Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis of individual patient data from ten randomised trials

Abstract

SummaryBackgroundNeoadjuvant chemotherapy (NACT) for early breast cancer can make breast-conserving surgery more feasible and might be more likely to eradicate micrometastatic disease than might the same chemotherapy given after surgery. We investigated the long-term benefits and risks of NACT and the influence of tumour characteristics on outcome with a collaborative meta-analysis of individual patient data from relevant randomised trials.MethodsWe obtained information about prerandomisation tumour characteristics, clinical tumour response, surgery, recurrence, and mortality for 4756 women in ten randomised trials in early breast cancer that began before 2005 and compared NACT with the same chemotherapy given postoperatively. Primary outcomes were tumour response, extent of local therapy, local and distant recurrence, breast cancer death, and overall mortality. Analyses by intention-to-treat used standard regression (for response and frequency of breast-conserving therapy) and log-rank methods (for recurrence and mortality).FindingsPatients entered the trials from 1983 to 2002 and median follow-up was 9 years (IQR 5–14), with the last follow-up in 2013. Most chemotherapy was anthracycline based (3838 [81%] of 4756 women). More than two thirds (1349 [69%] of 1947) of women allocated NACT had a complete or partial clinical response. Patients allocated NACT had an increased frequency of breast-conserving therapy (1504 [65%] of 2320 treated with NACT vs 1135 [49%] of 2318 treated with adjuvant chemotherapy). NACT was associated with more frequent local recurrence than was adjuvant chemotherapy: the 15 year local recurrence was 21·4% for NACT versus 15·9% for adjuvant chemotherapy (5·5% increase [95% CI 2·4–8·6]; rate ratio 1·37 [95% CI 1·17–1·61]; p=0·0001). No significant difference between NACT and adjuvant chemotherapy was noted for distant recurrence (15 year risk 38·2% for NACT vs 38·0% for adjuvant chemotherapy; rate ratio 1·02 [95% CI 0·92–1·14]; p=0·66), breast cancer mortality (34·4% vs 33·7%; 1·06 [0·95–1·18]; p=0·31), or death from any cause (40·9% vs 41·2%; 1·04 [0·94–1·15]; p=0·45).InterpretationTumours downsized by NACT might have higher local recurrence after breast-conserving therapy than might tumours of the same dimensions in women who have not received NACT. Strategies to mitigate the increased local recurrence after breast-conserving therapy in tumours downsized by NACT should be considered—eg, careful tumour localisation, detailed pathological assessment, and appropriate radiotherapy.FundingCancer Research UK, British Heart Foundation, UK Medical Research Council, and UK Department of Health.

Influence of ABCB1 C3435T and C1236T gene polymorphisms on tumour response to docetaxel-based neo-adjuvant chemotherapy in locally advanced breast cancer patients of South India

“…Studies have shown a significant increase in pathological response in primary breast cancer patients when docetaxel was given as sequential therapy with doxorubicin and cyclophosphamide in a neo‐adjuvant setting . Safety of NACT is comparable with adjuvant chemotherapy in several randomized trials . These findings have encouraged the use of docetaxel in neo‐adjuvant settings.…”

“…6 Safety of NACT is comparable with adjuvant chemotherapy in several randomized trials. 7 These findings have encouraged the use of docetaxel in neo-adjuvant settings. NACT followed by surgery and adjuvant radiation therapy is the standard care of treatment for patients with locally advanced breast cancer (LABC).…”

Early detection of changes in phospholipid metabolism during neoadjuvant chemotherapy in breast cancer patients using phosphorus magnetic resonance spectroscopy at 7T

“…It has been shown that the desired tumor size reduction is not accomplished with NAC in up to 31% of patients who will have stable or even progressive disease. 4 In order to identify patients who will have stable or progressive disease, it is important to identify biomarkers that can assess the response to NAC at an early stage in the individual patient. This could enable the adjustment of systemic therapy and avoid toxicity and the related costs of ineffective treatment.…”

Single-cell Transcriptomics reveals multi-step adaptations to endocrine therapy

“…The outgrowth of primary luminal breast cancer (BCa) is driven by nonmutated estrogen receptor α (ERα), with all patients receiving adjuvant endocrine therapy after curative surgery (ET). This strategy significantly delays clinical relapse but does not abrogate it completely, as about ~3% of the patients each year come back with overt relapse, inevitably leading to further metastatic development [1][2][3] . The frequency of relapse remains constant up to 20 years after surgery making ETresistance the most critical clinical problem for the management of these patients 4 .…”