Adjuvant chemotherapy in operable breast cancer: cyclophosphamide, methotrexate, and fluorouracil versus chlorambucil, methotrexate, and fluorouracil--11-year results of Swiss Group for Clinical Cancer Research trial SAKK 27/82.

Senn, Hans; Maibach, Rudolf; Castiglione, M.; Jungi, W. F.; Cavalli, F.; Leyvraz, Serge; Obrecht, J.P.; Schildknecht, O; Siegenthaler, Paul‐André

doi:10.1200/jco.1997.15.7.2502

Cited by 11 publications

(8 citation statements)

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“…[4][5][6][7][8][9][10] Nonetheless, our study shows that the overwhelming majority (80%) of node-positive patients who die within the 26 years after diagnosis still die of breast cancer recurrence despite the use of CMF-based adjuvant chemotherapy. In addition, the DFS at 20 years is only 23%.…”

Section: Discussionmentioning

confidence: 91%

“…Improvement in survival from adjuvant chemotherapy has also been shown in a population-based study. 7 Long-term outcome results have been reported in some individual trials of adjuvant chemotherapy, [8][9][10][11] but these reported results appropriately focus on the DFS and OS produced by one systemic treatment compared with a control treatment or no treatment. In this report, we focus not on which regimen produced a better result but on the natural history of node-positive breast carcinoma treated with CMF-based adjuvant chemotherapy.…”

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confidence: 99%

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Natural History of More Than 20 Years of Node-Positive Primary Breast Carcinoma Treated With Cyclophosphamide, Methotrexate, and Fluorouracil–Based Adjuvant Chemotherapy: A Study by the Cancer and Leukemia Group B

Weiss

Woolf

Demakos

et al. 2003

JCO

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Section: Discussionmentioning

confidence: 91%

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confidence: 99%

Natural History of More Than 20 Years of Node-Positive Primary Breast Carcinoma Treated With Cyclophosphamide, Methotrexate, and Fluorouracil–Based Adjuvant Chemotherapy: A Study by the Cancer and Leukemia Group B

Weiss

Woolf

Demakos

et al. 2003

JCO

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“…Chlorambucil was used in the treatment of breast and ovarian cancer until the late 1970s (Barker & Wiltshaw, ; Williams et al , ; Senn et al , ). These early studies did not show a significant benefit of chlorambucil, possibly because its effect was obscured by the lack of molecular markers (e.g.…”

Section: Discussionmentioning

confidence: 99%

“…ª 2019 The Authors EMBO Molecular Medicine 11: e9982 | 2019 below), these results support chlorambucil re-evaluation in cancer patients with BRCA mutations. Chlorambucil was used in the treatment of breast and ovarian cancer until the late 1970s (Barker & Wiltshaw, 1981;Williams et al, 1985;Senn et al, 1997). These early studies did not show a significant benefit of chlorambucil, possibly because its effect was obscured by the lack of molecular markers (e.g.…”

Section: Discussionmentioning

confidence: 99%

Chlorambucil targets BRCA 1/2‐deficient tumours and counteracts PARP inhibitor resistance

et al. 2019

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Due to compromised homologous recombination ( HR ) repair, BRCA 1‐ and BRCA 2‐ mutated tumours accumulate DNA damage and genomic rearrangements conducive of tumour progression. To identify drugs that target specifically BRCA 2‐deficient cells, we screened a chemical library containing compounds in clinical use. The top hit was chlorambucil, a bifunctional alkylating agent used for the treatment of chronic lymphocytic leukaemia ( CLL ). We establish that chlorambucil is specifically toxic to BRCA 1/2‐deficient cells, including olaparib‐resistant and cisplatin‐resistant ones, suggesting the potential clinical use of chlorambucil against disease which has become resistant to these drugs. Additionally, chlorambucil eradicates BRCA 2‐deficient xenografts and inhibits growth of olaparib‐resistant patient‐derived tumour xenografts ( PDTX s). We demonstrate that chlorambucil inflicts replication‐associated DNA double‐strand breaks ( DSB s), similarly to cisplatin, and we identify ATR , FANCD 2 and the SNM 1A nuclease as determinants of sensitivity to both drugs. Importantly, chlorambucil is substantially less toxic to normal cells and tissues in vitro and in vivo relative to cisplatin. Because chlorambucil and cisplatin are equally effective inhibitors of BRCA 2‐compromised tumours, our results indicate that chlorambucil has a higher therapeutic index than cisplatin in targeting BRCA ‐deficient tumours.

