bluuebunny/crossref_metadata_2025_split huggingface dataset:
Racial differences in acute toxicities of FEC 100 chemotherapy in patients with breast cancer
Authors: Han H. S. , Reis I. , Kuroi K. , Toi M. , Suzuki E. , Syme R. , Chow L. , Yip A. , Zhao W. , Nimmagadda R. , Gluck S. 
Published: August 2020

e11515 Background: Racial disparities in breast cancer outcomes are attributed to differences in baseline tumor characteristics, stage, and socioeconomic factors. However, little is known about racial differences in treatment-related toxicities. We hypothesized that racial and ethnic differences result in differential tolerance to chemotherapy and possibly compromise to the dose intensity of adjuvant/neoadjuvant chemotherapy. Methods: Data was collected from 4 international collaborating centers (University of Miami, JBCRG (Japan Breast Cancer Research Group), University of Hong Kong, and Tom Baker Cancer Center) at which patients of different ethnic background have been treated for non metastatic breast cancer with same adjuvant or neoadjuvant chemotherapy of FEC 100: fluorouracil 500 mg/m2, epirubicin 100 mg/m2, and cyclophosphamide 100 mg/m2). Racial/ethnic differences in toxicities were assessed by first episode of grade 2 or higher toxicity. Analysis of data was performed at the University of Miami. Results: Treatment-related toxicities are compared according to four race/ethnicity groups (120 Caucasian from USA and Canada (C), 16 African American (AA) from USA and Canada, 141 Japanese Asian (JA), and 23 Asian from Hong Kong (HKA)) (Table). JA and HKA had a significant higher rate of grade 3 or higher toxicity compared with C or AA women; 65%, 61%, 28%, and 31% respectively. However, there were no significant differences in chemotherapy dose intensity or density across the 4 race/ethnicity groups. Conclusions: This unique study noted racial differences in acute toxicity in women with breast cancer who were treated with FEC 100 chemotherapy. However, there are several limitations including the retrospective nature of our study, differences in practice across four countries, and different number of patients available for comparison. This study is ongoing and further statistical analyses are planned when a larger sample size is reached. [Table: see text] No significant financial relationships to disclose.
Response to neoadjuvant chemotherapy and outcome based on breast cancer subtype
Authors: Guerrero-Zotano A. , Gavila J. , Climent M. A. , Juan M. J. , Guillem V. , Ruiz A. 
Published: August 2020

e11516 Background: Gene expression profiling identifies several breast cancer subtypes with different chemosensitivity and outcome. We used immunohistochemistry surrogate markers to classify tumors according to known breast cancer subtypes and examined the relationship between neoadjuvant chemotherapy (NAC) response and long-term end points, including distant disease-free survival (DDFS) and overall survival (OS). Methods: Review of clinical and pathological data from 271 breast cancer patients treated in our institution with NAC between 1991–2008. Breast cancer subtypes were defined as follows: Luminal A: Estrogen receptor positive (ER+) and/or progesterone peceptor positive (PR+), human epidermal growth factor receptor 2-positive (Her-2+); Luminal B: ER+ and/or PR+,Her-2+; Basal: ER-,PR-,Her-2-;HER2: ER-,PR-,Her-2 +. ER and PR positive scored as positive if tumor cell nuclear staining was at least 2+. Her-2 scored as positive if test DAKO scored 3+ or FISH ratio Her-2/CEP-17>2.2. Results: 121 (45.8%) patients were classifed as Luminal A; 22 (8.1%) as Luminal B; 75 (27.7%) as Basal, and 50 (18.5%) as HER2. Most patients (63%) received NAC based on anthracyclines and taxanes. 36% Her-2+ patients were treated with NAC based on trastuzumab, and 43% received trastuzumab as adjuvant treatment. Response and outcome results are shown below (Table). Independently from subtype, only four patients out of 58 with pCR relapsed. Among patients who didn´t achieved pathologic complete response (pCR), basal and HER2 subtypes have the worst outcome (4 years SG 80% and 72% respectevely) compared with Luminal A (4 years SG: 94.7%), (log-rank p=0.009). Conclusions: Basal and HER2 tumor despite high chemosensitivity have worst long term outcome, particularly if pCR is not achieved after NAC. [Table: see text] No significant financial relationships to disclose.
Variations in care for operable breast cancer and outcomes between rural and metropolitan centers in Australia
Authors: Craft P. S. , Buckingham J. , Dahlstrom J. E. , Beckmann K. , Zhang Y. , Stuart-Harris R. , Jacob G. , Roder D. , Tait N. 
Published: August 2020

