bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of the prognostic value of the shed antigen of HER2/neu in premenopausal breast cancer patiens in the TABLE study
Authors: Luftner D. , Pechlivanis K. , Geppert R. , Stroux A. , Possinger K. 
Published: March 2020

11007 Background: The HER-2/neu oncoprotein is a transmembrane tyrosine kinase that belongs to the family of epidermal growth factor receptors. It is known to be overexpressed in 20–40% of breast cancers. Increased serum HER-2/neu (sHER-2/neu) concentrations at the beginning of adjuvant breast cancer therapy have been shown to be of prognostic importance (Mehta et al, 1998). Using the sera from the Takeda® Adjuvant Breast Cancer Study with Leuprorelin (TABLE study), we tested for the prognostic value of sHER-2/neu. Methods: A total of 133 premenopausal, node-positive, hormone-receptor positive patients received either 11.25 mg of leuprorelin s.c. every 3 months over 2 years or CMF chemotherapy for 6 cycles. Blood samples were collected at baseline and at 3, 6, 12, 18, 24 and 30 mo. The primary endpoint of the study was to determine the relapse-free survival (RFS) after 2 years. sHER-2/neu was measured using a standardized ELISA (upper limit of normal 15 ng/ml). As the baseline sHER-2/neu concentrations ranged from 3.8–14.0 ng/ml, results were grouped in terciles. Data were analyzed using Kaplan-Meier and Cox Proportional Hazards survival analysis. Results: Material was available from 80 patients in leuprorelin arm and 53 patients in CMF arm. 65 of 133 patients had relapsed during the follow-up time of up 7 years after treatment. The median RFS was 62.9 mo. The RFS time depended on the concentrations of sHER-2/neu at baseline: RFS was significantly shorter in patients of the third tercile with sHER-2/neu levels >8.8 ng/ml than in patients of the first tercile with levels <7.2 ng/ml (p=0.0232). Five years after initial therapy, we found that 73% of patients in the first tercile group of baseline sHER-2/neu had no relapse. In the second tercile, 63.3% of patients were relapse-free, while in the third tercile only 47.2% of patients had not suffered from a relapse. Conclusions: Higher sHER-2/neu concentrations at the beginning of adjuvant therapy in the TABLE-Study have a prognostic importance for RFS. This observation was evaluated irrespective of the HER-2/neu tissue status and could be of clinically importance for adjuvant therapy with the monoclonal anti-HER-2/neu antibody trastuzumab or other anti-HER-2/neu targeted therapies. No significant financial relationships to disclose.
Outcomes in double-negative (HER2/PR negative) LABC phenotype treated with cisplatin-based primary chemotherapy: Impact of intensified regimen
Authors: Ionta M. T. , Atzori F. , Deidda M. C. , Murgia M. , Frau B. , Coinu A. , Barca M. , Eltrudis F. , Minerba L. , Massidda B. 
