A group of British researchers has found that with only minimal changes in clinical parameters because of a lack of perfect correlation between pathologists’ results, there is a significant difference in the 10-year predicted mortality on Adjuvant! Online, a breast cancer risk assessment tool. The findings highlight the inconsistency of chemotherapy decision-making with the sole use of Adjuvant! Online. They presented their results on Wednesday, December 7, at the San Antonio Breast Cancer Symposium. 

Although prognostic factors have been used for years to determine the benefit of adjuvant chemotherapy in breast cancer, reporting of the size and grade of the tumor is affected by interobserver variability, which may change decisions on chemotherapy. 

Conversely, genomic testing tools (such as Oncotype Dx) are reproducible. The researchers sought to quantify the effect of pathologic discordance on the Adjuvant! Online results on a cohort of patients who also underwent Oncotype Dx testing.

A total of 143 patient histologies were included in the analysis. The researchers used results from the phase III WSG-Plan B trial concerning central versus local grade discrepancy rates to randomly change the grade and size of the tumors as follows.

  • 61% of grade 1 cancers were upgraded to grade 2.
  • 2% of grade 1 cancers were upgraded to grade 3.
  • 4% of grade 2 cancers were downgraded to grade 1.
  • 26% of grade 2 cancers were upgraded to grade 3.
  • 1% of grade 3 cancers were downgraded to grade 1.
  • 25% of grade 3 cancers were downgraded to grade 2.

In 20% of patients, tumor size was changed.

  • 8–10 mm was changed to 11 mm.
  • 11–13 mm was changed to 10 mm.
  • 18–20 mm was changed to 21 mm.
  • 21–23 mm was changed to 20 mm.
  • 28–30 mm was changed to 31 mm.
  • 31–33 mm was changed to 30 mm.
  • 48–50 mm was changed to 51 mm.
  • 51–53 mm was changed to 50 mm.

Additionally, 10% of patients had the estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) status changed.

The group found that if only the grade was altered, the subsequent predicted 10-year mortality on Adjuvant! Online was substantially changed from 1 to 0.788. If both grade and tumor size were altered, the coefficient was 0.836. With the altered ER status, the result dropped from 1 to 0.749, and with the HER2 change, the spearman correlation was minimally changed to 0.742.

The researchers said, “This is one step further in understanding the lack of correlation between Adjuvant! Online and Oncotype Dx and the inconsistency of chemotherapy decision making with the sole use of Adjuvant! Online.”