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“…After 1987, in prognostic surveys and various new adjuvant treatment studies, based on these surveys investigators separated patients into distinct groups according to the number of metastatic axillary lymph nodes (e.g. 1-3 and Ͼ 3 positive lymph nodes [8][9][10][11][12] ; 1-3, 4 -7, and Ͼ 7 positive lymph nodes 13 ; 1-3, 4 -10, and Ͼ 10 positive lymph nodes 14,15 ; and 1-3, 4 -9, and Ն 10 positive lymph nodes [16][17][18] ). In studies of the use of bone marrow-supported, adjuvant high-dose chemotherapy in high-risk patients, patient groups were comprised of those patients with Ն 10 metastatic lymph nodes.…”

Section: Discussionmentioning

confidence: 99%

Prognostic value of the 2002 TNM classification for breast carcinoma with regard to the number of metastatic axillary lymph nodes

Duraker¹,

Çaynak²

2005

Cancer

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BACKGROUNDThe American Joint Committee on Cancer (AJCC) TNM classification for breast carcinoma had not been changed for 15 years, since the publication of the third edition in 1987. However, in the sixth edition, published in 2002, significant modifications were made with regard to the number of metastatic axillary lymph nodes. The authors investigated whether the sixth edition of the TNM classification provided more reliable prognostic information compared with the third edition.METHODSThe records of 1230 patients who underwent surgery for invasive breast carcinoma between 1993 and 1999 were reviewed. Each patient was assigned to axillary lymph node and disease stage groups according to the 1987 and 2002 AJCC TNM classifications. Disease–free survival (DFS) curves were calculated and plotted using the Kaplan–Meier method and the two‐sided log‐rank test was used to compare the survival curves of the patient groups.RESULTSOf the 1067 patients who were classified as having Stages II and III disease according to the 1987 classification, 411 (38.5%) were shifted to higher disease stages using the 2002 classification. Among the 1987 Stage IIA, Stage IIB, and Stage IIIA patients, the DFS rates of the patients who were shifted to higher stages of disease were significantly worse than those of the patients for whom the stage of disease was not changed. Among those patients classified as having T4anyNM0 (Stage IIIB) disease according to the 1987 classification, there was no survival difference noted between those patients with T4N0,1,2M0 disease (who formed the Stage IIIB group) and those with T4N3M0 disease (who formed the Stage IIIC group) according to the new staging system. Of the 221 patients who formed the new Stage IIIC group, 12.2% were classified as having Stage IIA disease, 42.1% as having Stage IIB disease, 38.9% as having Stage IIIA disease, and 6.8% as having Stage IIIB disease according to the 1987 classification. The survival rates of these Stage IIA, Stage IIB, and Stage IIIA patients were not found to be significantly different; however, the survival of patients in the Stage IIIB group was found to be significantly worse than the survival of the patients in the other disease stage groupings, and the patients in the Stage IIIC group were not a prognostically homogeneous group. On the basis of these results, the authors placed patients with T4anyNM0 disease in the same group (Stage IIIB). When the 2002 classification was rearranged in this manner, patients with Stage IIIC disease formed a homogeneous group; the 5‐year DFS rate of patients with Stage IIIB disease was found to be significantly worse than that for patients with Stage IIIC disease (P = 0.0011).CONCLUSIONSIn the 2002 TNM classification for breast carcinoma, patients with T4anyNM0 disease should form a distinct stage grouping and this stage grouping (Stage IIIC) should be placed before Stage IV, and Stage IIIB disease groupings should include patients with T1,2,3N3M0 disease. In this way, the authors hope that the 2002 AJCC TNM classification, which provides more reliable prognostic information than the 1987 classification, will become more refined. Cancer 2005. © 2005 American Cancer Society.

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Adjuvant chemotherapy in operable breast cancer: cyclophosphamide, methotrexate, and fluorouracil versus chlorambucil, methotrexate, and fluorouracil--11-year results of Swiss Group for Clinical Cancer Research trial SAKK 27/82.

Cited by 11 publications

References 11 publications

Natural History of More Than 20 Years of Node-Positive Primary Breast Carcinoma Treated With Cyclophosphamide, Methotrexate, and Fluorouracil–Based Adjuvant Chemotherapy: A Study by the Cancer and Leukemia Group B

Natural History of More Than 20 Years of Node-Positive Primary Breast Carcinoma Treated With Cyclophosphamide, Methotrexate, and Fluorouracil–Based Adjuvant Chemotherapy: A Study by the Cancer and Leukemia Group B

Chlorambucil targets BRCA 1/2‐deficient tumours and counteracts PARP inhibitor resistance

Prognostic value of the 2002 TNM classification for breast carcinoma with regard to the number of metastatic axillary lymph nodes

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