bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relationship between tumor characteristics and HER2/neu overexpression with response and outcome in locally advanced breast cancer (LABC) patients (pts) treated with neoadjuvant anthracycline-based chemotherapy (CHT)
Authors: Fernandez Sagarra A. J. , Alvarenga C. , Alvarenga M. , Kraft M. L. , Teixeira L. C. 
Published: March 2020

10698 Objectives: To retrospectively evaluate the relationship between HER2/neu status, pts’ characteristics, prognostic factors and clinical outcome in LABC women treated with neoadjuvant anthracycline-based CHT. Patients and Methods: 118 pts. with stage IIIA-B LABC, excluding inflammatory cancer, were included. HER2 overexpression was evaluated by immunohistochemistry (IHC), only IHC 3+ were defined as positive. The disease-free survival (DFS) was calculated according to Kaplan-Meier method. Fisher test, hazard ratios with 95% interval confidence, and Cox or Wilcoxon models were used. Kruskall-Wallis was used for comparison between medians. Results: Median age was 49 y (range: 31–69); 66 were pre-menopausal, 43 were stage IIIA and 77 IIIB; 59 pts. were N2. Primary tumor average size was 70 mm; 44 tumors were ER+, 43 PR+, 26 (22%) HER 3+, 104 histological grade III, 57 nuclear grade III. Seventy-four pts. (62.7%) achieved objective responses, with 7 complete clinical remissions. There was 1 progressive disease and only 3 pts. (2.5%) didn’t undertake mastectomy. After surgery, four pts. (3.5%) were evaluated as pathological complete remission, 6 (5.2%) with microscopic residual disease and 105 with macroscopic residual tumor. The median DFS was 19 months for the whole group and 39,6 and 31,6 for those achieving complete pathological remission and microscopic residual disease, respectively. There was no association between HER2/neu overexpression and pts’ characteristics, tumor prognostic factors nor with clinical or pathological responses. Negative PR, high tumor nuclear grade, clinical stage IIIA and complete clinical response were predictive factors for pathological response. In multivariate analysis, only pathological lymph node status was prognostic factor for DFS. Conclusions: There was no significant association between HER2 overexpression, tumor prognostic factors and clinical or pathological response to neoadjuvant CHT. Negative PR, high nuclear tumor grade, clinical stage IIIA and clinical complete response were associated to complete pathological response. Lymph node status was a strong prognostic factor for DFS. No significant financial relationships to disclose.
Addition of weekly paclitaxel (P) after dose intensified epirubicin/cyclophosphamide (EC) (NECTA-protocol) as primary systemic chemotherapy (PST) in locally advanced breast cancer (LABC) improves pathologic response rate (pCR) in comparison to peoperative dose intensified EC
Authors: Lex B. , Popovic M. , Russu V. , Gilster T. , Volkholz H. , Tulusan A. H. 
Published: March 2020

10712 Background: Green M et al. (Proc Am Soc Clin Oncol 2002, abstract 135) demonstrated an improvement of pCR up to 28,8% by changing the preoperative application of 3 weekly P 225 mg/m2 (q21) to weekly P 80 mg or 150mg/m2 (q7) completed by 4 cycles FAC. Our study-group observed a pCR of 6% after 3 preoperative cycles of dose-intensified EC (120 mg/600 mg/m2 q14 or q21) in LABC. Dose-density (q14) did not improve pCR (Euler U et al. Proc Am Soc Clin Oncol 2002, abstract 126). As a consequence we studied the preoperative effect of 12 cycles P 80 mg/m2 (q7) after 3 cycles EC (120 mg/600 mg/m2 q21) . Methods: Between 2002 and 2005 61 patients (pts) with LABC (T2–4/N0–2/M0) were operated after PST with the NECTA-protocol. Irradiation after breast conserving therapy (BCT) was obligate. Immunohistochemical analysis were performed in tumor tissues from core biopsy before PST and from surgery. Results: The medium age was 49,2 yrs, 29,2% had negative ER-status, 48,1% negative PR-status and 22% HER2 overexpression. 76,2% had a cT2-tumor, 18,6% a cT3-tumor and 5,1% a cT4-tumor, 48,3% clinically showed positive lymph nodes. The medium follow up was 27 months (2–41 months). The clinical and pathological response rate was 94,8%. pCR was diagnosed in 8,6%. BCT was feasible in 94,8%. The documented recurrence rate was 14,7% (9 pts: 4 with local relapse, 3 with metastases and 2 with simultaneous local and distant recurrence), 8 pts with recurrence had a cT2-tumor. In the meantime 3 pts died. Conclusions: The additional treatment with weekly paclitaxel after EC induced a high rate of clinical and pathological response. The rate of conservative surgery was very high (94,8%). In the retrospective analysis NECTA-regime improved pCR. In comparison to other taxane-based PST-protocols pCR-rate (8,6%) was low. A phase III study will compare the NECTA-regime with the classical EC-regime in PST. No significant financial relationships to disclose.
Safety and efficacy trial of preoperative sequential chemo-radiation therapy for the surgery sparing treatment (SST) in early breast cancer (EBC): Japan Clinical Oncology Group trial (JCOG0306)
Authors: Mukai H. , Watanabe T. , Mitsumori M. , Tsuda H. , Nakamura S. , Masuda N. , Asaga T. , Yamamoto N. , Kaba H. , Aogi K. 
Published: March 2020

