bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictors of permanent menopause after chemotherapy for early-stage breast cancer in premenopausal women
Authors: Moore H. C. , Kim J. , Rodriguez C. , Budd G. T. , Rybicki L. 
Published: August 2020

575 Background: Optimal choice of endocrine therapy for early-stage breast cancer differs with menopausal status. While amenorrhea is common during adjuvant chemotherapy, there is currently no available test to establish when menopause is permanent. The aim of this study was to determine the age cutoff after which resumption of menses is unlikely following chemotherapy and to assess what additional risk factors may predict for persistent menopause at 5 years after initiation of chemotherapy. Methods: One hundred patients treated with chemotherapy for early-stage premenopausal breast cancer and who remained alive and free of recurrence at least 5 years from the start of treatment were enrolled. Participants were evaluated for current menstrual status and for baseline potential risk factors for menopause: age at start of chemotherapy, race, BMI, smoking history, age at menarche, irregular menses prior to chemotherapy, presence of menses during chemotherapy, type of chemotherapy regimen, hormonal therapy, ovarian protection during chemotherapy, and number of doses of alkylating agent (cyclophosphamide). Recursive partitioning analysis (RPA) was used to identify the age cutoff that best predicts permanent menopause; additional risk factors were assessed using logistic regression analysis. Results: Median age at start of chemotherapy was 43 (range 26–49). RPA identified age >42 at the start of chemotherapy as a significant predictor of permanent menopause (p < 0.001). Cessation of menses during chemotherapy was also associated with permanent menopause (p < 0.001). Both variables remained significant in multivariate analysis (p < 0.001), with the combination of these factors being associated with a 95.4% chance of permanent menopause. Conclusions: In this series, fewer than 5% of premenopausal patients who were at least 42 years old and who experienced cessation of menses during chemotherapy experienced any return of menses over at least 5 years. Upfront use of aromatase inhibitors as adjuvant endocrine therapy for premenopausal hormone-receptor positive breast cancer warrants further investigation for those who are at least 42 years of age and who experience amenorrhea with chemotherapy. No significant financial relationships to disclose.
Efficacy of oral tegafur-uracil (UFT) as adjuvant therapy as compared with classical cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) in early breast cancer: A pooled analysis of two randomized controlled trials (N-SAS-BC01 trial and CUBC trial)
Authors: Ohashi Y. , Watanabe T. , Sano M. , Koyama H. , Inaji H. , Suzuki T. 
Published: August 2020

578 Background: It has been reported that adjuvant oral UFT might be more effective in patients with estrogen receptor (ER)-positive breast cancer (Noguchi et al, J Clin Oncol 2005). 2 randomized clinical trials comparing the efficacy of oral UFT (2 years) with that of classical CMF (6 courses) have been conducted in patients with resected early breast cancer. One study was the N-SAS-BC01 trial (Watanabe et al, J Clin Oncol, in press), conducted in patients with node-negative, high-risk breast cancer. The other was the CUBC trial (Inaji et al, ASCO 2004), performed in patients with node-positive breast cancer. We have performed a pooled analysis of these two randomized trials. Methods: A pooled analysis was performed using individual patient data from the two randomized trials. Hazard ratios (HR) were determined with the Cox regression stratified by study and adjusted for the clinical characteristics of age, tumor size, nodal status, histological type, ER and PgR. The hypothesis was that UFT was noninferior to CMF in all patients or ER-positive patients in terms of relapse-free survival (RFS). Non-inferiority of UFT was concluded if the upper limit of two-sided CI for the HR of RFS did not exceed 1.30; the significance level of CI was determined by the Hochberg multiplicity adjustment (alpha=0.05:two sided). Results: A total of 1,057 patients were analyzed (CMF n=528, UFT n=529). Median follow-up time was 6 years. HR was 1.04 (95% CI: 0.78–1.40) for relapse in all patients and 0.79 (97.5% CI: 0.49–1.27) in ER-positive patients. The table shows HR for RFS according to ER status and age. Conclusions: UFT is noninferior to CMF in terms of inhibiting recurrence of ER-positive early breast cancer. In particular, UFT may be more effective in patients with ER-positive tumors who are 50 years or older. [Table: see text] [Table: see text]
Epirubicin plus cyclophosphamide followed by docetaxel plus trastuzumab and bevacizumab as neoadjuvant therapy for HER2-positive locally advanced breast cancer (LABC) or as adjuvant therapy for HER2-positive pathologic stage III breast cancer (PS3BC): A phase II trial of the NSABP Foundation Research Group
Authors: Smith J. W. , Buyse M. , Rastogi P. , Geyer C. , Jacobs S. , Patocskai E. , Wolmark N. 
