bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inter- and intra-country variations in the use of trastuzumab in Norway, Spain and Sweden
Authors: Wilking N. , Bergh J. , Wilking U. , Jönsson B. 
Published: March 2020

1069 Background: Breast cancer mortality is similar in Norway, Spain and Sweden (14–16/100,000 Age Standardized Rate). There are only small regional differences in incidence and mortality within the countries. Trastuzumab (T) was approved for metastatic breast cancer (MBC) in Norway, Spain and Sweden in second half of year 2000. T represents a unique new treatment for MBC that delays disease progression and improves survival. HER2 over expression (H+) is used to identify patients eligible for trastuzumab treatment (T). Methods: This study use sales data from IMS Health and incidence and mortality data from regional and national cancer registries as well as data from International Agency for Research on Cancer. We examines the variation in the use of T in different health care regions of Norway (4 regions), Spain (19 regions) and Sweden (6 regions) as well as differences in use between the countries. These results were also put into a global comparison. Results: There are marked differences in both the rate and level of uptake between the countries. Three years after approval the Spanish uptake was close to 90 % and twice the Swedish and 3–4 times the Norwegian uptake. The regional variations within the countries are of the same magnitude, a factor 2–3. Based on an assumed H+ rate of 25% and a treatment time of 38 weeks we estimate the proportion of H+ MBC patients that have been treated with T during the period 2000–2005 to be 24% in Norway; 66% in Spain and 44% in Sweden. In all countries there has been an increase in the use during the second half of 2005, indicating a use also in the adjuvant situation. T was approved for adjuvant treatment of BC in Europe in April 2006. Conclusions: Access of trastuzumab to patients with MBC in Norway, Spain and Sweden has been very variable. Spanish MBC patients have had earlier access to T than Swedish patients. Norwegian patients have had the lowest access. Regional differences in the use are in the magnitude of a factor 2–3. On a global level the Spanish uptake is in line with the uptake in the USA, Switzerland and Austria; the Swedish uptake is at an average European level and the Norwegian uptake is at a low level, similar to Czech Republic, Hungary, New Zealand, Poland and the UK. No significant financial relationships to disclose.
Translational correlates, including outcome for patients with ER-/PR-/HER2- (triple negative (TNeg)) disease from N0234, a phase II trial of gemcitabine and erlotinib for pts with previously treated metastatic breast cancer (MBC)
Authors: Thome S. , Hobday T. , Hillman D. , Aubry M. , Lingle W. , Reinholz M. , Graham D. , Flynn P. , Moreno A. , Perez E. 
Published: March 2020

1071 Background: N0234 is a phase II trial of gemcitabine at 1000 mg/m2 days 1 and 8 of a 21 day cycle and erlotinib at 150 mg daily in patients with previous therapy with either an anthracycline or a taxane for MBC. A partial response (PR) rate of 17% has been reported (ASCO 2005). Recent information suggests that over-expression of the EGFR pathway is frequent in patients with TNeg MBC. Methods: Tissue and serum were obtained for translational studies of ER, PR, HER2, and proteins related to EGFR pathway on tissue using immunohistochemistry; CK19, mammoglobin, and TTK on circulating tumor cells (CTCs). Markers were evaluated centrally, blinded to patient outcome. Complete data were available in 57 of 59 eligible patients; 20/57 patients (pts) were TNeg. Results: A PR rate of 25% and clinical benefit rate (PR + stable disease > 6 months)of 25% was observed in TNeg pts as compared to a PR rate of 14% (p = 0.30) and clinical benefit rate 22% (p= 0.75) for non-TNeg pts. Median progression free survival 72 days vs 98 days (p=0.13) and overall survival 227 days vs 738 days (p<0.001) were shorter for TNeg pts. Translational results for the EGFR pathway proteins and CTC analysis is forthcoming. Conclusions: The combination of gemcitabine and erlotinib appears to be as active in the non-TNeg and TNeg subset of patients on this trial. TNeg patients had an inferior clinical result, confirming the poor outcome seen in these patients. Data for the remaining biomarkers potentially predictive of activity will be presented. Supported by CA-25224, CA-37404. [Table: see text]
Multicenter study of weekly trastuzumab, paclitaxel and carboplatin followed by a week of rest every 28 days in patients with HER2+ metastatic breast cancer (MBC)
Authors: Ruiz M. , Salvador J. , Bayo J. , Lomas M. , Moreno A. , Valero M. , Bernabé R. , Vicente D. , Jiménez J. , Lopez-Ladrón A. 
Published: March 2020

