bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human chorionic gonadotropin (HCG) induction of apoptosis in breast cancer
Authors: Carter W. B. , Sekharam M. 
Published: March 2020

10658 Background: Apoptotic induction in cancer cells may improve the efficacy of local or systemic therapy. Human Chorionic Gonadotropin (HCG) injection directly into Kaposi’s sarcoma or melanoma has been shown to increase the apoptotic index in these tumor types. The rapid induction of apoptosis in breast cancer immediately preceding local or systemic therapy may improve the response to therapy or local control. We hypothesized that HCG would rapidly increase the apoptotic index in breast cancer after intratumoral injection. The primary objective of this preclinical trial was to determine if intratumoral injection of HCG would significantly increase the apoptotic index in breast cancer xenografts. Methods: Using a human breast cancer xenograft model in Nude mice, 5 × 106 SK-BR3 human breast cancer cells were injected subcutaneously into each flank of nu/nu mice. When the tumors reached 6 mm, 50 uL (100 U/mL) of non-recombinant, naturally occuring HCG (A.P.L., Wyeth) or saline vehicle control was injected directly into the xenograft tumors. After 24 hrs, the tumors were harvested, and the xenografts tested for proliferation (Ki-67) and apoptosis (by TUNEL assay). The apoptotic index was calculated (apoptosis/proliferation) and statistical analysis performed using paired T-test. Results: Seven pairs of SK-Br3 xenografts were tested. There were no differences in proliferation by Ki-67 determination between control or treated xenografts. Apoptosis increased in HCG treated xenografts compared to vehicle controls. Apoptosis increased from a mean of 5% (range 1– 20%) in control xenografts to a mean of 28% (range 1–70%) in HCG treated tumors (p = 0.038). Conclusions: Naturally-derived HCG induces apoptosis in human breast cancer xenografts after intratumoral injection. Substantial induction of apoptosis may improve the efficacy of local and systemic therapy in breast cancer. Injection of HCG into breast tumors immediately prior to surgical, radiation, or systemic therapy has the potential to improve local control or response to treatment. Futher elucidation of potential synergy with therapeutic modalities is justified. No significant financial relationships to disclose.
Phase II study of an epirubicin and docetaxel (ET) combination as pre and post-operative systemic therapy in patients with early stage breast cancer (EBC)
Authors: Nishimura R. , Rai Y. , Mitsuyama S. , Toyoshima S. , Iwasaki H. , Ichinose I. , Tamura K. , Matsuo F. , Hara S. , Yano H. 
Published: March 2020

10660 Background: The goal of chemotherapy (CT) for EBC is to achieve a high pathologic complete response (CR) leading to an increase in the rate of breast conserving surgery (BCS). ET is one of the most active CT regimens for metastatic breast cancer. The primary endpoint of this study was to evaluate clinical response Methods: Eligible patients (pts) were newly diagnosed with EBC and had large primary tumors (stage II-III, > 3 cm). Forty-seven pts were enrolled and received epirubicin 60 mg/m2 followed by docetaxel 60 mg/m2 every 3 weeks for 4 cycles before surgery. Within 4 weeks after surgery, 4 additional cycles of ET were given to the pts who responded to ET. Results: Forty-five pts were evaluable for safety and clinical response. The median age was 47 (range, 29–75). The tumor size was T2 in 44% of the pts, T3 in 36%, and T4 in 20%. ER and PgR were both positive in 40% of pts, while both negative in 31%. HER2 was positive in 33% of pts. Four cycles of ET at full dose were given to 96% of pts prior to surgery. The clinical response was 73% including 7% CR (95% CI 58–85%); the BCS rate was 36%. Central pathologic review was performed in 37 pts showing disappearance of all tumor cells (grade 1) in 1 patient (3%) and 2 pts (5%) achieved a grade 2 response (in situ carcinoma in the operated breast) by Chevallier’s criteria. Grade 3–4 toxicities included neutropenia (71%), leukocytopenia (69%), febrile neutropenia (18%) and anorexia (9%). Twenty-four of 33 pts who responded to ET received additional ET after surgery. Conclusions: ET showed a high clinical response in previously untreated EBC with acceptable toxicity. In order to improve pathological CRs further, the doses and treatment schedule of this regimen needs to be improved. Currently, we are following the pts to assess differences in survival between pts with or without additional adjuvant ET. No significant financial relationships to disclose.