Published: August 2020

580 Background: A previous phase II study evaluating the combination of trastuzumab (tras) and bevacizumab (bev) as first-line therapy in HER2 + MBC showed a response rate of 54%. The purpose of this trial is to determine the cardiac safety profile of these agents with docetaxel (T) following epirubicin plus cyclophosphamide (EC) in women with LABC and PS3BC and the activity in those with LABC. Methods: Since June 2007, 75 women with HER-2 + LABC or PS3BC have begun epirubicin 90 mg/m2 IV plus cyclophosphamide 600 mg/m2 IV q3wks x 4 followed by docetaxel 100 mg/m2 IV q3wks x 4. Targeted therapy: Cohort A (neoadjuvant), bev 15 mg/kg IV with Cycle 4 of EC, continued with the first 3 cycles of T. Standard weekly tras with 4 cycles of T. Postop, bev 15 mg/kg IV and tras 6 mg/kg IV q3wks to complete 1 yr of targeted therapy. Cohort B (adjuvant), bev 15 mg/kg q3wks for 4 cycles and weekly tras with T. After chemotherapy, bev and tras q3wks to complete 1 yr of therapy. Primary endpoints were the rate of cardiac events in both cohorts and pCR rate in breast/axillary lymph nodes in Cohort A. Results: Median age was 50 yrs. In Cohort A, 28 (53%) patients (pts) were stage IIIA, 20 (38%) stage IIIB, and 5 (9%) stage IIIC. 13 (25%) had inflammatory BC. A pCR occurred in 19 of the first 36 pts (53%). Toxicity information on the first 73 pts in both cohorts showed that grade 2 LVEF dysfunction has developed in 5 pts and grade 3 LVEF dysfunction in 2, 1 with NYHA Class II and 1 with Class III symptoms. The latter met criteria for a cardiac event. Conclusions: The regimen is active with an acceptable preliminary rate of cardiac toxicity. Updated results will be presented. This trial is conducted with the support of Genentech. [Table: see text]
Bevacizumab beginning concurrently with a sequential regimen of doxorubicin and cyclophosphamide followed by docetaxel and capecitabine as neoadjuvant therapy followed by postoperative bevacizumab alone for women with HER2-negative locally advanced breast cancer (LABC): A phase II trial of the NSABP Foundation Research Group
Authors: Rastogi P. , Buyse M. , Swain S. , Jacobs S. , Robidoux A. , Liepman M. , Dy P. , Geyer C. , Wolmark N. 