1083 Background: The addition of Carboplatin to Trastuzumab and Paclitaxel improves the efficacy in HER2+ metastatic breast cancer (MBC). We have conducted a multicenter Phase II study to investigate the efficacy and safety of this combination given weekly × 3 followed by 1 week of rest. Primary endpoint was objective response rate and secondary endpoints were time to progression, overall survival and to study the toxicity profile of the combination. Methods: Between August 2003 and April 2006, 40 patients with HER2+ MBC (IHC 3+ or FISH+) have been included in the study. Pats received Trastuzumab (loading dose of 4 mg/kg/wk and 2 mg/kg/d following wks), Paclitaxel (80 mg/m2) and Carboplatin (AUC 2) all given weekly × 3 followed by 1 week of rest. Treatment was given until disease progression or unacceptable toxicity. Results: 40 pats had baseline data available. Median age was 54 yrs (range 29–75). 38 (95%) pats received prior adjuvant or neoadjuvant treatment. 11 (27,5%) pats have received one prior CT line for metastatic disease. 87,5% pats had PS 0 or 1 at study entry. Disease sites were liver 16 (40%), bone 12 (30%), lymph nodes 13 (32,5%) and lung 8 (20%). 19 (47,5%) had = 2 lesions. 97,5% had measurable disease. 36 pats have been evaluated for response: 11 CR (31%, 95% CI: 15–46%), 11 PR (31%, 15- 36%), 9 SD (25%, 9–36%), 5 PD (14%, 2–26%) and 4 NE resulting in an ORR of 61% (95% CI: 45–77%) and tumor growth control rate (RR+SD) of 86% of patients (95% CI: 75–97%). Median TTP was 12.1 mo (95% CI: 8.8–19.9 mo) and median duration of response and OS have not been reached yet. For a time of observation of 35 mo, the OS is 80,6%. 37 patients have received 194 cycles with a median of 5 cycles. Grade 3–4 toxicities/pats were: 3(7.5%) anaemia, 2 (5%) leucopenia, 8(20%) neutropenia, 1 (2,5%) febrile neutropenia, 1 (2,5%) trombopenia, 2(5%) asthenia, 2(5%) diarrhea, 3(7.5%) nausea, 2(5%) vomiting, 3(7.5%) mucositis Conclusions: This interim analysis shows an interesting activity with this regimen. One week of rest may be of better convenience for the patient and hospital but also may improve the tolerability profile and efficacy of the combination. Further results would be available for presentation. No significant financial relationships to disclose.
Efficacy and safety of trastuzumab plus vinorelbine as second-line treatment for women with HER2-positive metastatic breast cancer beyond disease progression
Authors: Bachelot T. , Mauriac L. , Delcambre C. , Maillart P. , Veyret C. , Mouret-Reynier M. , Van Praagh I. , Chollet P. 
Published: March 2020

1094 Background: There is increasing evidence that women with HER2-positive metastatic breast cancer (MBC) benefit from continued trastuzumab (H) therapy beyond disease progression (PD). In a Phase II multicentre 2-step trial we evaluated women for their response to second-line treatment with H + vinorelbine (N) following PD after receiving first-line H + taxane for HER2-positive MBC. Methods: Women aged =18 years with HER2-positive MBC received H (8 mg/kg loading dose followed by 6 mg/kg q3w or 4 mg/kg loading dose followed by 2 mg/kg qw) + N (30 mg/m2 days 1 and 8 q3w) until PD. The primary end point was overall response rate (ORR); secondary end points included time to progression, time to treatment failure, overall survival and safety. Data from a planned interim analysis are presented. Results: Seventeen out of a planned 50 patients (pts) were enrolled between June 2003 and October 2006, with a mean age of 54 years (range 42–70). Nine pts had hormone receptor-positive disease at baseline and 17 pts had HER2-positive disease (16 pts IHC 3+; 1 pt IHC 2+ and CISH+). Pts had previously received H in combination with paclitaxel (9 pts) or docetaxel (8 pts) as first-line therapy for MBC. Pts received a median of 6 treatment cycles with H + N (range 2–14), with 2 pts receiving H q3w and 15 pts receiving H qw. ORR was 29%, with 2 pts showing a complete response, 3 pts experiencing a partial response and 4 pts achieving stable disease lasting 6 months. Eight pts experienced PD. Re-treatment with H + N was well tolerated beyond PD, with grade 3/4 haematological toxicities being the most common serious adverse events, leading to a delay and dose reduction of N. No relevant cardiac toxicities were reported, with only 2 grade 1 cardiac events. All pts withdrew, 14 due to PD. Conclusions: This interim analysis indicates that treatment with Herceptin plus chemotherapy beyond PD is active (ORR 29%) and well tolerated, and provides further evidence that re-treatment with H is a promising therapeutic option. Pt accrual is ongoing and updated results will be presented. No significant financial relationships to disclose.
Monitoring of circulating tumor cells during systemic therapy allows distinguishing breast cancer patients at risk for relapse
Authors: Pachmann K. , Camara O. , Lobodasch K. , Clement J. , Dengler R. , Hoeffken K. 
Published: March 2020