Published: March 2020

11024 Background: It is widely assumed that HER2-negative and hormone receptors negative tumors (Triple-Negative as TN) are associated with poor outcome and would benefit from intensified chemotherapy and/or from specific EGFR-targeted therapies.Nevertheless, the lack of PR expression in presence of ER-pos tumors, (Double-Negative as DN) could reflect an aberrant growth factor signaling, identifying a more aggressive phenotype than ER-pos/PR-pos tumors that could contribute to the tamoxifen resistance and that could benefit from tailored specific treatment such as TN pts. Aim of our retrospective study was to evaluate,the clinical outcome among a group of LABC pts, according to the treatment’s schedule (standard vs intensified) and TN or DN phenotype. Methods: Between June 1996 and November 2001, 72 consecutive LABC pts, (77 % T4abc; 23 % T4d) median age 51 (29–70), ER/PR-neg 37,5%; ERpos/PR-neg 33%, were treated with primary PEV regimen (cisplatin 50 mg/m2; epirubicin 100 mg/m2; vinorelbine 25 mg/m2):q 3wks x 4 cycles in the first 24 pts (Standard); q 2 wks x 6 cycles in the subsequent 48 pts (Intensified), followed by adjuvant RT,CMF and TAM ± LH-RH ; 50 pts of 72 were IHC assessable for both HER2 and HR: 39 pts (78%) were identified as HER2-neg; 25 (64%) of 39 were HER2-neg/PR-neg irrespective of ER status, (any ER), of whom 12 were ER-neg (TN )and 13 were ER-pos ( DN ). Results: At a median follow up of 88 months (58–123) DFS was 20% and 80%; 20% and 100%; 20% and 62,5% in standard group and in intensified group respectively; OS was 40% and 80%; 40% and 100%; 40% and 62,5% in standard group and in intensified group respectively. Conclusions: Our findings suggest that DN as well as TN pts benefit from intensified primary chemotherapy. Therefore, tailored treatments are warranted for DN as well as TN pts. In addition, our data indicate that association of HER2-neg with PR-neg independently of ER expression (any ER) could be correlated with a more aggressive phenotype. [Table: see text] No significant financial relationships to disclose.
Impact of the ATAC trial on prescribing of hormonal therapy in breast cancer
Authors: Connolly R. M. , Barron T. I. , Bennett K. , Feely J. , Kennedy M. J. 
Published: March 2020

11028 Background: The arimidex, tamoxifen, alone or in combination (ATAC) trial recommended use of anastrazole over tamoxifen as initial adjuvant hormonal therapy of early breast cancer in postmenopausal women. The aim of this study was to investigate the impact of the publication of the ATAC trial in December 2004 on subsequent prescribing of hormonal therapy to Irish women =55 years old. Methods: The Irish HSE-PCRS pharmacy claims database was used to identify all women =55 years old, commenced on tamoxifen or an aromatase inhibitor as initial hormonal therapy, between July 2000 and June 2006. A segmented regression analysis of an interrupted time series was used to detect changes in the trend and level of anastrazole prescribing after publication of the ATAC trial in December 2004 and the prior updates in November 2003 and June 2002 (presented December 2001). β coefficients and 95%CI are presented where appropriate. The absolute change in anastrazole prescribing and 95%CI are also calculated for selected months. Statistical analysis was performed using SAS version 9.1. Significance at p<0.05 is assumed. Results: A cohort of 7,604 women =55 years old, commenced on initial hormonal therapy, was identified from the HSE-PCRS database, 2,206 (29%) of these women were prescribed anastrazole. In the month following publication of the final results of the ATAC trial there was a 17.6% (95% CI 10.8%, 24.5%) absolute increase in anastrazole prescribing. This represented a statistically significant increase in the level of prescribing (level change β=18.1 95% CI 11.3, 24.9 p<0.0001). There was also a significant change in anastrazole prescribing trend after presentation of the first ATAC update (slope change β=0.98 95% CI 0.59, 1.37 p<0.0001). Conclusion: The publication of the final ATAC trial data resulted in a significant increase in the prescribing of anastrazole. This is objective evidence that oncologists respond rapidly to clinical trial results. It is unclear whether the significant increase in anastrazole prescribing after the first ATAC update is an appropriate response to an interim analysis. No significant financial relationships to disclose.
Phase I/II study of a 3 weekly liposome-encapsulated doxorubicin/docetaxel/pegfligrastrim in combination with weekly trastuzumab as primary treatment in HER2 positive (HER2+) early stage breast cancer (ESBC) patients (pt). GEICAM 2003–03 study
Authors: Antón A. , Ruiz A. , Seguí M. A. , Calvo L. , Muñoz M. , Lao J. , Vázquez C. , Fernández L. 