Oral vinorelbine plus capecitabine (oral vincap) combination in patients with advanced breast cancer (ABC)
Authors: Lorusso V. , Spada M. , Giampaglia M. , Misino A. , Calabrese R. , Latorre A. , Monticelli G. , Guida M. , Sambiasi D. 
Published: March 2020

10673 Background: Vinorelbine i.v. and capecitabine are two of the most effective single agents in previously treated advanced breast cancer (ABC). A number of studies have been reported with the combination of these agents. Actually, the availability of oral formulation for vinorelbine allows a full oral combination of the two agents. The aim of this study was to evaluate the activity and toxicity of this novel combination. Patients and Methods: Thirty-eight advanced breast cancer patients (pts) refractory to anthracyclines and taxanes were included in this study. Treatment consisted of vinorelbine 60 mg/m2 (days 1 + 8), and capecitabine 2000 mg/m2 (days 2–7 and 9–16) every 3 weeks. The pt characteristics were: median age 53 years (range 37–77 years); ECOG PS 0–1 in 35 pts (92.1%), and PS 2 in 3 pts (7.8%); ER+/PgR+ 20 pts (52.6%) and ER−/PgR− 11 pts (28.9%). Dominant sites of disease were visceral in 19 pts (50.0%), bone in 10 pts (26.3%), soft tissue in 9 pts (23.6%). Results: A total of 228 courses were given with a mean of three cycles/pt (range 1–12). Five pts (13.1%) had no toxicity at all. Hematologic side-effects were: neutropenia G2-G3 in 7 pts (18.9%), and G4 in 1 pt (2.7%), anemia G1 in 11 pts (29.7%), G2-G3 in 5 pts (13.5%), thrombocytopenia G1 in 6 pts (16.2%) and G3 in 1 pt (2.7%). Non-hematologic side-effects were: fatigue G1 in 5 pts (13.5%), hand-foot syndrome G1 in 2 pt (5.4%) and G2 in 2 pts (5.4%), nausea/vomiting G1 in 2 pts (5.4%), G2 in 3 pts (8.1%) and G3 in 1 pt (2.7%), constipation G1 in 2 pts (5.4%), peripheral neurotoxicity G1 in 3 pts (8.1%) and G2 in 1 pt (2.7%), gastric pain G1 in 2 pts (5.4%), stomatitis G1 in 3 pts (8.1%) and G2 in 1 pt (2.7%). Out of 38 pts assessable, we observed 2 (5.4%) CR, 13 (34 %) PR, 14 (37.8%) SD, and 9 (26.3%) PD. The median time to progression was 4.5 months (range 1–18 months), the median response duration was 7 months (range 2–18 months), and the median survival duration was 10 months (range 2–26+). Conclusions: The oral vincap combination was well tolerated and effective in ABC. In fact, this regimen achieved results comparable to the previously reported combinations of capecitabine and i.v. vinorelbine. The oral vincap should be considered as an alternative to single agent capecitabine or vinorelbine in ABC refractory to antra-taxane combination. No significant financial relationships to disclose.
Preliminary results of a phase II study of neoadjuvant treatment with docetaxel (T), doxorubicin (A) and capecitabine (X) in locally advanced or inflammatory breast cancer (LABC)
Authors: Perez Manga G. , Méndez M. , Palomero M. I. , Quibén R. , Belón J. 
