Survival outcomes of breast cancer patients with brain metastases: Single center experience from Northern India.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e13003-e13003
Author(s):  
Hari Krishna Raju Sagiraju ◽  
Ajay Gogia ◽  
Dayanand Sharma ◽  
S. V. S. Deo ◽  
Sandeep Mathur
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Brain Metastasis ◽  
Brain Metastases ◽  
Metastatic Disease ◽  
Cancer Diagnosis ◽  
Survival Outcomes ◽  
Her2 Positive ◽  
Pathological Characteristics ◽  
Time Of Presentation

e13003 Background: Brain metastasis (BM) is a poor prognostic factor for survival among breast cancer (BC) patients. Very few studies reported in the literature have challenged this premise, suggesting that time to the occurrence of brain metastasis and the survival times following brain metastasis differ significantly between BC subtypes. The purpose of this study was to evaluate the clinico-pathological characteristics associated with brain metastasis free survival (BMFS), survival after brain metastases (SABM) and overall survival among Indian women with BC and BM. Methods: Among 621 patients treated for metastatic BC from 2015 to 2018 at All India Institute of Medical Sciences-New Delhi, 79 (12.7%) patients were identified to have BM. Of these ten individuals have presented with BM at the time of presentation. Survival analysis and Cox proportional hazards models were fitted to explore clinco-pathological factors that are associated with survival outcomes in these individuals. Results: Median age of the sample is 42 years (range:22-64). Triple negative breast cancers (TNBC) accounted for 25.3% and HER2 positive were 49.4% in our sample. Median time for the occurrence of BM from cancer diagnosis was 20.5 months (95% CI:14.7-26.2) in the overall sample, while among TNBC and HER2 positive tumors was 14.1 and 20.6 months respectively. In Cox multivariable model, T4stage [Hazard Ratio (HR) (95%CI): 2.4(1.1-5.3)], having a metastatic disease other than to brain at the time of presentation [HR(95%CI): 2.8(1.5-5.4)] and TNBC [HR(95%CI): 2.7(1.1-6.7)], was observed to be significantly associated with BMFS. Median SABM was 7.9 months (95% CI 5.2–16.2) and the median overall survival from the cancer diagnosis was 32.4 months (95% CI 23.4–40.8). Adjusted for age, only the presence of multiple brain lesions (>2) was significantly associated with SABM [HR (95%CI): 2.4(1.1-5.2)]. However, TNBC [HR (95%CI): 2.9(1.2-7.4)]and baseline metastatic disease [HR (95%CI): 2.2(1.2-4.2)] were significantly associated with overall survival following cancer diagnosis in these individuals. HER2 positivity was not associated with BMFS or SABM in this cohort. Conclusions: In this single-institutional study, clinical T4 stage, TNBC subtype and baseline metastatic disease have shown to be significantly associated with BMFS and overall survival. These results suggest that women in Indian population with these baseline clinico-pathological characteristics at the diagnosis of breast of cancer should be frequently monitored for BM.

RADT-03. OUTCOMES OF PATIENTS WITH HER2-POSITIVE BREAST CANCER METASTATIC TO BRAIN TREATED WITH HER2-TARGETED SYSTEMIC THERAPY AND STEREOTACTIC RADIOSURGERY

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi41-vi41
Author(s):  
John Shumway ◽  
Marina Torras ◽  
Katherine Reeder-Hayes ◽  
Trevor Jolly ◽  
Elizabeth Dees ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastasis ◽  
Stereotactic Radiosurgery ◽  
Systemic Therapy ◽  
Survival Outcomes ◽  
Maximal Dimension ◽  
Her2 Positive ◽  
Intracranial Metastasis ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

