bluuebunny/crossref_metadata_2025 huggingface dataset:
Circulating tumor cells (CTCs) detection in a randomized phase II trial of neoadjuvant chemotherapy for large operable and locally advanced breast cancer (REMAGUS 02): Preliminary results
Authors: Pierga J. Y. , Mathiot C. , Extra J. M. , Tresca P. , Asselah J. , Sigal-Zafrani B. , Brain E. , Diéras V. , Mignot L. , Marty M.
Published: March 2020

10637

Background: The presence of CTCs in blood from metastatic breast cancer patients before first line chemotherapy and persistence of CTCs after initiation of treatment, are predictive of shorter overall survival (Cristofanilli M; et al, 2005, J Clin Oncol 23:1420–1430). CTCs could be used as a surrogate marker. The aim of this study was to determine if CTC were present in the blood of patients who received neoadjuvant chemotherapy (CT) for large operable and locally advanced breast cancer, before initiation of CT (preCT) and at the end of CT before surgery (postCT). Methods: 7.5 ml of blood were obtained on CellSave tube from patients included in an ongoing randomized phase II trial. All patients received 4 cycles of Epirubicin-Cyclophosphamide every 3 weeks followed by 4 cycles of docetaxel associated with or not trastuzumab for HER2 positive patients and with or not celecoxib for HER2 negative patients. CTCs were immunomagnetically separated and fluorescently stained with the CellSearch kit. Cells were classified using the CellSpotter Analyzer as CTCs if they stained positive for DAPI (nuclear dye), and cytokeratin 8, 18 and 19, and if they stained negative for the leucocyte-specific antibody CD45. Results: From 10/2004 to 12/2005, preCT blood samples were obtained in 60 patients, analyzed in 56 for technical reasons. At least one CTC was detected in 15/56 (27%, CI 95%: 15.5–38.5%), 1 to 17 cells per sample (median 1.5). With a threshold of 2 cells, 8/56 (14%, CI 95%: 5–23%) patients were classified positive. At time of analysis, pre CT and post CT samples from the same patient were available for 19 patients. Six had >1 CTC/sample before CT (31.5%) and only one (1/6, 17%) remained positive after CT. Thirteen were negative for CTC before CT and 2/13 (15%) became positive after CT, with only one cell per sample. Conclusions: CTCs can be detected in blood of patients with large operable or locally advanced breast cancer before initiation of neoadjuvant CT and can be monitored during treatment. Longer follow-up and a larger number of patients are expected before correlating these data with tumor response and survival.

No significant financial relationships to disclose.
Liposomal doxorubicin (M) plus gemcitabine (G) as first line treatment in metastatic breast carcinoma: A phase I-II study
Authors: Colomer R. , Tusquets I. , Calvo L. , Dorca J. , Adrover E. , Sanchez-Rovira P. , Rifa J. , De La Haba J. , Virizuela J. A. , Beltran M.
Published: March 2020

10651

Background: We designed a phase I-II trial to determine the combination dose of liposomal doxorubicin (Myocet) plus gemcitabine (Gemzar), and to evaluate the safety and feasibility of the regimen Methods: Patients with histologically confirmed breast cancer, untreated distant metastasis, age >18 years old, left ventricular ejection fraction (LVEF) >50% and adequate bone marrow, renal and hepatic function were included in the study. Patients received up to six cycles of treatment. No G-CSF support was used prophylactically. LVEF was repeated at 3, and 6 months, and every 6 months thereafter. Results: Phase I: After 6 patients, the recommended dose was M (55 mg/m2) D1 and G (900 mg/m2) D1 and 8, administered every 21 days. Phase II: 53 patients have been enrolled; 52 are included in the safety analysis and 42 in the efficacy analysis. The median age of the population was 61 years of age (32–79). ECOG PS was 0 in 55%, 1 in 41%, 2 in 4%. Postmenopausal status in 87%. Main histology was ductal carcinoma (85%). Prior adjuvant anthracyclines had been administered in 19 cases (median dose of doxorubicin: 300 mg/m2, or epirubicin: 425 mg/m2). Metastasic lesions were in liver (25), lung (17), bone (16), and lymph nodes (25). Patients received a median number of 5 cycles (range 1–6). Median relative dose intensity was 83% for M and 75% for G. Grade III-IV hematologic toxicity per administered cycles was: leukopenia (21.9%), neutropenia (31.2%), febrile neutropenia (4 %), and thrombocytopenia (7.4%). Grade III-IV non-hematologic toxicities were stomatitis (4.8%), nausea (1.7%), vomiting (2.2%), asthenia (2.6%) and diarrhea (0.8%). Thirteen of 52 pts (25%) had alopecia grade III-IV. No signs or symptoms of cardiac impairment have been seen. An objective response rate of 62% was obtained (95% CI: 45.6- 76.4%). Two patients had complete response (4.8%), 24 partial response (57.1%), 10 stable disease and 6 progressive disease. The response rate was similar in patients with or without previous adjuvant anthracyclines (68.5% and 61%, respectively). Conclusions: The combination of liposomal doxorubicin plus gemcitabine has high efficacy and low toxicity in advanced breast cancer patients, and may be a valuable option in patients that have received adjuvant anthracyclines.