e11517 Background: The causes of variation in breast cancer survival remain uncertain. Care provided to women with breast cancer may vary in relation to both the care setting and characteristics of the clinicians. Methods: To compare the outcomes of management of breast cancer treated in rural and metropolitan centers, a prospective audit of breast cancer in a region of Australia was undertaken. Over a nine-year observation period 2102 women with invasive breast cancer underwent potentially curative surgery. Treatments received, including systemic adjuvant therapy, were compared to contemporary guideline-based indicators. Breast cancer specific mortality was analyzed using Cox proportional hazards models. Results: Overall agreement of received treatment with the indicators was high. Women treated within rural centers were, however, much less likely to receive post operative radiotherapy after breast conserving surgery (86.4% vs. 97.0%; p<0.001). The overall recurrence rate, including distant metastases, for all women was 11.6%. Local or regional recurrence was more frequent in rural centers compared with metropolitan centers (4.1% versus 2.1%; p=0.05). Breast cancer mortality was increased in women with large tumors, high grade disease, and positive axillary lymph nodes. Non-compliance with treatment guidelines was associated with a trend towards increased breast cancer mortality (HR=1.55; p=0.056). After adjustment for these factors and patient age, undergoing surgery in rural centers was associated with increased breast cancer mortality (HR=1.84; p<0.001). Although women treated in rural centers were older, their cancer stage and tumour characteristics were similar to those of women treated in metropolitan centers. Non-cancer related mortality was elevated in women treated in rural centers compared with women travelling to a city for surgery (HR=2.08; p=0.005). Conclusions: Increased non-cancer related mortality in rural treated women suggests increased medical co-morbidity in this group, which may have influenced treatment choices and outcomes. Low rates of adjuvant radiotherapy were noted for women treated in rural centers. In addition, clinically significant differences in outcome, including breast cancer mortality, were observed. No significant financial relationships to disclose.
Trastuzumab cardiotoxicity: FDA review of four adjuvant breast cancer clinical trials leading to trastuzumab marketing approvals
Authors: Fedenko K. , Cortazar P. , Keegan P. , Pazdur R. 
Published: August 2020

e11520 Background: Trastuzumab can result in sub-clinical and clinical cardiac failure manifesting as congestive heart failure (CHF), and decreased left ventricular ejection fraction (LVEF). Methods: Data was reviewed from 9837 patients in four randomized trials (NCCTG 9831, NSABP B-31, HERA, and BCIRG-06) that supported trastuzumab HER2 overexpressing adjuvant breast cancer approval. Results: Trastuzumab can cause left ventricular cardiac dysfunction, arrhythmias, hypertension, disabling cardiac failure, cardiomyopathy, and cardiac death. Herceptin can also cause asymptomatic decline in LVEF. There is a 4−6 fold increase in the incidence of symptomatic myocardial dysfunction among patients receiving trastuzumab as a single agent or in combination therapy compared with those not receiving trastuzumab. The highest absolute incidence occurs when trastuzumab is administered with an anthracycline. Clinical trials NCCTG 9831, NSABP B-31, and BCIRG-06 included arms with doxorubicin- cyclophosphamide (AC) followed by a taxane plus trastuzumab. Among 32 patients receiving adjuvant chemotherapy from studies NCCTG 9831 and NSABP B-31 who developed CHF, one patient died of cardiomyopathy and all other patients were receiving cardiac medication at last follow-up. Approximately half of the patients recovered to a normal LVEF (defined as ≥ 50%) on continuing medical management at the time of last follow-up. In BCIRG-06 the incidence of CHF was six (6) fold higher in the AC followed by docetaxel plus trastuzumab arm as compared to AC followed by docetaxel. There was a lower incidence of CHF in the non-anthracycline TCH (docetaxel, carboplatin and trastuzumab) arm in BCIRG-06 comparable to trastuzumab monotherapy. Conclusions: Cardiotoxicity manifesting as sub-clinical and clinical cardiac failure is a known side effect of trastuzumab. In an era where trastuzumab is given earlier in the treatment of breast cancer (adjuvant setting), the safety of continuation or resumption of trastuzumab in patients with trastuzumab-induced left ventricular cardiac dysfunction has not been studied. No significant financial relationships to disclose.
Epirubicin (E) followed by cyclophosphamide, methotrexate, 5-fluorouracil (CMF) versus paclitaxel (T) followed by epirubicin and vinorelbine (EV) in patients (pts) with high-risk operable breast cancer
Authors: Boccardo F. , Rubagotti A. , Guglielmini P. , Sismondi P. , Farris A. , Amadori D. , Agostara B. , Gambi A. , Catalano G. , Faedi M. 
Published: August 2020

