The optimal time to deliver adjuvant chemotherapy has not been defined, although benefit for early chemotherapy (<20 days of surgery) was previously reported in pre-menopausal women with oestrogen-receptor (ER) negative cancers. More recently, a SEER database study demonstrated that overall survival declined with delays of ≥ 60 days.
We conducted a retrospective study of all patients who received adjuvant anthracycline and/or taxane-based chemotherapy at RMH 1993-2010. Data were collected for clinico-pathological features, surgery, radiotherapy and chemotherapy regimens. The primary endpoint was 5-year disease-free survival (DFS) in patients commencing chemotherapy <31 days after surgery (early chemotherapy) compared to ≥ 31 days (delayed chemotherapy). Secondary endpoints included 5-year overall survival (OS) by early vs delayed chemotherapy, and outcomes in subgroups of patients defined by age, nodal status and ER and HER2 receptor status.
We identified 2003 eligible patients, 99.5% female, median age 50, 82.7% ductal, 57% grade 3, median tumour size 2.2cm, 57.1% with involved lymph nodes (median 1 node), 68% ER positive, 15.7% HER2 positive, 24.6% HER2 unknown. Median follow-up was 115 months. There was no difference in 5-year DFS rate in patients treated with early compared to delayed chemotherapy (81% vs 82% HR 1.13, 95% CI 0.91 -1.40, p = 0.324). No sub-group was identified in whom DFS was significantly affected by delaying chemotherapy. Five year OS rate was similar in patients who received early or delayed chemotherapy (90% compared to 91%, (HR 1.16, 95% CI 0.86-1.57, p = 0.321). For patients with triple negative breast cancer (TNBC, n = 250), mortality was twice as high in patients whose adjuvant chemotherapy was delayed compared to those receiving chemotherapy <31 days of surgery. (HR = 2.18, 95% CI: 1.11-4.30, p = 0.02). Five year OS rate was 77% (95% CI 0.82-0.94) in TNBC patients who received late chemotherapy compared to 89% (95% CI 0.82-0.94) in those receiving early chemotherapy.
Although delayed adjuvant chemotherapy did not affect DFS in our study, in patients with TNBC, delaying adjuvant chemotherapy beyond 30 days significantly reduced 5-year overall survival, and should therefore be avoided when possible.
The Royal Marsden NHS Foundation Trust.
Has not received any funding.
All authors have declared no conflicts of interest.