[Table: see text]
Ten-year experience with weekly chemotherapy in metastatic breast cancer patients: Multivariate analysis of prognostic factors
Authors: Nistico’ C. , Cuppone F. , Bria E. , Giannarelli D. , Mottolese M. , Novelli F. , Natoli G. , Astorre P. , Terzoli E.
Published: March 2020

10652

Introduction: Weekly administration of chemotherapy represents an emerging option for the treatment optimization of metastatic breast cancer (MBC). Moreover, evidences suggest a intriguing mechanism of action for weekly paclitaxel, which involves pro-apoptotic and anti-angiogenetic pathways. In order to identify clinical and biological prognostic factors for weekly chemotherapy outcome, we performed a multivariate analysis in a 10-years experience of weekly 1st line chemotherapy for MBC patients. Methods: The original databases of phase II trials of MBC patients undergone 1st line weekly chemotherapy were collected. Clinical and biological co-variables were screened for the eventual relationship with time to progression (TTP) and overall survival (OS) into a Cox model. Results: From 1990 to 2003, 184 patients were enrolled in 3 consecutive phase II studies, to evaluate activity and tolerability of weekly epirubicin with lonidamine, or vinorelbine or paclitaxel, for 24 weeks. All patients were evaluable for clinical variables, while histological samples were available in only 40 patients. At a median follow-up of 24 months, median TTP was 9 months (95% CI 8–10) and median OS 34 (95% CI 24–42). Independent variables were: response (HR 2.34, p < 0.0001), receptor status (HR 1.62, p = 0.01) Performance Status (PS) (HR 2.31, p < 0.0001) for TTP, and response (HR 1.86, p = 0.005), PS (HR 2.81, p < 0.0001), dominant metastatic site (HR 2.27, p < 0.0001), enrollment period (HR 2.51, p = 0.001) for OS. Although no biological factors entered the Cox model due to the small sample size, some sub-populations showed negative trend in survival. Conclusions: In our series of patients undergone weekly chemotherapy for MBC, independent prognostic factors for survival improvement were responders, PS 0–1, non-visceral dominant metastatic site, and enrollment period. Further greater populations are needed to extensively screen for biological prognostic factors.

No significant financial relationships to disclose.
Continous low dose oral chemotherapy administration in heavily pretreated breast cancer patients
Authors: Pavese I. , Di Palma M. , Capuano G. , Satta F.
Published: March 2020

10664

Background: The efficacy and the antiangiogenic effect of low dose continous (metronomic) administration of chemotherapy are well known. In thi study we tested the clinical activity of oral Ciclophosphamide (CTX) and Methotrexate (MTX) in advanced breast cancer (ABC). Methods: From november 2004 to september 2005 35 ABC patients were enrolled. Median age 59 (range 36–74), ECOG PS 0–2. All patients received at least two prior chemotherapeutic regimens (range 2–4). Metastatic sites were as follow: liver (16), lung (6), bone (9) and skin (4). patients with CNS involvement were excluded. All patients received CTX at the dose of 50 mg/die and MTX at the dose of 2.5 mg twice daily on days 3 and 4 of each week. After two months of treatment patients were re-evalated for disease response. Results: All patients were evaluable for response. After 2 months of treatment we observed 3 PR (8.5%) and 12 SD (34%), for an overall RR of 42%. 23 patients experienced PD. On the whole treatment was well tolerated, with mild toxicity; no patients discontinued treatment due to toxicity. Grade 2 or 3 neutropenia was observed in 14/35 patients and grade 2 trombocytopenia was observed in 9/35 patients. No grade 4 toxicity was observed. Conclusions: Metronomic administration of chemotherapy is well tolerated even in pretreated patients and shows moderate activity in advanced breast cancer

No significant financial relationships to disclose.
Partial breast irradiation (PBI) concurrent with adjuvant dose-dense doxorubicin and dyclophosphamide (ddAC) chemotherapy in early-stage breast cancer: Preliminary safety results from a feasibility trial
Authors: Zellars R. C. , Frassica D. , Stearns V. , Fetting J. H. , Armstrong D. K. , Myers L. , Tsangaris T. N. , Jacobs L. , Lange J. R. , Wolf A. C.
Published: March 2020

10675

Background: Adjuvant anthracycline-based chemotherapy regimens and radiation therapy as part of breast conservation therapy (BCT) are given sequentially to avoid excessive skin toxicity. PBI employs a shorter course of radiation therapy to a smaller breast field and is the subject of randomized efficacy trials. Concurrent administration of PBI and adjuvant chemotherapy would decrease duration of therapy, allow more women to pursue BCT, improve compliance, and potentially enhance local control. Methods: To examine the feasibility, safety, and short-term risk of recurrence of concurrent PBI with adjuvant ddAC, we are conducting a prospective one-stage, single-arm trial of PBI during the first 2 of 4 cycles of ddAC (60 and 600 mg/m2, respectively) delivered q14d with growth factor support. Patients (pts) with T1–2 N0–1 breast cancer and lumpectomy margins ≥ 3mm are eligible. PBI starts within 3 days of first chemo dose and treats the lumpectomy bed plus margin with 270 cGy fractions × 15 (4050 cGy total). Primary endpoints (skin/soft tissue toxicity and cosmetic outcome) are graded by a panel of physicians using commonly accepted scales. Digital images at baseline, during, and q 3–6 months after PBI are obtained for comparison. Additional chemo and endocrine Rx post ddAC given at the physician’s discretion. We report preliminary safety data. Results: Between 11/04 and 9/05, 10 pts were enrolled and received study therapy (accrual goal = 42); 2 pts also received dd paclitaxel 175 mg/m2 post ddAC. All pts received planned PBI (med. f/u 6 mos, range 3–12 mos). 2 pts missed 1 and 2 cycles of ddAC because of stomatitis (Gr 3) and diverticulitis, respectively. 3 other pts had 1–2 wk chemo delay because of hand-foot syndrome, brief pulmonary syndrome, and febrile neutropenia. No pts developed radiation dermatitis > Gr 1 or radiation recall. All pts had cosmetic outcome grades of good or excellent shortly after completion of therapy. No pts with ≥ 6 mos f/u since PBI had late skin toxicity. Conclusion: Early results suggest that PBI concurrent with ddAC appears feasible and safe. Trial enrolment continues and longer f/u is required. (Funded by The Breast Cancer Research Foundation).

