2–3, N0–2, M0) received 4 cycles of EC (cyclophosphamide, 600 mg/m2 and epirubicin, 90 mg/m2) q2 weeks followed by two cycles of DXe (docetaxel, 36 mg/m2 days 1, 8, and 15 and capecitabine, 1250 mg/m2 days 5–18) q 28 days, with pegfilgrastim support. The study was designed as a Simon’s two-step phase II study. The primary end point of the study was the incidence of pCR defined as the absence of invasive cancer in the breast at definitive surgery. Results: Thirty-nine out of 41 enrolled patients were evaluable for response to treatment (one patient withdrew from the study for G4 neutropenia after the first EC cycle, and the other for therapy refusal after the 4 EC cycles). A pCR was observed in 10 patients for a total pCR rate of 25.6%. Interestingly, all but one of the 10 pCR cases showed ER/PR-negative/Her2-positive tumors. A clinical response (CR or PR) detected by palpation and by imaging was observed in 37 patients, for an overall response rate of 95%. Twenty-nine patients (75%) underwent breast-conserving surgery. The treatment was well tolerated: one patient experienced G3 mucositis and another patient required a 25% dose reduction of capecitabine because of hand-foot syndrome. There was no case of cardiac toxicity, thrombocytopenia or any other serious adverse event. Conclusions: The dose-dense sequential combination EC/DXe is endowed with good antitumor activity and limited toxicity, allowing a high rate of pCR and breast conservation. Thus, this regimen can be considered for further clinical trial. No significant financial relationships to disclose.
The risk of breast cancer recurrence in the sentinel lymph node era
Authors: Gold L. P. , Cheng Z. , Tafra L. , Sawyer K. , Verbanac K. , Rosman M. 
Published: March 2020

10600 Background: Sentinel lymph node biopsy (SLNB), the preferred method of axillary staging in early breast cancer, is more sensitive and accurate compared to axillary node dissection. However, this data has not been incorporated into current prognostic models estimating the risk of breast cancer recurrence. We hypothesize that prognostic models based on data in the pre-SLN era underestimate survival and exaggerate benefits resulting from adjuvant therapy. In order to evaluate this hypothesis, we examined the disease free survival (DFS) and overall survival (OS) in an IRB approved, prospective, multicenter study of SLNB. Methods: From 1996–2005, 564 patients who had invasive disease in whom a SLN was found were examined from two experienced sites . Data was analyzed with regards to SLN status, tumor size, grade, lymphovascular invasion (LVI), age, estrogen receptor (ER) status and use of chemotherapy with respect to DFS and OS. Results: Median age was 57 years, tumor size was 1.5 (range 0.08–10.5) cm and follow-up was 46.2 (range 1–104.5) months. The SLN was positive in 31.2% of patients. The Kaplan-Meier (K-M) 5 year estimate of OS was 94.5(±1)% and DFS 88(±2)%. Tumor grade and size, LVI, ER- and +SLN significantly correlated with poorer DFS and OS by univariate analysis. By multivariate analysis, however, SLN status was the only statistically significant predictor for DFS (p = 0.004; HR = 3.4; CI = 1.5 - 8.0) and OS (p = 0.0051; HR = 7.3; CI = 1.8–29.4). SLN negative patients showed K-M 5 year DFS and OS estimates of 94(±)% and 97.4(±1)% respectively. There was no significant difference in DFS for SLN- patients treated with or without chemotherapy (p = 0.3). Conclusions: SLN status was the only significant predictor of DFS and OS. In node negative patients, we observed a higher DFS and OS than current statistical models based on historical data would have predicted. In this new era of SLNB, the magnitude of benefit from adjuvant therapy in sentinel node negative patients should be re-evaluated. No significant financial relationships to disclose.
Positive predictive factors for residual disease in re-excision specimens of early stage breast cancer
Authors: Haideri N. A. , Moormeier J. , Arora N. 
Published: March 2020

