Clonal Hematopoiesis as a Marker of Genetic Damage Following Adjuvant Chemotherapy for Breast Cancer: Pilot Study to Evaluate Incidence

1999 ◽  
Author(s):  
Charles A. Coltman ◽  
Jr.
Keyword(s):  
Breast Cancer ◽  
Pilot Study ◽  
Adjuvant Chemotherapy ◽  
Genetic Damage ◽  
Clonal Hematopoiesis

5-Year Results of Dose-Intensive Sequential Adjuvant Chemotherapy for Women With High-Risk Node-Positive Breast Cancer: A Phase II Study

1999 ◽  
Vol 17 (4) ◽  
pp. 1118-1118 ◽  
Author(s):  
C. Hudis ◽  
M. Fornier ◽  
L. Riccio ◽  
D. Lebwohl ◽  
J. Crown ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Pilot Study ◽  
Adjuvant Chemotherapy ◽  
Disease Free Survival ◽  
Free Survival ◽  
Dose Dense ◽  
Disease Free

PURPOSE: We conducted a phase II pilot study of dose-intensive adjuvant chemotherapy with doxorubicin followed sequentially by high-dose cyclophosphamide to determine the safety and feasibility of this dose-dense treatment and to estimate the disease-free and overall survival in breast cancer patients with four or more involved axillary lymph nodes. PATIENTS AND METHODS: Seventy-three patients received adjuvant treatment with four cycles of doxorubicin 75 mg/m2 as an intravenous bolus every 21 days, followed by three cycles of cyclophosphamide 3,000 mg/m2 every 14 days with granulocyte colony-stimulating factor support. RESULTS: Seventy-one patients were assessable, and all but two completed all planned chemotherapy. There was no treatment-related mortality. The most common toxicity was neutropenic fever, which occurred in 39% of patients. Median disease-free survival is 66 months (95% confidence interval, 34 to 98 months), and median overall survival has not yet been reached. At 5 years of follow-up, the disease-free survival is 51.7%, and overall survival is 60.0%. There is no long-term treatment-related toxicity, and no cases of acute myelogenous leukemia or myelodysplastic syndrome have been observed. CONCLUSION: Our pilot study of doxorubicin followed by cyclophosphamide demonstrates the safety and feasibility of the sequential dose-dense plan. Long-term follow-up, although noncomparative, is promising. However, this regimen is associated with a higher incidence of toxicity (and also higher costs) than the standard dose and schedule of doxorubicin and cyclophosphamide, and therefore it should not be used as conventional therapy in the absence of demonstrated improvement of outcome. Randomized trials testing the dose-dense approach have been completed but not yet reported. Because the sequential plan can decrease overlapping toxicities, it is an appropriate platform for the addition of newer active agents, such as taxanes or monoclonal antibodies.

Screening for clonal hematopoiesis as a predictive marker for development of t-AML following adjuvant therapy for breast cancer (S0012)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 11051-11051
Author(s):  
M. L. Slovak ◽  
V. Bedell ◽  
D. Lew ◽  
K. S. Albain ◽  
G. K. Ellis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Neoadjuvant Therapy ◽  
Weekly Paclitaxel ◽  
Genetic Damage ◽  
Study Objective ◽  
Hematopoietic Stem ◽  
Clonal Hematopoiesis ◽  
Post Surgery

11051 Background: A serious complication associated with breast cancer treatment is the increased risk for development of therapy-related acute myeloid leukemia (t-AML). To evaluate and possibly identify patients (pts) at high risk for development of t-AML, the Southwest Oncology Group asked whether dose-intensive adjuvant regimens for high risk breast cancer pts induced genetic damage to hematopoietic stem cells (HSC), defined by the emergence of clonal hematopoiesis, an early marker of HSC damage. Methods: 274 pts consented to the clonal hematopoiesis study objective of S0012, a randomized clinical trial of standard doxorubicin and cyclophosphamide followed by weekly paclitaxel (arm 1, 129 pts) vs. weekly doxorubicin and daily oral cyclophosphamide plus G-CSF followed by weekly paclitaxel (arm 2, 145 pts) as neoadjuvant therapy for inflammatory and locally advanced breast cancer. Two different clonality assays were used: the HUMARA (HUMan Androgen Receptor) Assay to estimate the incidence of early genetic damage by clonal proliferation and microsatellite instability (MSI) testing at 5 loci (Bat 26, Bat 40, APC, Mfd, D2S123), common ‘hotspots‘ in t-AML, to screen for loss of heterozygosity or defective DNA mismatch repair mechanisms. Blood samples were evaluated prior to treatment and at 6 and 12 mos post-surgery for emergence of clonal hematopoiesis. Results: Of the 274 pts enrolled, follow-up clonal hematopoiesis samples were available for 195 pts; 96 pts on arm 1 and 99 pts on arm 2. Both HUMARA and MSI results were negative for clonal hematopoiesis in 96% of samples analyzed. In 14 cases, the HUMARA assay suggested that a clonal population was present, but MSI analysis was negative. No cases were HUMARA+/MSI+. With a median follow-up of 19.6 mos, only one pt has developed t-AML 3 yr 5 mos post randomization. Her clonal hematopoiesis test samples at 6 and 12 mos following treatment were negative. Conclusions: Clonal hematopoiesis assays performed within the first year following neoadjuvant therapy and surgery on S0012 failed to identify an emerging clonal HSC population. Longer clinical follow-up will be necessary to define the positive predictive value of detecting clonal hematopoiesis in the 14 HUMARA+/MSI- cases as a harbinger of t-AML. No significant financial relationships to disclose.

Offering a choice between two adjuvant chemotherapy regimens: a pilot study to develop a decision aid for women with breast cancer

1999 ◽  
Vol 37 (3) ◽  
pp. 283-291 ◽  
Author(s):  
Ellen Irwin ◽  
Andrew Arnold ◽  
Timothy J. Whelan ◽  
Leonard M. Reyno ◽  
Patricia Cranton
Keyword(s):  
Breast Cancer ◽  
Pilot Study ◽  
Adjuvant Chemotherapy ◽  
Decision Aid

scholarly journals The effects of short-term fasting on tolerance to (neo) adjuvant chemotherapy in HER2-negative breast cancer patients: a randomized pilot study

BMC Cancer ◽  
2015 ◽  
Vol 15 (1) ◽  
Author(s):  
Stefanie de Groot ◽  
Maaike PG Vreeswijk ◽  
Marij JP Welters ◽  
Gido Gravesteijn ◽  
Jan JWA Boei ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Pilot Study ◽  
Adjuvant Chemotherapy ◽  
Cancer Patients ◽  
Breast Cancer Patients ◽  
Short Term ◽  
Neo Adjuvant Chemotherapy
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