The impact of epoetin-alpha on anemia, red blood cell (RBC) transfusions, and survival in breast cancer patients (pts) treated with dose-dense sequential chemotherapy: Mature results of an AGO phase III study (ETC trial)

569 Background: Dose-dense chemotherapy has been shown to have a significant advantage in disease-free survival (DFS) and overall survival (OS) in high risk breast cancer pts, but leads to a higher number of RBC transfusions (CALGB C9741, AGO-ETC). Controversial results have been reported regarding the influence of Epoetin-alpha on DFS and OS in cancer pts. Methods: From 12/98 until 4/03, 1,284 pts were recruited into a multi-center phase-III trial. Breast cancer pts with at least 4 involved lymph nodes and below 65 years of age were randomized between a standard regimen (4 × EC followed by 4 × Paclitaxel) and a dose-dense arm consisting of three courses each of epirubicin (150 mg/m2), paclitaxel (225 mg/m2) and cyclophosphamide (2,500 mg/m2) at 2 weeks interval (ETC). A second randomization ± Epoetin-alpha was performed in the ETC arm only (150 IU/kg/sc three times weekly). Results: In 10/06, 1255 (98%) pts were evaluable. 658 pts were randomized in the dose-dense ETC arm, of whom 333 received Epoetin-alpha. Median follow- up is 62 months. Anemia was seen significantly more often in the ETC-arm alone compared to treatment with Epoetin-alpha (p<0.0001). Altogether, 11% of all patients were treated with RBC transfusions. Standard EC->T treatment resulted in 1% RBC transfusions, but 28% in the ETC arm alone vs. 13% in the ETC + Epoetin-alpha-arm (p<0.0001) received RBC transfusions. Despite this significantly higher transfusion rate the median Hb-value dropped from 12,8g/dl at cycle 1 to 10,7g/dl at cycle 9 in the ETC arm alone. In contrast the same value remained stable with Epoetin-alpha (12,4g/dl at cycle 1 and 9 each). At a median follow-up of 62 months, there is no difference between the ETC-arm alone and the ETC + Epoetin-alpha-arm concerning 5-year DFS and OS ((71% vs. 72% (p=0.86) and 83% vs. 81% (p=0.89)). Conclusions: The dose-dense adjuvant ETC-regimen significantly improves DFS and OS but is combined with relevant hematological toxicity. Epoetin-alpha significantly reduces the number of RBC transfusions and prevents anemia. However, the prevention of anemia has no influence on DFS and OS in the adjuvant treatment with dose-dense ETC. [Table: see text]

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Updated Survival Analysis after a Median Follow-up of 12 Years of an Anthracycline-Containing Adjuvant Prospective Multicentre, Randomised Phase III Trial on Dose-Dense Chemotherapy in Primary Node-Positive, High-Risk Breast Cancer Patients

Breast Care ◽

10.1159/000491792 ◽

2018 ◽

Vol 14 (3) ◽

pp. 159-164

Author(s):

Mattea Reinisch ◽

Oleg Gluz ◽

Beyhan Ataseven ◽

Jens-Uwe Blohmer ◽

Marek Budner ◽

...

Keyword(s):