10604 Background: Breast conservation followed by radiation is the treatment in patients with Stage 0, 1, 2, breast cancer. Patients with positive, close or indeterminate margins on excisional biopsy typically undergo reexcision. Residual tumor is identified in 32% to 62% of reexcision specimens as reported in several studies. Such patients undergo subsequent surgery. This study analyzed the pathological specimens of patients undergoing reexcision, to identify characteristics that may predict residual disease. Methods: Patients with the AJCC Stage 0, 1, 2, were identified from Jan 95–Dec 02 with positive, close or indeterminate/unknown margins. All specimens were inked and patients undergoing reexcision were included. Pathological specimens with positive margins, undergoing reexcision were reviewed. Of the 211 patients studied, 159 were eligible. Age, stage, pathologic type, differentiation, microclacifications, extensive intraductal component, lymphovascular invasion, estrogen receptor status, progesterone receptor status, Her 2 neu, S phase and lymph node involvement were evaluated to predict residual disease. Univariate analysis was performed to evaluate the different variables independently. The P values obtained were 2 sided. Results: 131 (82.3%) specimens with positive margins underwent reexcision. Residual cancer was identified in 66 (41.5%) patients. Well differentiated tumors can be an independent predictor of residual disease based on the P value of 0.025 found in this study. Stage 2B, DCIS, microcalcifications and extensive intraductal component was frequent in re-excision specimens, but not significant. Conclusions: Incidence of residual carcinoma is significant in patients undergoing reexcision, making it difficult to identify a group with positive margins where a reexcision can be avoided. Therefore patients with positive margins should typically undergo reexcision, followed by radiation for comprehensive treatment of their early stage breast cancer. [Table: see text] No significant financial relationships to disclose.
Antisense oligonucleotide targeted to the transferrin receptor gene suppresses tumor growth and lung metastases in 4T1 mammary adenocarcinoma mouse model
Authors: Jiang X. , Israyeeyan A. , Boykin E. , Lomax L. , Head J. F. , Elliott R. L. 
Published: March 2020

10616 Iron is required for the activity of ribonucleotide reductase and synthesis of DNA. Cellular surface transferrin receptors (TfR) are the principal transport protein for iron into cells. It has been reported that inhibition of TfR gene expression leads to the suppression of tumor cell growth in cell culture. In the present study, an antisense oligonucleotide targeted to the transferrin receptor gene was used to treat 4T1 mammary adenocarinoma in cell culture and a mouse model. The cytotoxicity of a 24-mer TfR antisense oligonucleotide was determined by 3[H]-thymidine incorporation in vitro. The sense and random sequence 24-mer oligonucleotides were used as controls. We found that TfR antisense inhibited mRNA expression of TfR and cell growth of the 4T1 cells in the dose-dependent manner. Mice bearing the 4T1 mammary adenocarcinoma were continuously treated for 14 days through subcutaneous implantation of Alzet osmotic mini-pumps. Tumor sizes were measured twice a week. Tumor necrosis and metastases were determined grossly at autopsy and by microscopy. Tumor metastases to lungs (all lung lobes) was scored by the following criteria: 0 = no metastasis, 1 = 1–2 foci/slide, 2 = 3–10 foci/slide, 3 = 11–20 foci/slide and 4 = >20 foci/slide. At 4, 7 and 10 days post-treatment, tumor sizes of the TfR antisense-treated group were significant smaller than control mice (p < 0.05, p < 0.05 and p < 0.05, respectively). At 14 days post-treatment, autopsy showed that 91.7% (11/12) of control mice had multiple metastatic foci on their lung surfaces, but only 16.7% (2/12) of TfR antisense-treated mice had metastatic tumor foci on their lung surfaces (p < 0.001). Primary tumor did not have significant necrosis in either group. Mean lung metastasis scores of 3.25 ± 1.06 in control group vs. 1.75 ± 1.49 in TfR antisense-treated group (p < 0.01) were determined by microscopy. In summary, TfR antisense inhibited cell growth in cell culture and primary tumor growth in mice, and reduced lung metastasis of the 4T1 mouse mammary adenocarcinoma. No significant financial relationships to disclose.
Split, low-dose docetaxel (D) and low-dose capecitabine (C) is an active regimen in metastatic breast cancer with minimal toxicity
Authors: Silva O. E. , Lopes G. , Morgensztern D. , Lobo C. , Abdullah S. , Doliny P. , Slingerland J. , Gluck S. , Santos E. , Welsh C. , Hurley J. 
Published: March 2020