10717 Background: The combination of preoperative anthracycline-containing regimen and taxane can obtain a pathological complete response (pCR) rate of around 30% for patients (pts) with EBC. To pursue higher pCR rate with maintaining good systemic control is necessary to put the SST practical in the future. The objective of this trial was to determine whether the addition of radiation therapy (RT) to chemotherapy (CT) could surpass the pCR rate of 50% in pts with EBC. Methods: We conducted a safety and efficacy trial of CT (4 courses of doxorubicin and cyclophosphmide (60/600 mg/m2) followed by 12 courses of weekly paclitaxel (80 mg/m2) and RT (whole breast 45Gy + boost 10Gy) sequentially as a primary therapy in pts with stage I-IIIA (5.0 cm ≥ tumor size ≥ 2.0 cm) BC. All pts received mastectomy or lumpectomy 12–16 weeks after completion of RT to maximize the effect of RT. pCR was assessed by the central pathological review board according to the pCR classification adopted by the National Surgical Adjuvant Breast and Bowel Project (NSABP). The study was designed to enroll 104 eligible pts with threshold pCR 35%, expected pCR 50%, alpha 0.05, beta 0.1, and additionally to have the width of 95% confidence interval (CI) within ±10% for sufficient precision of pCR. Results: Between June 2004 and April 2005, 108 pts were enrolled in this trial. Median age was 50 years (range 23–69). 1 pt had T1, 95 T2, and 3 T3 tumors (2 pts’ data are missing and 7 pts’ data have not been collected). 58% (59/101) were ER+, 49% (49/101) were PgR+ and 31% (31/101) had HER2 overexpression. Based on the planned interim analysis, the Data Monitoring Committee recommended to terminate the trial for insufficient pCR rate of the first 7 eligible patients (0% (0/7), 95% CI: 0–41.0%). Toxicities were within expected range. Conclusions: Preoperative sequential chemo (AC followed by paclitaxel) -radiation therapy is not considered to be promising for accomplishing enough pCR rate. No significant financial relationships to disclose.
Trends in systemic management (SM) for the treatment of locally advanced breast cancer: Data from a regional cancer centre
Authors: Dent S. F. , Verma S. , Azzi J. , Vandermeer L. , Spaans J. 
Published: March 2020

10728 Background: Locally advanced breast cancer (LABC) accounts for less than 5% of women diagnosed with breast cancer in North America each year. The scarcity of clinical trials addressing the SM of these women continues to represent a challenge for clinicians. Methods: A retrospective database was developed using the American Joint Committee on Cancer (AJCC) 2002 staging classification for all women who presented to TOHRCC with LABC between Jan 1/02-April 1/05. Information was obtained from clinic charts and patient self-reported questionnaires. Results: Outcomes reflect the SM of the first 50 women entered into our database. Median age at presentation was 57 years (range 28–88); 62% were post-menopausal; and hormonal status was 52% estrogen receptor (ER) positive and 54% progesterone receptor (PR) positive. Surgery was performed prior to chemotherapy in 50% of patients (pts).The majority (90%) of pts received SM as follows: 38% anthracyclines (A) alone (52% epirubicin, 26% adriamycin, 2% both); 7% taxanes (T) alone (33% paclitaxel, 66% docetaxel), 53% received both T and A regimens, and 2% received other types of chemotherapy (gemcitabine,vinorelbine,capecitabine). The addition of trastuzumab to the SM of HER2-positive pts has also been observed. Hormone therapy was given to 22 pts (44%) of whom 82% were ER or PR-positive: tamoxifen (27%); aromatase inhibitors (AIs; 50%); both tamoxifen and AIs (23%). Pts were treated with AIs as follows: anastrozole (73%); fulvestrant (9%), and atemestane (9%). In pts with measurable disease receiving neoadjuvant SM; 7(35%) had a complete clinical response and 13 (65%) had a partial response; mean tumour size decreased from 7.5 cm (range 2–22) to 2.8 cm (range 0–8). Pathological complete response rates and improved survival rates have been observed and will be reported in detail. Conclusions: These results represent our first analysis of treatment outcomes in women with LABC using the new AJCC system. This database highlights the increased utilization of T and AIs in the SM of these pts, which seems to translate into the increasingly observed improvements in overall survival. Microarray studies to further explore predictability of treatment outcomes are planned. No significant financial relationships to disclose.
Phase II study of gemcitabine (Gem) + docetaxel (D) in combination with trastuzumab (T) in patients (pts) with HER2-overexpressing metastatic breast cancer (MBC)
Authors: Fescina D. R. , Gradishar W. , Orlando M. , Rubinsak J. , Haney L. , Wang Y. 
Published: March 2020