Breast Cancer ◽

Multivariable Analysis ◽

Disease Free Survival ◽

Distant Metastases ◽

Phase Iii ◽

Axillary Lymph Nodes ◽

Axillary Lymph ◽

Breast Cancer Patients ◽

Dose Dense

Purpose: Although dose-dense (dd) chemotherapy plays a fundamental role in the treatment of breast cancer (BC), a variety of trials have presented divergent survival results. Here, we present data of patients with more than 3 positive axillary lymph nodes (+aLN) receiving dd chemotherapy after a median follow-up period of 12.3 years. Methods: In the years 1996-2000, 231 patients with invasive BC, ≥pN2a and no evidence of distant metastases were recruited to receive treatment A, i.e. dd 3 × epirubicin (E, 90 mg/m2) + paclitaxel (P, 175 mg/m2) every 2 weeks (q2w) followed by 3 × cyclophosphamide (C)/methotrexate/5-fluorouracil (CMF, 600/40/600 mg/m2, q2w), or treatment B, i.e. 4 × E + C (C, 600 mg/m2) q3w followed by 3 × CMF q3w. Results: 113 patients in arm A and 113 patients in arm B were analysed after an updated median follow-up of 12.3 years. The median age was 55 years, with a median number of 6 +aLN, 50.4% had a T2 and 79.2% hormone receptor-positive BC. The disease-free survival (DFS) rate was 53.1% in arm A and 42.5% in arm B (adjusted p = 0.027). The overall survival (OS) rate was 54.9% in arm A and 48.7% in arm B (adjusted p = 0.058). In the multivariable analysis, the tumour burden was a significant predictor for DFS and OS. Conclusion: The adjuvant use of dd chemotherapy led to a statistically significant improvement of DFS after a follow-up of 12.3 years.

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10-yr follow-up results of NSABP B-32, a randomized phase III clinical trial to compare sentinel node resection (SNR) to conventional axillary dissection (AD) in clinically node-negative breast cancer patients.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.1000 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 1000-1000 ◽

Cited By ~ 5

Author(s):

Thomas B. Julian ◽

Stewart J. Anderson ◽

David N. Krag ◽

Seth P. Harlow ◽

Joseph P. Costantino ◽

...

Keyword(s):

Breast Cancer ◽

Clinical Trial ◽

Disease Free Survival ◽

Outcome Data ◽

Phase Iii ◽

Absolute Difference ◽

Breast Cancer Patients ◽

Significant Difference ◽

M Estimates

1000 Background: NSABP B-32, the largest surgical prospective randomized phase III trial was designed to compare overall survival (OS), disease-free survival (DFS), and morbidity between SNR alone vs SNR + AD in SN negative (-) pts. We present 10 yr outcome data for primary endpoints as well as updated data on the effect of occult metastases, found later in the SN by central, detailed pathologic analysis. Methods: 5,611 women with operable, clinically N0, invasive breast cancer were randomized to SNR + AD (Group [Grp] 1) or to SNR alone with AD only if SNs were positive (Grp2). 3,989 (71.1%) of 5,611 pts were SN-. 3,986 (99.9%) of these SN- pts had follow-up information: Grp 1: 1,975, Grp 2:2,011. Median time on study was 9.4 yrs. Cox proportional hazard models adjusting for study stratification variables were used to compare OS and DFS between the two groups. Two-sided p values were used. HR values > 1 indicate a more favorable outcome in Grp 1 Results: At 10 yrs, there continues to be no significant difference in OS between the two groups (HR: 1.11, p = 0.27). 10 yr Kaplan-Meier (K-M) estimates for OS are 87.8% for SNR alone and 88.9% for SNR + AD. There continues to be no significant difference in DFS between the two groups (HR: 1.01, p=0.92). 10-yr K-M estimates for DFS were 76.9% for both groups. Occult nodal disease was originally detected in 3,884 pts (15.8%) with SN- on initial H and E analysis. Comparisons between the groups with and without occult disease yielded an adjusted HR for OS: 1.25 (p = 0.08) with an absolute difference at 10 yrs of 2.8% and a HR for DFS: 1.24 (p = 0.018) with an absolute difference of 4.1%. The cumulative incidences of local-regional events were low (10-yr values: SNR 4.0%, SNR+AD, 4.3%) and not significant (HR: 0.95, p = 0.77). Conclusions: At 10 yrs there continues to be no significant differences in OS and DFS between SNR and SNR + AD in pts with negative SN. The relative increase in risk of DFS and OS for pts with occult SN metastases remains stable. Support: PHS grants: NSABP: U10CA-12027, U10CA-37377, U10CA-69651, U10CA-69974; VT Ca Cntr: P30 CA22435; DNK: 5RO1CA074137 NCI Dpt HHS. Clinical trial information: NCT00003830.

