Tumor size, grade impact long-term breast cancer distant recurrence risk
medwireNews: Tumor size and grade are the strongest predictors of long-term distant recurrence free survival in people with lymph node-negative, estrogen receptor (ER)-positive, HER2-negative breast cancer, show 25-year data from the STO-3 trial.
The secondary analysis, by Linda Lindström (Karolinska Institutet, Stockholm, Sweden) and colleagues, also revealed that individuals with larger tumors, lower tumor grades, and progesterone receptor (PR)-positive status, derive significant long-term benefit from tamoxifen treatment.
The STO-3 trial took place in Stockholm between 1976 and 1990, during which 1780 postmenopausal women with lymph node-negative, ER-positive, HER2-negative breast cancer were randomly assigned to receive up to 5 years of adjuvant tamoxifen therapy or no endocrine treatment.
The current analysis, including 565 participants, showed that after 25 years the distant recurrence rate was significantly lower among participants with smaller versus larger tumors, at 12%, 22%, and 34% for T1a/b, T1c, and T2 tumors, respectively.
Furthermore, after adjustment for age, period of primary diagnosis, tumor size and grade, PR and Ki-67 status, and STO-3 treatment assignment, the risk for distant recurrence was a significant 69% and 42% lower for T1a/b and T1c tumors, respectively, relative to T2 tumors.
Tumor grade also impacted distant recurrence, with rates of 14%, 21%, and 31% in people with grade 1, 2, and 3 tumors, respectively. In the adjusted analyses, grade 1 tumors were associated with a significant 52% lower risk for distant recurrence compared with grade 3 tumors, but there was no significant difference in risk between grade 2 and 3 tumors.
PR and Ki-67 status were also not significantly associated with long-term distant recurrence risk.
When Lindström and team assessed the long-term benefit of tamoxifen according to these clinical markers, they found that the long-term risk for distant recurrence was significantly reduced with tamoxifen versus placebo in people with T1c (hazard ratio [HR]=0.53) and T2 tumors (HR=0.34) but not in those with T1a/b tumors.
Tamoxifen was also associated with a significantly reduced long-term risk for distant recurrence in people with grade 1 (HR=0.24) or grade 2 tumors (HR=0.50), a PR-positive status (HR=0.38), medium-to-high Ki67 expression (HR=0.39), or low Ki67 expression (HR=0.45).
Further analysis showed that that tumor size was the most important characteristic associated with long-term distant recurrence-free survival, followed by receipt of tamoxifen among people with larger (T1c and T2) tumors.
The study findings are published in JAMA Network Open.
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