bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictors of brain relapse in HER-2 positive metastatic breast cancer (MBC) patients (pts)
Authors: Duchnowska R. , Czartoryska-Arlukowicz B. , Radecka B. , Szostakiewicz B. , Sosinska K. , Karpinska A. , Dziadziuszko R. , Kubiatowski T. , Staroslawska E. , Szczylik C.
Published: March 2020

10508

Background: Brain relapse is a common occurrence in HER2-positive breast cancer pts. We assessed factors determining the risk of this event in a large unselected series of HER2-positive MBC pts. Methods: Study group included 233 consecutive HER2-positive (IH 3+ or FISH+) MBC pts (median age 53 years); 49% premenopausal, 49% postmenopausal and 2% with unknown menopausal status. Dominant site of disease included viscera (78%), soft tissue (11%) and bones (10%). Of the 206 pts (88%) with known steroid receptor status, ER+/PgR+, ER+/PgR-, ER-/PgR+, ER-/PgR- phenotypes included 58%, 15%, 5% and 21% of pts, respectively. Prior (neo)adjuvant chemotherapy, endocrine therapy or a combination thereof was administered in 40%, 6% and 35% of pts, respectively. Disease-free interval to the development of MBC ranged between 0 and 142 months (median 16 months). 184 pts (79%) received trastuzumab for MBC, usually in combination with chemotherapy. Statistical analysis included contingency tables, chi-square test, Kaplan-Meier survival analysis and Cox proportional hazard model. Results: Median follow-up from the development of MBC was 25 months (range 0.5–130 months). 54 pts (23%) developed brain metastases after a median of 13 months (range, 0 to 81 months). Cumulative risk of brain relapse was 11% (95% CI: 7–16%) and 24% (95% CI: 17–32%) at one and two years, respectively. Trastuzumab treatment was associated with insignificantly reduced risk of brain metastases (HR 0.63, 95% CI 0.29–1.39, p = 0.25). In the univariate analysis, premenopausal status was the only significant factor associated with increased risk of brain relapse (HR 2.56, 95% CI 1.28–5.00, p = 0.008). Conclusion: HER-2 positive MBC pts carry high risk of brain relapse, in particular prior to menopause. Protective role of trastuzumab warrants further research.

[Table: see text]
Pejorative factors identification for survival in patients with brain metastases from breast carcinoma treated with whole brain radiation therapy
Authors: Le Scodan R. , Massard C. , Fourme E. , Guinebretiere J. , Goupil A. , De Lalande B. , Cohen-Solal C. , Moisson P. , Floiras J. , Labib A.
Published: March 2020

10513

Background: To determine overall survival and independent prognostic factors for patients with brain metastases from breast carcinoma treated with whole brain radiation therapy (WBRT). Methods: From January 1998 through December 2003, 132 patients with brain metastases (BM) from breast carcinoma were treated with WBRT (median dose: 3000 cGy/ 10 fractions). We analyzed a number of potential predictors of survival after WBRT: age, presence of other systemic metastases, performance status, RTOG recursive partition analysis (RPA) class (1–2 vs 3), total dose of WBRT, number of brain metastases, interval between primary tumor and brain metastases, SBR score, tumor receptor hormonal (RH) status, lymphocyte count (< 700 vs ≥ 700 G/L), serum lactate dehydrogenase and HER-2 overexpression. The survival time with BM was defined as the time from the date of BM to the date of death or date of last of follow-up. Multivariate analysis was used to determine the effect of prognostic factors on overall survival using the Cox proportional hazard model. Results: One hundred and seventeen patients received exclusive WBRT. Surgery was followed by WBRT in 14 patients and stereotactic radiosurgery was followed by WBRT in 1. The median survival with BM was 6 months (range: 0–52). The 1-year and 2-years survival rates were 31% (CI95%: 23.5–39.8) and 16% (CI95%: 9.8–24.9). In multivariate analysis, RTOG RPA class III, lymphopenia (<700) and negative tumor RH status were independent prognostic factors for poor survival. Moreover, analysis of Her-2 overexpression was performed in 53 patients and 43% BM patients overexpressed Her-2. In preliminary analysis, Her-2 status was not a prognostic factor of survival. A complete analysis is ongoing and will be presented at the meeting. Conclusions: This large study confirms the value of established prognostic factors such as the RTOG RPA score and some less-well recognized factors such as lymphopenia and tumor RH status.

No significant financial relationships to disclose.
Effect of tibolone on tumor angiogenesis parameters in short-term treated women
Authors: Frankenne F. E. , Munaut C. , Wijzen F. , Planellas Gomez J. , Kloosterboer L. , Foidart J.
Published: March 2020

10519

Background: Large recent studies have shown increased mammographic density, breast pain and a marginally increased risk of breast cancer in women treated with continuous combined estrogen/progestogen (ccEPT), while tibolone has a minimal effect. A placebo-controled clinical trial (STEM), approved by several ethical comities, has been initiated to assess effect and potential mechanism of action of tibolone on breast tumor. We present the results on 12 angiogenesis-related parameters. Methods: 102 women with breast cancer who had to undergo a mastectomy were treated for 2 weeks with tibolone 2.5 mg/day or placebo. RNA was extracted from tumor snap-frozen biopsies (paired before and after treatments) and reverse-transcripted into 2 cDNA batches on which 6 distinct PCRs were performed in duplicate per parameter/sample. A vascular density (VD) index was determined on CD31 specifically stained tumor sections by counting 10 fields per section on 5 distinct sections per biopsy. Results: The validity of the VD evaluation is highlighted by the high correlation coefficient (r = 0.81) between the data within the placebo group at a 2 week interval. In the tumor samples, no change of the VD index was seen. Since it could be argued that VD index could not correctly reflect a modulation of angiogenesis after only 14 days of treatment, we looked at a potential change of the expression of a large array of angiogenesis-related factors (VEGFs, VEGFRs, PAI-1). No modification of the expression in any of these factors was observed. Conclusions: Our data lead to conclude that, in this study, tibolone displays a neutral effect on angiogenesis in breast tumor.

