bluuebunny/crossref_metadata_2025 huggingface dataset:
Anastrazole treatment in breast cancer does not cause androgenic effect
Authors: Mundia M. , Ali M. F.
Published: March 2020

10614

Background: Aromatse Inhibitors are a class of drugs that inhibit tumor growth in hormone receptor positive breast cancers in postmenopausal women. They exert their action by inhibiting the enzyme aromatse involved in the last step in conversion of Androgens to estrogens. They are currently used extensively in both advanced and adjuvant treatments. Methods: Clinical Charts of postmenopausal women, with estrogen receptor positive breast cancer, receiving the non-steroidal aromatse inhibitor, Anastrazole 1 mg daily at a community oncology practice were evaluated for androgenic effect of the drug. Review included presence of clinical Hirsutism and serum testosterone levels. Results: There were 33 women, receiving Anastrazole, 29 for adjuvant therapy, and 4 for metastatic disease. Age 51–77years (median: 63 years), Duration of Anastrazole therapy 6 months to 42 months (median: 18 months), There was no Clinical evidence of hirsutism noted. Serum testosterone levels varied from 9 ng/ml to 58 ng/ml. (Normal range: 14–76 ng/ml) in 32 women. 1 woman had a serum testosterone level of 86 ng/ml with no clinical hirsutism. The most common side effect of Anastrazole was arthralgias, seen in three women. Conclusions: Anastrozole 1 mg daily does not appear to cause any clinical androgenic effect, or elevation of serum testosterone levels.

No significant financial relationships to disclose.
Trastuzumab associated with successive cytotoxic therapies beyond disease progression in metastatic breast cancer
Authors: Garcia-Saenz J. , Martin M. , Bueno C. , Sampedro T. , Lopez-Tarruella S. , Puente J. , Villalobos L. , Rodriguez L. , Garcia B. , Casado A. , Diaz-Rubio E.
Published: March 2020

10617

Background: Whether trastuzumab should be continued after tumor progression remains unknown.We describe the activity of successive trastuzumab-containing regimens in patients with HER2-overexpressing metastatic breast cancer, as well as the response rate, time to progression and predictive factors for response. Methods: Descriptive retrospective study of trastuzumab activity in patients with HER2-overexpressing metastatic breast cancer treated at our hospital from 10/1999 to 07/2005. Results: 93 consecutive patients were evaluated obtaining an objective response rate (OR) for first-time administration of trastuzumab of 46.2%; stable disease (SD) 24.7%; clinical benefit (CB) 71%. Median time-to-progression (TTP) was 5 months (range: 1–39+). A total of 47 pts (50.5%) received a second trastuzumab-containing regimen with an OR of 29.8%; SD 21.3%; CB 51.1%; TTP 4 months (range: 1–31). A total of 21 pts (22.6%) received a third trastuzumab-containing regimen; OR 38.1%; SD 23.8%; CB 61.9%; TTP 4 months (range: 1–30+). A total of 10 pts (10.8%) received a fourth trastuzumab-containing regimen; OR 20%; SD 20%; CB 40%; TTP 4 months (range: 1–37). 5 pts (5.4%) received a fifth trastuzumab-containing regimen; OR 0%; SD 60%. Age < 45 years is a significant prognostic factor (p: 0.005, 95% CI, OR 5.6 (1.5–20.6)). A better response rate in the successive trastuzumab-containing regimens was observed, when there was a response in the first regimen: p = 0.04; 95% CI; OR 3.84 (1.07–14.65). With a follow-up of 16,5 months 45 pts (48,4%) are alive. Conclusions: Trastuzumab-containing therapies beyond disease progression in metastatic breast cancer show activity. There were more responses in younger pts. Those pts who had a previous response to trastuzumab therapy were more likely to respond to successive trastuzumab-containing regimens. Additional controlled studies are needed to test this approach.

No significant financial relationships to disclose.
Impact of pre-operative three different regimens on breast-conservation surgery (BCS) and pathological complete response rates (pCR) in locally advanced breast cancer (LABC) in Pakistani patients
Authors: Alidina A. G. , Lal A. , Khan S.
Published: March 2020

10628

Background: Locally advanced breast cancer accounts for 28% (n 350) of all breast cancer cases (1370 patients) treated at our Aga Khan University Hospital over the last 15 years. This is sharp comparison to the US data (only 3–6% of all cases). Methods: Patients with LABC who received surgery upfront were excluded. One hundred and seventy cases receiving PC were evaluated. Patients receiving TAC (taxotere, Adriamycin and cyclophosphamide)chemotherapy (n 60) were evaluated in a prospective Phase II study (2003- ongoing). These were then compared with FAC/AC or CMF regimens given from1998–2005, the data of which were extracted for Breast Cancer Tumor registry. Women were eligible if they were; histological confirmed invasive infiltrating carcinoma, clinical TNM: T3, T4, N2, N3, M0, as per AJCC (6th edition), PS 0–1, with adequate renal, liver and hematological functions. Patients were treated with regimens TAC containing T (75 mg/m2), A (50 mg/m2) and C (500 mg/m2) or FAC: F (500 mg/m2), A (50 mg/m2) and C (500 mg/m2) or A (60 mg/m2) C (600 mg/m2) and CMF: C (600 mg/m2), M (40 mg/m2) and F (600 mg/m2) q3wk 2 to 4 cycles. Type of surgery depended upon the response rates and the patients’ desire. Balance to complete a total of 4–6 cycles of chemotherapy was given in the adjuvant setting. Adjuvant hormone therapy was given for receptor positive cases. Results: Demographics, response rates, BCS and toxicities are reported in table. Conclusions: Locally advanced breast cancer is common in this region, owing to lack of screening. Preoperative TAC chemotherapy leads to impressively higher response rates, pathological complete response rates and probability of BCS, than when compared with FAC/AC chemotherapy or CMF chemotherapy, given in the same setting. Where as survival data of patients with TAC is not available, we feel that this will be superior to AC/FAC or CMF, given higher pathological complete response rates.