Published: March 2020

10678 Background: Previous studies suggest that combined treatment of chemotherapy + surgery + radiotherapy has a high survival rate in pts with locally advanced or inflammatory breast cancer. Primary objective was evaluate response rate. Secondary objectives were time to progression and toxicity profile of neoadjuvant chemotherapy T, A and X in pts with LABC. Methods: Eligibility criteria: Pts with histological confirmation of LABC, ECOG PS ≤ 2, age ≤ 75 years, LVEF > 50%, and adequate bone marrow, renal and hepatic function. Prior systemic therapy, surgery or radiotherapy for breast cancer was not allowed. Pts with invasive bilateral breast cancer were not included. Treatment: T (30 mg/m2) iv day 1, 8 and 15, A (50 mg/m2) iv day 1 and X (1500 mg/m2 o.d.) days 1–14, in a 4 weeks course. This scheme was repeated up to 4 cycles followed by surgery. According to investigator criteria pts receive a maximum of six cycles. Radiotherapy and hormonal treatment are allowed depending on molecular markers. Expression of markers was performed by inmunohistochemistry before chemotherapy. Results: 36 pts were included in this analysis, with a median age of 48 years (25–69). ECOG PS was 0 in 32% of pts and 1 in 68%. Hormonal receptor status was ER+ 43%, PR+ 34% and C-erb2+ 52%. A total of 131 cycles (median 4, range 1–4) were administered. Median relative dose intensity was 86% for T, 91% for A and 93% for X. Two patients are still undergoing treatment; of 34 evaluable pts for efficacy, 11 achieved CR, 22 PR and 1 PD resulting in an ORR of 97% (CI 95%: 92–100). Surgery was performed in 34 pts: 3 (9%) of them achieved pathological CR and one additional patient had non invasive carcinoma. Grade III/IV toxicity per patient was neutropenia (69%), leucopenia (53%), febrile neutropenia (8%), mucositis (14%), diarrhea (11%), nausea/vomiting (6%), dysgeusia (3%) and asthenia (3%). Median follow up time was 8.8 months. Conclusions: T, A and X every 28 days administered during 4 cycles as neoadjuvant chemotherapy in LABC is an active regimen with a manageable toxicity profile before surgery. No significant financial relationships to disclose.
Introducing a new scoring system based on HER2/neu, p53 oncogenes results and mammographic findings for prediction of tumor grade in breast cancer
Authors: Guity M. , Mokri M. , Shakiba M. , Atri M. 
Published: March 2020

10687 Background: During recent years, several oncogenes have been introduced in relation to breast cancer including her2 and P53. These are related with initiation, degree of progression, invasion and prognosis of breast cancer. In this research the rate of positivity of these oncogenes in 150 patients with invasive ductal carcinoma is introduced and the correlation of the results of a new scoring system comprised of mammograms, P53 and her2 with the tumor grade is assessed. Methods: 150 cases of invasive ductal carcinoma of a private clinic were chosen. The diagnosis of cancer and its grade was confirmed by pathology. All patients underwent mammography befor surgery and the results were classified according to BIRADS system to benign (groups of I and II in BIRADS): Score I, suspicious (group III in BIRADS): Score II and malignant (groups of IV and V in BIRADS): score III. P53 and her2 presence were assessed by immunohistochemical studies and the results were classified as negative (score I) and positive (score II). The final score of each patients was calculated by adding scores of all three studies (P53, her2, mammography) which ranged between 3 to 7. Results: The average age of the patients was 48.2 + 11.2 years; most of them were between 30–50 years old. Three had benign mammograms (2%), 81 had suspicious (54%) and 66 had malignant findings (44%). We showed positive P53in 59 (39%), positive her2 in 69 (46%) and high grade tumor in 77 (51%) patients. On scoring, 2 patients gained 3 (1.3%), 36 scored 4 (24%), 53 patients received 5 (35.3%), 37 reached 6 scores (24.7%) and 22 patients received 7 scores (14.7%). Placing scores 3 and 4 in one group and scores 5–7 in another, the sensitivity and negative predictive value of the system for high grade tumors reached 97.7% and 89.5% respectively. By placing scores 3–6 in one group and score 7 in another, the specificity and positive predictive value of the system reached to 100%. Conclusions: The results of mammography, P53 and her2 seems to have a good correlation with tumor grade, meaning when all three parameters are positive, the patients’ tumor is almost always high grade. No significant financial relationships to disclose.
