Second malignancies following adjuvant chemotherapy:6-year results from a Belgian randomized study comparing cyclophosphamide, methotrexate and 5-fluorouracil (CMF) with an anthracycline-based regimen in adjuvant treatment ofnode-positive breast cancer patients

Bernard-Marty, Chantal; Mano, Max S.; Paesmans, Marianne; Accettura, Caterina; Munoz-Bermeo, R.; Richard, Thomas J.; Kleiber, K.; Cardoso, Fátima; Lobelle, Jean Pierre; Larsimont, Denis; Piccart, Martine; Leo, Angelo Di

doi:10.1093/annonc/mdg204

Cited by 46 publications

(35 citation statements)

References 17 publications

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“…Over the past few decades, adjuvant chemotherapy for BC has undergone major changes, expanding from the classical cyclophosphamide, methotrexate and 5-fluorouracil (CMF) regimen used in the 1970s, to anthracycline-containing regimens in the 1990s, to the recent incorporation of taxanes (paclitaxel and docetaxel) into anthracycline-based regimens (7)(8)(9)(10) for the treatment of node-positive or even lower-risk patients. In 1976, Bonadonna et al (11) reported the efficacy of CMF as an adjuvant treatment for patients with node-positive BC.…”

Section: Overview Of Adjuvant Therapymentioning

confidence: 99%

Second malignancies after breast cancer: The impact of adjuvant therapy

Dong

Chen

2014

Molecular and Clinical Oncology

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Abstract. Second malignant neoplasms (SMNs) are potentially life-threatening late sequelae of the adjuvant therapy for breast cancer (BC). The increased risk of SMNs is associated with adjuvant chemotherapy (development of secondary acute myeloid leukemia and myelodysplastic syndrome) and hormonal therapy (risk of uterine cancer secondary to tamoxifen treatment). Previous studies have demonstrated an increased risk of SMNs associated with alkylating agents, topoisomerase-II inhibitors, granulocyte-stimulating factors and estrogen receptor modulators. Furthermore, analytical investigations have demonstrated that BC patients may be at an increased risk of leukemia following chemotherapy. In addition, correlations between an increased dose of hormonal therapy and solid tumor risk have been identified. Considering the ongoing alterations in the treatment of BC, with respect to lowering the daily as well as the cumulative dose of chemotherapeutic agents, it is anticipated that leukemias will have a considerably lower impact on BC survivors in the future. However, diligent follow-up is required to accurately evaluate the long-term risks associated with chemotherapy.

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Section: Overview Of Adjuvant Therapymentioning

confidence: 99%

Second malignancies after breast cancer: The impact of adjuvant therapy

Dong

Chen

2014

Molecular and Clinical Oncology

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“…6 Decisions regarding the use of adjuvant therapy are strongly influenced by the risk of disease recurrence and death. These risks are assessed by examining prognostic factors of breast cancer, such as axillary lymph-node metastasis, age, and some tumor characteristics (e.g., size, histologic and nuclear grades, and estrogen and progesterone receptor status).…”

Section: A U T H O R P R O O Fmentioning

confidence: 99%

Relationship between Genotoxic Effects of Breast Cancer Treatments and Patient Basal DNA Integrity

Ceballos

Funes

Massa

et al. 2014

J Environ Pathol Toxicol Oncol

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Radiotherapy and chemotherapy cause genotoxic side effects that are highly variable among patients. In this study, we evaluated DNA integrity using the comet assay in peripheral blood lymphocytes from breast cancer patients before ("pre-treatment patients"; n = 47) and after ("post-treatment patients"; n = 24) radiotherapy and/or chemotherapy treatment and from healthy donors (n = 15). Comet evaluation was made by visual (types 0-4) and digital (percentage of DNA remaining in the comet head = % head DNA) analysis. The association between the level of DNA damage and cancer prognostic factors was assessed. The treatments caused a significant increase in DNA damage registered by both visual (p < 0.001) and digital (p < 0.001) analyses. No significant associations between the level of DNA damage in pre-treatment patients and cancer prognostic factors were found. A significant correlation between the comet results from each patient before and after treatment (r = 0.64, p = 0.001) was observed. The % head DNA in post-treatment samples from patients with a high level of DNA damage before treatment (30.3 ± 3.1%, p < 0.01) was lower than in post-treatment samples from patients with a low-to-medium level of DNA damage before therapy (49.2 ± 4.4%). These results support the usefulness of the comet assay as a sensitive technique to evaluate basal DNA status and DNA damage caused by cancer treatments. The comet assay could contribute to treatment decisions, especially by taking into account the patient's basal DNA damage before therapy.

