Breast cancer markers of long term survival and tamoxifen benefit identified in 25 year study

By Michael Woodhead

6 Jul 2021

When used as adjuvant endocrine therapy in breast cancer, tamoxifen works best against larger, less aggressive, PR–positive tumours, according to results from a long term follow up study.

In postmenopausal women with lymph node–negative, ER-positive/ERBB2-negative breast the markers most significantly associated with long-term survival were tumour size followed by tumour grade and progesterone receptor–positive status, researchers from Sweden report in JAMA Network Open.

They said that while clinically used breast cancer markers were known to provide short-term survival estimates for up to 10 years after primary diagnosis, there was little data on longer term survival.

They therefore performed a secondary analysis of factors associated with survival in 565 postmenopausal women with lymph node–negative, oestrogen receptor–positive, and ERBB2-negative breast cancer who participated in the Stockholm tamoxifen randomised clinical trial (STO-3), which ran from 1976 to 1990.

Women in the trial were randomised to receive up to five years of tamoxifen or no endocrine therapy.

At follow up of up to 25 years, there was a significant difference in distant recurrence–free interval (DRFI) observed by tumour size (88% for T1a/b vs 76% for T1c vs 63% for T2 tumours; log-rank P < .001) and tumour grade (81% for grade 1 vs 77% for grade 2 vs 65% for grade 3 tumours; log-rank P = .02) but not by PR status or Ki-67 status.

Patients with smaller T1a/b and T1c tumours and grade 1 tumours showed a significant reduction in the long-term risk of distant recurrence compared with patients with larger (T2) tumours and grade 3 tumours, respectively.

For tamoxifen therapy, a significant benefit was seen in patients with larger tumours for T1c tumours (HR, 0.53] and for T2 tumours (HR 0.34), lower tumour grades  for grade 1 tumours (HR, 0.24) and  for grade 2 tumours (HR 0.50), and PR-positive status (HR, 0.38).

Tumour size as the most important characteristic associated with survival, and survival among patients with the smallest tumours (T1a/b) was solely estimated by tumour size. Among patients with larger tumours, treatment with tamoxifen therapy was the second most important variable associated with survival

The study investigators said it was also notable that a long-term treatment benefit was observed among patients with PR-positive tumours and in patients who had low and medium to high Ki-67 expression.

They cautioned that the findings came from a trial conducted before aromatase inhibitors were a recommended treatment option for patients with ER-positive breast cancer, and the duration of tamoxifen treatment was shorter, and the treatment dosage higher than current recommendations.

Nevertheless, they said the results provided the first data on breast cancer markers that are associated with patient survival and treatment benefit for up to 25 years after diagnosis.

“This study’s findings suggest that tumour size and tumour grade is associated with long-term survival, and patients with larger tumours, lower tumour grades, and progesterone receptor–positive status experienced significant treatment benefit with receipt of tamoxifen therapy,” they concluded.

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