Abstract OBJECTIVE For patients with HER2-positive breast cancer metastatic to brain, HER2-directed systemic therapies are increasingly used with stereotactic radiosurgery (SRS). These include monoclonal antibodies such as trastuzumab (H) and pertuzumab (P), antibody-drug conjugates such as ado-trastuzumab emtansine (T-DM1), and tyrosine kinase inhibitors such as lapatinib. Limited data exist regarding appropriate timing with SRS and outcomes of this treatment regimen. METHODS A single-institution retrospective review collected clinical data on patients with breast cancer metastatic to brain who were treated with SRS from 2009-2020. Statistical analyses were performed using the Kaplan-Meier method and chi-square statistic. RESULTS Of 82 patients with breast cancer metastatic to brain treated with SRS, 33 (40%) were HER2-positive, 18 of whom were hormone receptor-positive. At brain metastasis diagnosis, 15 patients (45%) had >1 intracranial metastasis (range 2-7), and the median brain metastasis maximal dimension was 2.0 cm. Fifteen patients had uncontrolled extracranial disease. After brain metastasis diagnosis, 9 patients (27%) were treated with systemic therapy first (T-DM1+/-HP, lapatinib+HP, chemotherapy+/-HP) followed by SRS at a median of 18.6 months after starting systemic therapy. Seven patients (21%) were treated with SRS first, followed by systemic therapy in 6 of these patients (multi-agent regimens, 4 including T-DM1 or lapatinib). Seventeen (52%) received concurrent systemic therapy and SRS (T-DM1+/-chemotherapy, lapatinib, HP, hormone therapy, chemotherapy). Median follow-up time was 21.1 months. Median overall survival was 24.8 months and not statistically different between treatment groups. Four patients (12%) developed symptomatic radionecrosis; 3 were on T-DM1 concurrent with SRS. CONCLUSION In this small patient sample, we noted favorable survival outcomes for patients with HER2-positive breast cancer metastatic to brain when treated with HER2-targeted therapies together with SRS. The sequence of systemic therapy and SRS does not appear to impact survival outcomes. Concurrent treatment with T-DM1 and SRS may be associated with higher rates of radionecrosis.

Trastuzumab prolongs overall survival in patients with brain metastases from Her2 positive breast cancer

2007 ◽  
Vol 85 (3) ◽  
pp. 311-317 ◽  
Author(s):  
Rupert Bartsch ◽  
Andrea Rottenfusser ◽  
Catharina Wenzel ◽  
Karin Dieckmann ◽  
Ursula Pluschnig ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Brain Metastases ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

scholarly journals Molecular and cellular mechanisms underlying brain metastasis of breast cancer

2020 ◽  
Vol 39 (3) ◽  
pp. 711-720 ◽  
Author(s):  
Mari Hosonaga ◽  
Hideyuki Saya ◽  
Yoshimi Arima
Keyword(s):  
Breast Cancer ◽  
Brain Metastasis ◽  
Brain Metastases ◽  
Cancer Cells ◽  
Metastatic Cancer ◽  
Breast Cancer Patients ◽  
Cellular Mechanisms ◽  
Her2 Positive ◽  
Cells Of The Microenvironment ◽  
The Brain

Abstract Metastasis of cancer cells to the brain occurs frequently in patients with certain subtypes of breast cancer. In particular, patients with HER2-positive or triple-negative breast cancer are at high risk for the development of brain metastases. Despite recent advances in the treatment of primary breast tumors, the prognosis of breast cancer patients with brain metastases remains poor. A better understanding of the molecular and cellular mechanisms underlying brain metastasis might be expected to lead to improvements in the overall survival rate for these patients. Recent studies have revealed complex interactions between metastatic cancer cells and their microenvironment in the brain. Such interactions result in the activation of various signaling pathways related to metastasis in both cancer cells and cells of the microenvironment including astrocytes and microglia. In this review, we focus on such interactions and on their role both in the metastatic process and as potential targets for therapeutic intervention.

Prognostic role of triple-negative subtype in breast cancer patients with brain metastases.

