High-Risk Breast Cancer Chemotherapy Efficacy Unchanged by Dose-Dense Strategy

Dose-dense tailored chemotherapy fails to boost breast cancer recurrence-free survival in women with high-risk early disease

medwireNews: For patients with high-risk early breast cancer, dose-dense tailored chemotherapy does not improve recurrence-free survival (RFS) compared with a standard regimen, PANTHER findings show.

In the open-label, phase III trial, 1006 women with nonmetastatic node-positive or high-risk node-negative breast cancer were randomly assigned to receive four cycles of leukocyte nadir-based tailored and dose-dense adjuvant epirubicin plus cyclophosphamides given every 2 weeks followed by four cycles of tailored dose-dense docetaxel every 2 weeks.

A further 1011 women were given standard-interval chemotherapy consisting of three cycles of fluorouracil and epirubicin plus cyclophosphamide every 3 weeks followed by three cycles of docetaxel every 3 weeks, the investigators explain in JAMA.

After a median of 5.3 years, breast cancer recurrence was reported in 118 patients in the tailored dose-dense group and 151 patients in the standard chemotherapy group, giving a nonsignificant hazard ratio (HR) of 0.79.

Five-year RFS, defined as time without local, regional or distant breast cancer relapse or breast cancer death, was achieved by a comparable 88.7% and 85.0% of patients, respectively.

“There was no heterogeneity in the effect of therapy intensification among prespecified subgroups, including hormone receptor status and HER2 status of the primary tumor”, write Jonas Bergh, from the Karolinska Institutet and University Hospital in Stockholm, Sweden, and co-authors.

“An individual patient data meta-analysis would help to assess whether chemotherapy dose intensification in early breast cancer should be reserved for specific subgroups of patients”, they suggest.

The secondary endpoint of event-free survival (EFS) – defined as time to relapse, contralateral breast cancer, other malignancy or death from any cause – was significantly better in the patients given the dose-dense tailored regimen than controls, with 5-year rates at 86.7% versus 82.1% and a HR of 0.79.

Nevertheless, the tailored dose-dense and standard treatment groups did not differ significantly with regard to 5-year rates of overall survival (92.1 vs 90.2%, HR=0.77) or distant disease-free survival (89.4 vs 86.7%, HR=0.83).

And patients given the tailored dose-dense regimen were more likely to experience grade 3 or 4 nonhaematological side effects, such as fatigue, musculoskeletal pain and neutropenic infection, at 52.6% versus 36.6% of controls.

As expected, haematological toxicity was also greater in the tailored dose-dense group, the researchers add.

Health-related quality of life at the end of treatment also significantly favoured standard chemotherapy on 13 of the 15 measures in the EORTC QLQ-C30 survey, while the EORTC QLQ-BR-23 questionnaire indicated that sexual functioning and chemotherapy side effects were worse with dose-dense chemotherapy.

In addition, “moderate” clinical differences favouring the control group were detected for some subscales, including global health status, role and social functioning and pain, while “small” differences were noted for physical and cognitive functioning, insomnia and diarrhoea.


Foukakis T, von Minckwitz G, Bengtsson N-O, et al. Effect of tailored dose-dense chemotherapy vs standard 3-weekly adjuvant chemotherapy on recurrence-free survival among women with high-risk early breast cancer. A randomized clinical trial. JAMA 2016; 316: 1888–1896; Advance online publication 8 November. doi:10.1001/jama.2016.15865

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