Published: August 2020

584 Background: Bevacizumab with chemotherapy improves outcomes in patients with metastatic breast cancer. The purpose of this trial was to determine the activity and safety profile of bevacizumab with chemotherapy in women with LABC. Methods: Between November 2006 and August 2007, 45 women with HER-2 negative LABC initiated preoperative standard AC x 4 followed by docetaxel 75 mg/m2 IV and capecitabine 825 mg/m2 BID days 1–14 (TX) every 21 days for 4 cycles. Bevacizumab 15 mg/kg IV was given concurrently with chemotherapy every 21 days for a total of 6 preoperative doses. Postoperatively, bevacizumab was resumed for a total of 10 doses. Primary endpoint was pathologic complete response rate (pCR) in the breast. The secondary endpoints include clinical response rates and toxicity. Results: The median age was 50 yrs (range 30–78). 30 patients had stage IIIA (67%), 12 stage IIIB (27%), and 3 stage IIIC (7%) disease. Of these, 10 (22%) had inflammatory breast cancer. 27 patients (60%) had ER-positive disease. A pCR in the breast was documented in 4/44 (9%) patients, which included negative axillary nodes. A complete clinical response was noted in 14/45 (31%). One patient did not have surgery due to progression. Toxicities included hand-foot (grade 2/3–33%/22%), mucositis (grade 2/3–49%/27%), and febrile neutropenia (grade 3–24%). Conclusions: This regimen demonstrated only modest activity with substantial toxicity, and does not appear to warrant further evaluation. This clinical trial is being conducted through the support of Genentech and Roche. [Table: see text]
Selective benefit of high-dose, platinum-containing, alkylating chemotherapy with stem cell rescue for patients with breast cancers with an expansive growth pattern on histology
Authors: Linn S. C. , Vollebergh M. A. , Hauptmann M. , Wessels L. F. , Nederlof P. M. , de Vries E. G. , Rodenhuis S. , Wesseling J. 
Published: August 2020

587 Background: Breast cancer (BC) cells lacking the DNA repair mechanism homologous recombination (HR), a feature of BRCA-deficient tumor cells, are hypersensitive to bifunctional alkylating agents. Metastatic BC patients whose tumors were scored as BRCA1-like with a BRCA1 Comparative Genomic Hybridization classifier had an impressive progression-free survival after platinum-containing (PC), high-dose alkylating (HDA) chemotherapy. BRCA1-like tumors showed an expansive growth (EG) pattern, were generally HER-2 negative and estrogen receptor (ER) negative (Vollebergh et al, Cancer Res. 2009, 69;[Suppl. 2]6050). To further investigate whether BRCA1-like tumors were chemosensitive in general, or were sensitive specifically to PC HDA chemotherapy, we studied outcome of stage III BC patients who had participated in a randomized trial of adjuvant 5 x FEC (5-fluorouracil, epirubicin, cyclophosphamide) versus 4 x FEC followed by high-dose CTC (cyclophosphamide, thiotepa, carboplatin) with autologous stem cell rescue (Rodenhuis et al, New Engl J Med. 2003). Methods: 162 Patients with an ER negative or low (<25% of tumor cells positive) and HER-2-negative tumor were selected from abovementioned trial. EG was used as a surrogate for ‘BRCA1-like'. Currently available whole slides of n = 99 patients were scored for EG. An interaction term was fitted to a multivariate proportional hazards model to evaluate whether effect of CTC treatment in terms of recurrence-free survival (RFS) was modified by EG. Results: While RFS after 5 x FEC was similar for the 15 patients with EG as compared to 38 without EG (33%, and 31% 10-year RFS, respectively), 10-year RFS after high dose CTC was better for the 16 patients with EG (81% (multivariate hazard rate [HR] of CTC versus FEC 0.11 [95% CI 0.02–0.53]) as opposed to the 30 without EG (53% [multivariate HR of CTC versus FEC 0.58 (95% CI 0.3–1.12)]); multivariate test for interaction p = 0.056). Conclusions: Using histological information, by determining the presence of an expansive growth pattern, we were able to identify a group of stage III breast cancer patients who selectively benefited from PC HDA chemotherapy. No significant financial relationships to disclose.
Evaluation of the incidence and of risk factors associated with trastuzumab-associated cardiac toxicity in routine clinical practice
Authors: Lemieux J. , Côté M. , Provencher L. , Simard I. , St-Pierre C. , Demers E. 