[Table: see text]
The International Core Literature Consensus (ICLC) : A tool for Resident training
Authors: Cook N. , Parkinson C. A. , Jagsi R. , Patel S. , Hughes-Davies L.
Published: March 2020

10545

Background: Teaching residents is a responsibility of almost all oncology attendings. Although much effort is put into direct teaching, there is often little attention paid to the structuring of reading. Many professional societies (including ASCO) publish detailed curriculum documents to guide study. However it is not clear how useful these are. They tend to be over-inclusive and offer no advice about what to read. We propose an alternative approach: The International Core Literature Consensus (ICLC). Here we have tested this approach using breast cancer as an example. Methods: We identified 40 highly cited breast oncology investigators and invited them to join an Expert Panel. The panel was asked to select the 100 most important papers in breast cancer. We define the ‘Core Literature‘ as those papers which a resident should have read by the end of their first rotation through a breast cancer service. We also surveyed residents to find out how useful they have found existing curriculum documents and what sort of curriculum they might find helpful. Results: Using the Expert Panel, we were rapidly able to define a core list of the 100 most important papers in breast cancer medicine. There was a surprising level of agreement between Experts (>90% concordance). Most of the disagreement was over whether some historically important but now out of date papers (such as the original Bonadonna description of CMF) should be included. Initial results from our residents survey suggest that although many residents (60%) are aware of the ASCO curriculum, few find it helpful (27%). Very few trainees have been given a detailed reading guide (9%) although all (100%) felt that it was very important to have such recommendations to guide their reading. Conclusions: Residents find the ASCO curriculum document unhelpful for structuring their reading and want better recommendations. We used an Expert Panel to define an International Core Literature Consensus, an alternative form of curriculum which our survey shows is closer to what residents find helpful. Such a core consensus could easily be constructed for every tumour site and updated every year.

No significant financial relationships to disclose.
Monitorization of primary therapy (PT) by additional imaging methods in locally advanced breast cancer (LABC)
Authors: Margelí M. , Cirauqui B. , Vallejos V. , Sánchez C. , Mariscal A. , Castellà E. , Rull M. , Torrente A. , Fraile M. , Barnadas A.
Published: March 2020

10580

Introduction: The response of locally advanced breast cancer (LABC) to Primary therapy (PT) may be monitored clinically and by mammography (MG). Magnetic resonance (MR) and 99mTc-sestamibi scintimammography (SMM) are increasingly being used. The aim of this study was to determine whether MG, MR and SMM are accurate indicators of tumour response to PT and whether they are predictors of histological response. Patients and Methods: A prospective observational study was approved at our institution and 52 patients( p) with core biopsy diagnostic of LABC and written consent were enrolled (mean age 52 years, SD 13) All p had clinical, MG, MR, SM assessment pre- and post- PT. Primary chemotherapy based on anthracyclines was administered as follows: 19 p FEC, 17 p AC-Docetaxel, 8 p Gemcitabine- Doxorubicine- Paclitaxel, 1 p FEC- Docetaxel and 1 p Carboplatin- VP16. 6 p were treated with hormone-therapy. RECIST criteria were considered for clinical response assessment and the same criteria was adapted for imaging and pathologic response. Results: After PT 33 tumours were considered not suitable for breast-conserving surgery. Based on histopathological findings, 10 (19%) lesions showed complete pathologic response, 30 (58%) partial response, 12 (23%) stabilization. No progression was detected. Clinical assessment of tumour complete response agreed with pathology in 40 of 52 tumours (78%), and with MG in 39 (78%). Correlation between MG and pathological findings was observed in 42 p (84%). Correlation between MR and pathological findings was observed in 42 p (82%). Correlation between SMM and pathological findings was observed in 31 p (66%). Among patients with complete pathologic remission, 9 of ten patients achieve a complete response by MR and SMM. Conclusion: In conclusion, our results don’t show that MR and SMM add any benefit to the diagnostic arsenal for predicting histopathological complete response to PT. However these new diagnostic methods should be considered in selected cases.

No significant financial relationships to disclose.
Tamoxifen-related endocrine symptoms in early breast cancer patients are relieved when it is switched to anastrozole
Authors: Massacesi C. , Zepponi L. , Rocchi M. B. , Rossini S. , Burattini L.
Published: March 2020