2011 ◽  
Vol 29 (27_suppl) ◽  
pp. 36-36 ◽  
Author(s):  
A. Mathew ◽  
M. Q. Rosenzweig ◽  
A. Brufsky
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Cohort Study ◽  
Prognostic Factors ◽  
Brain Metastases ◽  
Triple Negative ◽  
Hazard Ratio ◽  
Her2 Positive ◽  
Risk Of Death

36 Background: Metastatic breast cancer (MBC) patients with brain metastases (BM) have a poorer prognosis compared to patients with metastases to sites such as bone or other visceral organs. The role of breast cancer subtypes such as triple negative (TN) status and its relationship with other known prognostic factors have not been well delineated in the context of metastatic disease to the brain. We conducted a retrospective single institution cohort study of MBC patients with BM to evaluate the association between TN subtype and overall survival from the diagnosis of BM. Methods: Baseline demographic and tumor specific data including ER, PR and HER2 status were collected on newly diagnosed MBC patients between January 1998 and December 2009. Overall survival was determined from the date of diagnosis of BM. Survival analyses were performed using the Kaplan-Meier method and Cox proportional-hazards model. Results: Data were available on 186 MBC patients with BM, of whom 156 died during a median follow-up of 10.2 months from the diagnosis of BM; median age was 47.9 years. 91% of patients were Caucasian; 25.3% had triple negative disease. Median survival from the period of diagnosis of BM in patients with triple negative disease was 7 months (Interquartile range, IQR: 3–13) as compared to 11 months (IQR: 5–22) in patients who were HER2-positive or ER/PR-positive. Multivariate analysis found a higher risk of death after BM for TN disease subtype, with a hazard ratio for death of 2.89 (95% confidence interval: 1.89–4.44; p<0.001), when adjusted for variables such as age and stage at initial diagnosis of breast cancer, race, the number of metastatic sites, and the use of metastatic chemotherapy. The administration of metastatic chemotherapy had a significant survival benefit in the analyses, with a hazard ratio for death of 0.52 (95% CI: 0.27–0.99; p=0.048). Conclusions: This retrospective cohort study in MBC patients with BM provides evidence for a greater risk of death in those with TN disease as compared to HER2-positive or ER/PR-positive subtypes even after adjusting for other prognostic factors.

scholarly journals TRLS-09. RTOG1119: PHASE II RANDOMIZED STUDY OF WHOLE BRAIN RADIOTHERAPY / STEREOTACTIC RADIOSURGERY IN COMBINATION WITH CONCURRENT LAPATINIB IN PATIENTS WITH BRAIN METASTASIS FROM HER2-POSITIVE BREAST CANCER

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i10-i10
Author(s):  
In Ah Kim ◽  
Kathryn Winter ◽  
David Peereboom ◽  
Paul Sperduto ◽  
Jennifer De Los Santos ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Targeted Therapy ◽  
Brain Metastasis ◽  
Brain Metastases ◽  
Disease Control ◽  
Stereotactic Radiosurgery ◽  
Surgical Resection ◽  
Response Rate ◽  
Her2 Positive ◽  
Positive Breast Cancer

Abstract The addition of trastuzumab to cytotoxic chemotherapy has improved outcomes for patients with HER2 positive breast cancer. Increased survival coupled with limited blood-brain barrier (BBB) penetration of trastuzumab may contribute to the increased incidence of brain metastasis in these patients. Half of these patients die of intracranial disease progression rather than extracranial disease. Therefore, strategies to improve survival must include increased CNS disease control in these patients. Lapatinib crosses the BBB and demonstrates modest activity against intracranial metastases. Based upon preclinical data and results of a phase I study, we hypothesized that lapatinib plus WBRT /SRS can improve the intracranial disease control compared to WBRT / SRS alone. A randomized phase II trial of WBRT (37.5 Gy/3 weeks) or SRS plus or minus concurrent lapatinib (daily 1000 mg for 6 weeks) was initiated. CNS penetrating HER2 targeted therapy is permitted throughout the study, but patients not on trastuzumab, pertuzumab or any other breast cancer therapy at study entry are not permitted to begin this therapy while on protocol treatment, but may begin it 24 hours after completion of protocol treatment. Eligibility includes HER2+ breast cancer with at least one measurable, unirradiated parenchymal brain metastasis. The two populations targeted for accrual include patients with 1) newly diagnosed, multiple brain metastases or 2) progressive brain metastases after stereotactic radiosurgery (SRS) or surgical resection of 1–3 metastases. Prior lapatinib is allowed. Patients are stratified by breast-specific graded prognostic assessment; use of non-CNS penetrating HER2 targeted therapy; and prior SRS or surgical resection. The primary endpoint is complete response rate in the brain 12 weeks after WBRT. Secondary endpoints include objective response rate, lesion-specific response rate, CNS progression-free survival, and overall survival. 140 of 143 target accrual have enrolled (4/22/2019).