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Postmastectomy internal mammary node radiation in women with breast cancer: a long-term follow-up study

Journal of Radiotherapy in Practice ◽

10.1017/s1460396915000278 ◽

2015 ◽

Vol 14 (4) ◽

pp. 385-393 ◽

Cited By ~ 3

Author(s):

Budhi S. Yadav ◽

Suresh C. Sharma ◽

Sushmita Ghoshal ◽

Rakesh K. Kapoor ◽

Narendra Kumar

Keyword(s):

Breast Cancer ◽

Disease Free Survival ◽

Breast Cancer Patients ◽

Internal Mammary Node ◽

Supraclavicular Fossa ◽

Long Term Follow Up ◽

Internal Mammary ◽

Postmastectomy Radiation Therapy ◽

The Impact

AbstractBackgroundTo observe the impact of internal mammary node irradiation (IMNI) on disease-free survival (DFS) and overall survival (OS) in postmastectomy women with breast cancer.Materials and methodsBetween 1978 and 1996, 153 women with stage II–III breast cancer were treated with postmastectomy radiation therapy (RT) with IMNI. Their clinical, pathological and treatment characteristics were matched with 166 patients without IMNI. The RT dose was 35 Gy to the chest wall and 40 Gy to the supraclavicular fossa and IMN in 15 fractions over 3 weeks with photons. All patients were planned with two-dimensional technique. Adjuvant chemotherapy was administered to 41% and endocrine therapy to 52% of the patients. Symptomatic patients were further assessed for late pulmonary and late cardiac effects.ResultsThe median follow-up period was 203 months (range, 182–224), and the median age was 44 years (range 20–73 years). The IMNI group had significantly more right-sided and inner/central quadrant tumours. Other characteristics were comparable between both the groups. DFS at 15 years with and without IMNI was 64 and 49%, respectively (p=0·0001). On multivariate analysis, IMNI was an independent, positive predictor of DFS [hazard ratio (HR), 2·89;p=0·0001]. Benefit of IMNI on DFS was more apparent in inner/central tumours [HR, 1·48; 95% confidence interval (CI), 1·02–2·88], N2–N3 patients (HR, 1·44; 95% CI, 1·09–2·10) and in those who received chemotherapy (HR, 1·70; 95% CI, 1·07–2·71). OS at 15 years with and without IMNI was 68 and 54%, respectively (p=0·0001). Late pulmonary toxicity was 1·5 versus 1% with and without IMNI, respectively. Late cardiac toxicity was 2·6 versus 1·8% with and without IMNI, respectively.ConclusionsIMNI significantly improved DFS and OS in postmastectomy breast cancer patients. Benefit of IMNI was seen in patients with central/inner tumours and N2–N3 disease. Late cardiopulmonary toxicities were comparable between the two groups.

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Adjuvant phase III trial to compare intense dose-dense adjuvant treatment with EnPC to dose dense, tailored therapy with dtEC-dtD for patients with high-risk early breast cancer (GAIN-2).

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.tps1137 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. TPS1137-TPS1137 ◽

Cited By ~ 1

Author(s):

Volker Moebus ◽

Helmut Forstbauer ◽

Grischa Wachsmann ◽

Andreas Schneeweiss ◽

Angelika Ober ◽

...

Keyword(s):