10597

Background: To determine how menopausal symptoms and quality of life changed when adjuvant tamoxifen has been suspended for any reason in favor of anastrozole in early breast cancer (BC) patients (pts). Methods: Major inclusion criteria: severe side effects or serious potential diseases caused by tamoxifen (20 mg die) that switched to anastrozole (1 mg die); confirmed early BC radically resected and with positive hormonal receptors; postmenopausal status; adjuvant chemo and/or radiotherapy suspended at least 4 wks before the hormonal switch. Exclusion criteria: discontinuation of tamoxifen for endocrine symptoms. Menopausal symptoms and health-related quality of life were assessed by the series of Functional Assessment of Cancer Therapy-Breast (FACT-B) plus endocrine subscale (ES) questionnaires at the switch and 3, 6, 9, and 12 months later. Sample size was decided by the effect size method (SD fixed as 0.5, effect of medium value). Score modifications were evaluated by one-way ANOVAS. Results: From Feb 2002 to Jun 2003, a total of 44 women were enrolled into the study. Discontinuation of tamoxifen was for: asymptomatic uterine problems (endometrium thickening or fibromatosis) in 56% of pts; cardiovascular disorders (mainly leg thrombosis and phlebitis) in 18%; patient’s refusal in 9%; GI persistent side effects in 5%; other reasons in 12% of pts. Endocrine symptoms ameliorated between baseline and 3 months, and stabilized thereafter. Mean ES scores improvement from baseline test was +3 (95% CI, 1 to 5), +4 (95% CI, 3 to 6), +5 (95% CI, 3 to 7), and +4 (95% CI, 3 to 6) at 3, 6, 9 and 12 months, respectively. FACT-ES global score had a mean improvement during 1-yr period of 9 points (95% CI 6 to 13, p < .0005), with 22 patients (50%) ever reaching an increase ≥ 5% of the baseline score. There also was a significant improvement in TOI score (+4 points, 95% CI 2 to 6, p < .0005), and physical and breast cancer subscales (+2, 95% CI 1 to 2, p < .001, and +1, 95% CI, 1 to 2, p < .001, respectively). Pts receiving anastrozole reported higher rate of mild arthritic and bone pain (27% vs 7%, p = .021). Conclusion: When a patient develops an endocrine symptom while on tamoxifen, a change in favor of anastrozole should be considered to minimize those symptoms and to improve quality of patient’s life.

No significant financial relationships to disclose.
Impact of taxanes on weight gain during neoadjuvant chemotherapy (Ctx) for breast cancer (BC)
Authors: Melisko M. E. , Millerick C. A. , Maniar P. , Moore D. , Rosenwein M. , Rugo H. S. , Esserman L.
Published: March 2020

10606

Background: Weight gain after the diagnosis of BC has been associated with increased risk of recurrence and mortality. Previous studies have documented weight gain after cyclophosphamide, methotrexate, and 5-fluoruracil (CMF) and adriamycin and cyclophosphamide (AC) chemotherapy, but the impact of taxane chemotherapy has not been described. Methods: We reviewed the charts of 119 patients (pts) who completed neoadjuvant Ctx between 1997–2005. Age, baseline body mass index (BMI), tumor size, nodal status, hormone receptor status, menopausal status, co-morbid illnesses and anti-depressant use were collected. Weight was recorded at each Ctx visit and at follow-up visits for two years. Results: 22 pts received AC only. 97 pts received AC followed by a taxane - 58 docetaxel (D), 39 paclitaxel (P). Median f/u time was 26.3 months. 66/119 (55%) of pts gained weight during Ctx, with a median change of + 1 pound (range -28 to +19.5 pounds) at the end of Ctx. 49/119 (41%) of pts gained weight during AC and 76/97 (78%) of pts gained weight during the taxane. Mean weight change after AC was -1.8 pounds compared to +3.2 pounds after the taxane (p < 0.001). Age, baseline BMI, and menopausal status prior to Ctx did not predict weight gain. There was no difference in weight gain between pts who received D vs. P (p = 0.19). 8/22 (36%) patients who received AC alone recurred, and 13/95 (14%) who received both AC and T recurred; however this was not statistically significant (p = 0.23). Total weight change during neoadjuvant Ctx did not predict recurrence; however weight gain during the AC portion was associated with a higher risk of recurrence when adjusted for weight gain during taxane Ctx (p = 0.035, Cox regression). Each one pound gained was associated with an 11% increase in risk of recurrence. Conclusions: Weight gain is common during neoadjuvant Ctx for BC, particulary during treatment with taxanes. Further follow up is required to establish if weight gain is maintained over time and to determine the impact of weight change on BC outcomes and health.

No significant financial relationships to disclose.
A phase II trial of trastuzumab (H) + capecitabine (X) as first-line treatment in patients (pts) with HER2-positive metastatic breast cancer (MBC)
Authors: Xu L. , Song S. , Zhu J. , Luo R. , Li L. , Jiao S. , Chen L. , Tao M. , Su Y. , Liu D.
Published: March 2020

10615

Background: The addition of H to a taxane provides significant clinical benefit, including prolonged survival, in HER2-positive MBC. H adds little to the toxicity of taxanes alone. As monotherapy, X has consistently high activity and favorable safety. The addition of X to docetaxel extends survival in MBC. Preliminary data [Bangemann et al. 2000] indicated that the combination of H + X is effective and well-tolerated for intensively pretreated HER2-positive MBC (ORR 47%). The current study evaluated the efficacy and safety of H + X in first-line MBC. Methods: 72 pts of a planned population of 100 pts were enrolled between Mar03 and Dec05. All pts had measurable (WHO criteria), HER2-positive (IHC 3+ or IHC 2+/FISH positive) and untreated MBC, KPS ≥60, and adequate organ function. H was administered as a 4mg/kg loading dose followed by 2mg/kg i.v. weekly (until disease progression) and X 1250mg/m2 bid d1–14 q3w (max 6 cycles). The primary endpoint was progression-free survival (PFS). Results: Baseline characteristics: median age 49 years (range 27–74), median KPS 90 (range 60–100). Principal tumor sites: lymph nodes (49%), lung (33%), liver (28%), breast (14%), thoracic wall (9%), chest (9%), other (12%). Prior treatment: surgery (77%), radiotherapy (21%), and adjuvant chemotherapy (58%), including anthracycline (35%), paclitaxel (7%), docetaxel (7%) and other (21%). 43 pts are evaluable for safety and efficacy. The remaining 29 pts are being analyzed. 6 pts received 3 cycles of H + X; the other 37 pts completed 6 cycles of treatment. 16 pts received H monotherapy after completing 6 cycles of H + X. 3 pts discontinued H due to disease progression. The most common grade 1/2 adverse events (AEs) were HFS (14%), neutropenia (14%), SGOT abnormality (16%), and SGPT abnormality (14%). Grade 3 HFS occurred in 4 pts (10%) with grade 3 myelosuppression in 1 pt (2%). AEs were mild and resolved in all pts. The overall response rate was 63%, including 5 CRs and 22 PRs. At a median follow-up of 6 months, median PFS has not been reached. Conclusions: The combination of H and X is a highly active and well-tolerated regimen for first-line treatment of HER2-positive MBC. Updated data will be presented.