No significant financial relationships to disclose.
Diagnosis of recurrent breast cancer: 18F-FDG PET/TAC as first choice
Authors: Mion M. , Chierichetti F. , Liessi G. , Bissoli S. , Milan E. , Oniga F. , Sartor L. , Bortolin M. , Vicario G. , Sgarbossa G. , Manente P.
Published: March 2020

10681

Background: we began using PET diagnosis in 1994 and since the beginning of 2000 we started with a PET/CT system. Aim of our study was to evaluate if this new imaging modality may be the first step in the detection of recurrence in patients with a history of breast tumors. Methods: we reviewed retrospectively 22 patients (mean age 60, range 46–76 years) already treated for a breast cancer. A total of 32 PET/CT scans were performed (repeated in 10 patients). All patients were submitted to other examinations, such as bone scintigraphy and liver ecography, but also mammography and CT scan. Results: 14/32 PET/CT were negative for recurrence in 10 patients (4 scans as a second one). In a mean follow up of 10 months, 1 case is not yet clear: in presence of relevant increase of Ca15.3 (up to 176 ng/ml) the first scan was negative and the second one evidentiated a pattern of lung inflammation. Among the other 13/14 negative scans, 3 patients presented ambiguous/positive bone scintigraphy for metastases, not assessed at the final diagnosis. 18/32 PET/CT scans were positive for local recurrence or distant metastases. Among these positive cases, a patient with normal bone scintigraphy presented a mild uptake of FDG in the right omerus. The second scan (5 months later) showed focal increased uptake of FDG in the same bone site, not evident in the CT images, and many small lung nodules, 1–2 mm size. In 3 patients PET localized muliple bone lesions, in 2 CT was completely normal. Finally, 1 out of the 18 positive results was false positive: a patients with a single lung nodule (1.5 cm) was submitted to surgery and the final diagnosis was benign lesion. PET/CT was crucial for the patient’s management in 19 out of 22 patients. Conclusions: recurrent breast cancer is generally characterized by multiple sites of metastases and few cases take advantage of surgical resection. In our group of 22 patients just 2 out of them received surgery (for local relapse and lung metastases). Therefore, in most cases a whole body examination, like PET/CT may be more useful respect to other modalities to assess how spread is the recurrence. Further data are needed but, in our preliminary experience, PET/CT seems to be the first choice to evaluate patients with previous breast cancer.

No significant financial relationships to disclose.
Phase II study of capecitabine (X) in combination with vinorelbine (N) in patients (pts) with pretreated metastatic breast cancer (MBC)
Authors: Batista N. , Estevez L. , Sánchez-Rovira P. , Velasco A. , Dómine M. , Lobo F. , Oramas J. , Cruz J.
Published: March 2020

10693

Background: X monotherapy is consistently effective and very well tolerated in pretreated MBC. N is also commonly used in this indication. In several studies, the combination of X + N led to response rates ranging from 43–67% in first-line MBC. As there are few data on the combination in pts with pretreated MBC, we evaluated the efficacy and safety of X + N in a multicenter phase II trial of pts previously treated with anthracycline- and taxane-containing regimens. Methods: Women >18 years of age with pretreated MBC, PS 0–2 and adequate organ function were enrolled to receive a 3-weekly regimen of XN: X 1000mg/m2 twice daily on days 1–14 and N 25mg/m2 on days 1&8, every 3 weeks up to a maximum of 6 cycles, disease progression or unacceptable toxicities. Results: A total of 32 pts were enrolled, median age 58 years (range 41–77), PS 0(74%), 1(19%), postmenopausal (61%). The most frequent sites of metastases were: liver (68%), nodes (36%), lung (36%). 58% of pts had ≥2 metastatic sites. 27 patients (87%) previously failed on anthracycline and taxane chemotherapy regimens. 152 cycles were administered with a median of 3 cycles/pt (range 1–10). Median relative dose intensity was 0.86 (0.51–1.01] for N and 0.85 (0.26–1.03] for X. All pts were evaluable for safety. The most common grade 3/4 clinical adverse events were vomiting (15%), asthenia (9%), and hand-foot syndrome (6%). Grade 3/4 hematological toxicities were: neutropenia (47%), leucopenia (9%), thrombocytopenia (3%). One pt died due to septic shock after the first cycle. 29 pts are evaluable for efficacy: the overall response rate was 52% (4 CR, 11 PR), with stable disease in 8 pts (28%). Median TTP was 7.5 months [95% CI, 5.7–9.8]. Conclusions: Our preliminary data indicate that the combination of X and N has promising clinical activity and good safety in pts with MBC who have failed prior taxane- and anthracycline-containing regimens.

No significant financial relationships to disclose.
Long median survival with capecitabine (X) single-agent therapy for patients (pts) with anthracycline- and taxane-pretreated metastatic breast cancer (MBC)
Authors: Largillier R. , Fumoleau P. , Clippe C. , Dieras V. , Orfeuvre H. , Lesimple T. , Culine S. , Audhuy B. , Serin D. , Bobadilla L.
Published: March 2020

