Reductions in cumulative dose of the third-generation adjuvant chemotherapy regimen 5-fluorouracil, epirubicin, and cyclophosphamide followed by docetaxel (FEC-D) were associated with worse survival outcomes in women with stage I-III HER2-negative breast cancer, according to study findings published in the Journal of the National Comprehensive Cancer Network.

Results of previous research demonstrated that administering a first-generation adjuvant chemotherapy regimen (eg, cyclophosphamide, methotrexate, and fluorouracil [CMF]) was associated with substantial overall survival benefits in women with early-stage breast cancer. Furthermore, reductions in the cumulative dose intensity of CMF (eg, less than 85% of full cumulative intensity) were shown to have a negative impact on survival.

Although additional survival benefits have been associated with the addition of an anthracycline or a taxane to adjuvant chemotherapy for breast cancer, similar results regarding the negative effects of reductions in total cumulative dose of cyclophosphamide, doxorubicin, and 5-fluorouracil (CAF) and 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) have also been shown. Nevertheless, the effect on survival of dose reductions in third-generation adjuvant chemotherapy regimens for breast cancer that include both an anthracycline and a taxane, such as FEC-D, is less well understood.

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This retrospective study included women with stage I-III HER2-negative breast cancer that was either hormone receptor-positive or -negative between 2007 and 2014 who had received between 4 and 6 cycles of adjuvant chemotherapy with FEC-D and at least 1 cycle of docetaxel (D) and were identified in the Alberta Cancer Registry.

Of the 1302 patients included in the study, 1100 received at least 85% of total cumulative FEC-D dose and 202 received less than 85% of total cumulative dose. Although the women who received a higher cumulative dose of chemotherapy were more likely to be younger and premenopausal, the only significant difference in pathologic disease features was a higher percentage of stage I disease among those who received the higher cumulative dose (9.7% vs 3.5%).

A key finding from this study was that at 5 years both disease-free survival (DFS) and overall survival (OS) were significantly lower for patients receiving less than 85% of the cumulative FEC-D dose compared with those receiving 85% or more of the cumulative dose (85.9% vs 79.2% [P =.025] and 88.8% vs 80.7% [P =.001], respectively).

“This finding supports the notion that even with the addition of taxanes, sustaining total chemotherapy dose at 85% or higher is important for maintaining clinical benefit,” the researchers noted.

Determinations of whether dose reductions were early (FEC), late (D only), or both revealed the following 4 patients subgroups:

  • FEC=100%/D ≥85% (n=791)
  • FEC=100%/D <85% (n=273)
  • FEC<100%/D ≥85% (n=109)
  • FEC<100%/D <85% (n=129)

Notably, both 5-year DFS and 5-year OS were higher for patients in the late dose reduction groups compared with those in the early dose reduction groups. For example, respective rates of 5-year OS were 90% in the first subgroup, 87.9% in the second subgroup, 83.5% in the third subgroup, and 75.2% in the fourth subgroup.

The researchers stated that “medical oncologists should strive to deliver full-dose FEC when prescribing adjuvant FEC-D chemotherapy for breast cancer. Prospective evaluation of the optimal dose for D cycles in this regimen is warranted.”


Veitch Z, Khan OF, Tilley D, et al. Impact of cumulative chemotherapy dose on survival with adjuvant FEC-D chemotherapy for breast cancer. J Natl Compr Canc Netw. 2019;17(8):957-967.