No significant financial relationships to disclose.
Pegylated liposomal doxorubicin (PLD) with cyclophosphamide (C) as 1st-line chemotherapy for metastatic breast cancer (MBC) patients previously treated with adjuvant anthracyclines
Authors: Vandenberg T. A. , Trudeau M. , Provencher L. , Panasci L. C. , Yelle L. , Rayson D. , Latreille J. , Clemons M. , Giroux M. , Pouliot J.
Published: March 2020

10627

Background: Anthracyclines (A) are key elements in adjuvant and metastatic chemotherapy regimens for breast cancer. Pre-exposure limits the utilization of A in advanced disease due to cumulative cardiotoxicity. PLD (Caelyx/Doxil) has equivalent activity to conventional doxorubicin in MBC. However PLD has reduced toxicity, including significantly less cardiotoxicity. Combinations of A+C are the backbone of many adjuvant therapies, thus C represents a logical drug to combine with PLD. Methods: MBC patients with measurable disease who completed anthracycline containing adjuvant therapy > 12 months ago were entered in a multi-center single arm phase II trial. They received PLD 35mg/m2 + cyclophosphamide 600 mg/m2 every 3 weeks. This study was powered to demonstrate an objective response rate > 25%. Results: Seventy three patients were enrolled. Prior adjuvant therapy included: AC (37%), CEF/FEC (28%), AC-T (15%), AT (7%), EC (7%). The median cumulative dose of prior A were 240mg/m2 and 580mg/m2 for doxorubicin or epirubicin, respectively. Median time since adjuvant chemotherapy was 4.4 years (1–14). Patients received a median of 6 cycles (2–10) of PLD + C. Major toxicities were; grade 3/4 neutropenia (7.5%), asymptomatic > 10% declines in LVEF (9%) (reversible upon discontinuation of PLD), grade 3/4 hand foot syndrome (6%). Other toxicities were uncommon and usually did not require discontinuation. The objective response rate (ORR) was 38% (4% CR and 34% PR), with an additional 32% having stable disease > 6 months for a clinical benefit of 70% (CB). ORR was similar for patients who had received adjuvant taxanes. Kaplan-Meyer estimated median time to progression was 31.5 weeks (23% progression free). Conclusions: The combination of PLD + C every 3 weeks in patients who have completed adjuvant anthracycline chemotherapy after more than one year prior is well tolerated and has a clinical benefit rate of 70%. This finding is similar to other commonly employed chemotherapeutic regimens for MBC and suggests that re-treatment with a non-cardiotoxic anthracycline following previous anthracycline therapy may be a reasonable therapeutic option for some patients.

[Table: see text]
Chemotherapy-related adverse events among breast cancer patients: A retrospective analysis of the SEER-Medicare database
Authors: Doyle J. J. , Hershman D. L. , Neugut A. I. , Stern L. S. , Katz L. M. , Dolgitser M.
Published: March 2020

10634

Background: Systemic chemotherapy is a common treatment option for female breast cancer (BC) patients. Chemotherapeutic agents often cause myelosuppression events (MEs), which may be costly and severe. Methods: Women ≥ 65 years of age diagnosed with stage I - III breast cancer from 1/1/92–12/31/99 within The Surveillance, Epidemiology and End Results (SEER)-Medicare database were analyzed. Using our extensive previous work with this BC cohort, a retrospective cohort study was conducted to assess the incidence and costs of MEs in chemotherapy-treated BC patients. Chemotherapies were captured using HCPCS codes; hospitalizations related to ME events (identified with ICD-9 diagnosis codes for anemia, thrombocytopenia, or leukopenia) were detected anytime after index date (date of first BC diagnosis). Total inpatient charges after index date were calculated. Results: 31,748 female BC patients were identified, 17.6% of whom received chemotherapy during follow-up. The mean age for these patients was 75.6 years (SD = 6.6, Range: 66–107). ME-related hospitalizations were significantly more likely in chemotherapy than non-chemotherapy patients, with 12.1% and 1.8%, respectively [OR = 2.3 (2.0–2.5)]; anemia in 8.6% and 5.1%, respectively [OR = 1.8 (1.6–1.0)], thrombocytopenia in 2.0% and 0.7%, respectively [OR = 2.9 (2.3–3.7)], and leukopenia in 4.4% and 0.5%, respectively [OR = 9.7 (7.8–12.1)]. Chemotherapy patients had significantly higher inpatient charges than patients without chemotherapy. Among chemotherapy patients, significantly higher inpatient charges were found in those with MEs than without ($15,297 vs. $4,211, p < 0.0001). Conclusion: Chemotherapy-related MEs were common among Medicare BC patients and led to substantial hospital charge increases.

