, ▁circul ating ▁tum or ▁cell ▁clusters ▁have ▁been ▁found ▁in ▁the ▁blood ▁of ▁patients ▁with ▁various ▁can cers . ▁It ▁was ▁assumed ▁that ▁collect ive ▁int ra vas ation ▁is ▁related ▁to ▁the ▁V EG F dependent ▁formation ▁of ▁dil ated ▁vas cul ature ▁and ▁the ▁accum ulation ▁of ▁int ra vas ated ▁tum or ▁clusters . ▁Furthermore , ▁groups ▁of ▁tum or ▁cells ▁can ▁enter ▁circul ation ▁through ▁dam aged ▁vessels ▁or ▁by ▁co operation ▁with ▁cells ▁in ▁the ▁E MT ▁state ▁and ▁cancer - associ ated ▁fib ro bl asts ▁that ▁dis rupt ▁the ▁ext rac ell ular ▁matrix ▁by ▁prote ases . ▁The ▁dependence ▁of ▁met ast asis ▁on ▁collect ive ▁migration ▁is ▁confirmed ▁by ▁the ▁results ▁of ▁our ▁own ▁research . ▁For ▁example , ▁the ▁presence ▁of ▁al ve olar ▁structures ▁in ▁tum ors ▁in ▁post men op aus al ▁breast ▁cancer ▁patients ▁is ▁associated ▁with ▁a ▁high ▁rate ▁of ▁l ym ph ogen ous ▁met ast asis , ▁whereas ▁the ▁risk ▁of ▁this ▁type ▁of ▁pro gression ▁in ▁pre men op ause ▁females ▁increases ▁with ▁an ▁increase ▁in ▁the ▁number ▁of ▁different ▁types ▁of ▁morph ological ▁structures . ▁The ▁latter ▁dependence ▁is ▁also ▁quant itative : ▁l ym ph ogen ous ▁met ast ases ▁were ▁detected ▁more ▁frequently ▁in ▁the ▁case ▁of ▁a ▁larger ▁number ▁of ▁al ve olar ▁structures ▁in ▁breast ▁tum ors . ▁Furthermore , ▁patients ▁with ▁al ve olar ▁structures ▁in ▁tum ors ▁had ▁a ▁low ▁met ast asis - free ▁surv ival ▁rate