Changes in Overall Survival over Time for Patients with de novo Metastatic Breast Cancer

Abstract

The purpose of this study was to determine the change in overall survival (OS) for patients with de novo metastatic breast cancer (dnMBC) over time. We conducted a retrospective cohort study with 1981 patients with dnMBC diagnosed between January 1995 and December 2017 at The University of Texas MD Anderson Cancer Center. OS was measured from the date of diagnosis of dnMBC. OS was compared between patients diagnosed during different time periods: 5-year periods and periods defined according to when key agents were approved for clinical use. The median OS was 3.4 years. The 5- and 10-year OS rates improved over time across both types of time periods. A subgroup analysis showed that OS improved significantly over time for the estrogen-receptor-positive/HER2-positive (ER+/HER2+) subtype and exhibited a tendency toward improvement over time for the ER-negative (ER−)/HER2+ subtype. In addition, median OS was significantly longer in patients with non-inflammatory breast cancer (p = 0.02) and patients with ER+ disease, progesterone-receptor-positive disease, HER2+ disease, lower nuclear grade, locoregional therapy, and metastasis to a single organ (all p < 0.0001). These findings showed that OS at 5 and 10 years after diagnosis in patients with dnMBC improved over time. The significant improvements in OS over time for the ER+/HER2+ subtype and the tendency toward improvement for the ER−/HER2+ subtype suggest the contribution of HER2-targeted therapy to survival.

Clinical Characteristics and Survival Outcomes of Patients with De Novo Metastatic Breast Cancer

“…The question of whether or not locoregional therapy is beneficial in such cases remains Anderson Cancer Center, better OS was observed in tumors with low nuclear grade and in patients who received locoregional treatment. 28 In addition, we found that molecular subtype largely affects the prognosis with the worst being the TN subtype. On the contrary, no difference was observed in HER-2 positive versus negative subtypes.…”

“…Without anti-HER2 directed therapy, the outcome of metastatic HER-2 positive disease would be extremely poor as the addition of trastuzumab to chemotherapy has been shown to reduce the relative risk of death by 20% in a randomized clinical trial by Slamon et al 29 Improvement of OS over time after the introduction of trastuzumab has also been demonstrated in the study published by Iwase et al in HR positive/HER-2 positive dnMBC. 28 Whereas, for TN disease, the results reported by denBrok et al showed only a slight difference in OS between patients who did or did not receive systemic treatment, highlighting the limitations of the currently available treatments and the need to employ novel medications in this subgroup. In fact, the introduction of immunotherapy is showing promising results in patients with metastatic triple negative breast cancer.…”

“…In a large series published by Iwase et al reviewing 1981 patients treated between 1995 and 2017 at MD Anderson Cancer Center, better OS was observed in tumors with low nuclear grade and in patients who received locoregional treatment. 28 …”

Heat shock factor 1 (HSF1) cooperates with estrogen receptor α (ERα) in the regulation of estrogen action in breast cancer cells

“…Another hypothesis suggests the ERα-independent action of estrogens via their metabolites, which can exert genotoxic effects, contributing to cancer development ( Yager and Davidson, 2006 ; Pescatori et al, 2021 ). Nevertheless, hormonal therapies targeting either estrogen production (i.e., aromatase inhibitors) or the hormone receptor itself such as selective ER modulators (SERMs; i.e., tamoxifen) and selective ER degraders (SERDs; i.e., fulvestrant) are widely used to block the mitogenic action of estrogens in patients with ER-positive breast cancer ( Renoir, 2012 ; Farcas et al, 2021 ), contributing to the decline in mortality from breast cancer in recent decades ( Iwase et al, 2021 ).…”

Prognostic Factors Research in Breast Cancer Patients: New Paths

“…They found a significant improvement in overall survival over time for the estrogen receptor-positive/HER2+ subtype, suggesting the contribution of HER2-targeted therapy to survival. In addition, having non-inflammatory breast cancer, hormone-positive disease, HER2+ disease and metastasis to a single organ conferred a longer overall survival [ 15 ].…”