No significant financial relationships to disclose.
Clinical pathologic status and expression of tumor markers in 5,000 Chinese breast cancers
Authors: Zhang J. , Hui R. , Liu P. , Yu Y. , Liu Y. , Hao X.
Published: March 2020

10644

Background: To evaluate the correlations of clinical pathologic status, expression of tumor markers and prognosis in 5000 Chinese breast cancer. Methods: A series primary operable breast cancers from 2002 to 2005 were studied in Tianjin Cancer Hospital. 55% of them are premenopausal and median age is 45 years old; 45% of them are postmenopausal and median age is 58 years old. All of the cases were reviewed by pathologist. ER, PgR, HER-2, p53, PCNA were measured by imunohistochemistry (IHC). Recurrence or metastasis were seen in 126 cases (median follow-up 30 months). Results: Negative axillary lymph nodes in 49.8%,and nodes positive in 50.2% (1 to 3 nodes positive in 28.3%, 4 to 9 nodes positive in 12.1% and over 10 nodes positive in 9.8%). Hermone receptor were observed in 51.7% ER+, 44.7% PgR+, 36.2% ER+/PgR+, 15.5% ER+/PgR−, 8.5% ER−/PgR+, 39.8% ER−/PgR−. HER-2 were observed in 56.8% her-2(-) ,21.7% her-2(+), 10.4% her-2(++) and 11.1% her-2(+++). p53 were observed in 34.4% (+) and PCNA were observed in 85.9% (+). Conclusions: First, Her-2 expression is shown positive correlation with positive axillary lymph nodes, especially remarkable correlated in the number of positive nodes in premenopausal patients. Second, Her-2 expression is shown negative correlation with ER and PgR. Third, Her-2 expression has no correlation with histologic grades of tumors and in some conditions has positive correlation with p53 and PCNA. Fifth, Her-2 expression has no correlation with recurrence, but positive correlation with distant metastasis. In general, Her-2 expression in breast cancer could be taken as the independent index for predicting prognosis. Status of axillary lymph nodes, expression of ER, PgR are the independent factor for expression of her-2. Expression of p53 and PCNA couldn’t be taken as the independent index for predict prognosis.

No significant financial relationships to disclose.
Gemcitabine and pegylated liposomal doxorubicin as salvage therapy in metastatic breast cancer (MBC)
Authors: Ghosn M. , El Karak F. , Kattan J. , Farhat F. , Nasr F. , Younes F. , Chahine G.
Published: March 2020

10645

Background: Doxorubicin and Taxanes are the most used drugs in front-line therapy for MBC. Patients with progressive disease refractory to these drugs are candidate to different salvage regimens. We investigated the combination of gemcitabine and pegylated liposomal doxorubicin as salvage option for these patients. Methods: This phase II study included gemcitabine (Gemzar) 1000 mg/m2 day 1, day 8 and pegylated liposomal doxorubicin (Caelyx) 25 mg/ m2 day 1 every 21 days. Inclusion criteria included measurable disease, performance status <2 according to the Zubrod scale, and no prior Gemzar or Caelyx treatment. Patients had to have one line of chemotherapy for metastatic disease. Responses were evaluated according to the RECIST criteria. Study Objectives were response rate, time to progression, and toxicity profile. Results: Between March 2003 and September 2005, 30 patients were enrolled. Mean age was 54 years [32–72]. 22 patients had two or more metastatic sites. Mean metastatic sites were liver (17), bone (12), lung (10) and pleura (5). 26 patients have had prior taxane treatment, and 21 prior anthracyclines. 144 cycles were delivered with a median of 6 per patient. There were 13 partial response, 11 stable disease, 5 progression and 1 unknown. Overall response rate was 43% with median response duration of 7 months (4–20+). 12 among the 13 objective responses were noted at visceral sites. During follow-up, 14 patients died. Median Survival time was 7 months. Median Time to progression was 7 months [0.5–20+]. The most encountered grade 3 or 4 toxicities were anemia in 5 pts, thrombopenia in one pt, neutropenia in 7 pts, neutropenic fever in 2 pts, hand-foot syndrome in 4 pts and stomatitis in 3 pts. No cardiotoxicity was noted. Conclusion: Salvage therapy for MBC could be successfully achieved by the combination of Gemcitabine and Pegylated liposomal doxorubicin (43% OR) according to our schedule. The tolerability was also acceptable. This schedule warrants further investigation.

No significant financial relationships to disclose.
Liposome-encapsulated doxorubicin plus cyclophosphamide as first-line therapy in metastatic breast cancer: A phase II study
Authors: Giotta F. , Lorusso V. , Monticelli G. , Calabrese P. , Filippelli G. , Valerio M. , Maiello E. , Quaranta M. , Colucci G.
Published: March 2020

10646

Background: The objective of this study is to evaluate the efficacy and toxicity of the liposome- encapsulated doxorubicin (TLC D-99) plus cyclophosphamide (CTX) as first-line treatment of metastatic breast cancer in light of the potential cardioprotective effect of TLC D-99 as compared to conventional doxorubicin. Furthermore the study is aimed also to understand the role of troponin I as a sensitive marker of left ventricular dysfunction. Methods: Sixty-three patients as defined in a phase II group sequential design will be enrolled. Since september 2004, fifty-four patients with untreated metastatic breast cancer were enrolled. They received TLC D-99 at the dosage of 60 mg/m2 plus CTX 600 mg/m2, with cycles repeated every three weeks. Cardiac function was assessed by ultrasonography at baseline and every three weeks, as well as troponin I dosage. Results: The principal characteristics of the 54 actually enrolled patients were as follows: median age 60 years (range 33–75), median WHO performance status 1 (range 0–2) and dominant disease site (viscera/bone/soft tissue) 36/10/8. To date 39 pts are evaluable: 8 complete responses and 18 partial responses were observed for an overall response rate of 67%; a further 9 pts had stable disease and the remaining 4 pts progressed. Median number of administered cycles was 6. Median duration of response was 10 months (range 3–15+) and median duration of survival was 12+ months (range 2+-15+). Hematological toxicity consisted in leucopenia (G1-G2) in 11 patients ed anemia (G1-G2) in 10 pts; G1 thrombocytopenia was observed only in 2 pts. Non-hematological toxicity was generally mild with G1-G2 nausea/vomiting in 14 pts e G2 mucositis in one patient. Hair-loss was registered in 12 pts and it was G2 in 6 pts. As to concer cardiac toxicity, one patient developed an asymptomatic 20% decline of left ventricular ejection fraction from the baseline value. Conclusions: The preliminary data show that the combination of TLC D-99 plus CTX is active and well tolerated, with no unexpected toxicity. The relationship between cardiac function and troponin I is underway.