scholarly journals Venous Thromboembolism Incidence and Impact on Survival in Patients with Brain Metastases

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 1-1
Author(s):  
Vaibhav Kumar ◽  
Xi Zhou ◽  
Benjamin Shiang Wu ◽  
Joshua Herb ◽  
Tzy-Mey Kuo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Brain Metastasis ◽  
Brain Metastases ◽  
Renal Cell Cancer ◽  
Renal Cell ◽  
Research Funding ◽  
Cell Cancer ◽  
Cox Proportional Hazards Model ◽  
Risk Of Death

Background: Patients with brain metastases are considered especially high risk for venous thromboembolism (VTE). The incidence of VTE following a diagnosis of brain metastases and the impact of VTE on overall survival among patients with brain metastases have not been well characterized. Methods: Using the linked Surveillance, Epidemiology and End Results (SEER) and Medicare databases between 2008-2015, we identified all patients ≥66 years with a primary diagnosis of lung, renal cell, breast cancer or melanoma and brain metastases (ICD-9-CM 198.3 present anytime in Medicare claims). Patients were required to have continuous Medicare part A and B enrollment from 12 months before and 12 months after diagnosis or until death. The primary outcome was incidence of VTE (deep vein thrombosis or pulmonary embolism or both) in the 12- months following a diagnosis of brain metastases. Patients with a VTE diagnosis prior to brain metastases were excluded. Incidence rates were calculated as VTE events per 100 patient years. Tumor specific multivariable Cox proportional hazards model adjusting for age, sex, race, time from primary cancer diagnosis to brain metastasis, comorbidities and VTE as a time varying covariate was used to assess the association of VTE and 12-month overall survival following a diagnosis of brain metastasis. Results: Among 154,918 individuals with a primary cancer diagnosis of interest, 21,623 (14.0%) had a brain metastasis diagnosis. Majority of patients with brain metastases had a primary diagnosis of lung cancer (N=19,141 (88.5%)), followed by melanoma (N=1,607 (7.4%)), renal cell cancer (N=576 (2.7%)) and breast cancer (299 (1.4%)). The baseline characteristics are highlighted in Table 1. Among these patients, VTE was diagnosed in 3,432 (15.9%). In the year following a diagnosis of brain metastasis, the incidence of VTE per 100 patient-years was highest among those with a diagnosis of renal cell cancer (19.4), followed by breast (16.3), lung (16.0) and melanoma (12.5). The median time to VTE from a diagnosis of brain metastasis is 1 month (IQR 0-3 months) and the cumulative incidence of VTE stratified by tumor type and accounting for the competing risk of death over 12 months is illustrated in Figure 1.The median overall survival following a diagnosis of brain metastasis was 2.7 months (95% CI 2.1-3.1 months). In a multivariable Cox proportional hazards model, a diagnosis of VTE following brain metastasis was associated with increased risk of death in patients with lung cancer (HR 1.23 (95% CI 1.18-1.28)), renal cell cancer (HR 1.36 (95% CI 1.06-1.75)) and melanoma (HR 1.32 (95% CI 1.12-1.55)), but not breast cancer (HR 1.16 (95% CI 0.80-1.69)). Conclusions: This large real-world retrospective cohort analysis demonstrates and quantifies the high tumor specific incidences of VTE among individuals with brain metastases. The VTE incidence rates observed are comparable to metastatic pancreatic cancer and highest in the initial 3 months following a diagnosis of brain metastasis. Furthermore, a diagnosis of VTE is associated with a reduced 12-month overall survival in this patient population. We are mindful to highlight the inherent limitations of claims data in identifying clinical events such as brain metastases and VTE, thus possible misclassification and selection biases should be considered when interpreting these findings. However, considering the complexity of managing VTE in this high-risk patient population and the high thrombotic burden demonstrated, these findings warrant further prospective validation. Disclosures Key: Takeda: Research Funding; Grifols: Research Funding; Uniqure: Consultancy; Novo Nordisk: Other: Chair of Grants Committee. Lund:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company; AbbVie: Research Funding.

