High-Dose Chemotherapy for Breast Cancer May Not Improve Long-Term Survival

No long-term survival benefit was found using high-dose chemotherapy in patients with stage III breast cancer, according to study findings published in JAMA Oncology.

High-dose chemotherapy did provide improved overall survival (OS) rates in high-risk patients, but it did not impact long-term risk of a second malignant neoplasm or major cardiovascular events.

“High-dose chemotherapy provides no long-term OS benefit for unselected patients with stage III (breast cancer),” wrote the researchers. “However, (high-dose chemotherapy) did improve long-term (breast cancer-specific survival) of unselected patients as well as the long-term OS in a subgroup of patients with 10 or more involved (axillary lymph nodes), resulting in 20-year benefit rate of 14.6%.”

The multicenter randomized clinical trial divided 885 patients (mean [SD] age, 44.5 [6.6] years) into 2 random categories: 442 to receive high-dose chemotherapy and 443 to receive conventional-dose chemotherapy. A median follow-up of 20.4 years determined that the 20-year OS estimate was 45.3% for patients who received high-dose chemotherapy and 41.5% for patients who received conventional-dose chemotherapy (hazard ratio [HR], 0.89; 95% CI, 0.75-1.06).

Even more, patients with 10 or more involved axillary lymph nodes saw an absolute difference in 20-year OS of 14.6% (HR, 0.72; 95% CI, 0.54-0.95) compared to a 2.2% difference (HR, 1.01; 95% CI, 0.81-1.27) for patients with 4 to 9 involved axillary lymph nodes (P= .05 for interaction).

In regard to breast cancer-specific survival, breast cancer was the preliminary cause of death for most patients in both groups (HDCT group, n = 204 [83.6%] vs CDCT group, n = 238 [91.2%]). Specifically, and comparably to effects to OS, the 20-year breast cancer-specific survival estimates were 52.3% for high-dose chemotherapy patients and 45.4% for conventional-dose chemotherapy patients.

“Our analysis confirms earlier results that [high-dose chemotherapy] has no significant OS benefit compared with [conventional-dose chemotherapy] for unselected patients with stage III (breast cancer),” wrote the researchers. “However, we found a 14.6% improvement in 20-year OS estimates with (high-dose chemotherapy) in the predefined subgroup of patients with 10 or more involved (axillary lymph nodes).”

When analyzing a second malignant neoplasm and cardiovascular disease, follow-up revealed 58 high-dose chemotherapy patients (13.1%) developed 65 malignant neoplasms, while 74 conventional-dose chemotherapy patients (16.7%) developed 81 malignant neoplasms. Overall, incidents of a second malignant neoplasm at 20 years was 12.1% (95% CI, 11.8%-12.4%) after high-dose chemotherapy and 16.2% (95% CI, 15.9%-16.6%) after conventional-dose chemotherapy (P= .10). Breast cancer was also found to be the most common second malignant neoplasm.

“Given the number of non-breast cancer deaths, breast cancer-specific survival results should be interpreted with caution, and we focus mainly on the OS results in this update analysis,” wrote the researchers.

This study had a number of limitations, starting with the standard systemic therapy for breast cancer, taxanes, platinum, and capecitabine, not being used for the study’s control group. This means the observed benefit from high-dose chemotherapy is likely smaller than the “contemporary control treatment.” Next, indirect effects from high-dose chemotherapy cannot be ruled out for patients because fewer patients in both groups remained premenopausal 30 months after randomization (5.9% vs 21.0%).

Moving forward, the researchers suggest assessing cardiovascular risk factors, monitoring and treatment should potentially be considered after high-dose chemotherapy.

Reference:

Steenbruggen T, Steggink LC, Seynaeve CM, et al. High-Dose Chemotherapy with Hematopoietic Stem Cell Transplant in Patients with High-Risk Breast Cancer and 4 or More Involved Axillary Lymph Nodes.JAMA Oncol. doi:10.1001/jamaoncol.2019.6276.