10618 Background: Successful therapeutic regimens in metastatic breast cancer must balance efficacy and tolerability. D and C is an active and commonly used doublet in this setting. D upregulates thymidine phosphorylase and thus potentiates the anti-tumor effects of C. A schedule with split, low-dose D in combination with low dose C could improve the therapeutic index of this regimen without compromising its clinical activity. Methods: Patients with previously untreated her2-neu negative metastatic breast cancer were included. A Simon 2-stage Phase II clinical trial was designed to assess the response rate (primary end-point), and toxicity of docetaxel 25 mg/m2 on days 1 and 8 in combination with capecitabine 750 mg/m2 bid on days 1–14 of a 21-day cycle. RECIST criteria were used for response assessment, which was performed every 2 cycles. Results: Thirty-one women have been enrolled. Median age was 55. Twenty patients had hormone receptor positive disease. Sites of metastasis were as follows: bone, 24 patients; liver, 14; lungs or pleura 14. A total of 189 cycles have been delivered (median: 4 cycles, range 1–33). Grade 3 and 4 toxicities were as follows: peripheral neuropathy, 2 patients; edema, 1 patient; skin, 1 patient. Two women had fever without neutropenia. Another patient had a gastric perforation but recovered without sequela. Twenty-two patients are available for response evaluation. One patient with a single bone metastasis had a complete response after chemotherapy followed by radiation. Partial responses were seen in 10 patients, for an overall response rate of 50% (95% CI, 30 to 70). Four women had stable disease and 7 had progressed at the time of first assessment. With a median follow-up of 15 months (range 1–26), the median time to treatment failure (all patients) was 7 months (range 1–26+). Median survival has not yet been reached. Out of 8 patients older than 65, seven were evaluable and 4 had a partial response. Conclusions: Split, low-dose Docetaxel and low-dose Capecitabine is an effective combination in the first-line treatment of patients with metastatic breast cancer. Toxicity with this schedule was minimal, making it an attractive regimen for further study. [Table: see text]
A population-based study of trastuzumab-mediated cardiotoxicity among early stage breast cancer patients treated with adjuvant trastuzumab
Authors: McArthur H. L. , Barnett J. , Chia S. 
Published: March 2020

10640 Background: Given the risk of cardiotoxicity demonstrated with trastuzumab (T) in the MBC literature, adjuvant T trials incorporated stringent cardiac monitoring. In 2005, several of these trials were reported with impressive DFS improvements. As a result of these trials, women in the province of British Columbia with HER-2 positive early stage breast cancer were offered T either concurrently or sequentially with their primary chemotherapy regimen. Given the paucity of data surrounding adjuvant T-mediated cardiotoxicity among the general population, we performed a retrospective review of cardiac toxicity among all patients receiving adjuvant T at the BCCA. Methods: Patients receiving adjuvant T between July 1, 2005 and December 31, 2005 either sequentially or concurrently with their primary chemotherapy regimen were identified by screening the BCCA pharmacy database. A chart review was conducted and the T start date; LVEF values at 0, 3 and 6 months; and patients with symptoms suggestive of congestive heart failure were identified. The mean LVEF values at 0, 3 and 6 months were calculated. Results: 133 patients received adjuvant T alone after completing their primary chemotherapy. The mean baseline LVEF was 60.5%. Of the 101 and 11 patients available for analysis at 3 and 6 months, the mean LVEF was 58.5% and 58.4%, respectively. 5 patients (3.8%) developed symptoms of CHF. 58 patients received adjuvant T concurrently with their primary chemotherapy (four cycles of AC followed by four cycles of concurrent paclitaxel and T). Of these, only 18 patients had an LVEF measured at 0 and 3 months, with a mean LVEF of 64.6% and 63.6%, respectively. Of the 7 patients who also had an LVEF measured at 6 months, the mean was 60.5% for an absolute decrease of 4.1% from baseline. One patient (1.7%) had symptomatic CHF. Conclusions: A clinically meaningful rate of cardiotoxicity is seen with both sequential and concurrent adjuvant T. In particular, we have demonstrated a higher rate of cardiotoxicity with adjuvant T alone than was observed in the HERA trial. These findings support ongoing stringent cardiac monitoring among the general population treated with adjuvant T. [Table: see text]
Routine staging radiology is not needed for all breast cancer patients
Authors: Kell M. R. , Healy C. , Martin Z. , Downey R. , Potter-Bierne S. , Gorey T. F. , Flannigan F. , Stokes M. 
Published: March 2020

