Leukemogenic potential of adjuvant chemotherapy for early-stage breast cancer: the Eastern Cooperative Oncology Group experience.

1995 ◽  
Vol 13 (7) ◽  
pp. 1557-1563 ◽  
Author(s):  
M S Tallman ◽  
R Gray ◽  
J M Bennett ◽  
D Variakojis ◽  
N Robert ◽  
...  

PURPOSE Since large numbers of patients with early-stage breast cancer now receive adjuvant chemotherapy containing cyclophosphamide, a known leukemogenic agent, it is important to determine the risk of secondary acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Therefore, we identified all cases of AML or MDS developing in patients treated on six clinical adjuvant chemotherapy trials conducted by the Eastern Cooperative Oncology Group (ECOG). PATIENTS AND METHODS The patients population included 2,638 patients with previously untreated primary operable breast cancer entered onto six clinical trials conducted by the ECOG between 1978 and 1987. There are 19,200 persons-years of follow-up study and a mean follow-up duration of 7.3 years. Clinical data were obtained from flow sheets submitted to the ECOG Data Management Office. RESULTS Of 2,638 patients at risk with 19,200 person-years of follow-up study, three patients developed MDS (two with a characteristic cytogenetic abnormality). Two patients developed acute leukemia; however, one had adult T-cell leukemia associated with human T-lymphotrophic virus type 1 (HTLV-1) and a second patient developed AML after receiving additional cyclophosphamide for metastatic breast cancer. The estimated incidence rate for MDS is three per 19,200 or 16 per 100,000 person-years of follow-up study with a 95 percent confidence interval of three to 46 per 100,000 person-years. If all five patients (three MDS and two acute leukemia) are included, the estimated incidence rate is five per 19,200 or 26 per 100,000 person-years of follow-up study with a 95 percent confidence interval of eight to 61 per 100,000 person-years. CONCLUSION These data suggest that the risk of secondary AML or MDS among patients with early breast cancer who receive standard-dose cyclophosphamide-containing adjuvant chemotherapy is not much higher than in the general population. However, physicians must remain alert to the possible long-term consequences of alkylating agent and anthracycline-based chemotherapy.

2004 ◽  
Vol 22 (14_suppl) ◽  
pp. 8027-8027
Author(s):  
M. Guida ◽  
M. R. Barulli ◽  
C. Stangalino ◽  
L. Mariani ◽  
A. Caraceni ◽  
...  

2014 ◽  
Vol 32 (26_suppl) ◽  
pp. 93-93
Author(s):  
Rebekah Young ◽  
Kimberly Gergelis ◽  
Shalom Kalnicki ◽  
Jana Lauren Fox

93 Background: Women with early-stage TN breast cancers are at increased risk for recurrence (RR) compared to other molecular subtypes, and are often treated with mastectomy without local adjuvant therapy. We wish to evaluate the RR for these women. Methods: In this single institution retrospective study, women with T1-2N0 TN breast cancer who underwent mastectomy between 2008-12 were identified from tumor registry. Adjuvant chemotherapy was allowed, but adjuvant radiotherapy (RT) was excluded. Of 3,000 cases reviewed, 52 women were identified. Median age was 58.5 (30–90). Lesions were high-grade (83%), and T1-2 (47%, 53%). 21 women (42%) had at least 1 risk factor. 5 women were BRCA+. Women underwent total mastectomy or modified radical mastectomy, and the majority (84%) had adjuvant chemotherapy. Results: At a median follow-up of 3.5 years (6-71 months), there were 8 recurrences (15.4%). 3 (5.8% of cohort) were locoregional (LR) only (2 chest wall (CW) and 1 ipsilateral axilla), 6 (11.5%) involved a concurrent LR and distant recurrence, and 2 (3.8%) were distant only. Median time to recurrence was 17.3 months. The isolated LR recurrences (LRR) were at 14, 15.6 and 15.1 months. Most women (41, 78.8%) were alive with NED. 3 were alive with disease, underdoing treatment, and 1 woman was disease free after treatment for CW recurrence. 8 patients (15.4%) are deceased, half from their cancer. On univariate analysis, there was no significant correlation (p>0.05) between age or high-risk features and RR (STATA v 11). Conclusions: T1-2N0 breast cancer patients are believed to have a low RR following mastectomy. TN disease, however, is more aggressive, and the question of irradiating early stage disease after mastectomy has arisen. A single institution, retrospective study found women with T1-2N0 TN disease fare better with BCT that includes RT, compared to mastectomy alone. Other studies have shown no statistical difference in RR between these 2 groups. We found an isolated LRR rate at 3.5 years of 5.8%. Follow-up and ultimately prospective data is needed to determine whether the isolated LRR warrants a change in treatment recommendations for this pt subset.


