Abstract P1-17-05: Benefit of endocrine therapy for metastatic breast cancer after loss of hormone receptor expression in patients with HR+/HER2- primary tumors
Authors: File Danielle , Abdou Yara , Wheless Amy , Dees Claire , Carey Lisa 
Published: March 2022

Background. Loss of estrogen receptor (ER) and/or progesterone receptor (PR) expression between primary breast tumors and metastases occurs in one-fourth of patients. Loss of hormone receptor (HR) expression is associated with inferior clinical outcomes however optimal treatment strategies in this setting have not been defined. Methods. Patients with HR+/HER2- primary breast tumors and subsequent HR-/HER2- metastatic biopsies, as determined by immunohistochemical staining, were identified using the University of North Carolina Metastatic Breast Cancer Clinical Database which includes patients diagnosed with metastatic breast cancer from 2001-2019. Patients with second primary breast cancers were excluded. Clinical features were assessed using chi-square testing. Survival was analyzed using univariate and multivariate Cox proportional hazards modeling. Results. 1,240 patients had known primary breast and metastatic biopsy receptor status. Of these, 427 patients had HR+/HER2- primary tumors with concordant metastases, while 71 patients had HR+/HER2- primary tumors with discordant metastases due to HR loss. Loss of HR expression was associated with higher grade (grade 3: discordant 59% vs concordant 38%, p=0.002), lower ER expression (ER ≥50%: discordant 56.8% vs concordant 93.1%, p&lt;0.001) and less frequent dual ER/PR expression in the primary tumor (ER+/PR+: discordant 57.7% vs concordant 80.4%, p&lt;0.001), as well as with shorter median disease-free interval (discordant 40.8m vs concordant 66.1m, p&lt;0.001). Patients with HR loss were more likely to have brain, skin and distant lymph node metastases than patients with HR+ metastases. Of patients with HR loss, 54/71 patients (76.1%) had HR- biopsies at the time of metastatic diagnosis, prior to treatment in the metastatic setting. Six patients had de novo metastatic disease with synchronous HR+ primary tumors and HR- metastases without prior therapy in any setting. Two patients had HR- metastases at metastatic diagnosis with subsequent HR+ metastases consistent with the primary tumor while two additional patients had HR+ and HR- biopsies from distinct metastatic sites taken within two months of each other. Six patients had HR+ metastases at diagnosis and subsequent HR- metastases. A greater proportion of patients with HR loss received chemotherapy in the first-line metastatic setting (71.4% vs 24.8%, p&lt;0.001). Median progression free survival on any first-line therapy was shorter for patients with HR loss (6.4m vs 11.2m, hazard ratio 1.8 (95% CI 1.18-2.74)). Median overall survival from initial diagnosis and metastatic diagnosis were also significantly shorter for patients with HR loss (70.4m vs 123.8m, hazard ratio 1.9 (95% CI 1.42-2.59) and 18.6m vs 45.9m, hazard ratio 2.0 (95% CI 1.49-2.73)). Of patients with HR loss at metastatic diagnosis, those who received endocrine therapy in the metastatic setting had superior outcomes compared to those who did not receive endocrine therapy (21.9m vs 9.6m, hazard ratio 0.303 (95% CI 0.14-0.65)). In multivariate analysis HR loss and lack of dual ER/PR expression on the primary tumor remained associated with inferior survival beyond metastatic diagnosis when accounting for age, race, T stage, nodal status and grade. Conclusion. Discordant HR status in untreated, synchronous breast primary tumors and metastases in patients with de novo metastatic breast cancer, as well as in patients with discordant metastatic biopsies obtained within two months of concordant biopsies, suggests tumor heterogeneity within individual patients irrespective of prior therapy. Improved outcomes with endocrine therapy in the metastatic setting despite loss of HR on the initial metastatic biopsy highlights the continued value of the primary tumor phenotype to guide therapy in the metastatic setting.

Citation Format: Danielle File, Yara Abdou, Amy Wheless, Claire Dees, Lisa Carey. Benefit of endocrine therapy for metastatic breast cancer after loss of hormone receptor expression in patients with HR+/HER2- primary tumors [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-17-05.