High dose chemotherapy with autologous stem cell rescue as a part of combined modality therapy in stage IIIB inflammatory breast cancer
Authors: Farjami S. , Waheed F. , Liu D. , Seiter K. , Ahmed T. 
Published: March 2020

10694 Background: Despite the improvements related to introduction of neoadjuvant chemotherapy, the prognosis of patients with inflammatory breast cancer remains poor. The purpose of this study was to evaluate the efficacy, feasibility and outcomes of high dose chemotherapy in this group of patients. Methods: Between June 1991 and January 1999, twenty eight patients with pathologically confirmed inflammatory breast cancer were consecutively enrolled in this study. All patients were rendered free of clinically evident disease by using chemotherapy (adjuvant, neoadjuvant or both) either alone or in combination with surgery. Following stem cell collection patients received HD-CT with thiotepa 250mg/m2 days 1, 2 & 3(total dose of 750mg/m2), mitoxantrone 40mg/m2 on day 1 and carboplatin 333mg/m2 on days 1, 2 & 3 ( total dose of 1gm/m2). Previously stored stem cells were infused on the seventh day of HD-CT chemotherapy. Eligible patients received radiation to the chest wall and tamoxifen for 5 years. Results: With median duration of follow-up of 46.9 months( range 15.1–177.2), the median overall survival (OS) and progression free survival (PFS) were 42.5 months (range 9.7–135.7) and 34.8 months (range 3.3–135.7), respectively. The multivariate analysis showed a significantly better EFS and OS in patients with estrogen receptor (ER) positive tumors ( P value ≥ 0.003). Mucositis and Infection were the most severe non-hematological toxicities. Grade four cardiac and pulmonary toxicities developed in one patient. There was no transplant related mortality. One patient developed myelodysplastic syndrome. Conclusions: The results of our study suggest that high dose chemotherapy with thiotepa, mitoxantrone and carboplatin is a safe and efficacious regimen in patients with stage IIIB inflammatory breast cancer. No significant financial relationships to disclose.
Axillary recurrence after negative sentinel node biopsy in patients with breast cancer
Authors: Cassanello G. E. , Xynos F. , Capellino P. H. , Bacigaluppi A. , Betti P. 
Published: March 2020

10700 Background: To evaluate axillary recurrences (AR) in patients with negative sentinel node subjected to no further axillary local treatment. Methods: From June 1st 2000 to April 30th 2005, 219 patients with negative sentinel node (SN) were evaluated and axillary recurrences were assessed. The SN was identified using Isosulfan Blue only. The lymph nodes were evaluated intraoperatively with imprint cytology and with standard H&E staining on permanent sections, sectioning lymph nodes every 3 mm. The false negative of imprint cytology was 6%. The mean age was 69.8 years (range 40–90), the average follow up was 17.6 months (range 1–48). Results: Three axillary recurrences (1.36%) and no distant metastasis were observed. The recurrences occurred 14,26 and 28 months after conservative treatment for ductal carcinoma with 1, 2 and 3 negative sentinel nodes respectively. At the time of recurrence axillary surgery revealed 1 of 11 positive axillary nodes with extra-capsular invasion, 6 of 19 positive axillary nodes with extracapsular invasion and 3 of 15 positive axillary nodes with extracapsular invasion Conclusions: In this short follow-up three axillary recurrence (1.36%) and no distant metastasis have been observed. In the case of axillary recurrences, extracapsular node invasion seems to be the rule. No significant financial relationships to disclose.