[Table: see text]

No significant financial relationships to disclose.
HER-2 status of the primary breast cancer in patients with relapse at least five years after the initial diagnose
Authors: Tomasevic Z. I. , Jovanovic D. , Radosevic-Jelic L. , Tomasevic Z. , Vasovic S. , Stamatovic L. , Jelic S. , Spasic J.
Published: March 2020

10631

Background: HER-2 status of the primary breast carcinoma in the subgroup of patients who relapsed after many years is not well known. The aim of this paper is to determine the HER-2 status of the primary breast cancer in patients with late relapse, defined as local recurrence, distant metastases or carcinoma in the contralateral breast, at least five years after the initial diagnosis Methods: During six month period (June-November 2005) 1256 patients were diagnosed with primary or relapsed breast cancer at the IORS. HER-2 (HercepTest, DAKO) status was determined on the archived pathological specimens of patients with late relapse. Results: One hundred eleven patients (111/1256; 8,8%) were diagnosed with late relapse. At the time of the initial diagnose, majority of patients have been treated for early breast carcinoma. Median age at the initial diagnose was 50 years (33–74). Initial tumor characteristic were: ductal carcinoma 49%; lobular carcinoma 41%;cancer mastitis 6,5%;not reported 3,5%; T1 34%; T2 52%; T3 4,5%; T4 6%;unknown 3,5%; Nodal status: positive 73,5%; negative 23%;not reported 3,5% Steroid receptor status: ER and/or PR positive 59%; both negative 14%; unknown 27%. Median time to relapse is 7 years, (range 5–29), the most frequent first relapse sites were: local recurrence (22%); carcinoma of the contralateral breast (18%); bone metastases (18%). Archived pathological specimens are identified for 63/111 (56,7%) patients and HER-2 status of the those primary breast carcinoma is: 0+ 36,5%; 1+ 34,9%; 2+ 9,5%; 3+ 14,2%; Thirty four patients (30,6%) had disease free interval 10 or more years, and HER-2 3+ in this subgroup is 17,6% (6/34). Conclusions: Long disease free interval in breast cancer patients is usually explained by initial more favorable cancer characteristics. Still, a significant percentage (14,2%) of our patients with median time to relapse of 7 years, initially had breast cancers with HER-2 3+.

No significant financial relationships to disclose.
Primary endocrine therapy with anastrozole for early operable primary breast cancer in the elderly: Early clinical and biological data
Authors: Cheung K. L. , Ying M. W. , Green A. R. , Agrawal A. , Paish C. E. , Winterbottom L. , Ellis I. O.
Published: March 2020

10647

Background: The initial treatment for early operable primary breast cancer (PBC) is surgery. Primary endocrine therapy with tamoxifen has been used in the elderly with estrogen receptor positive (ER+) PBC who refuse or are unfit for surgery. Current randomized data showed superiority of aromatase inhibitors (AIs) over tamoxifen in neoadjuvant, adjuvant and metastatic settings, it is possible that AIs may be a better therapeutic option in this context. We report the early clinical and biological data in using primary anastrozole for ER+ operable PBC in the elderly. Methods: Elderly (> 70) patients with ER+ early operable PBC (< 5cm), who refused or were unfit for surgery, and who had contraindications to tamoxifen, were treated with anastrozole 1mg daily as primary endocrine therapy. All had disease assessable by UICC criteria and received treatment for ≥ 6 months unless they progressed prior. Standard immunohistochemical staining was performed on tumor tissue, obtained by core biopsy, for ER, progesterone receptor (PgR) and HER2. Positivity for ER and PgR was defined by H-score ≥ 50, and HER2 positivity was defined as 3+. Results: Thirty-two patients received anastrozole as described during a two-year period. Thirty (93.8%) patients reached clinical benefit (CB = objective response (OR) + durable stable disease) at 6 months, with 11 (34.4%) ORs (complete response + partial response). Anastrozole was well tolerated with no patients withdrawn due to side effects. All patients had ER+ tumors. The response status at 6 months is stratified according to PgR and HER2 is shown in the table . Conclusions: Early clinical data has shown excellent efficacy and tolerability of anastrozole as primary endocrine therapy for early operable PBC in the elderly. The PgR and HER2 status did not appear to predict response within this group of ER+ tumors, but there was a trend towards a better quality of response (more ORs) for PgR positive/ HER2 negative tumors. Follow-up for longer-term efficacy assessment is continuing.

[Table: see text]

[Table: see text]
Neoadjuvant, biweekly, dose-dense chemotherapy with epirubicin (E) and cyclophosphamide (C) followed by docetaxel (T) in primary breast cancer (BC)
Authors: Cramer E. , Moers C. , Zarghooni V. , Bosse K. , Mallmann P. , Warm M.
Published: March 2020