scholarly journals NCOG-05. MANAGEMENT OF BRAIN METASTASIS IN TRIPLE NEGATIVE BREAST CANCER

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii130-ii130
Author(s):  
Ravi Medikonda ◽  
Siddhartha Srivastava ◽  
Timothy Kim ◽  
Yuanxuan Xia ◽  
Mira Patel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Radiation Therapy ◽  
Brain Metastasis ◽  
Brain Metastases ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Whole Brain ◽  
Whole Brain Radiation ◽  
Brain Radiation

Abstract Brain metastasis is common in patients with breast cancer, and those with triple negative status have an even higher risk. Stereotactic radiosurgery (SRS) is preferred to whole brain radiation therapy (WBRT) in most patients. However, triple negative status is currently not considered when determining optimal radiation therapy. Given the aggressive nature of triple negative breast cancer, we evaluated a role for WBRT for all patients in this cohort. We conducted a single-institution retrospective cohort study to determine whether triple negative patients with brain metastases have a higher burden of intracranial disease and whether type of initial radiation therapy affects overall survival for this cohort of patients. 85 patients met the inclusion criteria for this study. 25% of patients had triple negative breast cancer, of which 91% received SRS and 53% of patients received WBRT. The average number of new brain metastases from time of initial brain imaging to radiation therapy was 0.67 (St.Dev:1.1) in the non-triple negative status patients and 2.6 (St. Dev:3.7) in the triple negative status patients (p=0.001). Using a cox proportional hazards model, it was found that whole brain radiotherapy does not significantly affect overall survival in patients with triple negative breast cancer (p = 0.96). Our findings highlight the highly aggressive intracranial nature of triple negative breast cancer. Indeed, the rate of increase in brain metastases is significantly higher for triple negative patients compared to non-triple negative patients. As a result, we evaluated whether triple negative patients would benefit from whole brain radiation regardless of findings on initial brain imaging. Despite 53% of patients receiving WBRT, our investigation found that there is no additional benefit to WBRT in triple negative breast cancer patients. These results suggest a need to re-evaluate the role of WBRT in the management of triple negative breast cancer.

scholarly journals Genomic Profiling Using The UltraSEEK Panel Identifies Discordancy Between Paired Primary And Breast Cancer Brain Metastases And An Association With Brain Metastasis-Free Survival

2021 ◽  
Author(s):  
Carlo Palmieri ◽  
Athina Giannoudis ◽  
Alexander Sartori ◽  
Lee Eastoe ◽  
Rasheed Zakaria ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastasis ◽  
Brain Metastases ◽  
Clinical Problem ◽  
Breast Cancers ◽  
Her2 Positive ◽  
Free Survival ◽  
Er Positive ◽  
Breast Cancer Brain Metastases ◽  
Cancer Panel

