Discerning the clinical relevance of biomarkers in early stage breast cancer

Breast Cancer Res Treat. 2017 Jul;164(1):89-97. doi: 10.1007/s10549-017-4238-0. Epub 2017 Apr 11.

Abstract

Purpose: Prior data suggest that breast cancer patients accept significant toxicity for small benefit. It is unclear whether personalized estimations of risk or benefit likelihood that could be provided by biomarkers alter treatment decisions in the curative setting.

Methods: A choice-based conjoint (CBC) survey was conducted in 417 HER2-negative breast cancer patients who received chemotherapy in the curative setting. The survey presented pairs of treatment choices derived from common taxane- and anthracycline-based regimens, varying in degree of benefit by risk of recurrence and in toxicity profile, including peripheral neuropathy (PN) and congestive heart failure (CHF). Hypothetical biomarkers shifting benefit and toxicity risk were modeled to determine whether this knowledge alters choice. Previously identified biomarkers were evaluated using this model.

Results: Based on CBC analysis, a non-anthracycline regimen was the most preferred. Patients with prior PN had a similar preference for a taxane regimen as those who were PN naïve, but more dramatically shifted preference away from taxanes when PN was described as severe/irreversible. When modeled after hypothetical biomarkers, as the likelihood of PN increased, the preference for taxane-containing regimens decreased; similarly, as the likelihood of CHF increased, the preference for anthracycline regimens decreased. When evaluating validated biomarkers for PN and CHF, this knowledge did alter regimen preference.

Conclusions: Patients faced with multi-faceted decisions consider personal experience and perceived risk of recurrent disease. Biomarkers providing information on likelihood of toxicity risk do influence treatment choices, and patients may accept reduced benefit when faced with higher risk of toxicity in the curative setting.

Keywords: Breast cancer; Congestive heart failure; Conjoint analysis; Genetic biomarker; Peripheral neuropathy.

MeSH terms

  • Adult
  • Aged
  • Anthracyclines / administration & dosage
  • Anthracyclines / adverse effects
  • Biomarkers, Tumor / genetics*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / physiopathology
  • Female
  • Heart Failure / chemically induced
  • Heart Failure / physiopathology
  • Humans
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / physiopathology
  • Neoplasm Staging
  • Peripheral Nervous System Diseases / chemically induced
  • Peripheral Nervous System Diseases / physiopathology
  • Taxoids / administration & dosage
  • Taxoids / adverse effects*

Substances

  • Anthracyclines
  • Biomarkers, Tumor
  • Taxoids