10656

Background: Primary chemotherapy is established in the treatment of local advanced BC. Two important advances are the chance to detect the clinical responders during the chemotherapy and an increasing rate of breast conserving surgery (BCS). According to the promissing results of dose-dense chemotherapy schedules in the adjuvant setting we tested the benefit of this approach in a primary chemotherapy protocol. Methods: This clinical trial (01/2003–11/2005) enrolled 93 females with advanced (cT2-cT4), non metastatic BC. The pts received four courses of E (90 mg/m2) and C (600 mg/m2) q2w, followed by four courses of T (100/75 mg/m2) q2w. The severe hand-foot-skin reaction NCI-CTG grade 3 during the T courses of the first pts (G1: n = 19) lead to a dose reduction of T to 75 mg/m2 for the following pts (G2: n = 73). During the first four cycles Pegfilgrastim was applied to prevent neutropenic complications. After every two cycles the actual tumor size was measured by clinical and sonographical examination. The clinical and pathological response, the toxicity and the rate of BCS were evaluated. Results: Pathological complete remission (pCR) of the invasive tumors was observed in 7/19 pts (G1) and 17/73 (G2), pathological partial remission (pPR) in 7/19 pts (G1) and 28/73 (G2), minimal response (pMR) in 3/19 pts (G1) and 14/73 (G2), a stable disease in 2/19 pts (G1) and 11/73 (G2). Two pts in group two showed a progressive disease (pPD). Three pts developed neutropenic fever and stopped the chemotherapy after the 5th and 6th cycle, respectively. One patient died after the 8th cycle in neutropenic sepsis. During this trial the main side effect of T was a hand-foot-skin reaction. Conclusions: This neoadjuvant dose-dense chemotherapy is a potent schedule for the treatment of primary BC. Using T with 75 mg/m2 instead of 100 g/m2 is generally better tolerated. The first group of pts treated with T 100 mg/m2 exhibited a higher frequency of pCR (36.8%) compared to the pts treated with 75 mg/m2 (pCR 23.3%), (p = 0.23). But the increased rate of severe side effects lead to an early dose reduction to 75 mg/m2 in this clinical trial.These first promissing results will be improved in an enlarged number of pts.

No significant financial relationships to disclose.
A phase II multicenter study of combination chemotherapy with capecitabine (C) and intravenous (iv) vinorelbine (V) in patients (pts) with pretreated metastatic breast cancer (MBC)
Authors: Davis A. J. , Lewis C. R. , Moylan E. J. , Parnis F. X. , Brew S. E. , Ackland S. P.
Published: March 2020

10665

Background: MBC pts have often already received, or are inappropriate for, anthracyclines and taxanes. 5-Fluorouracil and vinorelbine is an active, well tolerated combination regimen. Capecitabine (C), a fluoropyrimidine carbamate derivative, has the advantage of oral administration. The aim of this study is to determine the efficacy and safety of C and iv vinorelbine (V) in pts with MBC. Methods: Between May 2003-June 2005 21pts with pretreated MBC, maximum of 1 prior metastatic regimen, received C 1000mg/m2 bd day 1–14 and V 25 mg/m2 iv d1+ d8 q21 days. All pts had measurable disease (RECIST), baseline KPS ≥ 80% and adequate baseline organ function. The primary endpoint was response; secondary endpoints were time to progression (TTP), duration of response, survival and safety. Results: Median age was 56 years (range 38–73); median KPS 90%. All pts had received anthracyclines and 62% taxanes. 20pts were evaluable for response and 21 for toxicity. Objective responses were seen in 7/20 (35%) (95% CI 18–57%), including 2 CR, and stable disease (SD) in 4/20 (20%) (95% CI 8–42%). Median duration of response was 6.9 mths (95% CI 4.7–13.1); TTP 5.8 mths (95% CI 2.8–6.8) and survival 12.2 mths (95% CI 8.7–15.7), with a median followup of 12.2 mths. The main toxicity was haematological with 15 episodes of G3 and one G4 neutropenia in 10 pts and 1 pt respectively and 2 episodes of G3 febrile neutropenia in 1 pt. Other G3 toxicities included diarrhoea, fatigue and hypokaleamia in 2 pts each and headache, anorexia, stomatitis, dehydration, and peripheral neuropathy in 1 pt each. There were no other G4 toxicities or treatment related deaths. The median dose intensity of C was 7941mg/m2/wk (85% of intended, range 51–102%) and for V 12.4 mg/m2/wk (75% of intended, range 48–100%). Conclusion: The combination of capecitabine and iv vinorelbine is active and generally well tolerated in pts with pretreated MBC. The recent availability of oral vinorelbine provides an opportunity to explore a fully oral combination chemotherapy regimen for pts with MBC.

[Table: see text]
Pathological response to neoadjuvant chemotherapy for inflammatory breast cancer (IBC). Critical evaluation of Chevallier’s and Sataloff’s classifications
Authors: Baranzelli M. , Cabaret V. , Vanlemmens L. , Desauw C. , Giard S. , Chauvet M. , Belkacemi Y. , Mailliez A. , Deschildre L. , Bonneterre J.
Published: March 2020

10666

Background: The aim of this study was to compare the two most frequently used pathological classifications to assess the response to chemotherapy (CT) in IBC. Methods: The pathological characteristics of 85 inflammatory breast cancers were reviewed. 52 patients (pts) had a post-CT mastectomy , 49 a tumor biopsy before CT and 16 both. Tumor types, grade, hormonal and Her status were evaluated before and after CT, when available. Results: Among 49 pts with initial biopsy, 1 had a high grade intraductular carcinoma and 48 an invasive carcinoma (42 ductular, 5 lobular, 1 mucinous). 27 (56%) invasive tumors were grade 3 and 21 (44%) grade 2, none was grade 1. Median value of mitotic index (Ki 67) was 23%. Hormone receptors (HR) were evaluable for 46 pts; 28 (61%) were negative. 13 (29%) out of 45 evaluable pts were Her2 3+. The pathological response was evaluated according to the Chevallier et Sataloff classifications in the 52 pts with post CT- mastectomy. According to Chevallier there were no grade 1(no microscopic invasive or in situ carcinoma) or 2 (microscopic in situ carcinoma without invasive carcinoma or axillary lymph node metastases), 44 (85%) were grade 3 (invasive carcinoma with fibrosis or sclerosis) and 8 grade 4 (no modification of initial tumor). There was no pathological complete response. According to Sataloff there were 4 grade TA (complete or nearly complete response), 15 (29%) TB (therapeutic response over 50%), 23 (44%) TC (therapeutic response above 50%), 10 TD (no evident therapeutic effect). There were 4 pathological complete responses out of 52 ( 8%). 16 pts had initial biopsy and post chemotherapy mastectomy. According to the OMS clinical classification there were 5 CR, 37 PR, 10 ST. Among the 4 pathological CR according to Sataloff (TA), 2 were CR and 2 PR. Conclusions: In our experience, there was a very poor correlation between the two pathological classifications and between pathological and clinical classifications. A clinical residual tumor can be due to fibrosis only. The classification used for the determination of the pathological response should always be given in clinical studies.

