bluuebunny/crossref_metadata_2025_split huggingface dataset:
A mathematical model to predict for pre-malignant or malignant diagnosis among patients with Birad 4 breast lesions
Authors: Laurent I. , Balleyguier C. , Rouzier R. , André F. , Marsiglia H. , Spielmann M. , Vielh P. , Delaloge S. 
Published: March 2020

10578 Background: Preoperative cytological or histological diagnosis of breast lesions is mandatory in order to avoid unnecessary surgical biopsies, but on the other side preoperative work-up may dangerously delay specific care of breast cancer. Solid lesions or microcalcifications (M) scored as Birad 4 are increasingly prevalent in western countries. A highly variable proportion of these lesions (20–80%) are breast cancer. Tools to help clinicians recognize cancers and preneoplastic lesions among true benign conditions may be very helpful in clinical practice. Methods: Radiological, clinical and pathological data of consecutive patients with Birad 4 breast M (N = 384 biopsies among 354 patients) or nodular lesions (N = 172 FNAC among 167 patients) seen in a multidisciplinary breast clinic were prospectively recorded. A multivariate analysis of factors predicting for a final cancer or pre-malignant diagnosis was performed and two nomograms were constructed using the R statistical package for both nodular lesions and M. They were validated by bootstrapping. Variables tested included age, size and palpability of lesion, Gail score, menopausal status, HRT use, progression of lesion (M), and presence of associated symptoms. Results: Median age was 57 years (18–92) for the entire population. Patients with nodular lesions were menopausal in 64.5%, median size of their lesion was 12 mm (4–50), 32% were palpable; 43% had a final diagnosis of breast cancer and 3.5% of atypical hyperplasia or LCIS. 69% of patients with M were menopausal, 31.25% had a final diagnosis of breast cancer and 9.8% of atypical hyperplasia or LCIS. Among patients with nodular lesions, age and palpability were the sole independent predictors of cancer or precancerous lesions (p = 0.04 and 0.004), but the other variables (Gail, menopause, HRT) added discrimination with a concordance index of 0.71. Among patients with M, the only independent predictive variable was the recent progression of the lesions (p = 0.01). The nomogram had a concordance index of 0.69. Conclusion: Our study provides two original nomograms for the prediction of the pre-malignant or malignant nature of recently discovered solid breast lesions and M. Gail model alone is not a highly useful tool in daily individual cancer prediction. No significant financial relationships to disclose.
Hepatic intra-arterial chemotherapy in patients with metastatic breast cancer
Authors: Fazio N. , Medici M. , Colleoni M. , Rocca A. , Torrisi R. , Orsi F. , Della Vigna P. , Bonomo G. , Monfardini L. , Goldhirsch A. 
Published: March 2020

10581 Background: Hepatic intra-arterial chemotherapy has been reported to produce higher response rate than systemic in patients (pts) with metastatic colorectal cancer. In breast cancer the liver is involved in up to 60% of cases and often conditions the prognosis. Nevertheless, only rare hepatic arterial infusion studies were published. Therefore, based on our previous experience in hepatic metastatic colorectal malignancies, we evaluated efficacy and toxicity of hepatic intra-arterial chemotherapy in pts with metastatic breast cancer. Methods: A three-day continuous arterial infusion (CAI) of fluorouracil 1000 mg/m2 q 24 hrs, with cisplatin 10 mg/m2 twice daily, and mitomycin-c 1 mg/m2 twice daily, was performed through a percutaneous radiological temporary trans-subclavicular catheter. Pts with responsive disease received up to four cycles every six weeks. Pts still responding could carry on with cisplatin and fluorouracil, without mitomycin-c. Pts were hospitalized and the catheter was removed upon end of infusion. Results: From 9.2000 to 6.2005, 25 pts with progressive liver metastases from breast cancer were treated. Nine had more than 50% of liver involvement. Fifteen had also extra-hepatic metastases. All had received antracyclines and 22/25 taxanes. Pts had a median of five previous chemotherapy lines. Median time from diagnosis of liver metastases to first CAI was 33 months (range: 7–110). Sixty-four total courses were administered, with a median of 2 (range: 1–7) per pts. Epigastric pain was the main clinical toxicity (54%) and iatrogenic gastro-duodenal ulcer, the main complication (28%). No relevant catheter-related complications occurred. Fifteen partial responses (60%) and eight stable diseases (32%) were observed. Response duration was 5.4 months (range: 2 - 27), time to progression 5.1 months (range: 2.5–29+), and median overall survival 13 months (range: 3.5+–32+). Conclusions: Hepatic arterial infusion of chemotherapy in heavily pre-treated pts with metastatic breast cancer is feasible and effective. A specific evaluation of quality of life should be performed to verify a real clinical benefit. An earlier timing during course of liver disease, and a shift to radiological implanted arterial port (allowing out-patient treatment), will be investigated. No significant financial relationships to disclose.
Manageable safety profile in patients with taxane-resistant metastatic breast cancer (MBC) treated with ixabepilone: Final report
Authors: Fornier M. N. , Martin M. , Klimovsky J. , Bunnell C. A. 
Published: March 2020