Breast Cancer ◽

High Risk ◽

Safety Data ◽

Disease Free Survival ◽

Phase Iii ◽

Breast Cancer Patients ◽

Luminal A ◽

Ki 67 ◽

Phase Iii Trial ◽

Dose Dense

TPS1137 Background: Intense dose-dense (idd) chemotherapy (CT) significantly improves overall survival in breast cancer patients. Two preceding trials explored iddETC vs a dd combination of EC-TX (GAIN) and dtEC-dtD vs conventional dosed FEC-D (Panther). Nab-paclitaxel (nP) provides a better toxicity profile and higher efficacy compared to solvent based taxanes and might be preferred in an idd regimen. Methods: This is a multicenter, prospective, randomized, open-label phase III trial comparing iddEnPC or dtEC-dtD as adjuvant CT. Pts with uni- or bilateral primary high risk node-positive (N+) breast cancer (BC) and centrally confirmed ER/PR/HER2 and Ki-67 status can be included. Luminal A pts are only recruited with N+ ≥4. Randomization to iddEnPC or dtEC-dtD will be stratified by biological subtype defined by hormone receptor, HER2 and Ki-67. The iddEnPC arm will receive epirubicin (150mg/m2) q2w x3 followed by nP (260-330mg/m2, dose to be determined in run-in phase) q2w x3, followed by cyclophosphamide (2g/m2) q2w x3. The dtEC-dtD arm will receive EC (38-120/450-1200 mg/m2) q2w x4 followed after 1 wk rest by docetaxel (60-100mg/m2) q2w x4. GAIN-2 will compare toxicity and efficacy of an idd regimen (EnPC) vs a dd regimen with modification of single doses depending on individual hematological and non-hematological toxicities. Primary objective is invasive disease-free survival (IDFS). Secondary objectives are survival by other definitions, compliance, safety, side effects of taxanes and subgroup analyses (by 0-3, 4-9 or 10+ involved nodes and Ki-67). Efficacy analyses are planned 60 mths after end of accrual, safety interim analyses after 200 and 900 pts have completed CT. It was assumed that dtEC-dtD will achieve a 5-yr IDFS of 75% and ddEnPC will improve IDFS to 79% (HR 0.819) with a power of 80% (α=0.05, ß= 0.2).GAIN-2 is registered under NCT01690702 Results: 75pts were recruited since 1stOct 2012. Recruitment (in total 2886 pts) is planned for 36 mths in 80-100 sites in Germany. Run-in safety data to be presented. Conclusion: GAIN-2 will compare the efficacy of adjuvant iddEnPC and dtEC-dtD in pts with early N+ BC. Clinical trial information: NCT01690702.

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Is Adjuvant Tamoxifen Recommended in Post-Menopausal Node-Negative Breast Cancer Patients with High Estrogen Receptor Values?

The International Journal of Biological Markers ◽

10.1177/172460080001500202 ◽

2000 ◽

Vol 15 (2) ◽

pp. 135-138 ◽

Cited By ~ 3

Author(s):

J.-L. Floiras ◽

K. Hacene ◽

F. Turpin ◽

F. Spyratos

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Disease Free Survival ◽

Adjuvant Tamoxifen ◽

Breast Cancer Patients ◽

Node Negative ◽

Node Negative Breast Cancer ◽

Post Menopausal ◽

The Impact

The impact of ER levels on the response to tamoxifen was evaluated in 1,623 postmenopausal primary breast cancer patients treated at our center (median follow-up 8.2 years). In patients receiving adjuvant tamoxifen a significantly longer disease-free survival (DFS) was observed when ER levels were elevated (p<0.00001). Very high ER (>424 fmol/mg protein) appeared to be detrimental in node-negative patients not treated with tamoxifen.

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Stromal Cell-Derived Factor 1α (SDF-1α) in Invasive Breast Cancer: Associations with Vasculo-Angiogenic Factors and Prognostic Significance

Cancers ◽

10.3390/cancers13081952 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1952

Author(s):

Elżbieta Zarychta ◽

Barbara Ruszkowska-Ciastek ◽

Kornel Bielawski ◽

Piotr Rhone

Keyword(s):