Published: August 2020

589 Background: Data on trastuzumab-associated cardiac toxicity (TACT) in routine clinical practice are scarce. Alcohol is a potential cardiotoxic but it has not been evaluated as a potential risk factor for TACT. Methods: This is a single institution retrospective study, conducted at the Centre des Maladies du Sein Deschênes-Fabia, Quebec City. Charts review was used to collect information on tumor, cardiovascular risk factors (coronary artery disease (CAD), heart failure, high blood pressure (HBP), obesity, diabetes), alcohol (yes/no), smoking (yes/no), type chemotherapy, anthracyclines doses, trastuzumab doses and left ventricular ejection fraction (LVEF). A questionnaire about smoking and use of alcohol (before chemotherapy, during chemotherapy and during trastuzumab alone) was administered to patients. TACT was defined as a decrease in the LVEF of ≥15% or ≥10% with a resulting LVEF < 50% or any follow-up LVEF of < 45%. Results: Data were collected on 117 patients with non-metastatic breast cancer who started adjuvant trastuzumab between 2002 and 2007. Questionnaires on alcohol use/smoking were administered to 61 patients from these 117 patients. Median age was 53 years old and 95.7% received anthracyclines-based chemotherapy. Median follow-up of LVEF was 16.3 months. TACT developed in 25.6% of patients (10.3 % with a decreased in the LVEF of ≥15%, 7.7% with a decreased in the LVEF of ≥10% with a resulting LVEF < 50% and 7.7% with a LVEF < 45%). None of the following risks factors for TACT were significant (using logistic regression): age (p =0.95), CAD (p = 0.29), HBP (p = 0.46), body mass index (p = 0.64), diabetes (p = 0.29), smoking (p = 0.9), anthracycline doses (p = 0.12), baseline LVEF (p = 0.26). Alcohol use was not associated with TACT (p = 0.76). Further data will be collected in next months about alcohol use. Conclusions: In routine clinical practice, TACT was observed in 25.6% of patients, which is higher than what was reported in trastuzumab phase III clinical trials. Results about alcohol use and TACT will be updated in the spring 2009. [Table: see text]
Effect of adjuvant chemotherapy on bone resorption marker beta C-telopeptide (B-CTX) in postmenopausal women
Authors: Ali S. M. , Chapman J. W. , Demers L. , Shepherd L. , Han L. , Wilson C. , Pritchard K. , Leitzel K. , Pollak M. , Lipton A. 
Published: August 2020

594 Background: In NCIC CTG MA.14, a randomized trial of tamoxifen versus tamoxifen + octreotide LAR, we found a measure of bone resorption, serum B-CTx, to be significantly associated with bone-only first recurrence. Administration of chemotherapy was permitted, and chemotherapy was a stratification factor (never, concurrent, sequential). It was unclear whether pretrial B-CTx serum levels would be affected by prior administration of chemotherapy, and whether timing of chemotherapy was associated with who had bone only, or bone and other site relapse. Methods: Serum B-CTx concentration (Serum CrossLaps Nordic Biosciences, Copenhagen, DN) was determined pretrial therapy in 621 of 667 primary breast cancer patients on MA.14. We tested for differences in continuous B-CTx levels in those who had assessment before (any) chemotherapy (included those who had none) versus those who were assessed after chemotherapy with an ANOVA test. We also used exact Fisher tests to examine whether there was an association between timing of (any) chemotherapy and 1) B-CTx values in upper 2.5% range for healthy pre-menopausal women; 2) bone only recurrence; and 3) concurrent bone and other relapse. Results: Serum B-CTx was assessed before (any) chemotherapy on 382/621 (61.5%) of patients, and after chemotherapy on 239/621 (38.5%). There were no significant differences in serum B-CTx values (p = 0.27). We found 92/621 (14.8%) of patients had high serum B-CTx levels compared with healthy pre-menopausal women; similar proportions of these women received chemotherapy after B-CTx assessment (p = 0.42). Furthermore, there were no differences in timing of (any) chemotherapy and those who had bone only recurrence (p = 0.48) or bone and other type of relapse (p = 0.76). Conclusions: Chemotherapy in the adjuvant setting had no significant effect on bone resorption marker B-CTX serum levels. No significant financial relationships to disclose.
