scholarly journals Opposing Effects of Granulocyte Colony-Stimulating Factor on the Initiation and Progression of Breast Cancer Bone Metastases

2021 ◽  
pp. molcanres.0243.2021
Author(s):  
Toru Hiraga ◽  
Susumu Ito ◽  
Toshihide Mizoguchi
Keyword(s):  
Breast Cancer ◽  
Bone Metastases ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Opposing Effects ◽  
Stimulating Factor

scholarly journals Granulocyte Colony Stimulating Factor Expression in Breast Cancer and Its Association with Carbonic Anhydrase IX and Immune Checkpoints

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1022
Author(s):  
Shawn C. Chafe ◽  
Nazia Riaz ◽  
Samantha Burugu ◽  
Dongxia Gao ◽  
Samuel C. Y. Leung ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Carbonic Anhydrase ◽  
Immune Checkpoint ◽  
Positive Association ◽  
Carcinoma Cells ◽  
Carbonic Anhydrase Ix ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Significant Positive Association ◽  
Stimulating Factor

Purpose: Granulocyte colony-stimulating factor (G-CSF) and hypoxia modulate the tumour immune microenvironment. In model systems, hypoxia-induced carbonic anhydrase IX (CAIX) has been associated with G-CSF and immune responses, including M2 polarization of macrophages. We investigated whether these associations exist in human breast cancer specimens, their relation to breast cancer subtypes, and clinical outcome. Methods: Using validated protocols and prespecified scoring methodology, G-CSF expression on carcinoma cells and CD163 expression on tumour-associated macrophages were assayed by immunohistochemistry and applied to a tissue microarray series of 2960 primary excision specimens linked to clinicopathologic, biomarker, and outcome data. Results: G-CSFhigh expression showed a significant positive association with ER negativity, HER2 positivity, presence of CD163+ M2 macrophages, and CAIX expression. In univariate analysis, G-CSFhigh phenotype was associated with improved survival in non-luminal cases, although the CAIX+ subset had a significantly adverse prognosis. A significant positive association was observed between immune checkpoint biomarkers on tumour-infiltrating lymphocytes and both G-CSF- and CAIX-expressing carcinoma cells. Immune checkpoint biomarkers correlated significantly with favourable prognosis in G-CSFhigh/non-luminal cases independent of standard clinicopathological features. Conclusions: The prognostic associations linking G-CSF to immune biomarkers and CAIX strongly support their immunomodulatory roles in the tumour microenvironment.

Effect of different chemotherapy regimens on peripheral-blood stem-cell collections in patients with breast cancer receiving granulocyte colony-stimulating factor.

1997 ◽  
Vol 15 (2) ◽  
pp. 684-690 ◽  
Author(s):  
T Demirer ◽  
C D Buckner ◽  
B Storer ◽  
K Lilleby ◽  
S Rowley ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Peripheral Blood ◽  
Peripheral Blood Stem Cell ◽  
Reference Group ◽  
Blood Stem Cell ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Cd34 Cells ◽  
Stimulating Factor

PURPOSE To evaluate the effects of chemotherapy regimens on peripheral-blood stem-cell (PBSC) yields in patients with breast cancer who receive granulocyte colony-stimulating factor (G-CSF). PATIENTS AND METHODS One hundred patients with breast cancer received cyclophosphamide 4 g/m2 for dose (CY) (n = 10), CY and etoposide 600 mg/m2 (CE) (n = 13), CE and cisplatin 105 mg/m2 (CEP) (n = 19), or CY and paclitaxel 170 mg/m2 (n = 58), followed by G-CSF. PBSC collections were initiated when the WBC count recovered to greater than 1 x 10(9)/L. A multivariate analysis was undertaken to evaluate the effects of different chemotherapy regimens and patient variables on PBSC collections as measured by the yield of CD34+ cells. RESULTS The medians of average daily CD34+ cell yields for patients who received paclitaxel plus CY, CE, and CEP with G-CSF were 12.9, 11.03, and 5.37 x 10(6)/kg, respectively, compared with 2.02 x 10(6)/kg in the reference group that received CY with G-CSF (P = < .0001, .002, and .09, respectively). On first-day collections, patients who received paclitaxel plus CY, CE, and CEP with G-CSF yielded medians of 11.07, 8.09, and 3.52 x 10(6) CD34+ cells/kg, respectively, compared with 0.90 x 10(6)/kg in the reference group that received CY with G-CSF (P = .0006, .02, and .09, respectively). The number of previous cycles of chemotherapy, previous radiotherapy, marrow involvement, and phase and stage of disease did not have statistically significant effects on CD34+ cell yield. CONCLUSION Combination chemotherapy regimens were superior to single-agent CY for the mobilization of CD34+ cells.