Abstract Purpose. Brain metastases (BM) are an increasing clinical problem. This study aimed to assess paired primary breast cancers (BC) and BM for aberrations within TP53, PIK3CA, ESR1, ERBB2 and AKT utilising the MassARRAY® UltraSEEK® technology (Agena Bioscience, San Diego, USA). Methods. DNA isolated from 32 paired primary BCs and BMs was screened using the custom UltraSEEK® Breast Cancer Panel. Data acquisition and analysis was performed by the Agena Bioscience Typer software v4.0.26.74. Results. Mutations were identified in 91% primary BCs and 88% BM cases. TP53, AKT1, ESR1, PIK3CA and ERBB2 genes were mutated in 68.8%, 37.5%, 31.3%, 28.1% and 3.1% respectively of primary BCs and in 59.4%, 37.5%, 28.1%, 28.1% and 3.1% respectively of BMs. Differences in the mutations within the 5 genes between BC and paired BM were identified in 62.5% of paired cases. In primary BCs, ER-positive/HER2-negative cases harboured the most mutations (70%), followed by ER-positive/HER2-positive (15%) and triple-negatives (13.4%) whereas in BMs, the highest number of mutations was observed in triple-negatives (52.5%), followed by ER-positive/HER2-negative (35.6%) and ER-negative/HER2-positive (12%). There was a significant association between the number of mutations in the primary BC and breast-to-brain metastasis-free survival (p=0.0001) but not with overall survival (p=0.056). Conclusion. These data demonstrate the discordancy between primary BC and BM, as well as the presence of clinically important, actionable mutations in BCBM. The UltraSEEK® Breast Cancer Panel provides a tool for BCBM that can be utilised to direct more tailored treatment decisions and for clinical studies investigating targeted agents.

scholarly journals Survival time and prognostic factors after whole-brain radiotherapy of brain metastases from of breast cancer

2020 ◽  
Vol 9 (7) ◽  
pp. 205846012093874
Author(s):  
Yukinori Okada ◽  
Mariko Kobayashi ◽  
Mio Shinozaki ◽  
Tatsuyuki Abe ◽  
Yoshihide Kanemaki ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Brain Metastasis ◽  
Brain Metastases ◽  
Survival Time ◽  
Whole Brain Radiotherapy ◽  
Whole Brain ◽  
Overall Survival Time ◽  
Brain Radiotherapy ◽  
Contrast Enhanced

Background Breast cancer has a poor prognosis due to the high risk of distant metastasis. Purpose To identify the prognosticators of brain metastasis from breast cancer treated by whole-brain radiotherapy. Material and Methods We evaluated patients diagnosed with primary brain metastasis without carcinomatous meningitis from breast cancer and had undergone whole-brain radiotherapy as initial treatment between 1 January 2010 and 30 September 2019. We investigated associations between overall survival time from diagnosis using cranial contrast-enhanced magnetic resonance imaging (MRI)/computed tomography (CT) and the following parameters: (i) age; (ii) sex; (iii) time to appearance of brain metastasis; (iv) other metastasis at appearance of brain metastasis; (v) blood test; (vi) symptoms at time of brain metastasis; (vii) whole-brain radiotherapy dose; (viii) whether whole-brain radiotherapy was completed; (ix) course of chemo- or radiotherapy; (x) subtype; (xi) additional irradiation after whole-brain radiotherapy; (xii) pathology; and (xiii) imaging findings. Results We evaluated 29 consecutive female patients (mean age 55.2 ± 12.1 years). Median overall survival time after diagnosis on cranial contrast-enhanced MRI/CT was 135 days (range 16–2112 days). Multivariate stepwise analysis of the three parameters of lactate dehydrogenase, dose, and subtype identified the following significant differences: Hazard Ratio (HR) for dose (discontinued, 30 Gy/10 fractions, 31.5 Gy/11 fractions, 32.5 Gy/11 fractions, 37.5 Gy/15 fractions) was 0.08 (95% confidence interval [CI] 0.02–0.30, P < 0.01), and HR for subtype (luminal, HER2, triple-negative) was 2.70 (95% CI 1.16–6.243, P < 0.01). Conclusion HER2-type and 37.5 Gy/15 fractions are good prognostic factor after whole-brain radiotherapy in breast cancer with brain metastases.

Sign in / Sign up

Export Citation Format

Share Document