CEA as a prognostic factor in locally advanced breast cancer patients undergoing neoadjuvant chemotherapy
Authors: Valeri N. , Battelli N. , Mariotti C. , Santinelli A. , Siquini W. , Gusella P. , Braconi C. , Lippe P. , Cascinu Prof S. 
Published: March 2020

10705 Background: CEA and CA 15.3 are most commonly used to evaluate disease progression in metastatic and recurrent breast cancer. Only few significant studies showed a potential predictive role of CEA and CA 15.3 in adjuvant or neoadjuvant setting. We evaluated the correlation between tumour markers level at diagnosis and outcome in locally advanced breast cancer patients treated with neoadjuvant chemotherapy. Methods: Patients with locally advanced breast cancer (T > 3.5 cm and T4) at diagnosis entered the study. All patients had to have initial negative staging (chest X-ray, abdominal ultrasonography, bone scintigraphy and CT scan), whereas all patients who developed metastatic disease in sites which were uncertain during initial staging were excluded. Tumour markers at diagnosis were considered negative if CEA was inferior to 5 ng/ml and CA 15.3 inferior to 35 U/ml. All patients received neoadjuvant chemotherapy (4–6 cycles with regimens containing Anthracyclines and Taxanes or FEC). Most of patients underwent radical mastectomy followed by sequential radiation therapy and adjuvant chemotherapy and/or hormonotherapy in hormonal responsive patients. Results: Fifty-three patients entered the study. At a median follow up of 73 months, 35 patients were disease free after adjuvant treatment (group A), whereas 18 patients developed metastatic disease during follow-up (group B). At diagnosis 14 patients had CA 15.3 greater than 34 U/ml (7 in group A and 7 in group B), 6 patients had CEA greater than 5 ng/ml (1 in group A and 5 in group B) and 18 patients had CEA or CA 15.3 greater than normal values (7 in group A and 11 in group B).We analyzed DFS and OS in patients with normal (CEA < 5 ng/ml, CA15.3 < 35 U/ml) and elevated (CEA ≥ 5 ng/ml, CA 15.3 ≥ 35 U/ml) tumour markers at diagnosis; DFS (p = 0.001) and OS (p = 0.03) were significantly reduced in patients with elevated CEA at diagnosis; differences were not statistically significant for CA 15.3 (p > 0.05). Conclusions: CEA levels before neoadjuvant treatment could represent an important prognostic factor and may influence the choice of treatment in locally advanced breast cancer patients . No significant financial relationships to disclose.
Docetaxel in advanced breast cancer (BC) in the community setting: Analysis of treatment and prognostic factors in 129 South African patients
Authors: Ruff P. , Pienaar R. , Gudgeon A. , Michaelis F. , Neethling H. 