No significant financial relationships to disclose.
In situ evaluation of residual breast tumor and tumor grade using medical hyperspectral imaging (MHSI)
Authors: Freeman J. E. , Yang S. , Panasyuk S. V. , Lew R. A. , Ngo D. , Faller D. V. , Rogers A. E.
Published: March 2020

10677

Background: MHSI is a camera-based technique providing spectral data regarding tissue chemistry for each pixel in an image. Over 30% of women suffer local recurrence after resection. Intraoperative assessment of residual tumor & tumor grade would optimize care. Methods: We studied 42 S-D rats w/ breast tumors induced by gavage of DMBA & 15 controls. Tumors were exposed & resected, intentionally leaving ∼1mm residual tumor pieces. Gross examination, histo-pathology & MHSI (total 335) were performed for tumors, tumor beds after partial and total resection & control sites. A visible light MHSI system (HyperMed,Waltham, MA) w/ 40μm resolution & algorithms based on spectral features of the surgical field were developed and implemented for this study. Gross observation at surgery represents truth, as small tumor pieces were left intentionally by the surgeon and recorded. Samples from tumor beds were collected and histopathologically analyzed. When seen, gross tumor was removed from tumor bed by the pathologist. Results: MHSI performed well at identifying tumor. The kappa statistic(κ) for gross vs MHSI (84%) is significantly higher than κ for gross vs histopathology (76%) where for the κ the estimated asymptotic standard error is 3%. MHSI associates more strongly with gross than histopathology does. 81 tissue samples were separated into histologic grade: 0 = normal, 1 = benign tumor, 2 = intraductal Ca, 3 = papillary & cribiform Ca, 4 = papillary & cribiform Ca with invasion &/or comedo Ca. The imaging team (blinded) assigned tumor grade to each MHSI image. Statistical analysis defined 3 histologic groups: 9 normal (grade 0) tissue, 18 benign & intraductal tumors (grades 1–2), 54 advanced tumors (papillary, cribiform with invasion/comedo Ca, grades 3–4). Both histopathology & MHSI identified all 9 normal samples. Of 18 samples in group 2 (benign/intraductal by histopathology), 17 were qualified as benign/intraductal by MHSI (94% sens) & 1 as advanced. Of 54 samples with adv tumors by histopathology, MHSI identified 48 (89% sens) as advanced & 6 as intraductal. Conclusions: MHSI may provide convenient intraoperative, near real-time images with useful data about residual tumor & tumor grade. Human trials are planned.

[Table: see text]
Pilot study of capecitabine combined with celecoxib (CapCel) for the treatment of far advanced metastatic breast cancer (MBC) patients (pts)
Authors: Fabi A. , Milella M. , Malaguti P. , Papaldo P. , Ferretti G. , Carlini P. , Gelibter A. , Felici A. , Sperduti I. , Cognetti F.
Published: March 2020

10680

Background: COX-2 is overexpressed during cancer progression in several solid tumors, including breast cancer, and constitutes an attractive therapeutic target. Selective COX-2 inhibitors, such as Celecoxib, have been successfully combined with fluoropyrimidine-based regimens, resulting in a lower-than-expected hematologic, GI, and skin toxicity rate. Methods: MBC pts who had progressed after at least one chemotherapy regimen for metastatic disease were eligible for the study. Capecitabine was administered at the starting dose of 1500–2000 mg/m2 daily for 14 days q3 wks. Celecoxib was administered at 200 mg b.i.d., continuously, starting on day 1. Dose escalation to Capecitabine 2000 or 2500 mg/m2 was allowed in the absence of toxicity > G1. Results: To date, 22 pts (median age: 55 yrs, range 35–81; ECOG PS 0: 21 pts) have been accrued; all pts had MBC and the majority had received adjuvant chemotherapy and hormonal treatment in the adjuvant and/or metastatic setting; all pts had been exposed to anthracyclines and/or taxanes. CapCel was administered as 2nd-, 3rd-, or ≥ 4th-line chemotherapy in 3, 10, and 9 pts, respectively. Capecitabine starting dose was 1500 mg/m2 in 9 pts and 2000 mg/m2 in 13 pts. Median number of cycles administered was 5 (range: 1–15). Toxicity was negligible: 1 pt experienced G3 neutropenia, 2 pts G3 skin/nail toxicity, and 1 pt G3 liver toxicity; all other toxicities were of grade ≤2. No Celecoxib-related GI or cardiovascular toxicities were observed. Capecitabine dose was escalated from 1500 to 2000 mg/m2 in 3/9 pts and from 2000 to 2500 mg/m2 in 2/13 pts, respectively, and reduced from 2000 to 1500 mg/m2 in 4/13 pts. Twenty pts are currently evaluable for response: 2 pts had PR (duration 48 and 49 wks, respectively), 15 pts had SD (median duration: 20 wks, range 12–44), and 3 pts progressed on therapy, for an overall clinical benefit rate of 40%. Median survival has not been reached. Conclusions: Overall, these preliminary results indicate that CapCel is extremely well-tolerated and has significant anti-tumor activity in a population of far advanced MBC pts. The study will continue to reach the projected accrual of 45 pts.