The Breast ◽  
2014 ◽  
Vol 23 (4) ◽  
pp. 445-452 ◽  
Author(s):  
Rune Gärtner ◽  
Mathias Kvist Mejdahl ◽  
Kenneth Geving Andersen ◽  
Marianne Ewertz ◽  
Niels Kroman

2010 ◽  
Vol 20 (10) ◽  
pp. 1102-1107 ◽  
Author(s):  
Inger Schou Bredal ◽  
Leiv Sandvik ◽  
Rolf Karesen ◽  
Oivind Ekeberg

2015 ◽  
Vol 33 (4) ◽  
pp. 340-348 ◽  
Author(s):  
Antonio C. Wolff ◽  
Amanda L. Blackford ◽  
Kala Visvanathan ◽  
Hope S. Rugo ◽  
Beverly Moy ◽  
...  

Purpose Outcomes for early-stage breast cancer have improved. First-generation adjuvant chemotherapy trials reported a 0.27% 8-year cumulative incidence of myelodysplastic syndrome/acute myelogenous leukemia. Incomplete ascertainment and follow-up may have underestimated subsequent risk of treatment-associated marrow neoplasm (MN). Patients and Methods We examined the MN frequency in 20,063 patients with stage I to III breast cancer treated at US academic centers between 1998 and 2007. Time-to-event analyses were censored at first date of new cancer event, last contact date, or death and considered competing risks. Cumulative incidence, hazard ratios (HRs), and comparisons with Surveillance, Epidemiology, and End Results estimates were obtained. Marrow cytogenetics data were reviewed. Results Fifty patients developed MN (myeloid, n = 42; lymphoid, n = 8) after breast cancer (median follow-up, 5.1 years). Patients who developed MN had similar breast cancer stage distribution, race, and chemotherapy exposure but were older compared with patients who did not develop MN (median age, 59.1 v 53.9 years, respectively; P = .03). Two thirds of patients had complex MN cytogenetics. Risk of MN was significantly increased after surgery plus chemotherapy (HR, 6.8; 95% CI, 1.3 to 36.1) or after all modalities (surgery, chemotherapy, and radiation; HR, 7.6; 95% CI, 1.6 to 35.8), compared with no treatment with chemotherapy. MN rates per 1,000 person-years were 0.16 (surgery), 0.43 (plus radiation), 0.46 (plus chemotherapy), and 0.54 (all three modalities). Cumulative incidence of MN doubled between years 5 and 10 (0.24% to 0.48%); 9% of patients were alive at 10 years. Conclusion In this large early-stage breast cancer cohort, MN risk after radiation and/or adjuvant chemotherapy was low but higher than previously described. Risk continued to increase beyond 5 years. Individual risk of MN must be balanced against the absolute survival benefit of adjuvant chemotherapy.


2004 ◽  
Vol 22 (14_suppl) ◽  
pp. 8027-8027
Author(s):  
M. Guida ◽  
M. R. Barulli ◽  
C. Stangalino ◽  
L. Mariani ◽  
A. Caraceni ◽  
...  

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e12509-e12509
Author(s):  
Lei Lei ◽  
Han-Ching Chan ◽  
Wang Xiao Jia ◽  
Tzu-Pin Lu ◽  
Skye Hung-Chun Cheng

e12509 Background: Dutch clinical risk criteria (low-risk definition: age > 35 years and (grade 1 with tumor ≤3cm, grade 2 with tumor ≤2cm, or grade 3 with tumor ≤1cm) have been used to stratify the benefit of MammaPrint and Oncotype DX for the decision-making regarding adjuvant chemotherapy for early-stage luminal breast cancer. We propose that the criteria could help to identify low-risk patients who could barely benefit from multi-gene testing. Methods: Breast cancer patients from Taiwan Cancer Database initially treated with primary surgeries between 2008 and 2012 who met the following criteria: (1) pathologic node-negative, (2) hormone receptor-positive, (3) HER2-negative, (4) undergone hormonal therapy, and (5) a minimum follow-up time of 5-year if free from any event, were enrolled in this study. Out of the total 2679 eligible patients, 1074 (40.1%) patients received adjuvant chemotherapy in addition to endocrine therapy. The study endpoints included breast cancer-specific survival (BCSS) and overall survival (OS). Kaplan-Meier statistics estimated the difference between clinical outcomes in low- and high-risk groups. Results: The median follow-up time of BSCC and OS was 5.9 years (range, 0-7 years) and 5.8 years (range, 0-7 years), respectively. There were statistical significances of 5-year BCSS (n = 2679) and 5-year OS (n = 2636) between low-risk and high-risk groups (in both endpoints, P < 0.0001). According to the Dutch criteria, low-risk patients with and without adjuvant chemotherapy had a 5-year BCSS of 99.0% vs. 99.2% and a 5-year OS of 98.4% vs. 97.4%, respectively. High-risk patients with and without adjuvant chemotherapy had a 5-year BCSS of 97.7% vs. 98.1% and a 5-year OS of 96.4% vs. 95.3%, respectively. Conclusions: The benefit of chemotherapy in low-risk patients classified by Dutch criteria might be very small since the breast cancer mortality was less than 1% with a minimum of 5-year follow-up. Dutch criteria cannot identify high-risk patients who would benefit from chemotherapy. We assumed that multi-gene testing in low-risk patients would not be cost-effective.


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