10587 Background: The epothilones, a new class of antineoplastic agents, promote tumor cell death by stabilizing microtubules and inducing apoptosis. Ixabepilone was selected from over 300 epothilone analogs due to its high in vivo efficacy, good metabolic stability and low protein binding. Methods: This international, multicenter, open-label Phase II trial was designed to assess the activity of ixabepilone in patients (pts) with highly resistant MBC who had progressed following taxane treatment. Eligible pts were aged ≥18 years with MBC (progressed on or within 4 months of taxane therapy [or within 6 months if adjuvant taxane only]). Pts were excluded if they had had ≥3 prior chemotherapy regimens for MBC or had ≥Grade 2 neuropathy. Ixabepilone (40 mg/m2 q3w) was administered as a 3-hour infusion for a maximum of 18 cycles, unless there was evidence of progressive disease and/or pts met discontinuation criteria. Toxicity was evaluated continuously. Results: Of 49 pts (median age 54 years, range 30–81), 86% of pts had received ≥2 prior chemotherapy regimens. Treatment-related adverse events (TRAEs) were manageable and mostly Grade 1 or 2 (45%). Treatment-related neuropathy was mostly sensory, mild-to-moderate, cumulative and reversible. Sensory neuropathy was managed mainly with dose reductions (12 out of 49 pts had their dose reduced due to neuropathy). Treatment-limiting or severe neuropathy generally resolved or lessened in intensity within 1–2 months after therapy discontinuation. Febrile neutropenia was reported in only 2 pts, in addition, 2 pts (4%) developed treatment-related infection with neutropenia. Only six pts (12%) required growth factor support for neutropenia during their treatment. Progressive disease was the most common reason for discontinuing the study (36%), with 16% discontinuing due to TRAEs. Conclusions: Ixabepilone demonstrates an acceptable safety profile, along with promising antitumor activity, in pts with clearly defined taxane-resistant MBC. [Table: see text] [Table: see text]
Docetaxel (Do) and liposomal pegylated doxorubicin in metastatic breast cancer (MBC) patients (pts): The French GINECO group experience
Authors: Guastalla J. P. , Largillier R. , Geay J. F. , Hardy-Bessard A. C. , Kirsher S. , Slama B. , Cretin J. , Orfeuvre H. , Goubely Y. , Pujade-Lauraine E. 
Published: March 2020

10589 Background: Taxanes and anthracyclins are among the most effective agents in MBC. Ca has a favourable cardiac toxicity profile and we tested Ca in combination with Do. Methods: Two successive Ca-Do regimens (Reg) were evaluated in first line MBC pts with performance status ≤ 2, and good organ function including normal MUGA scan. Reg A (n = 53 pts): Ca 35 mg/m2/d1 q4wks + Do 40 mg/m2/d1 q2wks according to previous phase I study results (Guastalla JP et al, Proc Am Soc Clin Onc 2004) and Reg B (n = 14 pts): Ca 30 mg/m2/d1 + Do 75 mg/m2/d2 every 3wks (Alexopoulos A et al, Ann Oncol 2004). Pyridoxine (250 mg/d) was given continuously during treatment (Tt). Results: The 67 pts had a median age of 58 yrs (range 37–77 yrs); others characteristics (%): ER+ (75), PR+ (51), HER2+ (9), adjuvant anthracyclin (54) and hormonotherapy (60), visceral disease (78). Both regimens induced unbearable toxicities (Tox) leading to premature stopping of the trial. Dose reduction, Tt delay and early stopping due to Tox were noted (% pts) in A:68, 36, 48 and B:57, 64, 54. Mucositis-skin Tox was the most severe Tox (% Gr2/3; A:40/15, B:43/21) and was observed in 21 and 40% of pts at cycle 2 and 4. Hematotoxicity was worse in reg B: Gr3/4 neutropenia (A:28/9, B:14/57), anemia (A:0/0, B:7/7) and thrombopenia (A:0/0, B:14/0), febrile neutropenia (A:6, B:14), Gr2–3 infection (A:13, B:28). Others Gr2–3 toxicities (> 10%) included alopecia (A:64, B:78), fatigue (A:54, B:57), nausea/vomiting (A:19, B:50). Three pts had a reduction of LVEF without clinical cardiac toxicity Conclusions: The combination of Do and Ca according to the 2 schedules tested in this study induced an unexpected high rate of mucositis and skin toxicity. No significant financial relationships to disclose.
Clinical significance of brain metastases occurrence in HER2 overexpressing metastatic breast cancer patients treated with trastuzumab
Authors: Mari V. , Chamorey E. , Italiano A. , Van Den Bos F. , Ferri-Dessens R. , Ferrero J. , Largillier R. , Ettore F. , Courdi A. , Paquis P. , Frenay M. 
Published: March 2020