No significant financial relationships to disclose.
Weekly paclitaxel in Japanese women with metastatic or advanced breast cancer
Authors: Rai Y. , Tajima T. , Tamura K. , Morishita Y. , Taki T. , Hisamatsu K. , Ito Y. , Seriu T.
Published: March 2020

10702

Background: Weekly administration of paclitaxel (WP) has been reported to be at least as well-tolerated and effective as conventional tri-weekly treatment (TP). The present study was to evaluate the efficacy and safety of weekly paclitaxel treatment for japanese women with metastatic or advanced breast cancer. Methods: Eligibility criteria included < 75 years of age, histologically-proven advanced or recurrent breast cancer, and performance status (PS) of 0 to 2. Patients were scheduled to receive at least one course of paclitaxel 100 mg/m2/week for 6 consecutive weeks followed by 1 week off. The present WP results were compared with the previous TP data generated by the same trial group in Japan. In the TP group, paclitaxel 210 mg/m2 was given every 3 weeks up to 3 cycles or more until tumor progression or severe toxicity was observed. Results: From December 2002 to July 2005, 69 patients were enrolled into the study of WP and 68 were eligible for evaluation. All were previously treated, and 51 of 69 patients (73.9%) had received anthracyclines prior to this study. The median age was 55 years (range 27–74), and 66 patients (95.7%) had PS of 0–1. Sixty nine patients have been analyzed for efficacy and toxicity by the evaluation committee. The median dose intensity was 81.25 mg/m2 per week. In total, 270 courses of WP were administered (median 3 courses; range 1–13). Three patients entered into complete remission (CR) and 28 achieved partial response (PR) by the WHO response criteria with a response rate (RR) of 44.9%, which is similar to RR in the historical TP group (RR of 33.9% in 62 Patients). Median duration of response was 238 days (range 91–631). Time to progression was 193 days. It is of note that grade 3–4 neutropenia was observed less frequently in WP as compared with TP (37.7 vs. 93.3%). Other major toxicities including peripheral neuropathy (PNP) appear to be similar between the two regimens through all toxicity grades of PNP (WP and TP group; 89.9% and 93.3%, respectively). Conclusion: WP appears to have similar or better efficacy with better toxicity profile as TP in patients with metastatic or advanced breast cancer.

No significant financial relationships to disclose.
First-line treatment of metastatic breast cancer with weekly abraxane (nab-paclitaxel: a 130 nm albumin-bound paclitaxel particle): A preliminary analysis of the phase II international oncology network ION-04–012 study
Authors: Mirtsching B. , Chidiac T. , Cosgriff T.
Published: March 2020

10707

Background: Abraxane (paclitaxel protein-bound particles) by intravenous weekly administration schedule has been demonstrated to be active and well tolerated in patients with metastatic breast cancer (MBC) refractory to prior taxane therapy. The purpose of this Phase II, open-label, non-randomized study is to evaluate the efficacy and safety of Abraxane administered weekly to patients with locally-advanced unresectable breast cancer (LABC) or MBC as first-line treatment. Methods: Patients ≥ 18 years with histologically confirmed LABC or MBC received Abraxane (125 mg/m2) by 30 minute IV infusion on days 1, 8, and 15 for the first 3 weeks of each 4-week cycle. HER2-positive patients received concurrent Herceptin given weekly throughout therapy, 4 mg/kg on week 1, and 2 mg/kg on subsequent weeks. Results: From March 11, 2005 to January 4, 2006, 28 patients were enrolled and 27 received study medication (included in this preliminary analysis). Patient accrual continues. Patient characteristics included: gender (M/F) 0/27, median age 60.5 years (range 36–83), ECOG performance status (0–1) 13/14, and HER2 status (±/missing) 6/18/3. A total of 285 cycles have been administered (median 3 [range 1–8]) with a median dose of 125 mg/m2 (range 0–130 mg/m2) and 6 dose modifications have occurred due to toxicity. Eighteen patients are still on study. CTC hematologic toxicities were grade 3 leukopenia (3.7% of patients) and grade 3 neutropenia (7.4%). Grade 3 nonhematologic toxicities were gastritis (3.7%), peripheral sensory neuropathy (7.4%), arthralgia (3.7%), and bone pain (3.7%). No grade 4 nonhematologic toxicities occurred. Conclusions: Preliminary data show that Abraxane given weekly at 125 mg/m2 (with or without Herceptin) for first-line treatment of MBC is well tolerated. Patient accrual continues in this study. Updated analysis of this study will be provided at the meeting.

No significant financial relationships to disclose.
Phase II study of capecitabine (X) as single agent in elderly patients (p) with metastatic breast cancer (MBC): Final results
Authors: Zamora P. , Álvarez de Mon M. , Calvo L. , Jara C. , Virizuela J. A. , Yubero A. , Chacón J. , Mira J. , González Barón M.
Published: March 2020

10709

Background: X is a selectively tumour-activated fluoropyrimidine active in solid tumours. Twice-daily oral administration of X enables chronic dosing that mimics a continuous infusion of 5-FU. In p with pretreated advanced BC, X is effective as monotherapy and also in combination with other agents. Some studies have shown that safety data of X in general population also apply to elderly p. The objective of this study is to evaluate the toxicity profile and response rate of X in elderly p with MBC. Methods: P histologically confirmed of breast adenocarcinoma, metastatic disease, age ≥70 years, ECOG PS <2, measurable disease and adequate bone marrow, renal and hepatic functions were included. Prior X, CNS metastases or radiotherapy within 4 weeks of treatment start was not allowed. P received X monotherapy 1250 mg/m2 b.i.d. (X 950 mg/m2 in p with creatinine clearance 30–50 ml/min), days 1–14 every 3 weeks for a maximum of 9 cycles. P can be previously treated with chemotherapy, hormonotherapy or radiotherapy for the metastatic disease. Clinical response was evaluated every 3 cycles (RECIST). Results: Twenty three p were enrolled with histology confirmed adenocarcinoma, median age was 77 years old (68–88) and ECOG PS 0/1 in 33%/67% of p. Surgery was performed in all p. Adjuvant chemotherapy and hormonotherapy was administered in 65% and 74% of p, respectively. Prior chemotherapy for MBC was administered in 13.0% of p. Median number of metastatic lesions was 3 (90% with ≥2 sites), in bone (57%), lung (43%), liver (43%) and lymph nodes (38%) mainly. A total of 117 cycles (median 4, range 1–9) were administered. Median RDI was 86% and 100% for X 1250 mg/m2 and X 950 mg/m2, respectively. All p were evaluable for toxicity. Grade III/IV toxicity per patient were hand-foot syndrome (13%), asthenia (13%), mucositis (9%), diarrhoea (9%), neutropenia (4%), thrombocytopenia (4%), nausea (4%) and vomiting (4%). Efficacy analysis: over 16 evaluable p, 2 achieved PR, 7 SD and 7 PD, resulting in an ORR of 13% (95% CI: 0–29). Median TTP was 7.5 months (95% CI: 4.5–10.5), median OS was 13.3 months (95% CI: 9.6–16.9) and one year survival 55.5% (95% CI: 33.7–77.2). Conclusions: Twice daily oral X seems to be an effective and well tolerated treatment in pretreated elderly MBC p.