Neoadjuvant biweekly dose-dense chemotherapy with fluouracil, epirubicin, and cyclophosphamide (FEC 90), followed by docetaxel in patients with HER2-neu negative primary breast cancer
Authors: Rodriguez-Abreu D. , Murias A. , García M. , Vega V. , Garcia C. , Mori M. , Báez-Acosta B. , Diez A. , Almenarez J. 
Published: August 2020

596 Background: A primary goal of therapy for large early stage breast cancers is to achieve breast conserving surgery (BCS) through tumor mass reduction with neoadjuvant chemotherapy. In addition, induction of pathological complete response (pCR) is reported to prolong disease-free survival. Encouraged by results from recent studies of dose-dense chemotherapy in the adjuvant setting, we studied preoperative treatment with biweekly 5-fluorouracil, epirubicin, and cyclophosphamide followed sequentially by triweekly docetaxel. Methods: Eighty-one women with stage IIA to IIIB breast cancer were entered into this trial between August 2003 and April 2008. Patients received 5-fluorouracil 600mg/m2, epirubicin 90 mg/m2, and cyclophosphamide 600 mg/m2 (q2w x 4 cycles) followed by docetaxel 100 mg/m2 (q3w x 4 cycles). Granulocyte colony-stimulating factor was administered each cycle to reduce the risk of neutropenic complication. After chemotherapy, patients underwent surgery, and received standard adjuvant radiotherapy and hormone therapy as usual clinical practice. The primary endpoint of this trial was pathological response rate and the secondary endpoints were BCS rate and toxicity. Results: A total of 79 patients were analyzed. The median age was 50y (28–74), the median tumour size was 4 cm. 50 patients (63.2%) were ER positive and/ o PR positive. 48 patients (60.7%) were pre-menopausal. Median follow-up was 36m, 64 patients had stage II (81%) and 15 had stage III (19%). Clinical response was seen in all cases. A pCR with no evidence of tumor in the breast and lymph nodes was confirmed in 21 patients (26.5%). BSC was performed in 61 patients (77.2%). Treatment was well tolerated, 8 patients (10.1%) had grade 3/4 hematological toxicity. Others adverse events including, anorexia, fatigue, nausea, vomiting, mucositis, myalgia, nail changes, peripheral neuropathy, hand-foot skin reactions were mild and manegeable. Conclusions: The neoadjuvant biweekly dose-dense chemotherapy with fluouracil, epirubicin and cyclophosphamide (FEC 90), followed by docetaxel is safe and demostrates a high pathological response rate (pCR) of 26.5% with an increase rate of BCS of 77.2%. No significant financial relationships to disclose.
Prediction of responsiveness to adjuvant anthracyclines in high-risk breast cancer patients
Authors: Brünner N. , Ejlertsen B. , Jensen M. , Nielsen K. V. , Balslev E. , Rasmussen B. B. , Willemoe G. L. , Hertel P. B. , Knoop A. , Mouridsen H. 