10593 Background: Recent data report that HER2 overexpressing metastatic breast cancer patients (HER+ MBC pts) treated with trastuzumab (T) have a high rate of Brain metastasis (BM). This study aimed to evaluate the prognostic significance of BM occurrence and the related clinical outcome in a specific patient population. Methods: All the HER+MBC patients treated with trastuzumab (with or without chemotherapy) between 09/1999 and 12/2004 were included in this study. Results: A total of forty three patients were enrolled into the study cohort. The median follow-up was 48 months (range, 11–166). Fifteen patients (35%) developped BM. The median interval from the the first MBC event to BM was 18 months (range, 1–65). In multivariate analysis; younger age was the only factor associated with BM occurrence (46 versus 57 years; p = 0.01). Patients with BM tend to have a longer median duration of response to T than patients without BM (16 months versus 13 months; p = 0.1). At the time of BM appearance, 6 of the 15 patients (40%) were still responding or had achieved extracranial stable disease while receiving trastuzumab. Twelve out of 15 (80%) pts received a whole-brain radiation therapy, and 8 pts continued to receive trastuzumab until extracranial disease progression. The median overall survival for patients diagnosed with BM was 10 months (range, 2–42). At three-year, there was no significant difference in overall survival rates between the two groups. The 3-YS was 63.5% and 66.7% for pts with or without BM, respectively; (p = 0.7). Conclusions: The BM occurrence in HER2+ MBC pts treated with Trastuzumab is not linked to tumour resistance, but likely related to the T inability to cross the blood-brain barrier. There is no impaired survival for these pts treated with effective and appropriate therapy. [Table: see text]
Hormone replacement therapy (HRT) in women with previously treated primary breast cancer: Update XII
Authors: Bluming A. Z. 
Published: March 2020

10596 Background: To assess the incidence of contralateral or recurrent breast cancer among women prospectively treated with HRT after initial breast cancer diagnosis. Methods: A community-based, prospective, single-arm, pilot study of HRT among 241 women with previously treated primary breast cancer. Results: Median duration of HRT is 83+ months (range 12+–161+). Median interval from initial surgery to initiation of HRT is 52 months (range 2–361 months). Follow-up to date is 100%. Actuarial disease-free survival (DFS), disease-specific survival (DSS), & median duration of HRT by stage are listed in the table. One hundred and fourteen patients have stopped HRT (47%), 57 because of anxiety about taking HRT (24%), 48 because of breast cancer development (20%), 3 because of the development of non-breast cancers, 2 died of nonmalignant disease, 3 because of HRT-associated symptoms, and 1 because of pulmonary emboli without clinical phlebitis. CHRT, as opposed to ERT, was administered to 50% of all patients and 57% of the 48 who subsequently developed breast cancer on study. Actuarial DFS to 20 years for T1N0 patients was 72% versus 63% for comparable T1N0 patients who did not receive HRT. Conclusions: No evidence to date of increased development, recurrence or of breast cancer-related death associated with post diagnosis HRT. [Table: see text] No significant financial relationships to disclose.
An evaluation of changes in biological markers (ER, PgR, or Ki67) after neoadjuvant chemotherapy (ET: epirubicin and docetaxel) in operable breast cancer
Authors: Tashima R. , Nishimura R. 
Published: March 2020