10710

Background: X (Xeloda) is an oral fluoropyrmidine with consistently high activity in MBC, a good safety profile with little myelosuppression and no alopecia, and the convenience of oral administration. The addition of X to docetaxel in anthracycline-pretreated pts also increases survival. This non-randomized phase II study was conducted to evaluate the efficacy, safety and impact on quality of life (QoL) of X in pts with MBC pretreated with anthracyclines and taxanes. Main findings from this trial have been published previously [Fumoleau et al. Eur J Cancer 2004;40:536–42]. Here we present mature data after a follow-up of 48 months. Methods: Pts with anthracycline- and taxane-pretreated MBC received X 1250 mg/m2 twice daily on days 1–14 every 3 weeks for a median of 6 cycles (range 1–15). Results: Baseline characteristics of the 126 pts enrolled were typical of a pretreated MBC population. X achieved complete/partial response or stable disease in 63% of patients (overall response rate, 28%). Median time to progression was 4.9 months (95% CI: 4.0–6.4).Median duration of response was 5.9 months (95% CI: 4.5–12.7). The only grade 3/4 events occurring in ≥ 10% of patients were diarrhea (10%) and HFS (21%). The most common grade 3/4 laboratory abnormality was granulocytopenia (14%). After a follow-up of 48 months, 8 patients are still alive. Updated median overall survival is 15.9 months (95% CI: 13.5–21.3). 1-, 2- and 3-year survival rates are 63%, 37% and 17%, respectively. QoL assessment showed that X treatment was associated with an increase in mean Global Health Score up to cycle 6, with the increase maintained at subsequent evaluations. Conclusions: X is highly active in patients with anthracycline- and taxane-pretreated MBC, leading to a long median survival of 15.9 months. X is also well tolerated and improves QoL.

[Table: see text]
Male breast cancer: Our experience
Authors: Tozzi L. , D’Addetta C. , Bisceglia M. , Murgo R. , Cilenti G. , El Jaouni M. , Latiano T. P. , Scaramuzzi G. , Parisi S. , Maiello E.
Published: March 2020

10733

Background: Male breast is an uncommon disease, accounting for <1% of all malingnancies in the man. In contrast to women with breast cancer, men with breast cancer are older and have more advanced disease. Methods: Data regarding 25 male patients who underwent surgery for breast cancer in the our Istitution between January 1994 and December 2005 were analyzed. The main characteristics of these patients included: median age 64 years (range 32–87); positivity family cancer history: specific 4 pts, non-specific 3, no circumstance 18; risk factors: obesity 6 pts, gynaecomastia 4, diabetes 5, liver transplant 1. Five cases of second neoplasia were observed: 2 patient with prostate cancer, 1 synchronous colon carcinoma, 1 head and neck cancer, 1 pancreatic cancer. Results: All but one pts (with syncrhronous metastases at presentation) underwent mastectomy. Pathological characteristics included: pT1 tumors 3 pts (12%); pT2 7 pts (28%), pT3 2 (8%), pT4 13 (52 %); infiltrating ductal carcinomas in 88% of cases; axillary lymph node involvement in 12 (50%); 22 patients had estrogen- and progesterone-receptor positive tumors, 2 pts negative, 1 pts unknown. After surgery 14 pts received RT, 13 pts hormonotherapy and 16 patients adjuvant chemotherapy (7 CMF, 9 anthracyclin-based therapy). Median disease free survival was 41.5 months (range 5–116).With a median follow-up of 66 months, we observed 12 deaths (10 pts for progressive disease) and the overall survival rate was 52% (13 pts; 11 disease-free). According to the family cancer history we observed 5/7 (71%) and 7/18 (39%) deaths in positive and negative cases, respectively. Conclusions: The approach to male breast cancer patients is similar to that for female patients. Our data confirm the suspected epidemiologic risk factors such as prostate cancer, gynecomastia and dietary factors; furthermore, cases with family cancer history seems to have a worse prognosis.

No significant financial relationships to disclose.
Gemcitabine in metastatic breast cancer
Authors: Bensalem A. , Bouzid K.
Published: March 2020

10735

Background: Gemcitabine (GEM) has shown efficacy in metastatic breast cancer (MBC). We conducted studies with GEM-based regimens to assess the efficacy and toxicity of GEM combined with other drugs in MBC. GEM was combined with docetaxel (DXL) in pre-treated MBC with an anthracycline-based regimen and GEM was combined with doxorubicin (DXR) in chemonaive patients (pts) with MBC. The studies’ objectives were to show clinically relevant hematologic toxicity and response rates among pts treated with GEM-DXL either in combination in pre-treated pts with anthracycline regimen or GEM-DXR in chemonaive pts with MBC to assess the efficacy of GEM in MBC either in neoadjuvant or first-line treatment. Methods: For GEM-DXL: 42 pts were enrolled; GEM: 1250 mg /m2 D1 & D8, DXL: 75 mg /m2 D1, every 21 days with classical premedication for DXL. For GEM-DXR: 51 pts were enrolled; GEM: 1250 mg /m2 D1 & D 8, DXR: 25 mg/m2 D1 & D8, every 21 days. Results: See table below. In the GEM-DXR group, surgery was performed in 30 pts, and 13 (43.2%) had histologically complete response. The median TTP in this group was 13.3 months (range, 2–53). Conclusions: GEM in MBC is very efficient and produced an interesting objective response and clinical benefit. This activity is consistent in either chemonaive pts or in pts with relapsing breast cancer.

[Table: see text]

No significant financial relationships to disclose.
Is the prophylactic use of colony stimulating factor and oral ciprofloxacin effective to prevent neutropenia in patients having docetaxel, doxorubicin, and cyclophosphamide for breast cancer as an adjuvant chemotherapy in Korea?
Authors: Suh Y. , Chun C. , Oh S. , Jung S.
Published: March 2020