Published: March 2020

10715 Background: Docetaxel has become a standard of care in BC, initially as salvage therapy, then as front line therapy for advanced disease and now in the adjuvant setting. Patients and Methods: A survey of the use of docetaxel in advanced BC in the community setting included 129 patients (128 females; 1 male) treated by 29 oncologists from 27 centers in South Africa from August 2002 until October 2003. Median age was 51 years (range 25–82 years). Median time between initial diagnosis and treatment was 27 months (range 6 days - 22 years). Although the survey was planned for advanced disease, 10 patients received adjuvant therapy; 59 received 1st line docetaxel and the rest 2nd line or more; major metastatic sites were bone (n = 57), liver (n = 45) and lung (n = 37); 47% patients were ER+, 30% ER- and 23% ER unknown; most had good PS (63 ECOG PS 0, 53 PS 1); 19 patients had no prior chemotherapy, 58 prior adjuvant therapy and 52 prior non-taxane chemotherapy for advanced disease. 62% patients received single agent docetaxel including 75–100mg/m2 3–4 weekly (38%) and 20–50mg/m2 weekly (19%) with 38% receiving docetaxel plus another drug. Results: At 1 year, 88 patients (68.8%) were alive. Log rank analysis showed age >40 years (p = 0.025) and PS 0 (p = 0.0000) were prognostic factors for survival, while post docetaxel chemotherapy (p = 0.062), 1st line vs more advanced disease (p = 0.3557), weekly vs 3–4 weekly docetaxel (p = 1.00), ER status (p = 0.1527) and menopausal status (p = 0.997) were not. Of 59 1st line patients, 40 (67.8%) were alive at 1 year. Age >40 years (p = 0.0015) and PS 0 (p = 0.031) as well as ER status (p = 0.011) and post docetaxel chemotherapy (p = 0.0436) were prognostic factors for survival, while menopausal status (p = 0.0609) and weekly vs 3–4 weekly docetaxel (p = 0.248) were not. 115 patients had 655 adverse events (AEs) including 111 serious AEs (SAEs) in 55 patients. 470 AEs were drug related with 54 SAEs including neutropenia (8), diarrhea (6) febrile neutropenia (5), emesis (5), cellulitis (3) and pneumonia (3). There were no treatment related deaths. Conclusions: Docetaxel alone or in combination is effective and well tolerated therapy in advanced BC especially in patients over 40 years of age with good PS (ECOG 0). Sponsored by Aventis Pharma (South Africa). No significant financial relationships to disclose.
Trastuzumab prolonged administration: Safety and toxicity profile in heavily pre-treated patients
Authors: Tomadoni A. E. , Wainstein R. C. , Rondinón M. N. 
Published: March 2020

10742 Background: HER2 over-expression was found to be an independent prognostic predictor of overall survival and time to relapse in breast cancer patients. Trastuzumab binds to the extracellular domain of HER2 cell receptor, thereby inhibiting the growth of breast cancer cells that over-express HER2. Objective: examine safety and toxicity profile of trastuzumab prolonged treatment (> 6 months) in heavily pre-treated HER2+ metastatic breast cancer patients. Methods: Between February 1999 and April 2005, 20 patients received weekly standard trastuzumab infusion until disease progression or serious adverse events. Population characteristics: median age: 46.6 years (30–65 years), ER+: 47.6%, PR+: 42.8%. Previous treatment: hormonotherapy: 12 patients (60%), two or more lines: 5 patients: (41.6%). All patients received previous chemotherapy: one line: 7 patients (35%), two lines: 10 (50%), three or more lines:3 (15%). Median trastuzumab treatment time was 11 months (6–36 months) Trastuzumab was administered as monotherapy in 5 patients (25%) and in combination in 15 patients (75%): 60% with docetaxel, 26.6% with paclitaxel, and 13.3 % with gemcitabine or vinorelbine Safety was primary trial end point, hence pre-treatment cardiac (baseline LVEF ≥55% by Echo or MUGA scan) and liver function assessment were required; and then, repeated each two months. Results: As regards cardiac adverse events, 2 patients (10%) receiving also docetaxel, developed supraventricular tachycardia reversible with 1 week treatment arrest. After 17 months, trastuzumab was discontinued in one of these two patients due to asymptomatic decrease in LVEF to 35 % (baseline LVEF:65%). An increase in transaninases (per 3ULN) was noted in one patient (5%) after 12 months of treatment. Liver function normalized after two weeks trastuzumab interruption. Allergic phenomena, as hot flashes or chills during first infusion was described in 3 patients (15%). In combination therapy, asthenia (20%), nausea (10%), anemia (10%), foot and hand syndrome (5%) and myalgia (5%) were observed. Conclusions: Prolonged tratuzumab administration in heavily pre-treated patients seems to be a safe approach with predictable profile and reversible toxicity with trastuzumab discontinuance and standard medical care. No significant financial relationships to disclose.