No significant financial relationships to disclose.
Phase II trial of nanoparticle albumin-bound paclitaxel (ABX) + capecitabine (XEL) in first line treatment of metastatic breast cancer (MBC)
Authors: Mintzer D. , Schwartzberg L. S. , Cobb P. , Henry D. , Epperson A. , Fortner B. V.
Published: March 2020

10731

Background: ABX and XEL both have substantial single agent activity in MBC. Taxane and anti-metabolic doublets improve response rate and TTP compared to singlet therapy. ABX given weekly has excellent safety and efficacy profile with maintenance of dose intensity. We designed this study to test the safety and efficacy of ABX + XEL given in a novel combination schedule. Methods: This phase II, multicenter open label study utilized ABX 125 mg/m2 IV on day 1, 8 and with no premeds and Xeloda 825 mg/m2 PO days 1–14 every three weeks. Entry criteria include measurable MBC by RECIST, no prior chemo for metastatic disease, > 6 months since adjuvant fluoropyrimidine and paclitaxel. A total of 50 patients (pts) are scheduled to be enrolled. Primary endpoint is objective response rate. Results: To date, 14 patients have entered on study. Safety analysis prespecified by the protocol is completed in the 1st six patients. No unique, unexpected or grade 4 toxicities have occurred. Two patients have grade 3 hand-foot syndrome, one had grade 3 neutropenia and one had grade 3 fatigue. Enrollment is continuing without change in dose/schedule. Response data is available in the first two cycles of therapy in 8 patients. At this point, two pts have achieved PR, four have stable disease and two have progressive disease. Conclusions: The combination of weekly ABX plus daily XEL orally at clinically effective doses is safe and shows preliminary evidence of efficacy. Complete enrollment of this trial is expected by May 2006 and updated results will be presented.

[Table: see text]
Early results of a phase I clinical trial of capecitabine in combination with CPT-11 for metastatic breast cancer (MBC) pre-treated with anthracycline and taxane
Authors: Kashiwaba M. , Inaba T. , Hayakawa Y. , Takiyama I. , Wakabayashi G.
Published: March 2020

10750

Background: Capecitabine (C) is administrated with other drugs to improve response rate of single agent and to extend time to progression for MBC expecting up-regulation of thymidine phosphorylase activity. Conversely, administration of CPT-11 (TOP) against MBC is less common while superiority of combination therapy C and TOP is established in metastatic setting of colorectal cancer. Therefore a phase I clinical trial was conducted to determine the recommended dose (RD) of TOP administrated with fixed dose of C (1,657 mg/m2/day) against MBC pre-treated with antracycline and taxane. Methods: Five dose level of CPT-11 (80, 90, 100,110 and 120 mg/m2) on Day 1 and 15 and C (1,657 mg/m2/day) on Day 1–21 were given every 28 days. A standard “3+3” design is used and dose limiting toxicity is defined in cycle 1. Results: To date, five patients were enrolled from October 2005 to January 2006 and 8 cycles were administrated without grade 3–4 toxicities as followed: 3 pts in Level I (TOP: 80 mg/m2), 2 pts in Level II (TOP: 90mg/m2). 5 pts have archived a response: PR in 1, SD in 2. Conclusions: Combination therapy C and TOP against MBC pre-treated antracycline and taxane is well-tolerated. Enrollment will continue until the RD is identified for further phase II clinical trial.

No significant financial relationships to disclose.
The analyses of disease free survival and overall survival in premenopausal and postmenopausal axillary node negative breast cancer patients
Authors: Bajic N. D. , Scepanovic D. D.
Published: March 2020

10757

Background: The aim of this study was to analyse in which order known traditional prognostic factors predict disease free survival (DFS) and overall survival (OS) in breast cancer patients (pts) who are patohystologicaly axillary node negative. Methods: From 1998 till 2004, 258 patients were treated of axillary node negative breast cancer. We analysed 3 and 5 years (yrs) DFS and 3 and 5 yrs OS for all patients as well as for premenopausal (96 pts, 37%) and postmenopausal (162 pts, 63%). The mean follow-up time for DFS was 60 months (mo) (min 30, max 136 mo) and for OS was 66 mo (min 36, max 140 mo). As prognostic factors for DFS and OS, age, tumour size, HG as well as adjuvant treatment (locoregional and systemic) were analysed accordingly. Fifty two patients (20%) were HG1 while 190 pts (74%), were HG2 & 3; 30 pts (11%) had tumour up to 1cm and 157 pts (61%) had tumours up to 3cm and 71 pts (28%) above 3cm. Radical mastectomy was performed in 92 pts (36%) while conservative surgery were performed in 166 pts (64%). Systemic therapy was applied in 224 pts (87% of which 57% were treated with hormonotherapy). Results: 3 yrs DFS for 258 treated pts were 87% - there was no statistically significant difference among pre- and postmenopausal pts; 5 yrs DFS were 73% with no statistically significant difference among pre- and postmenopausal group of pts (p > 0.05). 3 yrs overall survival were 94% and 5 yrs 80% with no statistically significant difference among pre- and postmenopausal pts (p > 0.05). There were statistically different DFS and OS among those pts treated with adjuvant radiotherapy as well as for those with adjuvant systemic therapy in both group of pts (p < 0.001). Also as independent prognostic factor for DFS and OS were HG (Cox regression model). Conclusions: Although, HG and adjuvant therapy are the most important prognostic factors for DFS and OS in premenopausal and postmenopausal patients, we found that there is no statistically significant difference between the groups respectively. However, life-expectancy for premenopausal patients is longer. Therefore further adjuvant therapy research is needed to achieve better DFS and OS in this group of pts.