10648 Background: Early stage breast carcinoma is unlikely to have undergone metastatic spread at the time of presentation. The utility of routine staging liver ultrasound (LUS) and bone scan (BS) in early stage disease is unclear. We postulate that early stage breast cancer patients do not need routine radiological staging. Methods: We studied 200 patients with a diagnosis of invasive breast carcinoma. 100 with symptomatic breast cancer (SBC) and 100 with screen detected (SD). Patients’ histology, tumour markers (CEA, CA 15.3), hormone receptor status, CXR, LUS and BS results were reviewed. Results: All patients underwent curative surgery for early stage invasive breast cancer. 3 patients had liver metastases diagnosed by LUS. Two of these patients were from the SBC and one from SD (grade ≥2, mean tumour size 2.2 cm). 4 patients had bony metastases diagnosed by BS. Three of these were from the SBC and one from SD (grade ≥2, mean tumour size 3.2 cm.). No patients with low-grade T1 tumours had signs of metastasis on BS or US. Conclusions: The incidence of metastatic disease is very low in newly diagnosed early stage breast carcinoma. Our results suggest that patients with low-grade T1 tumours do not need staging BS or US. No significant financial relationships to disclose.
Paclitaxel (P), pegylated liposomal doxorubicin (PLD) and trastuzumab as 1st-line chemotherapy (chemo) in HER2/neu-positive (+) metastatic breast cancer (MBC)
Authors: Karabelis A. , Kosmas C. , Mylonakis N. , Tsakonas G. , Evgenidi K. , Kallistratos E. , Sava L. , Nikolopoulou A. , Gassiamis A. , Valavanis C. 
Published: March 2020

10663 Background: Addition of trastuzumab (Herceptin, H) to successive neoadjuvant taxane+anthracycline-based chemo in patients (pts) with HER-2 (+) breast cancer significantly increases the pathological complete response (CR) rates. PLD has considerably less cardiotoxicity compared to parent drug. The aim of the study was to evaluate the activity and safety of combining H with PLD and P as 1st-line chemo in HER-2 (+) MBC pts. Methods: Inclusion criteria were: histologically confirmed MBC or relapsed after adjuvant chemo, ≥1 measurable lesion, adequate organ function, ECOG-PS 0–1, left ventricular ejection fraction (LVEF) by MUGA ≥55% (reevaluated after cycles 3 and 6). HER-2 positivity was determined by IHC and confirmed with CISH. Chemo was administered as follows: H 6mg/kg (8mg/kg-1st cycle) infused over 90min, PLD 35mg/m2 over 1hr, and P 175mg/m2 over 3hrs on day 1, with prophylactic G-CSF, recycled every 3 weeks. In responders, H was administered as consolidation (6mg/kg/3wks) until disease progression. Results: From 10/2003–10/2005, 19 female HER-2 positive MBC pts were enrolled. Median age: 68 (range, 42–78). Metastatic sites were: lung 6, liver 1, bone 3, lymph nodes 11, soft tissue 5 [median: 2 (range, 1–4)]. Pts received a median of 6 (range, 1–8) for a total of 102 cycles. PLD was started at 35 mg/m2, but in pts with grade 3 hand-foot syndrome (HFS) dose was reduced by 25% (6 pts), or the drug was omitted for 1 cycle (1 pt). 17 pts completed 3–6 cycles and were evaluable for response, all treated patients were evaluable for toxicity. Response rates (RR) were 71%; CR 41%, PR 30%, SD 29%, with no PD. Two pts rendered operable had pCR. Toxicities were: HFS; grade 4: 1, grade 3: 6 (overall 37%), grade 3–4 neutropenia: 4, grade 3 anemia: 1, grade 3–4 mucositis: 2, and grade 2 alopecia: 19. Neither significant LVEF decline, nor symptomatic cardiac event was observed. It is too early to provide data on response duration, TTP, and OS, and these will be available at the meeting. Conclusions: H+P+PLD as 1st-line chemo in HER-2(+) MBC pts is a very active and well tolerated regimen with no significant morbidity/mortality. HFS was the most relevant toxicity. The study is ongoing. No significant financial relationships to disclose.