10730 Background: Addition of T to chemotherapy (chemo) is assoc. with improved overall survival (OS) in pts with HER2+ tumors. Combination chemo has shown improvements in PFS and OS over single agent in recent phase III studies. Pre-clinical models suggest that the combination of G and D appears to be synergistic and that either agent is also synergistic with T. Objectives: This multi-institutional study was designed to determine overall RR (primary endpoint), TTP, OS and the toxicity profile of the combination of G + D + T as first-line therapy for MBC pts. Design: Pts with measurable HER2-overexpressing (FISH+) MBC, no prior chemo in the metastatic setting, adequate end-organ function and PS 0–2, received Gem 1,000 mg/m2 over 30 min on days 1 and 8 + D 75 mg/m2 day 1 and T on day 1 (8 mg/kg over 90 min on cycle 1, then 6 mg/kg over 30 min on subsequent cycles) of a 21-day cycle, until progressive disease or undue toxicity. Results: 8 pts have been enrolled over a period of 16 months. Median age: 53 years (range 40–74); ER status ±: 5/3 pts; ECOG PS 0 = 3 pts, 1 = 4 pts, 2 = 1 pt; Prior adjuvant therapy: Chemo ± Hormonal 3, Hormonal only 3, T 1. Sites of Disease: All pts had visceral involvement (Lung 4, Liver 5) and 5 pts ≥ 2 sites of metastatic disease. Total number of cycles administered was 52; median per pt. 7 (range 4–10). Median delivered dose intensity for G, D and T was 91%, 92% and 100% respectively. Toxicity was generally manageable. One pt discontinued therapy due to adverse events (grade 3 pneumonitis). Grade 3/4 neutropenia occurred in 27% and 10% of cycles; no grade 3/4 anemia or thrombocytopenia were recorded; Non-Heme toxicities of grade 2/3, included with dyspnea (0/2 pts), emesis (2/1), fatigue (4/1), diarrhea (1/1), dehydration (0/1), constipation (1/0). Complete alopecia was observed in 2 pts. No symptomatic cardiac toxicity was recorded. Best Overall RR assessment (N = 8): CR 3, PR 4, SD 1, PD 0, for an ORR of 7 out of 8 pts or 88% (95% CI: 47%–100%). Only 3 pts have progressed, and no pt has died. Progression-free survival at 1 year is 58%. Conclusion: According to this limited experience, the combination of G + D + T in front-line MBC is well tolerated and active. Study was discontinued due to slow accrual as of Feb 2004. Supported by Eli Lilly & Company. [Table: see text]
Aromatase inhibitors (AIs) with or without GnRH agonist as first-line hormone therapy in pre- and post-menopausal Korean women with metastatic breast cancer (MBC): Clinical outcomes in correlation with tumor ER/PR/HER2 status
Authors: Ro J. , Lee K. S. , Nam B. H. , Lim H. S. , Kwon Y. , Kong S. Y. , Seo J. A. , Lee E. S. 
Published: March 2020

