Data on the recurrence of breast tumors fit a model in which dormant cells are subject to slow attrition but can randomly awaken to become malignant

TY - JOUR

T1 - Data on the recurrence of breast tumors fit a model in which dormant cells are subject to slow attrition but can randomly awaken to become malignant

AU - Stein, Wilfred D

AU - Litman, Thomas

PY - 2006

Y1 - 2006

N2 - We successfully modeled the recurrence of tumors in breast cancer patients, assuming that: (i) A breast cancer patient is likely to have some circulating metastatic cells, even after initial surgery. (ii) These metastatic cells are dormant. (iii) The dormant cells are subject to attrition by the body's immune system, or by random apoptosis or senescence. (iv) Recurrence suppressor mechanisms exist. (v) When such genes are disabled by random mutations, the dormant metastatic cell is activated, and will develop to a cancer recurrence. The model was also fitted to data on the survival of pancreatic cancer patients. The time course of cancer recurrence in a group of poor prognosis breast cancer patients could not be linked to the over- (or under-) expression of any gene in the primary tumors from which the recurrent tumors derived. Thus, the recurrence of the tumor in breast cancer patients appears to be a random event. Inasmuch as the kinetics of cancer recurrence in published data sets closely follows the model found for the appearance of sporadic retinoblastoma, tumor recurrence could be triggered by mutations in awakening- suppressor mechanisms. The retinoblastoma tumor suppressor gene was identified by tracing its occurrence in familial retinoblastoma pedigrees. Will it be possible to track the postulated cancer recurrence, awakening suppressor gene(s) in early recurrence breast cancer patients?

AB - We successfully modeled the recurrence of tumors in breast cancer patients, assuming that: (i) A breast cancer patient is likely to have some circulating metastatic cells, even after initial surgery. (ii) These metastatic cells are dormant. (iii) The dormant cells are subject to attrition by the body's immune system, or by random apoptosis or senescence. (iv) Recurrence suppressor mechanisms exist. (v) When such genes are disabled by random mutations, the dormant metastatic cell is activated, and will develop to a cancer recurrence. The model was also fitted to data on the survival of pancreatic cancer patients. The time course of cancer recurrence in a group of poor prognosis breast cancer patients could not be linked to the over- (or under-) expression of any gene in the primary tumors from which the recurrent tumors derived. Thus, the recurrence of the tumor in breast cancer patients appears to be a random event. Inasmuch as the kinetics of cancer recurrence in published data sets closely follows the model found for the appearance of sporadic retinoblastoma, tumor recurrence could be triggered by mutations in awakening- suppressor mechanisms. The retinoblastoma tumor suppressor gene was identified by tracing its occurrence in familial retinoblastoma pedigrees. Will it be possible to track the postulated cancer recurrence, awakening suppressor gene(s) in early recurrence breast cancer patients?

KW - Breast Neoplasms

KW - Female

KW - Follow-Up Studies

KW - Genes, Neoplasm

KW - Humans

KW - Models, Biological

KW - Neoplasm Metastasis

KW - Neoplastic Cells, Circulating

KW - Pancreatic Neoplasms

KW - Prognosis

KW - Recurrence

KW - Survival Analysis

M3 - Journal article

C2 - 17102622

SN - 1538-4101

VL - 5

SP - 2348

EP - 2353

JO - Cell Cycle

JF - Cell Cycle

IS - 20

ER -