11006 Background: Recent refinement of methods, allowing detection of minimal numbers of residual cells from malignant tumors have reactivated the debate, to what extent single tumor cells in lymph nodes, bone marrow and peripheral blood can be considered as “micrometastases”. The presence of such cells, indeed, reflects only the first step in the metastatic process, dissemination, and the formation of metastases from such cells seems to be quite ineffective. If, however these cells react to therapy in an identical way as the tumor itself, these cells can be used to monitor therapy response very early during primary systemic (neoadjuvant) therapy, during adjuvant therapy, where no other target is available to control therapy success and already during therapy initiation in metastatic disease. Methods: Circulating epithelial cells were enumerated from 1 ml of anticoagulated blood after red blood cell lysis, staining of live cells with a fluorochrome labeled anti-epithelial antibody and automated microscopy before and after each chemotherapy cycle for monitoring of therapy success. Results: The response of the peripherally circulating cells of 35 patients with breast cancer treated with neoadjuvant chemotherapy varied from marginal (less than tenfold) to highly responsive (more than thousand fold) already during the first three to four courses and showed identical response to therapy as the whole tumor with a correlation of p > 0.9. The method was subsequently applied to monitor the response of such cells in the adjuvant treatment. In the first 25 patients with a follow up of more than 4 years, an increase in cell numbers already from the begin of therapy or following an initial response was observed in 20% of patients and all of these patients have subsequently relapsed (p<0,0001). These results have now been corroborated in a total of 148 patients, confirming a hazard ratio of 25 for relapse in the following 5 years for patients with increasing cell numbers during therapy independent of therapy regimen and a significance of p<0.0001. Conclusions: Quantitative monitoring of circulating tumor cells can be used as a tool for therapy survey in breast cancer in the absence of manifest tumor. No significant financial relationships to disclose.
Bevacizumab and albumin-bound paclitaxel treatment in metastatic breast cancer
Authors: Link J. S. , Waisman J. R. , Nguyen B. , Jacobs C. I. 
Published: March 2020

1101 Background: Miller, et al demonstrated the combination of bevacizumab and paclitaxel has significant activity in metastatic breast cancer. Because paclitaxel albumin bound (PAB) has been shown to have less toxicity, a better tumor delivery and possibly better response for metastatic breast cancer, we combined it with bevacizumab (B) to treat women with metastatic breast cancer. Methods: This is a retrospective analysis. Billing records from March 2005 through December 2006 were reviewed to obtain all patients treated consecutively with a combination of PAB (80–125mg/m2 days 1,8,15 or 170–200 mg/m2 every 14 days on a 28 day cycle) and B (10mg/kg every 14 days). A total of 40 women were identified. A minimum of two courses were given. All women had received a minimum of 3 prior chemotherapy regimens including anthracyclines 34/40 and taxanes 35/40. Patients were monitored for response using RECIST criteria based on PE, and PET/CT imaging. Six women with bone only disease were monitored with PET, CT/MRI and tumor markers. All response data were confirmed by independent review. Results: 20 women had objective responses to the PAB/B regimen (3CRs and 17PRs) for an overall response rate of 50%. Another seven women had stable disease (SD) for a mean duration of 212 days. Thirteen women progressed. The mean time to progression for the responders was 132 days. Toxicity was acceptable with fatigue (9 gr 2), neuropathy (4 gr 2, 1 gr 3), anemia (2 gr 2, 2 gr 3), and hypertension (3 gr 2) being the most common complaints. Two patients were discontinued due to a possible CNS hemorrhage into a metastatic brain lesion. There were no other treatment discontinuations due to non-tolerance Conclusions: In our limited series of consecutive woman with advanced, heavily pretreated metastatic breast cancer treated with PAB (Abraxane) and bevacizumab (Avastin), we saw a 50% objective response rate (3CR, 17PR). The regimen was well tolerated with acceptable toxicity. Another seven women had stable disease for an average duration of >200days giving an objective response rate + SD of 67%. No significant financial relationships to disclose.
MammoSite brachytherapy for low-risk breast carcinoma: Toxicity, cosmetic evaluation and quality-of-life results of a phase II study
Authors: Belkacemi Y. , Chauvet M. , Giard S. , Villette S. , Lacornerie T. , Bonodeau F. , Baranzelli M. , Bonneterre J. , Lartigau E. 
Published: March 2020