No significant financial relationships to disclose.
Capecitabine + epirubicin + cyclophosphamide (CEX) has comparable safety to 5-FU + epirubicin + cyclophosphamide (FEC) as neoadjuvant therapy in patients (pts) with operable breast cancer (BC): Early safety findings from a randomized phase III trial
Authors: Roché H. , Deporte R. , Berton-Rigaud D. , Coudert B. , Tubiana-Mathieu N. , Ferrero J. , Orfeuvre H. , Audhuy B. , Bobadilla L. , Fumoleau P.
Published: March 2020

10655

Background: FEC100 is an established regimen in early-stage BC. Substituting capecitabine (X) for 5-FU in the neoadjuvant setting is logical. Here we present interim safety findings from a phase III trial of CEX vs. FEC as neoadjuvant chemotherapy in operable BC. Methods: Between Mar 04 and Jan 05, 60/182 planned pts were randomized to receive CEX (X 900mg/m2 bid d1–14, epirubicin 100mg/m2 and cyclophosphamide 500mg/m2 d1) or FEC (short i.v. infusions of 5-FU 500mg/m2, epirubicin 100mg/m2 and cyclophosphamide 500mg/m2 d1), q3w x4. Surgery with lymph node dissection was performed <5 wks (±1 wk) after last course of treatment. The primary endpoint was pCR. All patients received 4 courses of docetaxel 100 mg/m2 d1 after surgery. All adverse events (AEs) were graded according to the NCI-CTC (v3.0) and the Hand-Foot Syndrome (HFS) classification. Peripheral blood mononuclear cells (PBMC) were evaluated for dihydropyrimidine deshydrogenase (DPD) deficiency. Results: Baseline characteristics in the CEX (n = 30) vs. FEC (n = 30) groups: median age (49.1 vs. 50.8 years); ER+/PR+ (60%/53% vs. 73%/37%). The median no. of cycles received was 4 in each group. The overall rate of AEs was very similar in the two groups, with no difference in grade 3/4 neutropenia. FEC was associated with more grade 3/4 nausea/vomiting (see table) . No evidence of PBMC DPD deficiency was observed. Conclusions: CEX and FEC are well tolerated in neoadjuvant BC. CEX offers the potential benefit of greater tumor exposure to 5-FU. Our findings also indicate that toxicity is not related to DPD activity. Recruitment is ongoing.

[Table: see text]

[Table: see text]
Accelerated partial breast irradiation with interstitial brachytherapy as the sole modality of radiation for women with low risk early stage breast cancer
Authors: Budrukkar A. N. , Sarin R. , Jalali R. , Badwe R. , Parmar V. , Nadkarni M. , Deshpande D. , Shet T. , Dinshaw K.
Published: March 2020

10661

Purpose: The aim of the study is to evaluate the safety and feasibility of radical brachytherapy for accelerated partial breast irradiation (APBI) and to study the outcome with respect to local control and survival. Materials and Methods: During May 2000 to December 2004, 115 women participated in the ongoing prospective study of APBI using interstitial brachytherapy as the sole modality of radiation for early breast cancer. Women with age > 40 years, single tumour up to 3 cm without diffuse microcalcification and clinically negative axilla were considered suitable. Brachytherapy was done either intraoperatively during the breast conserving surgery or postoperatively using 2–4 planes. Tumor bed demarcation was done with radiopaque clips placed during surgery, CT scans, ultrasonography and/or fluoroscopy. Cavity with 1cm margin was treated based on orthogonal pair of X rays to a dose of 34 Gy in 10 fractions over 1 week with twice daily fractionation using high dose rate iridium source. Results: Implant was done postoperatively in 35 patients while in remaining patients it was done intraoperatively. Implant procedure was tolerated well by all the patients. In 8 patients only 3 or 4 fractions of HDR Brachytherapy were delivered and this was followed by 45 Gy/25 # whole breast radiation therapy for following reasons: positive nodes (4), EIC positive (3) and poor implant coverage (1). At a median follow up of 23 months, the actuarial local control rate is 100%. Three year actuarial disease free survival is 93% while the overall survival is 100%. Complications included fat necrosis in 5 and wound gape in 4 patients. Cosmesis was good to excellent in 60% of the patients. Conclusion: In this ongoing prospective study, APBI using radical interstitial implant was well tolerated and appears to be safe and feasible in appropriately selected patients. Further follow up is needed for confirm the long term safety of the procedure.