Five-day course of granulocyte colony-stimulating factor in patients with prolonged neutropenia after adjuvant chemotherapy for breast cancer is a safe and cost-effective schedule to maintain dose-intensity.

1996 ◽  
Vol 14 (5) ◽  
pp. 1573-1580 ◽  
Author(s):  
A Ribas ◽  
J Albanell ◽  
J Bellmunt ◽  
L A Solé-Calvo ◽  
B Bermejo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Treatment ◽  
Dose Intensity ◽  
Cost Effective ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Median Percentage ◽  
Subsequent Cycle ◽  
Intent To Treat ◽  
Stimulating Factor

PURPOSE To analyze the safety and efficacy of a short course of granulocyte colony-stimulating factor (G-CSF) to maintain dose-intensity of subsequent cycles of chemotherapy after a prior episode of prolonged neutropenia, without febrile complications, in patients receiving adjuvant treatment for breast cancer. PATIENTS AND METHODS Thirty-two patients undergoing adjuvant cyclophosphamide, methotrexate, and fluorouracil (CMF) or doxorubicin-CMF for stages I to II breast cancer were included after having chemotherapy delays due to neutropenia (absolute neutrophil count [ANC] < 1.5 x 10(9)/L) on day 22. G-CSF was administered subcutaneously on days 15 to 19 of each subsequent cycle. RESULTS None of the patients included in this study had to be admitted to the hospital for fever and neutropenia. The median percentage of the projected dose-intensity for CMF or doxorubicin-CMF on an intent-to-treat basis was 0.994, which was significantly higher than the delivered dose-intensity before the start of G-CSF treatment (P < .0001). Patients who received concomitant G-CSF and radiotherapy achieved a similar dose-intensity as patients who did not undergo radiotherapy. Seven patients discontinued G-CSF treatment due to musculoskeletal pain. These patients had more subsequent cycle delays because of day 22 neutropenia than the 25 patients who followed the G-CSF schedule (P = .0028). CONCLUSION A 5-day course of G-CSF in patients with prior chemotherapy delays due to prolonged neutropenia seems to be a safe and cost-effective schedule to maintain CMF or doxorubicin-CMF dose-intensity in the adjuvant treatment of breast cancer.

Phase I/II study of 72-hour infusional paclitaxel and doxorubicin with granulocyte colony-stimulating factor in patients with metastatic breast cancer.

1996 ◽  
Vol 14 (3) ◽  
pp. 774-782 ◽  
Author(s):  
J S Fisherman ◽  
K H Cowan ◽  
M Noone ◽  
A Denicoff ◽  
S Berg ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Phase I ◽  
Overall Response Rate ◽  
Response Rate ◽  
Metastatic Breast ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Stimulating Factor ◽  
Doxorubicin Administration

PURPOSE We conducted a phase I/II trial of concurrently administered 72-hour infusional paclitaxel and doxorubicin in combination with granulocyte colony-stimulating factor (G-CSF) in patients with previously untreated metastatic breast cancer and bidimensionally measurable disease. PATIENTS AND METHODS We defined the maximum-tolerated dose (MTD) of concurrent paclitaxel and doxorubicin administration and then studied potential pharmacokinetic interactions between the two drugs. Forty-two patients who had not received prior chemotherapy for metastatic breast cancer received 296 total cycles of paclitaxel and doxorubicin with G-CSF. RESULTS The MTD was determined to be paclitaxel 180 mg/m2 and doxorubicin 60 mg/m2 each by 72-hour infusion with G-CSF. Diarrhea was the dose-limiting toxicity (DLT) of this combination, with three of three patients developing abdominal computed tomographic (CT) scan evidence of typhlitis (cecal thickening) at the dose level above the MTD. All patients developed grade 4 neutropenia (absolute neutrophil count [ANC] < 500 microL), generally less than 5 days in duration. This combination was generally safely administered at dose levels at or below the MTD. The overall response rate was 72% (28 of 39 patients; 95% confidence interval [CI], 55% to 85%), with 8% complete responses (CRs) (three of 39; 95% CI, 2% to 21%) and a median response duration of 9 months. The median overall survival time for all patients is 23 months, with a median follow-up duration of 28 months. Pharmacokinetic studies showed that administration of paclitaxel and doxorubicin together by 72-hour infusion did not affect the steady-state concentrations of either drug. CONCLUSION Concurrent 72-hour infusional paclitaxel and doxorubicin can be administered safely, but is associated with significant toxicity. The overall response rate of this combination in untreated metastatic breast cancer patients is similar to that achieved with other doxorubicin-based combination regimens. The modest complete response rate achieved suggests that this schedule of paclitaxel and doxorubicin administration does not produce significant additive or synergistic cytotoxicity against breast cancer.

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