e11521 Background: > 3 N+ pts have a poor outcome, even in the presence of otherwise favourable phenotypic features. CT, alone or combined with endocrine therapy (ET) in hormone receptor (HOR)+ pts, is the gold standard for these women. However questions still exist about the optimal CT regimen. Methods: 244 >3N+ pts were randomized to either four 3-weekly courses of E (100 mg/sqm,d 1)followed by four 4-weekly cycles of CMF (600, 40, 600 mg/sqm, dd 1,8)(E-CMF:N=122)or four 3-weekly courses of T (175 mg/sqm, d1) followed by four 3-weekly cycles of EV (E:75 mg/sqm, da 1; V: 25 mg/sqm dd 1,8;.) (T-EV:N=122). After CT, tamoxifen (plus a LH-RH analog in menstruating women ) was given for 5 years to all HOR+ pts.S was the primary end-point. Results: At 82 mos median f-up, S and RFS did not differ significantly between groups (7-yr S: E-CMF:76%,T- EV:74%;adjust. HR: 0.89;0.54–1.49;p=0.7; 7-yr RFS: E-CMF:67%,T-EV:63%;adjust. HR: 0.95;0.61–1.47;p=0.8;).Cox analysis confirmed no difference between treatments. However RFS forest plots showed some heterogenity in CT effect according to HOR and HER2 status: E- CMF was superior to E-TV in HOR + pts (HR=0.43; CI 0.20–0.93 p=0.03),irrespective of HER2 status, but it was inferior (HR=1.91;CI 0.48- 7.64;p=0.4) in triple negative pts. The two regimens showed different toxicity profiles;however toxicities were manageable and there were no difference in the %of pts receiving all the 8 planned CT cycles (E-CMF: 87.6%;T-EV:81.1% p=0.2) or who discontinued CT (E-CMF: 12.8%; T-EV: 18.9% p=0.2). Conclusions: T-EV was not superior to E-CMF which,combined with ET, still represents an adequate choice for this high risk pts subset, especially for HOR+ pts. No significant financial relationships to disclose.
Adjuvant breast cancer: FDA approval overview
Authors: Cortazar P. , Johnson J. , Justice R. , Pazdur R. 
Published: August 2020

e11529 Background: Improved disease-free survival (DFS) in randomized controlled trials (RCT) is the primary basis for approval of adjuvant breast cancer (ABC) treatments. Methods: Review of clinical trials leading to new drug approvals for ABC. Results: DFS is a composite endpoint defined as the time from randomization to the earliest occurrence of invasive loco-regional recurrence, invasive contralateral breast cancer, DCIS, distant metastases, second primary tumors or death from any cause. Trials supporting marketing approval have used inconsistent DFS definitions that included different components of this endpoint. Basis of paclitaxel approval following AC was superior DFS (HR= 0.78; 95% CI 0.67–0.91, p=0.002) and overall survival (HR=0.74; 95% CI 0.60–0.92, p=0.0065). Trastuzumab approval as part of a treatment regimen was based on 4 clinical trials that showed improved DFS. Docetaxel approval was based on improved DFS of the docetaxel-containing combination regimen TAC compared to FAC (HR: 0.74; 2- sided 95% CI=0.60–0.92, p=0.0047). Doxorubicin approval was based on a meta-analysis of six ABC trials comparing doxorubicin- containing regimens to CMF. Analyses demonstrated that doxorubicin-containing regimens retained at least 75% of the historical CMF adjuvant effect on DFS (HR: 0.91; 95% CI 0.82–1.01) and OS (HR: 0.91; 95% CI 0.81–1.03). Epirubicin approval was based on a longer relapse free survival (RFS) of the epirubicin-containing combination therapy (CEF-120) compared to CMF (HR=0.76; 95% CI 0.60–0.96, p=0.013). Tamoxifen approval was based on an overview of tamoxifen adjuvant therapy. Ten-year survival was 61.4% for tamoxifen vs. 50.5% for control (p < 0.00001) and RFS was 59.7% for tamoxifen vs. 44.5% for control (p < 0.00001). Anastrozole approval was based on a longer DFS (HR: 0.87; 95% CI=0.78–0.97, p=0.0127). Letrozole was based on a superior DFS (HR= 0.62; 95% CI 0.49–0.78, p=0.00003). Exemestane approval was based on improved DFS (HR: 0.65; 95% CI=0.53–0.79, p=0.00001). Conclusions: Although DFS was the basis for approval in most of the ABC clinical trials, the endpoint definition varies between trials. DFS definition should be standardized in ABC clinical trials to permit consistent interpretation and analysis and to facilitate cross-trial comparisons. No significant financial relationships to disclose.
Early recurrence of breast cancer after sentinel node navigation surgery: A multicenter prospective study in Japan
Authors: Imoto S. , Morita S. , Kitajima M. , Aikou T. , Kitagawa Y. 
Published: August 2020