11016 Background: The MammoSite is a device that was developed with the goal of making breast-conserving surgery more widely available. Our objective was to evaluate the MammoSite device performances after an open cavity placement procedure and quality of life in highly selected patients with early-stage breast cancer. Methods: From March 2003 to March 2005, 43 patients with T1 breast cancer were enrolled in a phase II prospective study. Twenty-five (58%) patients were qualified for HDR brachytherapy delivery. The median age was 72 years (range: 60–75). Twenty-five (58%) were treated with high-dose rate brachytherapy using the MammoSite applicator to deliver 34 Gy prescribed at 1 cm from the balloon surface in 10 fractions over 5 to 8 days. Results: The main disqualifying factor was pathologic sentinel node involvement. After a median follow-up of 13 months, there were no local recurrences. Seventeen (68%), 13 (52%), 7 (28%), 5 (20%) and 4 (16%) patients had erythema, seroma, inflammation, hematoma and infection, respectively. Only 2 patients developed telangiectasia. At 3 months breast erythema grade ≥ 2 was significantly correlated to cosmetic results (12.5% in the ‘good to excellent‘ versus 57% in the ‘poor to fair‘ group; p = 0.045). The strongest trend of excellent cosmetic outcome was observed in patients with skin spacing ≥ 19 mm (50%) compared to patients with < 19 mm (11%; p = 0.087). At 1 year the rate of ‘good to excellent‘ cosmetic results was 84%. Significant changes in QoL were observed for emotional and social well-being between 3 and 12 months. At 24 months only emotional well-being subscore changes were statistically significant (p = 0.015). Param Conclusions: To our knowledge, this is the first study since the initial FDA clinical study showing the feasibility of MammoSite brachytherapy procedure as a sole therapy in highly selected patients older than 60 years. This is also the first report on QoL during and after APBI using HDR brachytherapy with a MammoSite device. The toxicity and cosmetic results are in the range of other series. Higher range of skin spacing allowed a significant reduction of the risk of telangiectasia. QoL evaluation indicate that baseline scores were satisfactory. Changes concerned mainly emotional and social well-being. No significant financial relationships to disclose.
BRCA mutation status and risk of secondary malignancy following chemotherapy for breast cancer
Authors: Wesolowski R. , Choueiri T. K. , Rybicki L. , Shealy A. G. , Casey G. , Weng D. , Moore H. 
Published: March 2020

11017 Background: Since the BRCA gene is responsible for excisional DNA repair, we hypothesized that breast cancer patients with BRCA mutation would be more susceptible to the induction of second malignancies following chemotherapy treatment than breast cancer patients who tested negative for BRCA mutations. Methods: Breast cancer patients tested for BRCA1 and BRCA2 mutations at the Cleveland Clinic were identified and evaluated for history of neoadjuvant or adjuvant chemotherapy and for the occurrence of subsequent non-breast primary invasive cancer. Patients with inadequate follow-up and those with inoperable disease at diagnosis were excluded from the analysis. Fisher’s exact test was used to compare different cohorts. The IRB at Cleveland Clinic approved the study. Results: Of 115 identified breast cancer patients tested for BRCA mutations, 77 met the inclusion criteria. Twenty-seven of these patients carried BRCA1 or BRCA2 mutations and 50 tested negative for these mutations. Twelve patients (44%) in the BRCA positive group and 8 patients (16%) in the BRCA negative group underwent prophylactic oophorectomy. Median follow-up for the two groups was 53.5 months (75 months in the BRCA positive group and 48.5 months in the BRCA negative group). Median age at diagnosis was 42 years (40.5 years in the BRCA positive group and 44.5 in the BRCA negative group). In the BRCA positive group 3 of 25 patients (12%) treated with chemotherapy developed second malignancies (ovarian cancer, transitional cell cancer in urinary tract and renal cell carcinoma) compared with none of the 2 patients who did not get chemotherapy (p= 1.0). In the BRCA negative group, 2/34 patients (6%), treated with chemotherapy developed second cancers compared with 2/16 patients (12%), who were not treated with chemotherapy (p=0.58). Cancers in the BRCA negative group included two bladder carcinomas in the chemotherapy treated patients and in the non-chemotherapy group, non-small cell lung cancer, uterine, ovarian, endometrial and peritoneal cancers. Conclusions: At more than 4-years of follow up, chemotherapy in operable breast cancer patients was not associated with an increase in the risk of secondary malignancy or with a differential effect on this endpoint by BRCA mutation status in this retrospective study. No significant financial relationships to disclose.
Validity of sentinel lymph node biopsy in breast cancer patients after neoadjuvant chemotherapy
Authors: Jinno H. , Asaga S. , Sakata M. , Kubota T. , Kitajima M. , Mukai M. , Kubo A. , Ikeda T. 
Published: March 2020