Published: August 2020

597 Background: HER-2, TOP2A, and TIMP-1 have shown predictive properties regarding benefit from anthracyclines in patients with breast cancer. In the present study, TIMP-1 IHC was integrated with TOP2A FISH and HER-2 status in two separate profiles. Methods: The DBCG 89-D trial randomized 980 high-risk Danish breast cancer patients to nine series of CMF or CEF. CEF was superior to CMF in terms of DFS and OS (Ejlertsen et al, EJC 2007). HER-2 status and TOP2A copy number changes were determined as described previously (Knoop et al, J Clin Oncol. 2005). TMA s were constructed and analyzed centrally for TIMP-1 expression by IHC (± tumor cell immunoreactivity). TIMP-1 was combined with HER-2 into a joint HT marker (HT-non-responsive (HT-NR): HER-2 normal and TIMP-1 positive or HT-responsive (HT-R): HER-2 positive and/or TIMP-1 negative) and with TOP2A into a joint 2T marker (2T-NR: TOP2A normal and TIMP-1 positive or 2T-R: TOP2A abnormal and/or TIMP-1 negative). Relationships between IDFS, OS and the HT/2Tprofiles were analyzed using multivariate regression analysis. Results: Among patients with a HT-R profile CEF was superior to CMF in terms of both invasive disease-free survival (IDFS) (HR 0.62; 95% CI 0.45–0.86; p = 0.004) and overall survival (OS) (HR 0.63; 95% CI, 0.45–0.87; p = 0.005). In patients with a HT-NR profile, no significant differences between CEF and CMF were demonstrated for IDFS or OS. A significant HT profile (HT-R or HT-NR) versus treatment (CEF or CMF) interaction was detected by the Wald-test for both IDFS (p = 0.036) and OS (p = 0.047). An even more pronounced separation was observed regarding the 2T profile, and in patients with a 2T-R profile treatment with CEF was superior to CMF in terms of IDFS (HR 0.48; 95% CI 0.34–0.69; p < 0.001) and OS (HR 0.54; 95% CI, 0.38–0.77; p < 0.001). No significant difference was observed in patients with a 2T-NR profile. A highly significant 2T profile versus treatment interaction was detected for IDFS (p < 0.001) and OS (p = 0.004). Conclusions: Profiles created by joining TIMP-1 with either HER-2 status or TOP2A gene status seems advantageous compared to the use of a single marker. [Table: see text]
Association of tobacco (T) use with risk of distant metastases (DM), tumor recurrence, and death in patients (pts) with HPV-positive (+) squamous cell cancer of the oropharynx (SCCOP)
Authors: Worden F. P. , Hooton J. , Lee J. , Eisbruch A. , Wolf G. T. , Prince M. , Moyer J. , Teknos T. , Chepeha D. B. , Bradford C. R. , Carey T. 
Published: August 2020

6001 Background: Chemoradiation (CRT) for HPV (+) SCCOP is associated with a more favorable prognosis than HPV-negative (-) SCCOP. However, the interaction of HPV and T in terms of etiology and disease progression remains unclear. HPV (+) SCCOP pts were prospectively studied to determine if T use was a key variable in discriminating which pts would develop DM, locoregional recurrences (LR), or second primaries (SP). Methods: From 1999–2007, 124 pts with stage III/IV SCCOP were enrolled in one of two CRT trials. Tumor specimens were analyzed for HPV presence and type. Use of T, determined via self-reporting and chart review, was recorded as both continuous (number of pack-yrs) and categorical (never, former, and current) variables. Former T users were subdivided into an early cessation group (quit ≥ 20 yrs prior to diagnosis) and a late cessation group (quit < 20 yrs prior to diagnosis). T use and HPV status were analyzed with respect to survival & the development of DM, LR, or SP. Results: Of the 124 pts, 100 (81%) were HPV (+), 22 of which developed disease progression (22%). Twenty-four were HPV (-), 12 of which had disease progression (50%). Seventeen of 124 pts (14%) developed DM [12 HPV (+), 5 HPV (-)]. Nine of 124 (7%) developed LR [5 HPV (+), 4 HPV (-)], and 8 of 124 (7%) developed SP [5 HPV (+), 3 HPV (-)]. Thirty-two HPV (+) pts were never-T users, 88% (28/32) of which remain alive with no evidence of disease; 3 died from other causes and 1 died of lung metastases from SCCOP. Sixty-eight were HPV (+) and had T exposure. Of 46 former T users, 37/46 (80%) are living. Twenty were HPV (+) and in the early cessation group, 35% (7/20) of which had disease progression [3 LR, 3 DM, 1 SP]. Twenty-six HPV (+) pts were former T users in the late cessation group, 11% (3/26) of which had disease progression [2 DM, 1 SP]. Of 22 HPV (+) current T users, 68% (15/22) are alive and 36% (8/22) have developed disease progression. Seventeen of the 24 HPV (-) pts were current T users, 47% (8/17) of which developed disease progression. Conclusions: Never-T users with HPV-positive SCCOP have improved survival & reduced risk of disease progression compared to HPV (+) & HPV (-) former & current T users. No significant financial relationships to disclose.