10613 Background: Neoadjuvant chemotherapy (NAC) is a valid option not only for advanced breast cancer but also for operable breast cancer. It was reported that disease-free and overall survival after NAC were equivalent to those after adjuvant therapy. The role of biological markers for the prediction of NAC may be evaluated using pathological responsiveness. In this study, we investigated the changes in biological markers such as estrogen receptor (ER), progesterone receptor (PgR), or Ki67 after NAC. Methods: Eligible patients (pts) were newly diagnosed with large primary tumors > 3 cm or positive nodes. Fifty-two pts were enrolled and received epirubicin 60 mg/m2 followed by docetaxel 60 mg/m2 every 3 weeks for 4 cycles before surgery. In 51 cases out of the pts, pre-treatment needle biopsies and surgical specimen were analyzed for expression of ER, PgR, Her-2/neu, p53 and Ki67 by immunohistochemistry, and these data were compared to the pathological response. The pathological response was evaluated using the criteria of Japan Breast Cancer Society. Results: The median age was 47 (range, 29–67) and the mean tumor size was 5.2cm (range, 1.5–14.5). The clinical response was 86%; the BCS rate was 73% and pathological response was 31% including 3 cases with pCR. Regarding changes in biology after NAC, an average rate of ER positive cells significantly fell in 37% from 47% and that of PgR positive cells also fell in 14% from 32%. Most of cases, whose tumors were changed to ER/PgR negative from ER/PgR positive, were premenopausal women accompanied with amenorrhea during the treatment. Patients with lower ER, PgR, or a higher proliferation had a significantly greater benefit from NAC. The overexpression of Her2 was not correlated to pathological response, while p53 staining had a predictive value. And patients with positive nodes had a significantly favorable disease-free survival. Conclusions: The clinical effect of NAC (ET regimen) and the BCS rate by NAC were high. Although the rates of ER and PgR positive cells and proliferation were significantly reduced by NAC, a lower ER, PgR, or a higher proliferation might reflect a good pathological response. A negative change of ER or PgR by NAC might correlate with amenorrhea in premenopausal pts. No significant financial relationships to disclose.
Correlation between vascular endothelial growth factor and c-met expressions in breast carcinoma
Authors: Matkowski R. , Gisterek I. , Suder E. , Lacko A. , Szelachowska J. , Ramsey D. , Kornafel J. 
Published: March 2020

10621 Background: Vascular endothelial growth factor (VEGF) is a specific mitogen and survival factor for endothelial cells and a key promoter of angiogenesis. This cytokine selectively induces cells proliferation and migration, increases permeability of microvessels and activates proteolitic enzymes involved in tumor invasiveness. C-met is tyrosine kinase receptor; its activation can increase tumorigenicity, induce cell motility and enhance invasiveness and metastasis. This protein can increase production of protease and urokinase which are associated with membrane degradation crucial for metastasis. The relationships between both cytokines are not clearly identified. In this study, we evaluated VEGF and c-met expression in homogenous group of 99 patients with stage II ductal breast carcinomas and analyzed correlations between both markers. Methods: Microscopic studies were performed on formalin-fixed, paraffin-embedded cancer tissues, obtained during surgery and stained routinely with haematoxylin and eosin. Expression of VEGF and c-met was evaluated using a standard immunoperoxidase technique and area with molecule expression, intensity of color reaction and product of both findings were counted. Association between markers expressions was tested by Spearman Correlation Coefficient. Results: Expression of c-met was found in 37 (37.37%) breast tumors, while expression of VEGF was observed in 67 (67.67%) cases. There were strong correlations between expressions of both cytokines. The relationships were found between area with molecules’ expression (p = 0.0438) and intensity of reaction (p = 0.0461), also in the product of both findings (p = 0.0229). Conclusions: The results of our study confirms hypothesis that c-met may act as an indirect angiogenic factor by inducing expression of VEGF. No significant financial relationships to disclose.
Toxicity and outcome data in a phase II study of weekly docetaxel in combination with erlotinib in recurrent and/or metastatic breast cancer (MBC)
Authors: Kaur H. , Silverman P. , Singh D. , Cooper B. W. , Fu P. , Krishnamurthi S. , Remick S. , Overmoyer B. 
Published: March 2020

