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Patient-centered simulations to assess the usefulness of the 70-gene signature for adjuvant chemotherapy administration in early-stage breast cancer

Abstract

Purpose

From the MINDACT trial, Cardoso et al. did not demonstrate a significant efficacy for adjuvant chemotherapy (CT) for women with early-stage breast cancer presenting high clinical and low genomic risks. Our objective was to assess the usefulness of the 70-gene signature in this population by using an alternative endpoint: the number of Quality-Adjusted Life-Years (QALYs), i.e., a synthetic measure of quantity and quality of life.

Methods

Based on the results of the MINDACT trial, we simulated a randomized clinical trial consisting of 1497 women with early-stage breast cancer presenting high clinical and low genomic risks. The individual preferences for the different health states and corresponding decrements were obtained from the literature.

Results

The gain in terms of 5-year disease-free survival was 2.8% (95% CI from − 0.1 to 5.7%, from 90.4% for women without CT to 93.3% for women with CT). In contrast, due to the associated side effects, CT significantly reduced the number of QALYs by 62 days (95% CI from 55 to 70 days, from 4.13 years for women without CT to 3.96 years for women with CT).

Conclusion

Our results support the conclusions published by Cardoso et al. by providing additional evidence that the 70-gene signature can be used to avoid overtreatment by CT for women with high clinical risk but low genomic risk.

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Abbreviations

95% CI:

95% confidence interval

ABC:

Adjuvant breast cancer trial

CMF:

Cyclophosphamide, methotrexate, and fluorouracil

CT:

Chemotherapy

DFS:

Disease-free survival

DMFS:

Distant metastasis-free survival

EBC:

Early-stage breast cancer

E-CMF:

Epirubicin followed by cyclophosphamide, methotrexate, fluorouracil

EORTC:

European organisation for research and treatment of cancer

FEC60:

Fluorouracil, epirubicin, and cyclophosphamide

FEC-D:

FEC60 followed by docetaxel

HRQoL:

Health-related quality of life

HR:

Hazard ratio

MINDACT:

Microarray in node-negative disease may avoid chemotherapy

NEAT:

National epirubicin adjuvant trial

QALYs:

Quality-adjusted life-years

TACT:

Taxotere as adjuvant chemotherapy trial

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Acknowledgements

This work was supported by the Cancer National Institute (INCa, MAP-MARKER, No. 2013-137).

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Correspondence to Etienne Dantan.

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Caruana, E., Foucher, Y., Tessier, P. et al. Patient-centered simulations to assess the usefulness of the 70-gene signature for adjuvant chemotherapy administration in early-stage breast cancer. Breast Cancer Res Treat 174, 537–542 (2019). https://doi.org/10.1007/s10549-018-05107-6

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Keywords

  • 70-gene signature
  • Breast cancer
  • Patient-centered outcomes
  • Stratified medicine
  • Adjuvant chemotherapy