No significant financial relationships to disclose.
Clinical and pathological characteristics of basal -like breast carcinomas
Authors: Gago F. , Ciocca D. R. , Mendiondo B. , Orozco J. , Tello O.
Published: March 2020

10768

Clinical and pathological characteristics of basal -like breast carcinomas. Background: Genetic studies have revealed different subtypes of breast carcinomas with particular molecular characteristics. Basal-like breast carcinomas are characterized by negative hormonal receptors and negative HER-2 receptor. We have compared basal-like breast carcinomas with a randomized control population selected from our data base of breast cancer. Methods: From 2127 breast invasive carcinomas, 716 were evaluated with immunohistochemical methods, considering the expression of estrogen receptors, progesterone receptor, HER-2 and p53 protein, between 1989 and 2005. According to the molecular classification the results were: 1) Luminal 398 (55.6%), 2) HER- 2 positive: 193 (26.9%) and 3) Basal-like 124 (17.5%). We retrospectively analyzed the age at diagnosis, menopausal status, tumor size, histological grade, histopathology, lymph node status, stage and the evolution of the breast cancer. The average follow-up was 66.2 months. The control group consisted of 170 patients. The statistical analysis was performed with chi-square test, Fisher’s test and the non parametric test of the Mac Nemar’s signs. Results: The median age at diagnosis was 52 years old. This is lower than the average age of the Tumor Register of Mendoza, that is 60 years (p: < 0.01). The basal-like carcinomas predominated in premenopausal women (p = 0.07), and had a higher proportion of high tumor grade (p ≤ 0.0001) and expression of p53 protein (p=0.01). There were not significant statistical differences concerning the tumor size, the lymph node status, histopathology, and the stage at presentation. The 5-year disease-free survival (DFS) of basal-like breast carcinomas was 71.7% and the 5-year overall survival (OS) was 83.3%. Whereas the DFS for the control group was 77.3% and the OS was 87.3%. Conclusions: The basal-like breast carcinomas are characterized by having a younger age at presentation, predominating in premenopausal women, and presenting a high tumor grade with overexpression of p53 protein.

No significant financial relationships to disclose.
Bin1 expression is lost in breast cancer
Authors: Ghaneie A. , Duhadaway J. B. , Zemba-Palko V. , Prendergast G. C.
Published: March 2020

10772

Background: Immune evasion is a major factor that limits the success of current treatment strategies with cytotoxic agents and immune therapy for breast cancer. Elevation of the immunomodulatory enzyme IDO in tumor cells was recognized as a mechanism of immune escape. Studies show that IDO is under genetic control of Bin1. Bin1 is a MYC-interacting adaptor protein which is attenuated in many malignancies and mouse knockout studies indicate that Bin1 loss elevates the STAT1- and NF-kB-dependent expression of IDO, driving escape of oncogenically transformed cells from T cell-dependent antitumor immunity. Mouse studies show that small-molecule inhibitors of IDO cooperate with cytotoxic agents to elicit regression of therapy refractory tumors. These findings suggest that Bin1 loss promotes immune escape by deregulating IDO and that IDO inhibitors may improve response to cancer chemotherapy. Methods: A cohort of breast cancer specimens collected at our institution over a five-year period was used for this retrospective study. The cohort consists of 56 specimens of early stage and 37 specimens of advanced stage ductal adenocarcinomas of the breast. Using immunohistochemistry, specimens were examined for the loss of BIN1 expression. Results: Bin 1 was lost in a significant fraction of breast cancer specimens. In the early stage group 76% had loss of nuclear expression and 23% loss of cytoplasmic expression. In the advanced stage group 84% had loss of nuclear staining and 38% had loss of cytoplasmic staining. Conclusions: Bin1 was lost in a significant fraction of breast cancer specimens. This finding indicates that loss of Bin 1 may play a significant role in immune evasion in human breast cancer. Animal studies have shown that loss of Bin1 can be antagonized by IDO inhibitors. This could have a significant implication for the treatment of human breast cancer. Immune escape induced by Bin1 loss could be restored through the administration of immunomodulators such as 1MT (1-methyltryptophan) in combination with chemotherapy. This could lead to a novel approach in the treatment of breast cancer.