10623 Background: Single agent weekly docetaxel (D) is an active agent in the treatment of MBC with response rates of 29% - 53%. Erlotinib (OSI-774, Tarceva) is a tyrosine kinase inhibitor directed against the epidermal growth factor receptor (EGFR), and is overexpressed in 30–40% of breast cancers. EGFR inhibition by erlotinib (E) and its possible modulation of growth factor synthesis by breast cancer (BC) cells is an attractive treatment target. This study was designed to assess the combination of D and E in previously untreated recurrent &/or MBC. Methods: Adult patients (pts) with histologically confirmed BC without prior chemotherapy for recurrence or metastases were eligible. Treatment plan was: D [35 mg/m2 iv infusion weekly x 3 q4wks] and E 150 mg/d uninterrupted (D+E). E was to be continued in 4 week cycles after maximum tumor response or disease stabilization [following a minimum of 6 cycles of D+E]. The overall survival (OS) was estimated by Kaplan-Meier method. Results: 31of 40 planned female pts were enrolled between 12/02 and 9/05. Median age 52 years, range: 29–79. The median number of cycles of D +E received was 4, (range 1–9) and of E following D+E was 4 (range 1–29). The first 26 pts received planned D dose of 35mg/m2. Because of non-hematologic toxicity, trial was subsequently modified to start D at 30mg/m2.11/31 (36%) were not evaluable due to toxicity. Hematologic grade 3 or 4 toxicity was seen in 45% cases. Principal non-hematologic grade 3–4 toxicities included nausea, diarrhea, and constitutional symptoms seen in 30% of the pts. 4/9 pts receiving E after D+E experienced hematologic, hepatic, constitiutional, and eye (1 each) grade 3 toxicity only. Best clinical response in the 20 evaluable pts included; PR 11(55%), SD 7 (35%), PD 2 (10%). OS (n = 31) was 71% at 12mos, 42% at 24 mos with median OS 23 mos. Conclusions: Combination therapy of advanced breast cancer with Docetaxel and Erlotinib showed promising activity with favorable response compared to other studies. The combination is associated with moderate to severe hematological and non-hematological toxicities. Randomized trials are warranted to further investivate the efficacy of this combination compared to single agent Docetaxel. (Support: Sanofi-Aventis & Genentech.) [Table: see text]
Capecitabine plus docetaxel (XT): A first line, phase II clinical trial in metastatic breast cancer
Authors: Vogel C. L. , Tan-Chiu E. , Gokce F. 
Published: March 2020

10624 Background: The XT combination originally published at (X) dosed at 1250 mg/m2 bid po x 14 days and (T) at 75 mg/m2 q3 weeks I.V. respectively yielded good response rates and an overall survival advantage compared with single agent docetaxel at 100 mg/m2. However, the toxicity profile of this regimen has led to major dose and schedule modifications by most oncologists. Methods/Results: We initiated a Phase II trial at doses of X at 900 mg/m2 bid po x 14 days and T at 36 mg/m2 d 1 and 8. Three responded and the mean no. of cycles for these patients was 3.8. Since four of 6 went off study because of toxicity two additional dose levels were studied in 6 patients each. A second cohort received X at 650 mg/m2 bid and T at 30 mg/m2. With 6 evaluable patients, four of 6 responded but all 4 required further dose reductions. Mean no. of cycles received was 4.2. A third cohort of 6 patients received X at 825 mg/m2 plus the lower T at 30mg/m2 who received a mean no. of cycles of 6. While only 1/6 responded 3 additional patients had stable disease with marked decreases in CEA or CA 15–3 suggestive of anti-tumor response. Only 1/6 required a dose reduction. Among the 18 patients, epiphora was described by 5 (28%). Only 3 patients developed significant leukopenia, and thrombocytopenia was not seen. T-induced nail changes were uncommon but were severe in one patient. Two patients at the first dose level, but only one at lower levels developed mucositis. Grade 1 anemia was common but managed easily with growth factor support. Conclusions: The response rate of 44% is encouraging with these lower doses of XT. We recommend further studies using X at 825 mg/m2 and T at 30mg/m2 since these doses were associated with encouraging response rate and a better toxicity profile than higher doses. Even at this higher dose of X dose reductions may well be needed. (Supported by a grant from Roche Laboratories, Inc.) No significant financial relationships to disclose.