Published: March 2020

11032 Background: The liposome-encapsulated form of doxorubicin (Myocet™) (M) seems to be safe in terms of cardiotoxicity in combination with standard doses of trastuzumab (H) and paclitaxel in BC. This phase I/II study of M, H, docetaxel (T) and pegfligrastrim (N) was designed to evaluate the efficacy and safety of the combination, and define the MTD, in order to examine the selected regimen in a phase II trial. Methods: Cohorts of 3 HER2+ (FISH+) ESBC pt were treated at fixed dose of N (6 mg) and H (2 mg/kg/week). M and T were administered at the following dose levels (DL) (mg/m2): DL0, 60/75; DL-1, 55/75; DL-2, 50/70; DL-3, 50/65; DL-4, 50/60. The MTD was defined as >1/6 pt in any cohort experiencing a predefined dose-limiting toxicity (DLT) in cycle (cy) 1 or 2. LVEF was assessed at baseline and every 2 cy. Results: Nineteen pt have been enrolled in phase I; all are evaluable for efficacy and toxicity. Median age was 45. Twelve pt (63%) were premenopausal. Median tumour size was 45 mm (20–80); 13 (68%) and 6 pt (32%) presented with stage II and IIIA BC respectively. Six (32%) of tumours were G3. DLT were G3 diarrhoea, febrile neutropenia, thrombocytopenia, infection, and G4 asthenia. Three additional pt were treated at DL-4 for confirmation of the recommended dose; none of them had a DLT. One pt (DL-2) experienced asymptomatic, reversible LVEF decrease to 49%. All pt have been assessed for pathological response: 6 (32%) and 5 pt (26%) achieved one pCR and one pPR in breast, defined as Miller and Payne score of 5 and 4, respectively. Conclusions: Concomitant administration of M plus THN is highly active regimen with manageable toxicity in pt with HER2+ ESBC tumours. DL-4 has been selected as the DL for the ongoing phase II study with an enrolment target of 59 pt. No significant financial relationships to disclose.
Randomized comparison of neoadjuvant docetaxel (D), epirubicin (E) and pegfilgrastim (P) (+ trastuzumab [T] in HER2+ patients [pts]) with and without capecitabine (C) for operable breast cancer (BC): Results of a planned safety analysis of ABCSG 24
Authors: Steger G. G. , Greil R. , Samonigg H. , Jakesz R. , Bartsch R. , Mlineritsch B. , Melbinger-Zeinitzer E. , Marth C. , Schippinger W. , Gnant M. F. 
Published: March 2020

11034 Background: ABCSG-24 is assessing the effect of adding C to DE and adding T to DE or DEC on pCR rate. Methods: Pts with operable BC (any T stage except T4d, N±, M0) scheduled for pre-operative chemotherapy were randomized to six 3- weekly cycles of D 75 mg/m2, d1 + E 75 mg/m2 d1 + P 6 mg d2, ± C 1,000 mg/m2 bid d1–14. Primary endpoint was pCR rate. After protocol amendment, HER2+ pts were also randomized to adjuvant ± neoadjuvant T. Results: From Nov 04 to Nov 06, 262 pts were enrolled, including 29 HER2+ pts. 145 are evaluable (DE: 74 pts, 400 cycles; DEC: 74 pts, 344 cycles). The table shows grade 3/4 adverse events (AEs) in >2% of pts in either arm. Febrile neutropenia was absent. Serious AEs occurred in 22% vs 20% of pts in DE vs DEC, respectively. Fewer pts in the DE than the DEC arm required dose reduction (0.5% vs 6.6% of cycles), withdrew consent (4% vs 13%) or were withdrawn by the investigator (1% vs 17%). Reasons for withdrawal by investigator were: HFS, stomatitis, mucositis, diarrhea, vomiting, peripheral neuropathy, fatigue, asthenia, docetaxel hypersensitivity, and asymptomatic liver enzyme elevation. No serious or grade 3/4 cardiac toxicity has occurred with T. Conclusions: Despite infrequent grade 3/4 AEs in both arms, more pts discontinued DEC than DE, by either patient’s or investigator’s choice. Since May 06, no DEC pts have withdrawn consent, perhaps because of improved pt education and symptom management. This finding reinforces the need for close monitoring and prompt management of AEs. The addition of C to DE presents no safety concerns. Efficacy results are due in 2008. [Table: see text] [Table: see text]
Bone mineral density in women with non-metastatic breast cancer: Effect of intravenous bisphosphonates given before adjuvant therapies
Authors: Alonso B. , Aleman R. , Rodríguez L. , Llanos M. , Cruz J. , Oramas J. , Rodríguez E. , García R. , Ponce S. , Batista J. 
