According to these
guidelines, adjuvant systemic treatment (hormonal therapy
or chemotherapy) is indicated in node-positive
patients, node-negative patients younger than 35 except
those with a grade I tumor ≤ cm, patients of 35 years
and older with a tumor larger than 1 cm and patients
older than 35 except those with a grade I (and grade II
until 2010) between 1 and 2 cm. Chemotherapy was
advised up to 70 years old followed by hormonal therapy.
Adjuvant Online [32] was used to calculate survival
increase due to chemotherapy and, if this was found
insignificant, chemotherapy was omitted. During the
study, the chemotherapy regimen was changed from
anthraclines-based to regimens that also included taxanes.
Trastuzumab treatment was given for one year.
There was no difference in treatment between CTCpositive
and CTC-negative patients since treating physicians
were blinded for CTC results. Follow-up was also
in accordance with these guidelines: every three months
in the first year with a yearly mammogram, every six
months in the second year with a yearly mammogram,
once a year from three to five years with yearly mammogram.
After five years, all patients younger than 60
were seen yearly with a mammogram. For patients older
than 60 this was once every two years. The ethics board
of Medisch Spectrum Twente, Enschede, The Netherlands
approved the study protocol and all patients provided
informed consent.