No significant financial relationships to disclose.
A phase II study of weekly gemcitabine and docetaxel in first and second line metastatic breast cancer
Authors: Isaacs C. , Wang A. , Warren R. , Wilkinson M. , Grana G. , Liu M. C. , Stearns V. , Park Y. H. , Novielli A.
Published: March 2020

10668

Background: Combination chemotherapy for metastatic breast cancer has generally been demonstrated to be associated with a higher response rate than single agent therapy, however such therapy is often accompanied by increased toxicity. Thus there is a need to develop well-tolerated combination chemotherapy regimens. Gemcitabine and docetaxel are both active agents in the treatment of this disease, and are effective and well tolerated when administered on a weekly basis. The purpose of this study was to evaluate the therapeutic efficacy and toxicity of weekly gemcitabine and docetaxel as first or second line treatment of metastatic breast cancer (MBC). Methods: Patients with measurable MBC who had received no more than 1 prior chemotherapy regimen in the metastatic setting were treated with gemcitabine 800 mg/m2 and docetaxel 30 mg/m2 on days 1 and 8 every 21 days without growth factor support. Results: Thirty-one patients were enrolled. Twenty-nine patients were evaluable for toxicity and 25 for efficacy. Median age was 55 (range 30 to 79). Visceral disease was the dominant site in 74% of patients. Doxorubicin and paclitaxel were previously administered in 74% and 48% of patients respectively. The overall response rate was 56% (complete response in 1 patient and partial responses in 13 patients). Stable disease was evident in 10 additional patients (38.4%). The progression free survival was 35 weeks (range 9 to 101 weeks) and the median overall survival was 17 months. Treatment was well tolerated with the majority of toxicities being grade 1 or 2 (85%). The only grade 3 (G3) or 4 (G4) toxicities observed were neutropenia in 14 participants (G3 41%; G4 7%), anemia in 4 (13%), G3 elevated transaminases in 3 (10%), G3 thrombocytopenia in 1 (3%), G3 flu-like symptoms in 2 (7%) and G3 edema in 1 (3%). Conclusions: The regimen of gemcitabine 800 mg/m2 and docetaxel 30 mg/m2 given two weeks out of three for MBC showed excellent overall response of 56% with very good tolerability. The findings from our trial compare well to the response rates of 36% to 79% seen in prior phase II trials utilizing higher doses of this combination chemotherapy.

[Table: see text]
Breast cancer wait times: Use of breast screening clinics affect presenting stage
Authors: Hodgins J. , Hamm C.
Published: March 2020

10686

Background: Wait times in the navigation of the diagnostic and therapeutic system of breast cancer have been increasingly investigated. It is inherently apparent that an earlier diagnosis would lead to an improved prognosis in breast cancer. In Ontario (Canada) Breast Screening Clinics (OBSC) allow direct access of patients to mammograms. Methods: A retrospective review of all breast cancer patients seen in the regional cancer centre in the year 2003 was performed. Wait times between the following events were recorded: first symptom to presentation to medical system, presentation to mammogram, mammogram to biopsy, biopsy to surgery, surgery to consultation at cancer centre. Results: In 2003, 277 new cases of breast cancer were seen at the regional cancer centre. Identified median waiting times were as follows: mammogram to diagnostic biopsy - 18.5 days, diagnostic biopsy to definitive surgery - 28 days; surgical consultation to definitive surgery - 13 days; definitive surgery to oncology consultation - 31 days. Some wait times were longer in those patients who did not have close geographic access to OBSC and a regional cancer centre: mammography to diagnostic biopsy was doubled (17 to 34 days) and surgical consult to surgical date was doubled (12 vs 26.5 days). Eighty per cent (n = 27) of patients identified by OBSC presented with Stage I or less breast cancer vs 37% of all other patients. Seventeen per cent of patients seen at the regional cancer centre were less than 50 years of age and not eligible for the OBSC. Conclusions: The wait times reported are in keeping with the current experience in Ontario, Canada.[1] It is most likely that access to a breast-screening clinic allows self-selection of a more highly motivated population. This population of patients consistently presented with earlier stage and more curable disease. The challenge that remains is to increase the number of patients that access breast-screening clinics. Presently, only 13% of presenting patients seen at the regional cancer centre were identified by the OBSC. We are identifying barriers to the use of this very effective strategy. [1] Cancer Care Ontario. Ontario Wait Times Strategy. www.health.gov.on.ca.

[Table: see text]
A phase II study of gemcitabine and liposomal doxorubicin (Lipo-Dox) as first line chemotherapy in the treatment of metastatic breast cancer
Authors: Yao N. , Kao W. , Chao T. , Hsieh R. , Lin J. , Su C. , Lo S.
Published: March 2020

10688

Background: To determine the overall objective response rate (ORR) of Lipo-Dox plus Gemcitabine in patients with metastatic breast cancer. Patients and Methods: We are conducting an open-label, non-comparative phase II clinical trial in Simon’s 2-stage optimal design to assess the efficacy and the safety of the treatment with Gemcitabine (Gems) plus Liposomal Doxorubicin (Lipo-Dox) in patients with metastatic breast cancer. All eligible subjects received Lipo-Dox 25 mg/m2 intravenous infusion over 1 hr and follow by gemcitabine 800 mg/m2 intravenously (iv) over 30 minutes on day 1, and receive gemcitabine 800 mg/m2 intravenously (iv) over 30 minutes only on day 8 in a 21-day cycle. Results: Between July 2004 and December 2005, a total of 21 patients were enrolled in the study and total of 136 cycles of chemotherapy were delivered with a median of six per patients (range 1–16). 17 patients (80.8%) who had at least one post-treatment evaluation and exposed to at least two cycles of treatment were included in this report. Characteristics of the 17 patients: All females; median age 52 years (range 36 - 68); 16 pts had a performance status (PS) of 0 or 1 and 1 had a PS of 2 (ECOG scale); Histology: All metastatic breast cancer. The response assessment of the 17 patients: Complete response was observed in 2, partial response in 5, stable disease in 8, and progressive disease in 2 patients. Overall response rate was 41.17%. Major grade 3/4 hematological toxicities were neutropenia in 9 pts, thrombocytopenia in 2 pt and leukopenia in 5 pts. Peripheral neuropathy was noted in 1 patient (grade 2). Other toxicities occurred during the treatment cycles were all manageable or tolerable. Patient recruitment, treatment and follow-up are still ongoing. Conclusion: Liposomal Doxorubicin used in the regimen reduces the incidence of alopecia (hair loss) to grade 1 compare to the conventional doxorubicin. This study, with an overall response rate of 41.1% (CR+PR) and a rate of stable disease of 47.05%, has shown a good activity with mild and acceptable toxicities of Gemcitabine (Gems) plus Liposomal Doxorubicin (Lipo-Dox) regimen in patients with metastatic breast cancer.