10736

Background: Recently, the combination chemotherapy including docetaxel (75 mg/m2), doxorubicin (adriamycin) (50 mg/m2), andcyclophosphamide (500 mg/m2) has been reported to be effective as an adjuvant treatment for the early breast cancer patients. Though a few studies have been published to show preventive effect of the routine use of G-CSF and oral antibiotics on the severe neutropenia. We prosepctively tried to compare the possible role of this prophylactic measure on the prevention of high-grade neutropenia in breast cancer patients having this regimen in Korea. Methods: We prospectively compared prophylactic user group (100 patients) with non-use group (100 patients). Stage II breast cancer patients were enrolled for this study. We used three-day prescription of G-CSF (150 ug/day) and oral ciprofloxacin (500 mg/day) five days after the completion of each cycle for the user-group. Results: The percentage of febrile neutropenia was strikingly decreased in the user group (p < .01). Number of patients showing grade II, III neutropenia didn’t show statistical difference between groups. Averge days required to recover from the neutropenia was 2.7days in two groups. The nadir of neutropenia was between 7–10 days after each cycle regardless of the prophylaxis. The duration of neutropenia seems to be dependent on the presence of the fever over 38’C after the chemotherapy. Once the fever developed, the neutropenia was becoming severer and more protracted. Conclusions: We think this combination chemotherapy effective to be used as an adjuvant treatment for the early breast cancer patients. But more care should be provided to prevent severe neutropenia after each cycle. Routine use of this prophylaxis failed to show significant differences in the rate of occurence of the severe neutropenia. But, we think that the prophylaxis seems to e effective to prevent febrile neutropenia. So, we suggest the routine prophylactic use of G-CSF and oral ciprofloxacin should be considered to be used in breast patients having docetaxel, adriamycin, and cyclophosphamide.

No significant financial relationships to disclose.
Monocentric retrospective analysis of locally advanced and inflammatory breast cancer (IBC) patients (pts) having received a neoadjuvant chemotherapy with docetaxel (D) and anthracyclines
Authors: Audhuy B. , Meyer C. , Nierges D. , Barats J. C. , Straub P.
Published: March 2020

10743

Background: Anthracycline-based neoadjuvant therapy is a standard treatment, but use of D in the preoperative setting increases clinical and pathological response, as monotherapy or as part of combination chemotherapy for preoperative setting. Our purpose was to assess the efficacy in pts who were treated with D and anthracyclines (doxorubicine A or epirubicine E) in neoadjuvant setting. Methods: Pts with histologically proven, unilateral breast cancer, T2-T4, N0-N2, M0 tumors received every 3 weeks an association of D and A or E, according to different schedules. This retrospective analysis was designed to evaluate the clinical and pathological response rate of this association. Results: Between October 1999 and December 2003 45 pts (44 women and 1 man) were treated with associations: 39 D and E or A, 3 D, A and vinorelbine, 1 D, A and capecitabine (X), 1 D, A and trastuzumab (H), 1 D, X and H; median age 47 [27–71] years; median number of cycles of chemotherapy: 4 [3–6]; median tumour diameter: 50 mm [20–150] with 6 IBC; median radiological size: mammography 32 mm [11–90], echography 32.5 mm [8–90]; tumour stage: 15 T2N0 (33%), 12 T2N1 (27%), 7 T3N0 (15%), 2 T3N1 (4%), 1 T3N2 (2%), 1 T4bN1 (2%), 1 T4cN2 (2%), 3 T4dN0 (7%), 2 T4dN2 (4%), 1 T4N0 (2%); tumour grade: 22 grade II (49%), 22 grade III (49%), 1 unknown; tumour histology : 31 ductal carcinoma (69%), 13 lobular carcinoma (29%), 1 mucineous carcinoma (2%); hormonal status: 29 positive (64%), 16 negative (36%). Among these pts, 13 had nodal curage concomitant with diagnosis biopsy. All pts were evaluable for clinical response: ORR was 91% (18 complete response CR 40%, 23 partial response PR 51%. Histological response was available in 32 pts: Chevallier classification pCR grade 1–2: 5 (11%), Sataloff TA /NA-NB 5 (16%). On 32 pts with postchemotherapy nodal curage, 16 had negative nodal disease. On these 16 pts, 8 were N0 at diagnosis, 5 N1 and 3 N2. Conclusions: Association of D and anthracyclines in breast carcinoma exhibits a high pathological response rate.

No significant financial relationships to disclose.
Nanoparticle albumin-bound (Nab) paclitaxel (P) in combination with bevacizumab (B) with and without gemcitabine (G): Early experience at the Braman Family Breast Cancer Institute
Authors: Lobo C. F. , Lopes G. , Silva O. , Gluck S.
Published: March 2020

10748

Background: Nab-P improves outcomes when compared against single agent cremophor-based P, as does the addition of bevacizumab or gemcitabine to the same agent. There are no available data regarding combinations of Nab-P with B and/or G. Ongoing investigational efforts are evaluating various doublets with these agents, but, to the best of our knowledge, not all 3 of them in the same regimen. All drugs are currently FDA-approved in the treatment of breast cancer. Methods: Review of single-institution experience, evaluating safety and preliminary evidence of activity with the use of Nab-P and B with and without G in heavily pretreated her2neu negative metastatic breast cancer patients. Assessment of response was undertaken by the investigators independently of treating physician. RECIST criteria were used. Three patients received Nab-P and B at the following doses: Nab-P 100 mg/m2, B 10 mg/kg every 2 weeks, and 2 patients received all 3 drugs as follows: Nab-P 100 mg/m2, G 1,000 mg/m2, B 10 mg/kg every 2 weeks. Results: Five women have been evaluated. Median age was 51 (range 34–69). Two patients had hormone-receptor positive disease and 3 had ER/PR/Her2neu-negative cancer. Prior number of regimens was 3 (range 2–7). Four patients had been treated with a taxane. One received both paclitaxel and docetaxel, and 3 docetaxel only. A median of 5 cycles have been administered (range 3–9). First-cycle grade 3/4 toxicity was seen in only one patient who had a baseline grade 2 thrombocytopenia that progressed to grade 3. The thrombocytopenia resolved without requiring transfusion and without any hemorrhagic complication. Another patient developed grade 2 peripheral neuropathy. Two patients are not yet assessable for response. At time of first evaluation 1 patient had progressive disease (Nab-P, B; 7 prior lines of treatment), one had stable disease (Nab-P, B, G; 3 prior lines of therapy, including docetaxel), and 1 had a partial response (Nab-P, B, G; 2 prior therapies, including docetaxel). Conclusions: These very preliminary data suggest that Nab-P in combination with B with and without G is a safe regimen and formal Phase I/II trials are being developed to confirm its clinical activity.