Published: March 2020

11038 Background: Adjuvant therapies shown survival improve of non-metastatic breast cancer (NMBC) patients, but they also decrease bone mineral density (BMD). Bisphosphonates are effective agents for the management of osteoporosis. Intravenous zoledronate, which is approved for the treatment of malignant hypercalcemia, multiple myeloma, and skeletal metastases, can suppress bone resorption and are often considered first-line therapy for the treatment of osteoporosis. We have analyzed the effects of chemotherapy on BMD of women with NMBC who received before adjuvant therapies intravenous bisphosphonates (zoledronic acid). Methods: We prospectively studied the effects of a single intravenous zoledronic acid dose (4 mg), on BMD of 74 women with NMBC (stage I-III), administred previous to the adjuvant therapies. The patients were referred to the Medical Oncology Service of University Hospital of Canary Islands between 2003 y 2006. Lumbar and hip BMD (g/cm2) was measured at diagnosis and after chemotherapy. The results were compared with a group of 80 patients with NMBC who received adjuvant therapy without intravenous bisphosphonates. Results: Breast cancer patients the median age was 52 ± 10 years old and the body mass index was 28,2 ± 5.5 kg/m2. At baseline there were not differences in BMD between the group that received bisphosphonates and the group with only chemotherapy at any of lumbar or femoral bone sites. In our study, the BMD after chemotherapy and intravenous bisphosphonates (n=74) significantly increased at femoral neck (0.805 ± 0.01, 0,826± 0.12; p=0.002) and trochanter (0.709 ± 0.01, 0.724 ± 0.01; p=0.002) and remained stable at lumbar, intertrochanter, total hip and Ward’s triangle; whether the group without bisphosphonates significantly decreased at lumbar (1.014 ± 0; 0.995 ± 0, p=0.0001), trochanter (0.701± 0; 0.690 ± 0, p=0,046), intertrochanter (1,095 ± 0; 1.078 ± 0, p=0.0001) and total hip (0,924 ± 0; 0.915 ± 0, p=0.046) areas (table). Conclusions: Women with NMBC are affected by early bone loss after adjuvant chemotherapy. Bisphosphonates intravenous (zoledronic acid) given before adjuvant therapy might be an effective treatment for this bone loss, increasing BMD or remaining stable. No significant financial relationships to disclose.
Adjuvant hormonal therapy (AHT) in women with early stage breast cancer (BC).
Authors: Song X. , Nicholas G. , Dent S. , Verma S. 
Published: March 2020

11053 Background: The ASCO technology assessment on adjuvant use of AI states that optimal AHT for a postmenopausal woman with HR-positive BC should now include an AI. We assessed uptake and patterns of AHT use in early stage HR-positive BC at a regional cancer center. Methods: A retrospective review of patients diagnosed with HR-positive early stage BC from January 2004 to December 2005 treated at our center was performed. Data included patient demographics, dates of diagnosis, treatment, last follow-up, AHT choices considered, patient compliance, and treatment toxicity. Patient risks for disease recurrence and mortality were estimated using adjuvantonline. Factors predicting a preference for AI use were identified using univariable and multivariable analysis. Results: 900 patients were identified for the stated period of time with HR-positive early stage BC. 340 patients have been evaluated. Median age was 59 years. Menopausal status was post-/ pre- in 267/73 patients. Stage was I/IIA/IIB in 202/95/43 patients. 267 patients were lymph node (LN) negative. ER, PR and Her2/neu status were positive/negative/unknown in 332/7/1, 292/46/2 and 11/69/260 patients. Initial AHT choice was tamoxifen/anastrozole/letrozole/exemastane/none in 196/79/9/2/54 patients. Of those started upfront on tamoxifen, plan to switch to an AI was stated in 41%. Statistically significant factors associated with any adjuvant AI use included disease stage, menopausal status as well as individual physician preferences. In further analysis, patients’ compliance and toxicity will be reported. Correlation of recurrence risk, as determined through adjuvantonline, with upfront selection of an AI has also been performed. Conclusion: Guidelines have stated the use of an AI (upfront, sequential or extended) should be considered in HR-positive early stage BC. Results from this study provide further insights on the uptake of such therapy as well as factors (disease related, patient and physician preferences) influencing adjuvant treatment decision-making. A prospective trial assessing treatment decision regarding AHT is also in progress. (This study is sponsored by the Canadian Breast Cancer Foundation) No significant financial relationships to disclose.
