The timing of breast cancer recurrence after mastectomy and adjuvant CMF chemotherapy supports a dormancy-based model for metastatic development

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9573 Background: Adjuvant chemotherapy may be regarded as a probe revealing features of the metastasis development, by changes induced in the recurrence timing. Methods: Two randomized clinical trials and a historical group of axillary node positive patients undergoing mastectomy, all treated at the Ist. Naz. Tumori of Milan, were analyzed. Study 1 involved 386 women (no further treatment vs. 12 cycles of CMF), Study 2 involved 459 women (6 vs. 12 cycles of CMF) and the historical group involved 575 patients (mastectomy alone). Discrete hazards of early recurrence (over 4 years), and recurrence risk reductions for treated patients relative to controls were estimated. Results: 1) recurrence rate reduction by CMF is mainly restricted to specific, temporally separate recurrence clusters at the first and third year, while the second-year recurrences are weakly affected; 2) prolonging adjuvant treatment from 6 to 12 months partially changes the recurrence timing, without affecting the overall treatment effectiveness; 3) findings are menopausal status independent. Conclusions: At least two different proliferative events, resulting in clinical appearance of the two metastasis clusters, should be assumed as occurring during treatment administration, when some other metastases are in a rather refractory status. The time distributions of both post treatment recurrence risk and CMF effectiveness are similar for both menopausal statuses, suggesting that the metastatic mechanisms may be substantially the same, although differently modulated. Cytotoxic chemotherapy changes differing recurrence dynamics of pre and post menopausal women to a common later recurrence pattern. These findings give further support to a metastasis development model based on tumour dormancy in specific micro-metastatic phases (single cells and avascular foci) and on acceleration of the metastatic process due to surgery. No significant financial relationships to disclose.