Tailored treatment in Older Patients
TOP-1: Omission of radiotherapy in elderly patients with low risk breast cancer

Breast cancer is the most common cancer type in women of 70 years and older,
accounting for over 4.000 patients per year in the Netherlands. The benefit of
standard adjuvant treatments in older patients with breast cancer are limited
and influenced by both patient related factors as well as tumor related
factors. Preventing over-treatment is therefore pivotal for these patients,
allowing reduced treatment burden, improved quality of life and cost efficacy.
However, in clinical practice, older women are mostly treated according to
general standards, not taking into account age specific factors. The Dutch TOP
consortium (Tailored treatment in Older Patients) aims at tailoring treatment
of older women with breast cancer by allocating treatment to those patients who
will benefit and to prevent overtreatment in all others.
Previous studies, including the recent PRIME-II study, showed that omitting
radiotherapy after breast conserving surgery in older patients is safe and does
not result in decreased survival. Despite these results, currently, 98% of
older patients with low risk breast cancer (obviating the need for adjuvant
systemic therapy) in the Netherlands, still receive adjuvant radiotherapy after
breast conserving surgery.

The main focus of the present proposal is a first step towards treatment
intensity de-escalation in older breast cancer patients. For this, we propose
to initiate the first TOP consortium study (TOP-1) that will study the effect
of omitting radiotherpay in elderly women with early stage breast cancer after
breast conserving surgery.

TOP-1 is a national, multicenter, non-randomized, single-arm, prospective
cohort study.

These patients will not receive adjuvant radiotherapy.

The immediate impact for 95% of the TOP-1 participants is to be justly spared
intensive radiotherapy and subsequent risk of side effects (such as fatigue,
possible lung and cardiac damage). The other 5% will develop a local
recurrence, which would not have happened with standard radiotherapy (3-fold of
this risk, from 2.5% to 7.5% at five years). The majority of these recurrences
can however effectively be treated with salvage surgery and previous studies
showed that patient survival will likely not be affected. This limited risk of
local recurrence increase for this particular patient population was deemed
acceptable following consultation with patient advocates.