Temporal trends in protocol-specified adjuvant chemotherapy dosing in obese patients with breast cancer
Authors: Greenman C. , Griggs J. J. 
Published: March 2020

11055 Purpose: Dosing of breast cancer adjuvant chemotherapy in obese women varies substantially, with up to 40% of obese women receiving reduced (compared to full weight-based) doses. Such variation indicates uncertainty about best practices. This study reports changes over time in protocol-specified dose determinations in heavy patients. Methods: The National Cancer Institute database of cooperative group trials was used to identify completed clinical trials of non-myeloablative breast cancer adjuvant chemotherapy. Dose determinations specified in each protocol were categorized into one of four groups: 1) full weight-based dosing, 2) dose reduction in heavy patients (ideal or corrected body weight used to calculate body surface area, BSA), 3) dosing in heavy patients left to physician’s discretion, or 4) no specific instructions. Results: Of 110 eligible clinical trial protocols identified, 61 (55%) were retrieved. Of the 16 protocols initiated before 1985, 15 (94%) either did not address dose determination (n = 6) or specified dose reduction (n = 9) in heavy patients. Of the 45 protocols initiated after 1985, 26 (58%) specified full weight-based dosing, 13 (29%) specified dose reductions, 4 (9%) left dosing in heavy women to the physician’s discretion, and 3 (7%) had no specific instructions for dose determinations in heavy patients. The difference in the use of full weight based doses before and after 1985 was statistically significant (p value = 0.0003, 2-sided Fisher’s exact test). One of the cooperative groups, which contributed 10 of the 45 (22%) clinical trial protocols since 1985, specifies a maximum BSA of 2.0 m2 for cyclophosphamide and doxorubicin in all protocols. Conclusions: Over the last two decades, dose determinations in clinical trial protocols have, with the exception of one cooperative group, specified use of actual body weight. Present-day dose reductions in obese patients who are not participating in clinical trials suggest a lack of diffusion of information about optimal dosing in obesity. The continued practice of limiting the doses of cyclophosphamide and doxorubicin in patients with a BSA over 2.0 m2 in the protocols of one cooperative group may contribute to persistent uncertainty about optimal dosing in heavy patients. No significant financial relationships to disclose.
Breast cancer after treatment of Hodgkin disease: Clinical outcome of 38 cases in 27 patients
Authors: Alm El-Din M. A. , Hughes K. S. , Goldberg S. I. , Raad R. A. , Taghian A. G. 
