| Breast cancer recurrence dynamics following adjuvant CMF is consistent with tumor dormancy and mastectomy-driven acceleration of the metastatic process. | |
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MedLine Citation:
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PMID: 15956037 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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PURPOSE: The aim of this study was to better understand human breast cancer biology by studying how the timing of metastasis following primary resection is affected by adjuvant CMF (cyclophoshamide, methotrexate, 5-fluorouracil) chemotherapy. PATIENTS AND METHODS: Discrete hazards of recurrence and recurrence risk reductions for treated patients relative to controls were analyzed for all patients enrolled in two separate randomized clinical trials [study 1 (386 women): no further treatment versus 12 cycles of CMF; study 2 (459 women): six versus 12 cycles of CMF] and a historical group (396 women: surgery alone) of axillary node-positive patients undergoing mastectomy. RESULTS: (i) Nearly all CMF benefit occurs during the first 4 years following resection/chemotherapy. (ii) The CMF recurrence rate reduction is largely restricted to two specific spans. These temporally separate recurrence clusters occur during the first and third year of follow-up, while the second-year recurrences are weakly affected. (iii) Prolonging adjuvant treatment from 6 to 12 months partially alters this recurrence timing, without appreciably affecting the overall recurrence rate. (iv) These effects upon the dynamics of post-resection occurrence are menopausal status-independent. CONCLUSIONS: At least two different therapeutically vulnerable proliferative events, resulting in clinical appearance of two metastasis temporally distinct clusters of post-resection cancer recurrence, apparently occur during the administration of adjuvant chemotherapy. Metastases that transpire outside of these temporal windows are refractory to adjuvant therapy. The dynamics of both post-treatment recurrence risk and CMF effectiveness are similar for both pre- and postmenopausal women, suggesting that post-resection mechanisms by which chemotherapy prevents metastases are similar, but of different magnitude in pre- and postmenopausal women. These findings are consistent with a metastasis model that includes tumor dormancy in specific micrometastatic phases (single cells and avascular foci) and with the acceleration of the metastatic process by the surgical resection of the primary breast cancer. |
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Authors:
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R Demicheli; R Miceli; A Moliterni; M Zambetti; W J M Hrushesky; M W Retsky; P Valagussa; G Bonadonna |
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Publication Detail:
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Type: Journal Article; Randomized Controlled Trial Date: 2005-06-14 |
Journal Detail:
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Title: Annals of oncology : official journal of the European Society for Medical Oncology / ESMO Volume: 16 ISSN: 0923-7534 ISO Abbreviation: Ann. Oncol. Publication Date: 2005 Sep |
Date Detail:
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Created Date: 2005-08-17 Completed Date: 2006-01-27 Revised Date: 2006-04-24 |
Medline Journal Info:
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Nlm Unique ID: 9007735 Medline TA: Ann Oncol Country: England |
Other Details:
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Languages: eng Pagination: 1449-57 Citation Subset: IM |
Affiliation:
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Istituto Nazionale Tumori, Milan, Italy. demicheli@istitutotumori.mi.it |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antineoplastic Combined Chemotherapy Protocols
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administration & dosage,
therapeutic use* Breast Neoplasms / drug therapy, pathology*, surgery Chemotherapy, Adjuvant Combined Modality Therapy Cyclophosphamide / administration & dosage, therapeutic use Disease-Free Survival Fluorouracil / administration & dosage, therapeutic use Humans Mastectomy* Methotrexate / administration & dosage, therapeutic use Neoplasm Metastasis* Recurrence |
| Chemical | |
Reg. No./Substance:
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0/CMF regimen; 50-18-0/Cyclophosphamide; 51-21-8/Fluorouracil; 59-05-2/Methotrexate |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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