e11530 Background: To assess lymphatic mapping technique and prognosis after sentinel node navigation surgery (SNNS), the Japanese society for SNNS conducted a non-randomized multi-center prospective study on SNNS in early breast cancer. Primary endpoint is to evaluate the success rate and adverse events of SNNS, and secondary endpoint is to observe the outcome of patients who underwent SNNS during 5 years. Methods: We demonstrated the results of primary endpoint at 2007 ASCO annual meeting (#606). Fourteen hundred and sixty-eight cases had pre-registration from 65 investigators at 23 institutions between July 2004 and October 2005. As 46 cases were withdrawn for some reasons and 11 cases were diagnosed as benign disease, 1,411 cases were entered in this study and will be observed until 2010. At this meeting, early recurrence at 3 years follow-up is reported. Results: As of June 2008, 38 of the 1,138 cases (3%) treated with SNNS alone and 16 of the 258 (6%) cases treated with SNNS followed by axillary lymph node dissection (ALND) relapsed. Seven cases died of disease. From the patient background, 50 cases had invasive ductal carcinoma, one had non-invasive ductal carcinoma, and three had special type. Thirty-three cases had negative nodes, 3 had micrometastatic nodes, and 18 had macrometastatic nodes. Fifty-two cases received chemotherapy and/or endocrine therapy. Regional recurrence including axillary, parasternal, and/or supraclavicular nodes was found in 11 cases after SNNS and in 2 cases after SNNS followed by ALND. Conclusions: Annual regional recurrence rate after SNNS was about 0.3%. SNNS in breast cancer is reliable to optimize surgical management in the axilla without increase of regional recurrence. No significant financial relationships to disclose.
Validation of Adjuvant!Online on Slovenian collective of early breast cancer patients
Authors: Ravnik M. , Sadikov A. , Snoj N. , Nussdorfer P. , Cufer T. 
Published: August 2020

e11532 Background: Adjuvant!Online is a very useful tool for prognosis assessment of early breast cancer (EBC) patients. In the validation study, made on mostly untreated (45%) Canadian EBC patients, Adjuvant!Online proved to be a very reliable prognostic tool. The aim of our study was to validate Adjuvant!Online on EBC patients mainly treated with some kind of adjuvant systemic therapy. Methods: 753 EBC patients diagnosed and treated at the Institute of Oncology Ljubljana, Slovenia, with at least 10-year follow-up were included into the study. All patients received radical local therapy. Adjuvant chemotherapy (ChT) was either CMF or anthracycline-based schema and hormonal therapy (HT) was mainly tamoxifen. Adjuvant!Online 8.0 individual prediction of OS was calculated (with default value of “minor problems” as comorbidity for all patients). The average prediction over all patients was compared to the observed 10-year OS. Results: The predicted and observed 10-year OS of the whole group were 65.5% and 61.5%, respectively. The differences between predicted and observed OS did not differ substantially in the subgroups of patients stratified according to the classical prognostic factors, however, a large difference was found when stratifying by adjuvant systemic therapy. The puzzling difference in patients without systemic therapy (ST) can be both due to small group size and due to special selection of these patients (comorbidity). Conclusions: According to our observation, Adjuvant!Online is a reliable tool for prognosis assessment in EBC patients treated with HT, but it seems to overestimate prognosis in patients treated with ChT, alone or in combination with HT. This is evident even for our collective of EBC patients mainly treated with the first generation ChT - CMF or anthracyclines. Apparently, both Adjuvant!Online and Overview overestimate the positive effect of ChT, disregarding the biologic characteristics of the tumors and inherent effect of HT in HR+ patients. [Table: see text] No significant financial relationships to disclose.
Serum molecular signatures of weight change during early breast cancer chemotherapy
Authors: Stebbing J. , Keun H. C. , Sidhu J. , Patterson M. , Bloom S. R. , Amber V. , Coombes C. , Marconell H. , Pshezhetskiy D. 
Published: August 2020

