Dormancy and spontaneous recurrence of human breast cancer in vitro.

Monolayer cultures of the human breast cancer cell line MDA-361 require insulin for growth and for maintenance of viability, as is evidenced by rapid and complete degeneration of the cells after the removal of insulin from the medium. Detachment from the plastic surface occurs within 24 to 48 hr, and the rare (less than 0.1%) cell that remains attached doubles every 3 to 4 weeks. Multicellular tumor spheroids, derived from this same tumor cell line, enter a dormant phase which lasts approximately 6 weeks, when insulin is removed from the medium. During this dormant period the multicellular tumor spheroids appear healthy and gradually become less dependent on and more responsive to insulin. This dormant period culminates in spontaneous regrowth in the absence of insulin after the sixth week, and this growth continues at least through 3 months. In this respect these multicellular tumor spheroids parallel the behavior of residual tumors in vivo; the residual tumor remains viable but nongrowing for a prolonged period only to resume growth following escape from the growth-limiting mechanism.