[Table: see text]
Randomized open label phase II study of pegilated liposomal doxorubicine (PLD) four or six-week scheduled in metastatic breast cancer (MBC) patients (p)
Authors: Ruiz M. , Bayo J. L. , Moreno Nogueira J. A. , Dorta J. , Casas A. M. , Morales M.
Published: March 2020

10751

Background: PLD has the advantage of delivering the active anthracycline directly to the tumour site, provide comparable efficacy to conventional doxorubicin with a more favourable toxicity profile and significantly less cardiotoxicity. The most frequent dosing schedule is 50 mg/m2 every 4 weeks. Recent studies have shown that PLD 60 mg/m2 every 6 weeks is an active and well tolerated treatment, and could be more convenient for the p. The primary objective was to evaluate response rate in six- and four-week schedule (arms A and B). Secondary objective was toxicity profile. Methods: P histologically confirmed of MBC, age 18–75 years old, ECOG PS ≤ 2, at least one measurable lesion and adequate bone marrow, renal, hepatic and cardiac function, were eligible. Prior chemotherapy with anthracyclines for MBC or adjuvant anthracycline-based regimen in the previous 12 months was not allowed. P were randomly assigned to receive PLD 60 mg/m2 i.v. in 1 hour every 6 weeks (arm A) or PLD 50 mg/m2 i.v. in 1 hour every 4 weeks (arm B). Results: Ten p have been included in the interim analysis over 11 enrolled, with median age of 50 years, ECOG PS 0–1 70% and stage IV 50%. Median time from diagnosis of metastatic disease was 9.2 months. Histology: 80% of p had ductal carcinoma, 10% lobular and 10% undifferentiated. Main tumour locations were lung (60%), liver (60%) and bone (40%). Two p had positive hormonal receptor status in arm A and 4 in arm B. Previous treatment included chemotherapy (80%), hormonotherapy (80%) and radiotherapy (40%). Up to date, a total of 15/17 cycles (median 3/3, range 1–6/1–5) were administered. Absolute dose intensity was 2.2 mg/day in arm A and 3.0 mg/day in arm B. Two p were not evaluated and over 8 evaluable p for efficacy (4 A and 4 B), 2 achieved partial response in arm A and 1 in arm B. Median time to progression was 168 days in arm A and 104 in arm B. The only grade III/IV toxicity was mucositis and stomatitis in 4 p. The most common grade I/II toxicities were palmar-plantar erythrodysesthesia (5p), anorexia (4p) and alopecia (4p). Conclusions: PLD at 50 mg/m2 every 4 weeks and 60 mg/m2 every 6 weeks are effective and well tolerated regimens in MBC p. The most relevant adverse events were mucositis and palmar-plantar erythrodysesthesia.

No significant financial relationships to disclose.
Infiltrating ductal carcinoma of male breast: A retrospective study
Authors: Puri T. , Malik M. , Gunabushanam G. , Sharma D. N. , Julka P. K. , Rath G. K.
Published: March 2020

10753

Background: A single-institution retrospective review of the clinical presentation, treatment and outcome of male breast infiltrating ductal carcinoma (IDC). Methods: Case records of 25 male patients with a histological diagnosis of infiltrating ductal carcinoma (IDC) of breast who were treated in a single institution between 1997 to 2004 were retrospectively reviewed. Results: Patients presented at a mean age of 56 years (range, 34 to 80 years). The presenting complaint was a painless lump in the breast in all the cases. The right breast was involved in 13 cases (52%). There were no cases of bilateral breast cancer. The distribution of patients by stage at presentation are: stage IIA (24%), IIB (20%), IIIA (8%), IIIB (40%), and IV (8%). None of the patients presented with stage I disease. One patient had lung metastases at presentation. Rest of the 24 patients (96%) underwent surgery (modified radical mastectomy, 22 patients; simple mastectomy, 2 patients). Fifteen patients (60%) received adjuvant local radiotherapy. All patients received adjuvant chemotherapy: As per departmental protocol, those presenting before 2000 were treated using a regimen of Cyclophosphamide, Adriamycin and 5-Fluorouracil. After 2000, Ebirubicin was substituted for Adriamycin. Three patients were further administered Docetaxel, the indication being disease progression after first line adjuvant chemotherapy. Estrogen & Progesterone receptor positivity was 64% and 60% respectively. Hormonal therapy (Tamoxifen 14 patients, Anastrozole 2 patients) was administered in these patients. The length of follow-up from time of presentation ranged from 4 to 100 months (mean, 28 months; median, 13 months). At the time of analysis, of the 25 patients, 18 patients (72%) remain disease free, whereas 7 patients (28%) developed progressive disease. Median survival was not reached at the present time. Conclusions: Breast cancer, specifically IDC tends to present at a later stage in males, due to a lack of screening for the disease. In the present series, as a result of the advanced stage of initial presentation, all patients received adjuvant chemotherapy. There is a need to improve awareness among males, of the possibility of a painless breast lump being the first symptom of an underlying malignancy.

