Tumor Size, Grade Tied to Long-Term Survival in Selected Breast Cancer Patients

NEW YORK (Reuters Health) – In women with lymph node-negative, estrogen receptor-positive/ERBB2-negative breast cancer, tumor size and grade were significantly associated with long-term survival and benefit from tamoxifen therapy in a secondary analysis of a randomized trial.

“We believe our findings, together with other study findings, are important to understand the lifetime risk for patients diagnosed with breast cancer, which should have a clinical implication,” Dr. Linda Lindstrom of the Karolinska Institutet and University Hospital in Stockholm told Reuters Health by email. “Our study suggests that tumor size and grade are independently important for patient survival more than two decades after a breast cancer diagnosis.”

“We also see a long-term benefit from tamoxifen treatment for patients with larger tumors,” she said. “If patients with smaller tumors wish to discontinue treatment, it could potentially be reassuring that a significant treatment benefit was not seen in smaller tumors.”

“On the other hand, oncologists who have patients with side effects from tamoxifen might be helped in encouraging patients by discussing our findings of a positive long-term benefit,” she said. “However, further studies are needed to confirm our findings and to better understand how patient and tumor characteristics influence long-term risk and benefit from tamoxifen.”

As reported in JAMA Network Open, Dr. Lindstrom and colleagues analyzed data from 565 women (mean age, 62) with lymph node-negative, ER-positive/ERBB2-negative breast cancer who participated in the randomized Stockholm tamoxifen trial (STO-3). The trial was conducted from 1976 to 1990; participants were randomized to receive adjuvant tamoxifen or no endocrine therapy for up to five years.

Distant recurrence-free interval (DRFI) – i.e., 25 years – was assessed using Kaplan-Meier and multivariable Cox proportional hazards analyses adjusted for age, period of primary diagnosis, tumor size (T1a and T1b, T1c, and T2); tumor grade (1-3); progesterone receptor (PR) status (positive vs. negative); Ki-67 status (low vs. medium to high); and STO-3 treatment.

A statistically significant difference in long-term DRFI was observed by tumor size (88% for T1a/b vs. 76% for T1c vs. 63% for T2) and tumor grade (81% for grade 1 vs. 77% for grade 2 vs. 65% for grade 3), but not by PR or Ki-67 status.

A significant reduction in the long-term risk of distant recurrence was experienced by patients with smaller tumors (hazard ratios, 0.31 for T1a/b and 0.58 for T1c) and grade 1 tumors (HR, 0.48) compared with those with larger (T2) and grade 3 tumors.

Further, a significant tamoxifen treatment benefit was observed among patients with larger tumors (HR, 0.53 for T1c and 0.34 for T2); lower tumor grades (HR, 0.24 for grade 1 and 0.50 for grade 2); and PR-positive status (HR, 0.38).

A recursive partitioning analysis showed that tumor size was the most important characteristic associated with long-term survival, followed by clinical trial arm among patients with larger tumors.

Dr. Robert Burton of Monash University in Melbourne, author of a related editorial, commented to Reuters Health, “It is not possible to interpret the causes of a decline in breast cancer mortality in a population of women…where screening participation and adjuvant therapy uptake are high.”

“Dar et al have reported on the 25-year mortality benefit of five years of tamoxifen in a selected subset of women. This is expected,” he said in an email. “In future studies, Dar and colleagues may wish to consider ascertaining all-cause mortality among participants in the Stockholm tamoxifen clinical trial who received adjuvant external beam radiotherapy,” his editorial concludes.

SOURCE: https://bit.ly/3qSxbra and https://bit.ly/3hmHr8f JAMA Network Open, online June 30, 2021.

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