No significant financial relationships to disclose.
Docetaxel (T) followed by capecitabine (X) as first-line chemotherapy in patients (pts) with metastatic breast cancer (MBC): Preliminary findings from a phase II study
Authors: Bayo J. L. , Lomas M. , Salvador J. , Ruiz M. , Moreno A.
Published: March 2020

10692

Background: X and T are highly active single agents in MBC. The XT combination leads to superior overall survival (OS), time to progression (TTP) and response rate (RR) vs. T alone in anthracycline-pretreated MBC [O’Shaughnessy et al. J Clin Oncol 2002]. The aim of this trial was to evaluate the efficacy and safety of sequentially administered T then X as first-line treatment in MBC. Methods: Pts ≥ 18 years with previously untreated, HER2neu-negative MBC, ECOG PS ≤ 2, were included in this prospective, multicenter, non-randomized, phase II study. Pts received 3 cycles of T (100mg/m2 d1) followed by 3 cycles of X (1250mg/m2 bid d1–14), every 3 weeks. Results: To date, 38 pts are evaluable for safety and 33 pts for efficacy. Baseline characteristics: median age 54.4 years (range 33–76); PS ≥ 1 50%; 36 (95%) pts had previous (neo)adjuvant anthracyclines, 8 (21%) concomitant with paclitaxel. The most frequent metastatic sites were: bone 47%, nodes 39% and liver 36%. 69% of pts had ≥ 2 metastatic sites. To date, 38 pts have received 3 cycles of T and 33 have also received 3 cycles of X. A total of 195 cycles have been administered: T 108 cycles (median 3, range 1–3); X 87 cycles (median 3, range 1–3). Dose reductions and interruptions for T vs. X were 32 vs. 21% and 21 vs. 21%, respectively. Median relative dose intensity: T 0.97 (range 0.62–1.00), X 0.93 (range 0.26–1.00). T grade 3/4 toxicities (37 evaluable pts): asthenia 19%, mucositis 16%, nausea 13%, febrile neutropenia 11%, rash 5%, diarrhea 5%, infection 3%. X grade 3/4 toxicities (33 evaluable pts): hand-foot syndrome 9%, diarrhea 9%, vomiting 9%, asthenia 6%, nausea 3%, anorexia 3%. In the 33 pts evaluable for efficacy, the RR was 61%, including 4 CRs and 16 PRs. At a median follow-up of 6.1 months, median TTP has not yet been reached. Conclusions: These preliminary results show that the sequential regimen of T followed by X is feasible, effective and well tolerated in first-line MBC, although giving X before T should also be investigated. Findings from a recent trial of XT vs. T followed by X [Beslija et al. ECCO 2005] suggest that XT should be standard in fit poor-prognosis pts with aggressive disease.

No significant financial relationships to disclose.
Weekly carboplatin and nab-paclitaxel plus trastuzumab, or plus or minus bevacizumab: Clinical response in patients with breast cancer
Authors: Bernstein J. A. , Schubbert T. , Kong K. , Mehta R. S.
Published: March 2020

10699

Background: We previously reported a high, complete pathological remission rate in the neoadjuvant setting using carboplatin and metronomic paclitaxel plus or minus trastuzumab (TC ± H) following anthracycline therapy in patients with HER2+ and triple negative (ER-, PR- and HER2-) breast cancer, respectively. [SABCS 2004 abstract #1110 & SABCS 2005 # 5056] . We now report the clinical outcome of patients with breast cancer who were treated with carboplatin and a 130-nm, albumin-bound form of paclitaxel (nab-paclitaxel) plus trastuzumab (nab-TCH) in HER2+ patients, or plus or minus bevacizumab (nab-TC ± B) in HER2- patients or trastuzumab-exposed HER2+ patients. Methods: Twelve consecutive patients with performance status of 0–2 were treated in the neoadjuvant or metastatic setting from April 2005 to December 2005. Of the 12 patients, 10 received prior anthracycline therapy, 10 received prior taxane therapy, 4 received prior carboplatin therapy, and 4 received prior trastuzumab therapy. Patients received carboplatin calculated at an area under the concentration-time curve (AUC) of 2 and nab-paclitaxel at 80–100 mg/m2 weekly for 3 weeks followed by 1 week of rest. Either concurrent trastuzumab therapy was administered at 4 mg/kg loading dose, followed by maintenance dose of 2 mg/kg/wk (3 patients) or concurrent bevacizumab therapy was administered at 10mg/kg every 2 weeks (8 patients). One patient received carboplatin and nab-paclitaxel alone. Results: At this point, 9 pts are evaluable. Eight of the first 9 patients achieved a major clinical response (89%, 95% CI: 52%−100%), with 2 of the 8 responders obtaining a documented complete clinical response. Of the 3 remaining patients, 1 had clinical resolution of malignant ascites, 1 had normalization of tumor marker, and 1 had resolution of pain at early follow up. None of the patients had neutropenic fever or grade 3/4 neuropathy or arthralgia. Conclusions: The above combinations (nab-TCH or nab-TC ± B demonstrated promising antitumor activity in patients with breast cancer in the neoadjuvant and metastatic breast cancer. We have initiated a phase II study exploring nab-TCH and nab-TCB (sequenced after doxorubicin and cyclophosphamide) in the neoadjuvant setting.

[Table: see text]