Factors improving overall survival in breast cancer patients with leptomeningeal disease (LMD): A single institutional retrospective review.

Abstract

Background Breast cancer-related leptomeningeal disease (BC-LMD) is a dire diagnosis for 5–8% of patients with breast cancer (BC). We conducted a retrospective review of BC-LMD patients diagnosed at Moffitt Cancer Center (MCC) from 2011–2020, to determine the changing incidence of BC-LMD, which factors impact progression of BC CNS metastasis to BC-LMD, and which factors affect OS for patients with BC-LMD Methods Patients with BC and brain/spinal metastatic disease were identified. For those who eventually developed BC-LMD, we used Kaplan-Meier survival curve, log-rank test, univariable, and multivariate Cox proportional hazards regression model to identify factors affecting time from CNS metastasis to BC-LMD and OS. Results 128 cases of BC-LMD were identified. The proportion of BC-LMD to total BC patients was higher between 2016–2020 when compared to 2011–2015. Patients with HR + or HER2 + BC experienced longer times between CNS metastasis and LMD than patients with triple-negative breast cancer (TNBC). Systemic therapy and whole-brain radiation therapy (WBRT) prolonged progression to LMD in all patients. Hormone therapy in patients with HR + BC delayed BC-CNS metastasis to LMD progression. Lapatinib delayed progression to LMD in patients with HER2 + BC. Patients with TNBC-LMD had shorter OS compared to those with HR + and HER2 + BC-LMD. Systemic therapy, intrathecal (IT) therapy, and WBRT prolonged survival for all patients. Lapatinib and trastuzumab improved OS in patients with HER2 + BC-LMD. Conclusions Increasing rates of BC-LMD provide treatment challenges and opportunities for clinical trials. Trials testing lapatinib and/or similar tyrosine kinase inhibitors, IT therapies, and combination treatments are urgently needed.

Demographic and clinical characteristics of patients with metastatic breast cancer and leptomeningeal disease: a single center retrospective cohort study

“…The relatively young median age of patients and high percentage of patients with de novo metastatic disease may reflect the referral pattern of younger, healthier patients to our academic center. Consistent with prior studies, most patients in our cohort had concurrent brain metastases and LMD [ 3 , 36 , 43 ].…”

“…Interestingly, there was also no difference in survival by the presence or absence of concurrent brain metastases. We found that patients who received CNS-directed therapy lived longer than those who did not receive CNS-specific therapy, and specifically patients who received IT therapy lived longer than those who did not receive IT therapy, as was also seen in the study by Wallace et al [ 36 ], whereas there was no difference in survival based on receipt of CNS-directed radiation therapy in our cohort. It is possible that IT therapy indeed prolonged OS for these patients, or more likely that patients who had advanced LMD or a poor performance status may not have been offered or chosen to pursue IT therapy.…”

“…al., are based on data primarily gathered from the 1990s and 2000s, and therefore look at outcomes prior to the availability of newer HER2-directed therapies and systemic therapies like antibody–drug conjugates. To our knowledge, the study by Wallace et al is one of the only more recent studies that evaluated patients with MBC and LMD from 2011 to 2020 and interestingly found similar numbers in median overall survival (4.5 months) compared to older cohort studies [ 36 ]. In this study, the authors found that systemic therapy, IT therapy, and WBRT prolonged survival for all patients, and showed that lapatinib and trastuzumab improved overall survival (OS) in patients with HER2 + MBC and LMD [ 36 ].…”

“…Most patients underwent a combination of radiation (64%), IT therapy (46%), and systemic therapy (20%) with an overall median survival of 3.5 months from date of LMD diagnosis [ 3 ]. Median overall survival varied across case series, ranging from 2 to 4.5 months, which was typically shorter in patients with TNBC (2–2.5 months) and longer in patients with HER2 + disease (5.2–8.4 months) [ 3 , 35 , 36 ]. There was significant variation among factors that improved overall survival in these case series.…”

“…Some studies found that receipt of any therapy or a combination of systemic or CNS directed therapy was beneficial to overall survival [ 37 – 39 ]. Other studies specifically found no benefit of radiation without IT or systemic therapy [ 36 , 40 ]. A few groups collected data on only IT therapy [ 41 ] or systemic therapy [ 35 , 42 , 43 ] and demonstrated an improvement in survival compared to no treatment.…”