e11534 Background: Weight gain in women receiving chemotherapy following breast cancer diagnosis has negative implications on quality of life and those who gain weight during treatment appear to be at higher risk of disease recurrence. The mechanism(s) implicated in chemotherapy associated weight gain are poorly understood. Methods: To investigate this further, we assessed the metabolic, cytokine and appetite related peptide alterations before and during adjuvant FEC chemotherapy for early breast cancer in post-menopausal women, and correlated these with body mass measurements. Specifically, we performed global metabolic profiling (metabonomics/ metabolomics) using 1H nuclear magnetic resonance spectroscopy of sequential sera, examined ghrelin immunoreactivity, performed radioimmunoassays for glucagon like peptide-1 (GLP-1) and peptide YY (PYY) and electro-chemiluminescent cytokine analyses (tumor necrosis factor-α and interleukin-6; TNF-α, IL-6) on the sequential samples. Results: In those who gained ≥ 1.5kg (on average ∼5% of initial body weight), several metabolite levels were positively associated with weight change, in particular lactate which was 55% greater in patients with increased body weight during chemotherapy compared to those with stable weight during chemotherapy (p<0.01; the pre-specified primary end-point). A significant inverse relationship was also observed between levels of TNF-α and weight change group (ρ 0.476, p<0.05). Baseline lactate, alanine and body fat were all prognostic for weight gain (ROC AUC >0.77, p<0.05). No significant associations were observed between any other parameter and weight gain, nor any parameter and tumor burden, including cytokine and appetite peptide alterations. Conclusions: Metabonomics identifies pathways perturbed during early chemotherapy for breast cancer, and establishes a positive association between serum lactate, body fat, TNF-α and substantive weight changes during chemotherapy. Interventions that target these processes may be clinically useful in breast cancer. No significant financial relationships to disclose.
Predictive factor for residual tumor after lumpectomy for close margins
Authors: Ozmen V. , Ozkan Gurdal S. , Muslumanoglu M. , Igci A. , Tuzlali S. S. , Ozcinar B. , Canbay E. , Kecer M. , Dagoglu T. 
Published: August 2020

e11538 Background: It is critical to obtain clear margins to minimize local recurrence after breast conserving surgery(BCS). When re-excisions are performed, there is often no residual disease in the new specimen, calling into question the need for re-excision(s) or mastectomy. The aim of the present study was to identify factors predicting a histologically positive re-excision specimen. Methods: Our prospective breast cancer database was queried for all invasive breast cancer patients who underwent a re-excision lumpectomy for either close or positive margins after an attempt at BCS. Close margins are defined as ≤ 2 mm for invasive carcinoma and presence of ductal carcinoma in situ(DCIS). Clinicopathologic features were correlated with the presence of residual disease in the re-excision specimen. Results: Between February 1997 and August 2008, 2054 patients with early breast cancer underwent surgical treatment in our breast unit. 939(45.7%) of them had BCS. In 543 patients(26.4%), re-excision required due to close margins on the permanent section analysis of their initial surgical specimens. 186 patients(34.3%) had previous excisional biopsy in other clinics. Median age of 543 patients was 50 years. In 290 patients(53.4%), mastectomy was performed due to positive surgical margin or poor cosmetic results. There were no residual tumors in re-excision(65.6 %) or mastectomy(42.4%) specimens of patients. The factors associated with tumor positive re-excision specimen were, age ≤50 years(p=0.044), lymphovascular invasion (p=0.029), multifocality(p<0.001), tumor size >2cm(p=0.008), presence of DCIS(p=0.018), focal margin positivity(p<0.001), DCIS at resection margin(p=0.008) and node positivity (p<0.001). Conclusions: Most of our patients with early breast cancer had unnecessary re-excisions or mastectomy to obtain clear surgical margins. In subset group of patients, re-excision or mastectomy may not be required. No significant financial relationships to disclose.