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St. Gallen endocrine response classes predict recurrence rates over time.

R H T Koornstra1, K J Beelen1, A D Vincent2

  • 1Department of Molecular Biology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands; Department of Medical Oncology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.

Breast (Edinburgh, Scotland)
|October 3, 2015
PubMed
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Highly endocrine-responsive (ER-H) tumors show tamoxifen benefit early but face late recurrence risks. This finding impacts optimal treatment duration for breast cancer patients.

Keywords:
Adjuvant therapyBreast cancerEndocrine responsivenessEstrogen receptorProgesterone receptorTamoxifen

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Area of Science:

  • Oncology
  • Endocrinology
  • Clinical Trial Analysis

Background:

  • The 2007 St. Gallen consensus defined endocrine response classes: highly endocrine-responsive (ER-H), incomplete endocrine-responsive (ER-I), and non-endocrine-responsive (ER-N).
  • Uncertainty exists regarding whether ER-I tumors are less responsive than ER-H tumors.
  • The study aimed to clarify recurrence rate variations over time among these endocrine response classes.

Purpose of the Study:

  • To investigate temporal variations in recurrence rates across different endocrine response classes.
  • To determine the most predictive response class definition for tamoxifen benefit.
  • To assess the impact of endocrine response on recurrence-free interval (RFI) in breast cancer patients receiving tamoxifen.

Main Methods:

  • Centralized revision of estrogen receptor (ER), progesterone receptor (PgR), HER2 status, and tumor grade for 646 patients from a tamoxifen trial.
  • Evaluation of St. Gallen classes for recurrence-free interval (RFI) and assessment of hazard changes over time.
  • Comparison of six alternative response class definitions to optimize ER and PgR cut-offs.

Main Results:

  • Failure of proportional hazards between endocrine response groups (p = 0.0001) indicated time-dependent effects.
  • The hazard ratio for recurrence risk shifted over time; ER-H tumors initially had lower risk (HR 0.5) but faced increased risk after six years (HR 1.9).
  • Optimal cut-offs for early RFI discrimination (first 4 years) in lymph node-positive patients were ER ≥ 50% and PgR ≥ 75%.

Conclusions:

  • Significant variability in endocrine therapy benefit was observed.
  • Patients with ER-H tumors experience greater benefit from adjuvant tamoxifen early on but are susceptible to late recurrences.
  • These findings suggest potential implications for optimizing the duration of endocrine therapy.