Published: March 2020

11059 Background: Many studies showed that women who are cured of HD have an increased risk of developing BC. Our purpose is to evaluate detection, pathology, management and prognosis of BC occurring after HD. Methods: Thirty-eight cases of BC in 27 survivors of HD were analyzed. All patients received supradiaphragmatic RT and 13 had also chemotherapy for HD. Results: The median age of the patients at diagnosis of HD was 25.5 years. The median interval to develop BC was 15.9 years. The median age at diagnosis of BC was 45.8 years. Ten women (37%) had bilateral disease; one of them had DCIS, 7 years before developing bilateral disease. Cancers were detected by mammography (59.4%), symptom presentation (24.3%), clinical examination (8%), and incidental during elective mastectomy (8%). Using Fisher’s Exact test, DCIS was more frequent (27%), where nodal involvement (29.6%), and ER positivity (81.5%) were paralleled that reported in general population. Thirty tumors (79%) were managed by mastectomy due to prior RT. Two women received RT following mastectomy. Eight tumors treated by lumpectomy, followed by RT in two women; one received whole breast RT, while the other received fractionated partial breast irradiation using 3D-conformal technique (50Gy/25 fractions) and she is doing well 1 1/2 years after RT. Adjuvant systemic therapy, given to 17 patients, was well tolerated. The median follow-up after BC was 61 months. Using Kaplan-Maier procedure, the 6-year actuarial relapse-free survival for node-negative BC after HD was 100%. Node positive patients had a significantly lower RFS of 58.3% ± 19% (P = 0.01). Conclusions: Compared to patients with primary BC, patients developing BC after HD are more likely to be younger, have bilateral disease and have more frequent DCIS. Other pathological features and prognosis are similar to that reported in general population. Patient awareness, breast examination and mammography should be part of the follow-up program for HD survivors. Mastectomy remains the standard of care in most of cases; however, lumpectomy followed by fractionated partial breast irradiation might be a reasonable approach to investigate for women who refuse mastectomy. No significant financial relationships to disclose.
Use of oblique supine magnetic resonance imaging in breast-conserving surgery following neoadjuvant chemotherapy
Authors: Nakamura R. , Sakakibara M. , Nagashima T. , Fujimoto H. , Arai M. , Hashimoto H. , Kaneoya K. , Ueda T. , Miyazaki M. 
Published: March 2020

11064 Background: The success of breast-conserving surgery (BCS) after neoadjuvant chemotherapy (NAC) is dependent on accurate assessment of the extent of surgical excision of the original tumor bed (OTB). However the difficulty in locating microscopic residual disease often leads to a high re-excision rate (RER) and large excision specimen area (ESA). Methods: Magnetic resonance imaging (MRI) scans in the oblique supine position are performed with the patient in the same posture as that adopted during surgery. Maximum intensity projection (MIP) images of MR coronary section images of OTB are generated and used for surgery. OTB images are copied onto transparent sheets overlaid on the MIP images. These images are projected onto the breast before surgery, and used to determine the lines for surgical excision. In the conventional method (CM), OTB is determined by ultrasonography (US) and CT images. The oblique supine MRI method (SMM) has been used at our hospital since 2005. In this study, 14 patients treated prospectively with SMM (12/05- 12/06) were compared with a series of 19 consecutive patients treated with CM (04/03–11/05). ESA and RER were analyzed. Re-excision was performed in cases with a calcified lesion or tumor within 1 cm of the excised margin by X-ray or US during surgery, or invasive cancer was detected within 1 mm by pathological examination. ESA was analyzed using NIH Image. All patients received anthracycline/taxane-based chemotherapy. Results: There were no significant differences in characteristics of patients in the initial stages (T1, 2) or pathological chemotherapy responses between SMM and CM groups. There were four T3.4 cases in the SMM group, but none in the CM group. Clinical responses in CM and SMM were as follows (cases): CR 6, 7; PR 12, 7; SD 1, 0, respectively. RER was significantly greater in CM (36.8%, n=7) than in SMM (7.1%, n=1) (P<0.05). Average ESA in SMM were 19.0 cm2 (n=2) in T1, 33.6 cm2 (7) in T2, and 59.3 cm2 (5) in T3.4, while corresponding values in CM were 49.4 cm2 (4) and 65.5 cm2 (15), respectively; ESA was significantly improved in SMM. Conclusions: SMM, which has the benefits of decreased ESA and RER with superior cosmetic results, is a reliable technique for BCS following NAC. No significant financial relationships to disclose.