Impact of progesterone receptor levels on prognosis in patients with advanced breast cancer with high levels of estrogen receptors and HER2− receiving endocrine therapy plus a CDK4/6 inhibitor in first line
BEFORE THE CDK4/6 INHIBITOR ERA, the effect of PR expression on prognosis had been studied in many cases, and it had been repeatedly shown that estrogen (ER)-positive, PR-negative breast cancer had a poor prognosis and was associated with endocrine resistance. For example, Kurozumi et al. indicated that the level of PR expression was an independent prognostic factor for HR-positive and HER2-negative patients with this type of cancer, especially when the level of Ki-67 expression was from 10% to 30%. And patients with PR <20% had a worse prognosis. A European retrospective analysis of the GEICAM/9906 study showed that ER-positive / PR-negative breast cancer had more pronounced tumor proliferation, a higher risk of recurrence and worse overall survival outcomes. Also, according to Rocca A et al. In patients receiving first-line endocrine therapy with an aromatase inhibitor alone, high PR (> 20%) was independently associated with longer time to progression.
The prognostic significance of PR status may be different WHEN A CDK4/6 INHIBITOR IS COMBINED WITH ENDOCRINE THERAPY. A pooled FDA analysis showed that all clinicopathologic subgroups of patients with HR-positive, HER2-negative advanced breast cancer benefited from CDK4/6 inhibitors in combination with endocrine therapy, regardless of PR expression. However, the authors noted that heterogeneity among patients included in the analysis may affect the results obtained in real-world practice. And in the PALOMA-3 study, patients with high PR expression showed longer survival in both the palbociclib plus fulvestrant or placebo plus fulvestrant arms. Shao X et al also found that PR ≥ 20% was associated with longer PFS in patients receiving CDK4/6 inhibitor combination therapy (8.5 vs 6.7 months), and PFS was significantly shorter in the PR-negative/low cohort.
The Impact of Progesterone Receptors on Prognosis in Breast Cancer Patients
The study we will now consider was initiated to evaluate the impact of progesterone receptor status on prognosis in patients with advanced breast cancer with high levels of estrogen receptors and negative epidermal growth factor receptor 2 (HER2-) who received a CDK4/6 inhibitor in combination with endocrine drugs as first-line therapy.
The study analysis included patients who were treated at the Oncology Hospital of Harbin Medical University. According to the degree of PR expression, patients were divided into the PR-high group (11-100% of cells expressing receptors), PR-low group (1-10% expressing cells) and PR-negative group (<1% of cells). Statistical methods were used to analyze the differences in progression-free survival (PFS) and overall survival (OS) between the groups.
Among 152 patients included in the study, 72 were PR-high, 32 were PR-low and 48 were PR-negative. During the follow-up of patients, the proportion of patients without relapse for ≥ 5 years was significantly higher in the PR-low and PR-high groups compared to the PR-negative group.
PR-negative patients were more likely to experience disease progression during the first 24 months of treatment than PR-high patients, which was identified as an important predictor of overall survival. Survival curve analysis showed that PFS and OS were significantly lower in the PR-negative group compared to the PR-high group. Importantly, patients who progressed within the first 24 months had shorter overall survival regardless of PR status.
Conclusion
The results of this study support the hypothesis that PR-negative tumor status is a risk factor in patients with advanced ER-high HER2-negative breast cancer who received a CDK4/6 inhibitor in combination with endocrine therapy in the first line. PR-negative patients had the shortest PFS and OS. In addition, regardless of PR status, disease recurrence within the first 24 months predicted shorter overall survival. The obtained data provide a reason to develop an individualized surveillance and treatment plan for patients with such characteristics.
Appointment to the doctor
CDK4/6 inhibitor in combination with endocrine therapy is the standard first-line therapy for patients with advanced hormone-positive (HR) breast cancer, and a large number of clinical trials have proven that the combination can improve the duration of antitumor response, partially prevent and overcome endocrine resistance, and provide a better prognosis for patients. However, markers that can predict the prognosis of the course of cancer are far from clear. Let us consider the significance of progesterone receptor (PR) expression on tumor cells as a possible predictive marker of the course of cancer.