11023 Background: Sentinel lymph node biopsy (SLNB) is a potential alternative procedure to conventional axillary lymph node dissection (ALND) in clinically node-negative breast cancer patients. Neoadjuvant chemotherapy (NAC) is a standard of care for patients with locally advanced breast cancer and indications of NAC have been widespread to operable breast cancer patients to facilitate breast conserving surgery. However, the validity of SLNB in breast cancer patients who received NAC is still controversial. Methods: Forty-six patients with stage II or III breast cancer who were treated with NAC from January 2002 to May 2006 were included in the study. Consecutive 122 patients who had SLNB without NAC during the same period were used as a control group. All patients underwent SLNB followed by completion ALND. Sentinel lymph node (SLN) was detected using a combined method of injecting isosulfan blue dye and small-sized technetium- 99m-labeled tin colloid (particle size: 200–400 nm in diameter) peritumorally and subcutaneously. SLNs were evaluated by means of H&E and immunohistochemical staining. Results: SLNs were successfully identified in 42/46 patients (91.3%) treated with NAC and 112/113 patients (99.1%) without NAC (p=0.01). Metastases in the SLNs were found in 16/42 patients (38.1%) with NAC and 32/112 patients (28.6%) without NAC (p=0.2). There were 5 false negative cases (false negative rate: 23.8%) in the NAC group and 2 false negative cases (false negative rate: 5.9%) in the control group (p=0.05). Accuracy of SLNB in the NAC group was also significantly inferior to the control group (88.1% vs. 98.2%, p<0.01). The presence of clinically positive axillary lymph nodes before NAC was not correlated with false negative rate. Conclusions: These data suggest that NAC might be considered a contraindication to SLNB even in patients with clinically negative axillary lymph nodes before NAC. No significant financial relationships to disclose.
Pattern of presentation and treatment of early primary breast cancer in the elderly
Authors: Parker H. K. , Winterbottom L. , Hassell K. , Ellis I. O. , Morgan D. A. , Cheung K. L. 
Published: March 2020

11030 Background: There is a high prevalence of breast cancer in the elderly population; however the majority of data available is obtained from younger patients. This study aimed to identify the patterns of presentation and treatment subsequently received by elderly women with early breast cancer. Methods: Patients included were >70 years and had operable primary breast cancer (<5 cm) managed in a dedicated clinic. Personal characteristics, patterns of presentation, pathological features of diagnostic needle core biopsies and treatments both recommended and received were reviewed in 265 consecutive female patients diagnosed over a 30-month period (between January 2004 and June 2006). Results: The mean age was 78.5 (range: 70–100 years). Majority (83%) presented with symptomatic cancer with the remaining ones detected through mammographic screening. These cancers were predominantly oestrogen receptor positive (histochemical (H) score >10) (84%) with high H scores (83% had H scores >200). Most of them were grade 2 (63%), followed by grade 1 and 3. Treatment undertaken was often in compliance with the clinicians’ advice if specifically recommended; however, when choice was given, there was a tendency to accept non-operative intervention. Documented reasons include surgical refusal, feeling un-fit for surgery and personal commitments disallowing post-operative recovery time. In addition, patients who received primary hormone therapy were on average 7 years older and suffered significantly more co-morbidity than those who had surgery. Conclusions: The elderly breast cancer population often receive different treatments possibly due to biological characteristics and personal reasons distinct from their younger counterpart. Further work is ongoing to link these findings to long-term clinical outcome. [Table: see text] No significant financial relationships to disclose.