10732 Background: Clinical outcomes of patients (pts) with MBC by AIs in comprehensive relationship with ER/PR/HER2 status have been scant that the study was performed to analyze their predictive values singly and in combination. Methods: 111 pts who took letrozole or anastrozole as first-line hormonal therapy for MBC were identified from the database at NCC Hospital between Nov. 2001 and Aug. 2005. Pts on AIs concomitantly with or immediately followed by chemotherapy were excluded. AIs/GnRH agonists were used when hormonal levels were not postmenopausal. ER/PR were scored strong, intermediate or weak. HER2+ was IHC 3+ or FISH+. HER2− was IHC 0, 1+ or 2+/FISH−. Clinical benefit (CB) included CR/PR/improving or SD ≥6 months. Results: Median age was 54 years (range, 29–78). Overall 66% achieved CB (CR/PR 18%, improving 26%, and SD ≥ 6mo 22%) with median TTP, 9 mo (range, 1–50, 95% CI, 7–11), and median survival, 41 mo (range, 2–50). Age, AIs with (20) vs. without (91) GnRH agonist, DFI ≤ vs. > 24 mo, adjuvant tamoxifen, or prior metastatic chemotherapy did not affect clinical outcomes. Disease sites (%) were bone (64), LN (52), lung/pleura (41), liver (25), breast (20) and skin (7). Bone only disease had longer TTP (p = 0.004), while liver involvement was associated with short TTP (p = 0.0001)/OS (p = 0.007). ER was 56% strong +, 21% intermediate +, 15% weak +, 5% - and 3% unknown, PR: 24% strong +, 23% intermediate +, 24% weak +, 23% -, and 5% unknown, and HER2: 23% +, 67% -, and 10% unknown. Staining intensity did not affect CB in ER+ tumors. More CB (p = 0.002)/longer TTP (p = 0.003) with strong/intermediate PR+ tumors vs. weak PR+/PR− tumors, and more CB with ER+/PR+ tumors vs. ER+/PR− tumors (P = 0.016) were observed. More CB with HER2− tumors vs. HER2+ tumors (p = 0.001), and with PR+/HER2− tumors vs. the rest (PR−/HER−, PR+/HER+, PR−/HER+) (p = 0.0007) were seen. HER2 positivity was associated with less CB (p = 0.0004)/shorter TTP (p = 0.0157) in ER+/PR+ tumors vs. no influence on CB (p = 0.245)/TTP (p = 0.52) in ER+/PR− tumors. Conclusions: AIs with or without GnRH agonist are effective therapy for pts with MBC, specifically with ER+/PR+/HER2− tumors regardless of ages. No significant financial relationships to disclose.
Age is not a prognostic factor in Korean women with breast cancer treated with breast conservative surgery and radiotherapy
Authors: Choi D. , Kim E. , Kim Y. , Lee M. , Park H. 
Published: March 2020

10740 Background: The median age of the breast cancer at diagnosis in Korean women is 45 years and a quarter of the patients are at age 40 or younger. The purpose of this study was to analyze the prognostic factors including age for patients treated with breast conserving surgery and radiotherapy. Methods: Two hundred and eleven breast cancer patients were treated with breast conserving therapy at Soonchunhyang University Hospital, Seoul, Korea, between May 1991 and May 2003. The radiation dose to the whole breast was 50.4 Gy over 5 weeks and boost doses of 10–14 Gy administered to the tumor bed in the majority of the patients (180/211). Nodal radiotherapy was delivered in patients with 4 or more node metastasis. Adjuvant chemotherapy was performed in most of the patients with node metastasis or tumors larger than 1cm, or younger patients. One hundred and thirty four patients received CMF regimen, 14 patients treated with CEF regimen. The median and minimum follow-up periods were 58 and 30 months respectively. Results: The average age at the time of operation was 41.9 years (median 42 years, range 23–67 years), and the mean tumor size was 2.03 cm (median 1.80 cm). One hundred and forty seven patients (69.7%) had pathologically node negative disease and fifteen patients had 4 or more lymph node metastasis. Local, regional relapse and distant metastasis occurred in 7, 3 and 10 patients respectively. The 5 year disease free, loco-regional relapse free and overall survival rate were 89.5%, 93.4%, 95.6%, respectively. Three patients among the 31 patients who received 50.4Gy or incomplete radiotherapy to the breast experienced loco-regional relapse. Age (40 years or less versus more than 40 years old) was not a prognostic factor in univariate analysis. T stage (p = 0.027), lymph node metastasis (p < 0.01) were significant factors for recurrences. By multivariate analysis, only lymph node status was a significant prognostic factor for treatment related failure. Conclusions: A breast conserving procedure is effective for patients with early stage breast cancer regardless of age in Korean women. Axillary lymph node status was the most important independent predictor for a recurrence, and more efficient treatment is required for these patients with lymph node metastasis. No significant financial relationships to disclose.
Clinical experience using fulvestrant in hormone responsive metastatic breast cancer
Authors: Bauerschlag D. O. , Schem C. , Jonat W. , Maass N. 
Published: March 2020

