PURPOSE: To comparatively analyse the risk of recurrence at given times after surgery for breast cancer patients receiving or not receiving adjuvant CMF. PATIENTS AND METHODS: A total of 1452 node positive patients, who entered controlled clinical trials carried out at the Milan Cancer Institute and underwent radical or modified radical mastectomy for operable breast cancer, were examined. In 575 cases no further treatment was performed, whereas 877 pts were given 6 or 12 courses of adjuvant Cyclophosphamide, Methotrexate, Fluorouracil (CMF). The recurrence risk was estimated by the event-specific hazard rate for first failure and distant metastases, and, following Efron, hazard rates were fitted by logistic regression models. RESULTS: The hazard rate for first failure and distant metastases showed a double peaked pattern for both treated patients and controls, with a first major peak at about 18-24 months from surgery (early metastases), a second minor peak at the 5th-6th year, and a tapered plateau-like tail extending over 10 years from surgery (late metastases). As expected, the recurrence risk of CMF treated patients was lower than the corresponding risk of patients undergoing surgery only. However, the difference was highly evident for early recurrences, while it declined and disappeared afterwards. CONCLUSION: Our findings confirm previous reports on patients not receiving adjuvant chemotherapy, suggesting that the recurrence risk for operable breast cancer has a multipeak pattern. As far as CMF treated patients are concerned, the unchanged peak timing together with the early recurrence risk reduction in comparison to controls are much more consistent with the real nonappearance of some early recurrences (putatively 'cured' patients) than with the delay in their manifestation. As late relapsing patients seem to have at most marginal benefits from adjuvant CMF, ways to recognize patients doomed to have late recurrence and new ways for treating micrometastases resulting in late recurrences are required.
PURPOSE: To comparatively analyse the risk of recurrence at given times after surgery for breast cancerpatients receiving or not receiving adjuvant CMF. PATIENTS AND METHODS: A total of 1452 node positive patients, who entered controlled clinical trials carried out at the Milan Cancer Institute and underwent radical or modified radical mastectomy for operable breast cancer, were examined. In 575 cases no further treatment was performed, whereas 877 pts were given 6 or 12 courses of adjuvant Cyclophosphamide, Methotrexate, Fluorouracil (CMF). The recurrence risk was estimated by the event-specific hazard rate for first failure and distant metastases, and, following Efron, hazard rates were fitted by logistic regression models. RESULTS: The hazard rate for first failure and distant metastases showed a double peaked pattern for both treated patients and controls, with a first major peak at about 18-24 months from surgery (early metastases), a second minor peak at the 5th-6th year, and a tapered plateau-like tail extending over 10 years from surgery (late metastases). As expected, the recurrence risk of CMF treated patients was lower than the corresponding risk of patients undergoing surgery only. However, the difference was highly evident for early recurrences, while it declined and disappeared afterwards. CONCLUSION: Our findings confirm previous reports on patients not receiving adjuvant chemotherapy, suggesting that the recurrence risk for operable breast cancer has a multipeak pattern. As far as CMF treated patients are concerned, the unchanged peak timing together with the early recurrence risk reduction in comparison to controls are much more consistent with the real nonappearance of some early recurrences (putatively 'cured' patients) than with the delay in their manifestation. As late relapsing patients seem to have at most marginal benefits from adjuvant CMF, ways to recognize patients doomed to have late recurrence and new ways for treating micrometastases resulting in late recurrences are required.
Authors: Jason R Ruth; Dhruv K Pant; Tien-Chi Pan; Hans E Seidel; Sanjeethan C Baksh; Blaine A Keister; Rita Singh; Christopher J Sterner; Suzanne J Bakewell; Susan E Moody; George K Belka; Lewis A Chodosh Journal: Breast Cancer Res Date: 2021-06-04 Impact factor: 8.408
Authors: Romano Demicheli; Gianni Bonadonna; William J M Hrushesky; Michael W Retsky; Pinuccia Valagussa Journal: Breast Cancer Res Date: 2004-10-11 Impact factor: 6.466
Authors: Megan C Madonna; Joy E Duer; Brock J McKinney; Enakshi D Sunassee; Brian T Crouch; Olga Ilkayeva; Matthew D Hirschey; James V Alvarez; Nirmala Ramanujam Journal: NPJ Breast Cancer Date: 2022-09-26
Authors: Michael Retsky; Gianni Bonadonna; Romano Demicheli; Judah Folkman; William Hrushesky; Pinuccia Valagussa Journal: Breast Cancer Res Date: 2004-05-14 Impact factor: 6.466
Authors: Nuria Ribelles; Lidia Perez-Villa; Jose Manuel Jerez; Bella Pajares; Luis Vicioso; Begoña Jimenez; Vanessa de Luque; Leonardo Franco; Elena Gallego; Antonia Marquez; Martina Alvarez; Alfonso Sanchez-Muñoz; Luis Perez-Rivas; Emilio Alba Journal: Breast Cancer Res Date: 2013 Impact factor: 6.466