No significant financial relationships to disclose.
Pattern of breast diseases in Kuwait Cancer Control Center, Kuwait
Authors: Alawadi S. A. , Delvadiya M. D.
Published: March 2020

10754

Background: The aim of this case series study is to evaluate the outline and pattern of female breast cancers in Kuwait. Methods: Our study consisted of data from 300 cases of female breast cancer seen in our outpatient department. Data on profile of their disease at presentation and known risk factors was retrieved. The analysis indented to examine the pattern of the disease and risk factor profile of the patients. Results: Out of 300 patients, 52% were Kuwaiti citizens, 24% were Arabs from other countries, 23% were of Asian origin and 1% was of other nationality. Their median age ± SD (Standard Deviation) was 50 ± 9.7 years. Most patients were younger than 55 years (77.4%) and were predominantly premenopausals (63%). Only 18% had stage I disease at presentation, whilst 54 %, 24 %, and 4% had stage II, III and IV disease, respectively. Among patients with known axillary nodal status (298 patients) 44.3% were node-negative whilst 39.6% and 16.8% had N1 and N2 disease, respectively. History of benign breast disease was positive in 9% and only 1% had breast biopsy done before the biopsy which diagnosed cancer. In 20.7% there was family history of breast cancer. Among them 11.7% had first degree relative with breast cancer, 3.3%, 7.3% and 1% patients had either mother, sister or both with history of breast cancer. Whilst 12% patients had second degree relatives with breast cancer, 3% patients out of them had both first and second degree relatives with breast cancer. History of alcohol ingestion was rare, only 0.7% patients were taking alcohol. 9.7% patients were nulliparous, while 10.7% patients had their first child after the age of 30 years. Breast feeding was common, 80 % patients breast fed their children and 43.3 % did that for more than 6 months. Age at menarche was 12 years or less in 34 % patients and age at menopause was more than 55 years in only 6.3% patients. Oral contraceptives were used by 38.7% patients, 12%, 9.3% and 17.3% patients used them for 2 or less, 2 to 5 or more than 5 years, respectively. Only 3% patients took hormone replacement therapy, 7 of them took that fore more than 2 years. Only 6 % patients gave history of smoking and only half of them were currently smoking. Conclusions: This data analysis suggested that pattern of breast cancer in Kuwait is similar to other countries in this region.

No significant financial relationships to disclose.
MIX —The first results of the ongoing prospective multicentre phase II study
Authors: Lux M.
Published: March 2020

10756

Background: The treatment of patiens with metastatic breast cancer (MBC) previously treated with anthracycline represents a significant challenge. Several studies have shown that oral capecitabine is an effective and well-tolerated agent. Mitomycin C has notable therapeutic activity and presents additive effects. Primary endpoints of this ongoing prospective, multi-centre, phase II study are to evaluate the safety and efficacy of the combination. TTP and QoL are secondary endpoints. Methods: Patients receive six cycles of mitomycin C 8 mg/m2, d1, and capecitabine 2,000 mg/m2, d1–14, q21d. 46 patients are planned for treatment, 17 patients are already enrolled. Evaluation (RECIST) has to be done after the fourth and sixth cycle. Safety is evaluated in all patients. Data for 16 patients were analysed, one patient has not be monitored up to date. Results: All patients have been pre-treated with anthracyclines and 62.5% with taxanes. 68.8% had multiple sites of metastases. 6.3% received just 1 cycle, 6.3% 2, 12.5% 3, 31.3% 4 and 43.8% 6 cycles. 11.3% of the cycles received dose reduction and 12.7% interval prolongation. Following grade 3- and 4-toxicities (NCI CTC) were observed in the 71 cycles: dyspnea [3 × grade 3 and 2 × grade 4; all occurred in patients with pulmonal metastases or pleural effusions], nausea (1 × grade 3), thrombopenia (2 × grade 3), fatigue (1 × grade 3), mucositis (1 × grade 3) and hand-foot-syndrome (4 × grade 3). Best response rates were: 18.8% progressive disease, 37.5% stable disease, 31.3% partial remission and 12.5% complete remission. Conclusions: The treatment with mitomycin C and capecitabine presents a favourable safety profile, which is well tolerated and active in this setting. The safety commission recommends the continuation after revision of the preliminary data.

No significant financial relationships to disclose.
Epirubicin and docetaxel is an effective neoadjuvant therapy for breast cancer: Result of a phase II study
Authors: Bova A. , Jennifer H. , Venkatappa S. , Ozer H. , Tfayli A.
Published: March 2020

10759

Background: Anthracyclines and Taxanes represent the 2 most active classes of chemotherapeutic drugs against breast cancer. This study assesses the efficacy of Epirubicin and Docetaxel as neoadjuvant therapy for women with breast cancer. Methods: This is a single institution, single arm, phase II study of Epirubicin given at 75 mg/m2 and Docetaxel at 75 mg/m2 every three weeks for 4 cycles prior to surgical excision in women with large breast cancers. Pegfilgrastim was routinely administered as primary prophylaxis against febrile neutropenia. Results: Of 18 patients enrolled on the study, 12 (66.7%) had a clinical response and 13 (72.2%) had a pathologic response, with a pathologic complete response of 5.6%. Premenopausal women and patients with estrogen receptor positive tumors had a higher response rate. One patient died due to sepsis and febrile neutropenia. Conclusions: Combination chemotherapy with Epirubicin and Docetaxel is highly active against breast cancer. With close monitoring for toxicity, this combination can be safely administered with mild side effects.

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The role of bisphosphonates and bone health issues in Japanese Breast Cancer patients: Efficacy of alendronate with aromatase inhibitors
Authors: Yamada K. , Kohno N. , Endoh K. , Kimura D. , Ueno F. , Ogata A. , Ohta D. , Kaise H. , Kato H.
Published: March 2020