Breast Cancer ◽

Invasive Breast Cancer ◽

Stromal Cell ◽

Prognostic Significance ◽

Disease Free Survival ◽

Breast Cancer Patients ◽

Roc Curve Analysis ◽

Stromal Cell Derived Factor ◽

A Prospective Study

(1) Background: Tumour angiogenesis is critical for the progression of neoplasms. A prospective study was designed to examine the utility of stromal cell-derived factor 1α (SDF-1α) and selected vasculo-angiogenic parameters for estimating the probability of disease relapse in 84 primary, operable invasive breast cancer (IBrC) patients (40 (48%) with stage IA and 44 (52%) with stage IIA and IIB). (2) Methods: We explored the prognostic value of the plasma levels of SDF-1α, vascular endothelial growth factor A (VEGF-A), the soluble forms of VEGF receptors type 1 and 2, and the number of circulating endothelial progenitor cells (circulating EPCs) in breast cancer patients. The median follow-up duration was 58 months, with complete follow-up for the first event. (3) Results: According to ROC curve analysis, the optimal cut-off point for SDF-1α (for discriminating between patients at high and low risk of relapse) was 42 pg/mL, providing 57% sensitivity and 75% specificity. Kaplan–Meier curves for disease-free survival (DFS) showed that concentrations of SDF-1α lower than 42 pg/dL together with a VEGFR1 lower than 29.86 pg/mL were significantly associated with shorter DFS in IBrC patients (p = 0.0381). Patients with both SDF-1α lower than 42 pg/dL and a number of circulating EPCs lower than 9.68 cells/µL had significantly shorter DFS (p = 0.0138). (4) Conclusions: Our results imply the clinical usefulness of SDF-1α, sVEGFR1 and the number of circulating EPCs as prognostic markers for breast cancer in clinical settings.

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Sequential Versus Concurrent Trastuzumab in Adjuvant Chemotherapy for Breast Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2011.36.7045 ◽

2011 ◽

Vol 29 (34) ◽

pp. 4491-4497 ◽

Cited By ~ 178

Author(s):

Edith A. Perez ◽

Vera J. Suman ◽

Nancy E. Davidson ◽

Julie R. Gralow ◽

Peter A. Kaufman ◽

...

Keyword(s):

Breast Cancer ◽

Adjuvant Chemotherapy ◽

Growth Factor Receptor ◽

Disease Free Survival ◽

Standard Of Care ◽

Phase Iii ◽

P Value ◽

Sequential Administration ◽

Taxane Chemotherapy

Purpose NCCTG (North Central Cancer Treatment Group) N9831 is the only randomized phase III trial evaluating trastuzumab added sequentially or used concurrently with chemotherapy in resected stages I to III invasive human epidermal growth factor receptor 2–positive breast cancer. Patients and Methods Patients received doxorubicin and cyclophosphamide every 3 weeks for four cycles, followed by paclitaxel weekly for 12 weeks (arm A), paclitaxel plus sequential trastuzumab weekly for 52 weeks (arm B), or paclitaxel plus concurrent trastuzumab for 12 weeks followed by trastuzumab for 40 weeks (arm C). The primary end point was disease-free survival (DFS). Results Comparison of arm A (n = 1,087) and arm B (n = 1,097), with 6-year median follow-up and 390 events, revealed 5-year DFS rates of 71.8% and 80.1%, respectively. DFS was significantly increased with trastuzumab added sequentially to paclitaxel (log-rank P < .001; arm B/arm A hazard ratio [HR], 0.69; 95% CI, 0.57 to 0.85). Comparison of arm B (n = 954) and arm C (n = 949), with 6-year median follow-up and 313 events, revealed 5-year DFS rates of 80.1% and 84.4%, respectively. There was an increase in DFS with concurrent trastuzumab and paclitaxel relative to sequential administration (arm C/arm B HR, 0.77; 99.9% CI, 0.53 to 1.11), but the P value (.02) did not cross the prespecified O'Brien-Fleming boundary (.00116) for the interim analysis. Conclusion DFS was significantly improved with 52 weeks of trastuzumab added to adjuvant chemotherapy. On the basis of a positive risk-benefit ratio, we recommend that trastuzumab be incorporated into a concurrent regimen with taxane chemotherapy as an important standard-of-care treatment alternative to a sequential regimen.

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