Tumor Size and Grade Associated With Long-Term Survival Following Tamoxifen Treatment in ER+/ERBB2- Breast Cancer

Tumor size and grade appeared to be associated with long-term survival in patients with estrogen receptor–positive/ERBB2-negative breast cancer who have undergone treatment with tamoxifen.

Tumor size and tumor grade were significantly associated with long-term survival in women who were treated with tamoxifen for estrogen receptor (ER)–positive/ERBB2-negative breast cancer, according to findings of a 25-year survival assessment published in JAMA Network Open.

Investigators identified a statistically significant difference in distant recurrence-free interval (DRFI) by tumor size, including T1a/b (88%), T1c (76%), and T2 tumors (63%; log-rank P< .001). Similar differences in DRFI by tumor grade were noted for grade 1 (81%), grade 2 (77%), and grade 3 (65%; log-rank P = .02) tumors. Progesterone receptor (PR) status and Ki-67 expression were not found to have statistical significance with DRFI outcomes.

“This secondary analysis of data from the Stockholm tamoxifen randomized clinical trial (STO-3), investigated whether clinically [utilized]] breast cancer markers were independently associated with long-term survival and tamoxifen treatment benefit. The findings indicated that, among this selected subgroup, tumor size and tumor grade were associated with long-term survival, and a significant tamoxifen treatment benefit was observed among patients with larger tumors, lower tumor grades, and PR-positive tumors,” the investigators of the study wrote.

The study included 565 post-menopausal women with a diagnosis of ER-positive/ERBB2-negative breast cancer. In this population, 520 (92.0%) patients had complete information available about their tumor characteristics. Of 559 patients, 168 (30.0%) had tumor sizes of T1a/b, 292 (52.2%) had T1c, and 99 (17.7%) had T2 at primary diagnosis. Of 557 patients, 128 (23.0%) had grade 1 tumors, 361 (64.8%) had grade 2, and 68 (12.2%) had grade 3.

Investigators used the Cox proportional hazards survival analysis to predict long-term survival. A significant reduction in the long-term risk of distant recurrence was identified in patients with smaller tumors (T1a/b and T1c) vs larger tumors (T2; T1a/b tumors: HR, 0.31; 95% CI, 0.17-0.55; T1c tumors: HR, 0.58; 95% CI, 0.38-0.88).

Those with grade 1 tumors had a reduced long-term risk of recurrence when compared with grade 3 tumors (HR, 0.48; 95% CI, 0.24-0.95). When comparing grade 2 and grade 3 tumors, there was not a statistical difference in long-term DRFI.

Patients with T1c tumors who received tamoxifen experienced a statistically significant reduction in long-term risk of distant recurrence (HR, 0.53; 95% CI, 0.32-0.89), as well as those with T2 tumors (HR, 0.34; 95% CI, 0.16-0.73). However, this was not observed among those with smaller tumors (T1a/b) when compared with patients who did not receive the adjuvant treatment. Additionally, patients who did receive tamoxifen compared with those who did not experienced a significant reduction in long-term risk of distant recurrence (HR, 0.24; 95% CI, 0.07-0.82) for grade 1 tumors and (HR, 0.50; 95% CI, 0.31-0.80) for grade 2 tumors. There was no significant benefit for grade 3 tumors.

PR-positive patients who received tamoxifen had a reduction in long-term risk distant recurrence over those who did not receive the adjuvant therapy (HR, 0.38; 95% CI, 0.24-0.62). Those with PR-negative disease experienced no notable long-term treatment benefit. Additionally, patients who took tamoxifen had medium to high Ki-67 expression (HR, 0.39; 95% CI, 0.17-0.92), and a low Ki-67 expression (HR, 0.45; 95% CI, 0.29-0.71) had a reduced long-term risk compared with those in the untreated arm.

“The findings of the present analysis suggest that tumor size is associated with the long-term risk of distant recurrence independent from other clinically used markers among patients with lymph node–negative, ER-positive/ERBB2-negative breast cancer,” the investigators concluded.

Reference:

Dar H, Johansson A, Nordenskjöld A, et al. Assessment of 25-year survival of women with estrogen receptor-positive/ERBB2-negative breast cancer treated with and without tamoxifen therapy: a secondary analysis of data from the Stockholm tamoxifen randomized clinical trial. JAMA Netw Open. 2021;4(6):e2114904. doi:10.1001/jamanetworkopen.2021.14904