10777

Background: Adjuvant hormonal therapy for postmenopausal breast cancer is now one of the most significant therapies in the world. From the results of the ATAC trial and the ITA trial, standard hormonal therapy for postmenopausal breast cancer has changed from tamoxifen to aromatase inhibitor. However concerning the rate of bone-relating complications including bone fracture, osteoporosis, a decrease in bone mineral density (BMD), aromatase inhibitor is reported higher than tamoxifen. According to the 2003 ASCO guidelines on the role of bisphosphonates in women with breast cancer, most women with newly diagnosed breast cancer are at risk of osteoporosis due to either their age or their breast cancer treatment. The Panel recommended an algorithm for patient management to maintain bone health. The purpose of the study is to investigate the efficacy of bisphosphonate for prevention from osteoporosis by aromatase inhibitor in Japanese women with breast cancer. Methods: From 2002 to 2004, we experienced 92 cases of postmenopausal Japanese women who underwent breast cancer operations and take aromatase inhibitor after operations in Tokyo Medical University hospital. We selected two medicines. One is Anastrozole (ArimidexR) as an aromatase inhibitor, and the other is Alendronate (BonalonR) as a bisphosphonate medicine.We investigated the change of BMD, calcium, bone absorption marker like NTX, I-CTP. Results: The value of NTX which patients take Alendronate with Anastrozole decreased about 40% than which patients take Anastrozole alone. Also the rate of bone-relating complications is lower.The mean value of BMD, % YAM, T-score, Z-score is 0.86, 81.0, −1.52, 1.47, respectively. Conclusions: The results suggest the efficacy of bisphosphonate for prevention from bone-relating complications osteoporosis by aromatase inhibitor in Japanese women with breast cancer.

No significant financial relationships to disclose.
The role of F-18 FDG PET/CT and breast MRI in the management of breast cancer
Authors: Iagaru A. , Masamed R. , Silberman H. , Keesara S. , Conti P. S.
Published: March 2020

10778

Background: F-18 FDG PET/CT combines functional and morphologic information in a single study, thus becoming a powerful imaging tool for diagnosis, staging and establishing the response to therapy in various malignancies, including breast cancer (BC). Breast MRI (BMRI) is gaining a major role in the management of high risk BC patients (pts), demonstrating high sensitivity and specificity for detection of small lesions. It is not clear whether to request both studies prior to therapy or opt only for one. We were therefore prompted to review our experience with PET/CT and BMRI in BC. Methods: This is a retrospective study of 21 pts with BC, 30–76 years old (average: 52±13.5), who had BMRI and PET/CT from June 2002 to May 2005. 6 pts (group A) had BMRI and PET/CT in the preoperative period (3–78 days, average: 25) and 15 pts (group B) had BMRI and PET/CT as follow-up after surgery (4–175 days, average: 51.3). The interval between the PET/CT and BMRI ranged 2–188 days (average: 52.7). Specificities and sensitivities for BC and metastases detection using PET/CT and MRI were calculated using pathology (17 pts) or clinical follow-up (4 pts) as gold standard. Results: In group A, BMRI identified BC in 4 pts, while PET/CT did so in 5 pts. All were proven to be malignancy on pathology. In group B, BMRI detected recurrent BC in 8 pts, with 88.9% sensitivity (95% CI: 56.5–98) and 83.3% specificity (95% CI: 43.6–96.9). In the same patient population, PET/CT was 33.3% sensitive and 91.7% specific. As a whole body exam, PET/CT revealed metastases in 6 pts (100% sensitive and 90% specific). Overall, sensitivities and specificities for BC detection were 85.7% (95% CI: 60.1–95.9) and 85.7% (95% CI: 48.7–97.4) for breast MRI, and 75% (95% CI: 40.9–92.8) and 92.3% (95% CI: 66.7–98.6) for PET/CT. Conclusions: BMRI is more sensitive than PET/CT for detection of breast lesions. However, PET/CT detected distant metastases in 6 of the 21 pts (100% sensitive, 90% specific). Larger prospective studies, with the addition of dedicated breast PET and dual time imaging are needed to define the sequence of studies during initial work-up. Our study suggests that PET/CT and BMRI should be considered complimentary imaging tools in the pre- and perioperative work-up of pts diagnosed with BC and at high risk for metastatic disease.

No significant financial relationships to disclose.
Combination procarbazine and temozolomide for temozolomide-resistant adult gliomas
Authors: Kavan P. , Huang F. , Roberge D.
Published: March 2020

11503

Background: As Temozolomide has become incorporated in the first line treatment of glioblastoma multiforme as well as the salvage therapy of many low-grade gliomas, we are increasingly faced with Temozolomide failures. There is currently no standard second-line chemotherapy for Temozolomide-resistant tumors. In what is usually a palliative setting, toxicity and convenience are important considerations in the choice of a second-line regimen. Methods: We reviewed our experience with a combination oral regimen for Temozolomide failure. The regimen consisted of a 28-day cycle with Procarbazine given at 100–150mg/m2/d on days 1–5, and Temozolomide at 150mg/m2/d on days 1–5. This was initiated at the time of radiological and/or clinical progression while on Temozolomide, and continued until further progression or toxicity was documented. Results: 12 patients, median age 52 (range 38–68), were treated with concomitant Procarbazine and Temozolomide at our institution since November 2004. All patients had histologically confirmed gliomas (glioblastoma multiforme (10), grade II oligodendroglioma (1), grade II oligoastrocytoma (1)), and all had undergone prior maximal safe resection and external beam radiotherapy. All patients were receiving Temozolomide, either in the adjuvant setting (after concurrent chemo-radiotherapy in 6 of 12), or as salvage monotherapy for recurrence. No patient met the RECIST criteria for PR. Patients progressed after a median of 2 cycles (range: 1–10) but the 6-month actuarial progression-free survival was 40% (80% of patients with SD had glioblastoma multiforme). No Grade 3 or 4 toxicity was seen. No patient discontinued treatment because of toxicity. The Procarbazine dose was prophylactically reduced (75mg/m2/d) in one patient with poor hematological tolerance to prior chemotherapy. Conclusions: The combination of Procarbazine and Temozolomide given in a 28-day cycle is a well-tolerated oral second-line regimen for glioma patients failing Temozolomide. The activity of this regimen is modest but prolonged progression-free survival can be seen.

[Table: see text]