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“…A separate analysis of this trial by Bernard-Marty noted that a total of 16 patients treated with high-dose EC developed second malignancies, compared with nine for intermediate-dose EC and 11 for CMF. 37 In the highdose EC arm there were three cases of acute myelogenous leukemia (AML) and one case of non-Hodgkin's lymphoma (NHL). Hence, although anthracyclinebased regimens appear more effective overall, they may be associated with an increased risk of second malignancies, especially AML, when anthracyclines are given in high total dose and this needs to be considered when selecting treatment for individual patients.…”

Section: Cmf Versus Other Regimens: Activity Anthracycline-containingmentioning

confidence: 99%

“…The coordinators of this trial concluded that prolongation of conventional anthracycline-based treatment beyond the current standard of four to six cycles is not to be recommended, predominantly because of the increased risk of AML. 37 With respect to second malignancies after taxanebased regimens, most trials are as yet not mature enough to report on second malignancies. However, the CALGB 9344 trial noted no difference in the rate of second malignancies between those patients who received AC only compared with those that received AC followed by paclitaxel.…”

Section: Second Malignanciesmentioning

confidence: 99%

Adjuvant chemotherapy for early breast cancer: Is cyclophosphamide, methotrexate and 5‐fluorouracil still the standard?

Stuart-Harris

Odell

Sturgiss

2005

Asia-Pac J Clncl Oncology

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Background : Oral cyclophosphamide, methotrexate and 5-fluorouracil (CMF) was one of the first combination chemotherapy regimens used as adjuvant chemotherapy for early breast cancer. The value of CMF in reducing both recurrence and mortality from early breast cancer has been firmly established by the overviews of randomized trials of polychemotherapy, which have used CMF as their standard. The purpose of this review is to review the usage of oral CMF and the variants of CMF and to compare both the activity and side-effects of CMF with more modern adjuvant chemotherapy regimens. Results : There are many variants of CMF but oral (or classical) CMF is probably more effective than intravenous (i.v.) CMF, at least in metastatic disease. When oral CMF is used in early breast cancer it reduces the annual hazard of recurrence by 24% and the annual hazard of mortality by 14% overall, although it appears more effective in younger patients. Anthracycline-based regimens are more effective for reduction of recurrence and mortality than CMF but are associated with more severe acute toxicities and potentially greater risks of long-term toxicities. Taxane-based regimens have not been compared with CMF directly; however, in comparison with anthracycline-based regimens, the early information suggests that taxane-based regimens may be even more effective. The acute toxicities of taxane-based regimens are probably less severe than anthracycline-based regimens, but their long-term toxicities are less well defined. Conclusion : Oral CMF as adjuvant chemotherapy for early breast cancer is the standard by which newer regimens are compared. Although newer regimens appear more effective than CMF, they may be associated with greater acute and potentially greater long-term toxicities than CMF. Thus, CMF remains the standard by which future regimens should be judged, either directly or indirectly.

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Second malignancies following adjuvant chemotherapy:6-year results from a Belgian randomized study comparing cyclophosphamide, methotrexate and 5-fluorouracil (CMF) with an anthracycline-based regimen in adjuvant treatment ofnode-positive breast cancer patients

Cited by 46 publications

References 17 publications

Second malignancies after breast cancer: The impact of adjuvant therapy

Second malignancies after breast cancer: The impact of adjuvant therapy

Relationship between Genotoxic Effects of Breast Cancer Treatments and Patient Basal DNA Integrity

Adjuvant chemotherapy for early breast cancer: Is cyclophosphamide, methotrexate and 5‐fluorouracil still the standard?

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