No significant financial relationships to disclose.
Detection of doxorubicin cardiotoxicity in patients with breast cancer by 99mTc-MIBI myocardial perfusion tomography
Authors: Morales-Vasquez F. , García S. , Lopez-Basave H. , Altamirano-Ley R.
Published: March 2020

10775

Background: Cardiotoxicity is a well-known side effect of several cytotoxic drugs especially of the anthracyclines and can lead to long term morbidity. Endomyocardial biopsy is the only specific test for early diagnosis of anthracycline-induce toxicity. Efforts are continuing on finding a more sensitive and reliable predictor of eventual clinic cardiac dysfunction. Therefore, it is crucial that careful monitoring to identify those patients patients who are at risk of developing unpredectible and some times-irreversible dysfunction. Serial measurement of left ventricular ejection fraction by radionuclide angiography remains a useful and widely adopted modality in monitoring patients that are receiving doxorubicin. Objective: To investigate the value of 99mTc-MIBI myocardial perfusion tomography to detect myocardial damage in patients with breast cancer under chemotherapy. Methods: Thirty patients were examined from May to December 2000 by electrocardiogram (ECG), nuclear angiography for detecting left ventricular ejection fraction (LVEF) and 99mTc-MIBI myocardial perfusion was performed before chemotherapy and after chemotherapy. Results: Fifteen patients were treated by continuos infusion over 24 hr, nine patients over 48 hr and 6 patients were treated by bolus. The patients presented with a decrease of > or = 9% in absolute ejection fraction at 200–320 mg/m2 with 99mTc-MIBI and 5% with nuclear angiography. Gated myocardial perfusion scintigraphy results were abnormal in four patients (12.9%). All patients were treated by continuos infusion and the radiotherapy was absent. Other factors were investigated: hypertension, diabetes, smoker and obesity. Conclusions: 99 mTc-MIBI studies are helpful in the assessment of doxorubicin cardiotocixity. Anthracyclines induced myocite injury symptomatic or asymptomatic; uptake at intermediate cumulative doses identifies patients at risk of cardiotoxicity before ejection fraction deteriorates. The 99-mTc-MI BI imaging may be a sensitive method for non invasive visualization of myocardial cell damage and useful in the early diagnosis of specific heart muscle disease. Doxorubicin cause silent myocardial ischemia.

No significant financial relationships to disclose.
Multicenter, prospective study of radiotherapy without surgery after AC followed by weekly paclitaxel for patients with inflammatory breast cancer: SBCCSG-04 study
Authors: Tabei T. , Sato K. , Inoue K. , Nakano S. , Kai T. , Futsuhara K. , Yamashita S. , Saito T. , Kuroda T. , Suemasu K.
Published: March 2020

10783

Background: Inflammatory breast cancer (IBC) is a rare and aggressive disease with a dismal outcome. It is still an open debate whether surgery is beneficial for patients with IBC. This study was conducted to evaluate treatment results when patients were treated by chemotherapy and radiotherapy (CRT) alone. Methods: 52 pts with nonmetastatic IBC were enrolled for a prospective registration trial from 9/01–11/04. A diagnosis required the presence of erythema, ridging, or peau d’orange, with or without dermal lymphatic invasion (DLI). All patients were invited to participate for an experimental protocol; 4 cycles of AC and 12 cycles of weekly paclitaxel (80 mg/m2) followed by radiotherapy. In patients who did not agree to the protocol, the decision about treatment was left to the patients/investigators. The primary endpoint was distant-disease-free survival, and the further endpoints were locoregional relapse (LR) and overall survival. Results: The mean follow-up was 25.7 months. 24 pts (46.2%) were planned for the protocol, but one pt (4%) was receipt surgery. Otherwise, 18 (64%) out of 28 pts have accepted mastectomy. The 2-year distant-disease-free, LR, and overall survival in patients treated with and without the protocol was 35.2 vs 61.0% (HR = 2.4, 1.1–5.3) and 55.2 vs 83.6% (HR = 2.9, 1.1–7.8), respectively. Surgery was not associated with the risk of LR (p = 0.48). There was marginally worse prognosis in patients with DLI. Conclusions: There was a limitation because this comparison had not been conducted a randomized fashion. However, CRT alone would be a feasible treatment schedule for a moderate percentage of patients with IBC.

No significant financial relationships to disclose.
Experimental study on Chinese ink as the dye for the sentinel lymph node biopsy
Authors: Wang S. , Xu K. , Liu X. , Zhou Q. , Geng Q. , Geng Q.
Published: March 2020

10785

Background: Sentinel lymph node biopsy (SLNB) is a very important method in detecting lymph nodes metastasis. There are several methods developed to detect sentinel lymph node. In this study, we will research on sentinel lymph node biopsy (SLNB) by using Chinese ink and study on its feasibility, clinical value and suitable concentration. Methods: Forty-two female rabbits were randomly divided into seven groups with 12 sides of mammaries (6 animals) in each group.The second mammary and the armpit of the same side were anatomized and injected 0.1 ml different dyes (1% isosulfan blue, 0.1%, 1%, 10%, 20%, 50%, 100% sterilized Chinese ink) at the base of the second mammary. We observed the dying time of the sentinel and the second lymph nodes and the fading time of the dying nodes. The pathological and histological examination of the sentinel lymph nodes were conducted in 5 minutes,1 hour and 2 weeks after the nodes were dyed by ink, respectively. The rabbits’ hearts, lungs, livers and kidneys were detected pathologic changes. Results: There was no obvious difference among different concentration ink on the dyeing time of the sentinel and second lymph nodes (P > 0.05),but distinctively different from 1% isosulfan blue (P < 0.05). There was no obvious difference between groups on the number of the dyed nodes (P > 0.05). But the nodes dyed by 0.1% ink were dyed too lightly to be found. The average fading time of the nodes dyed by 1% isosulfan bluewas 33.9 minutes, and the nodes dyed by ink were still dyed deeply 2 weeks after the experiment. The pathologic examination showed that the carbon aggregated in the lymph nodes sinus 5 minutes after the nodes were dyed, but was phagocytosed by Macrophage (MΦ) 1 hour after dyed. The groups (0.1%, 1%, 10% ink) showed good histology image, however, groups (20%, 50%, 100% ink) showed too much carbon aggregation to disturb the observation. There were no difference in blood routine and pathologic change between these two groups. Conclusions: Chinese ink of concentration 1% to 10% is a useful dye of SLNB according chromaticity, histological observation and security. This dye had latency clinical value and was a new type of the dye for SLNB.

No significant financial relationships to disclose.