10749 Background: We report our clinical experience using the steroid estrogen receptor antagonist Fulvestrant to treat postmenopausal women with hormone sensitive metastasized breast cancer. We discuss the position of Fulvestrant in the endocrine treatment cascade, taking into account the new application guidelines for aromatase inhibitors. Methods: Data from 16 female patients and one male patient treated with Fulvestrant were analyzed. We describe the time point in the treatment cascade when Fulvestrant was administered and the resulting time to progression (TTP). The reviewed cohort was heterogeneous regarding the initial tumor size, the therapy and the progression of the tumor, respectively. The patients were 54 years of age at the time of diagnosis. The estrogen receptor was positive in all cases. Results: Fulvestrant was usually given as the last step in the endocrine treatment cascade (n = 14). The mean TTP was 5.7 months (n = 13). 3 patients are still under successful treatment with Fulvestrant. No common side effects as usually caused by endocrine therapies with Tamoxifen and aromatase inhibitors were documented. Conclusions: The specific estrogen receptor down-regulator Fulvestrant is a valid and well tolerated endocrine treatment option in heavily pre-treated and metastasized breast cancer patients (TTP 5.7 month). Also in the clinical situation of Tamoxifen resistant tumors, Patients could benefit from Fulvestrant. 3rd generation aromatase inhibitors are now used for the first-line treatment of breast cancer in postmenopausal women. Shifting the sequential endocrine therapy cascade might need a new positioning of Fulvestrant. No significant financial relationships to disclose.
Three years follow up in patients with stage III breast cancer: Single institution experience
Authors: Stojkovski I. , Kraleva S. , Smickoska S. , Crvenkova S. 
Published: March 2020

10752 Background: Purpose of this study is to estimate impact of different prognostic factors and treatment procedures on overall survival of patients with stage III breast cancer, treated at the Institute of Radiotherapy and Oncology (IRO) in Skopje, Macedonia. Methods: Retrospective analysis of patient records of forty four patients with stage III breast was performed. Before admitting at IRO, each patient undergoes surgical treatment, which comprises of radical mastectomy with ipsilateral axillary dissection. Patients were classified according to TNM system of AJCC. All patients were divided in groups according to primary tumor size (unknown, less than 5 cm and more than 5 cm), positive lymph nodes (4–9 positive lymph nodes or more than 9 positive lymph nodes), adjuvant chemotherapy (CMF like, antracyclines based and taxanes based) and elective radiation of thoracic wall and regional lymph nodes (with or without radiation). Results: Statistical analysis of data was performed with Kaplan Meier estimation and log-rank test. In our series only tumor size has significant impact on overall survival of patient (p = 0.0134). Nodal status, type of adjuvant chemotherapy used and radiation has no significant impact on overall survival. Conclusions: Further analysis and longer follow up of this subgroup of patients is necessary to estimate value of different prognostic factors and treatment modalities. No significant financial relationships to disclose.
Differential expression of the 150-kd oxygen-regulated protein (ORP150) in benign, pre-malignant and malignant breast tissue
Authors: Stojadinovic A. , Hooke J. , Shriver C. D. , Kovatich A. , Nissan A. , Ponniah S. , Peoples G. E. , Moroni M. 
Published: March 2020

10770 Background: Heat shock protein, ORP150, plays a role in hypoxia/ischemia and angiogenesis. Preliminary studies demonstrate increased ORP 150 expression in human cancer, and associate its over expression with aggressive tumor biology. This study further evaluates ORP150 expression in different stages of breast cancer, such as benign, pre-malignant and malignant breast lesions and correlates it with clinical-pathological data. Methods: Sixty-six prospectively collected paraffin-embedded breast tissue sections were reviewed for diagnostic confirmation (normal, n=25; DCIS, n=20; invasive breast cancer (Ca), n=21) and stained using ORP150 antibody immunohistochemistry (IHC). Antibody-staining levels in the benign, DCIS and invasive component of each lesion were reviewed independently by two pathologists and scored: 0 (lowest) to 3+ (highest). Clinical-pathological data was compared with ORP150 staining using ANOVA or T-Test as appropriate with significance determined by p<0.05. Results: Significant differential ORP150 staining was detected in benign-normal versus benign adjacent to invasive cancer, as well as in benign adjacent to DCIS versus benign adjacent to invasive cancer. ORP150 expression in the invasive portion of the breast cancer correlated significantly with tumor grade and absence of hormone receptor expression, presence of lymphovascular invasion and lymph node metastasis. Conclusions: ORP150 expression in breast cancer is associated with poor prognostic histological factors. As ORP150 is differentially expressed in benign tissue adjacent to invasive cancer, further study is warranted to determine its utility in detecting occult invasive cancer within benign biopsy specimens, as well as its putative role in tumor-stromal cell interactions. [Table: see text] No significant financial relationships to disclose.