Upfront stereotactic radiosurgery for brain metastases from triple-negative breast cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e14014-e14014
Author(s):  
Ran An ◽  
Yan Wang ◽  
Fuchenchu Wang ◽  
Akshara Singareeka Raghavendra ◽  
Chao Gao ◽  
...  

e14014 Background: Triple-negative breast cancer (TNBC) is an aggressive subtype with high propensity of brain metastases (BM). Outcomes after upfront stereotactic radiosurgery (SRS) for BM from TNBC patients are not well defined. We evaluated outcomes and identified prognostic factors for such patients. Methods: We reviewed 57 consecutive patients treated with upfront SRS for BM from TNBC in May 2008–April 2018 at a large-volume cancer center. Endpoints were overall survival (OS) from BM diagnosis and freedom from BM progression (FFBMP) after initial SRS. BM progression was defined as local and/or distant brain failure (LBF or DBF) after initial SRS; LBF was radiographic progression of treated lesions, assessed by a neuroradiologist or treating physician excluding post-radiation changes or radiation necrosis. Kaplan-Meier and Cox proportional hazard regression analyses were used to estimate survival outcomes and identify prognostic factors. Results: In this cohort of 57 patients with a median age of 53 y (range 26–82) at BM diagnosis and follow-up time of 12.2 months (mo, range 0.8–97.5), median time to BM development from TNBC diagnosis was 23.7 mo (range 0.7‒271.1). Estimated median OS time from initial BM diagnosis was 13.1 mo (95% CI 8.0‒19.5). In univariate analysis, Karnofsky performance score (KPS) > 70 (p = 0.03), having < 3 BMs (p = 0.016) at BM diagnosis, and BM as first site of metastasis (p = 0.041) were associated with longer OS. On multivariate analysis, KPS ≤70 was associated with higher risk of death (HR 3.0, p = 0.03). Of 46 patients with imaging follow-up for FFBMP assessment, 29 (63%) developed BM progression after initial SRS with an estimated median FFBMP of 7.4 mo (95% CI 5.7–12.7). Median times to LBF and DBF were 10 mo (range 0.3–97) and 5.9 mo (range 0.3–90.8). Estimated cumulative LBF rate was 17.8% (95% CI 2%–31.1%) and DBF 61.1% (95% CI 40.8%–74.4%) at 12 mo. Number of BMs at BM diagnosis (≥3 vs < 3) was not associated with FFBMP (p = 0.7). Of the 29 patients with BM progression, 5 did not receive salvage radiation therapy (RT) and 24 received salvage RT (SRS, whole-brain radiation [WBRT], or both SRS+WBRT). Receipt of salvage RT was associated with longer survival (median 21.7 mo vs. 7.0 mo for no salvage RT, p < 0.0001) and did not differ by type of salvage RT (median OS 18.6 mo for WBRT; 26.2 mo for SRS+WBRT; 35.9 mo for SRS, p = 0.08). Conclusions: We reported a median OS of 13.1 mo and FFBMP of 7.4 mo in TNBC patients with good local control. Good KPS was independent prognostic factor for better OS. FFBMP did not differ by number of SRS-treated brain lesions ( < 3 vs ≥3). Further prospective studies of larger numbers of patients needed for more accurate comparisons of treatment types.

2021 ◽  
Vol 3 (Supplement_3) ◽  
pp. iii21-iii21
Author(s):  
Ran An ◽  
Yan Wang ◽  
Fuchenchu Wang ◽  
Akshara Singareeka Raghavendra ◽  
Chao Gao ◽  
...  

Abstract Background Triple-negative breast cancer (TNBC) is an aggressive subtype with high propensity of developing brain metastases (BM). Clinical outcomes and prognostic factors after stereotactic radiosurgery (SRS) for BM were not well defined. Methods We identified 57 consecutive TNBC patients (pts) treated with single fraction SRS for BM during 05/2008–04/2018. Overall survival (OS) from BM diagnosis and freedom from BM progression (FFBMP) after initial SRS were evaluated. BM progression was defined as local and/or distant brain failure (LBF, DBF) after SRS. Kaplan-Meier analyses and Cox proportional hazard regression were used to estimate survival outcomes and identify prognostic factors. Results The median time to BM development from TNBC diagnosis was 23.7 months (mo) (range 0.7‒271.1). Median OS was 13.1 mo (95%CI 8.0‒19.5). On univariate analysis, Karnofsky performance score (KPS) &gt;70 (p=0.03), number of BMs &lt;3 (p=0.016), and BM among the first metastatic sites (p=0.04) were associated with longer OS. On multivariate analysis, KPS ≤70 was associated with higher risk of death (HR 3.0, p=0.03). Of 46 pts with adequate imaging follow-up, 29 (63%) had intracranial progression with a median FFBMP of 7.4 mo (95% CI 5.7–12.7). At 12 mo the estimated cumulative DBF rate was 61.1% (95%CI 40.8%–74.4%) and LBF rate was 17.8% (95%CI 2%–31.1%). Number of BMs (≥3 vs &lt;3) was not associated with FFBMP (p=0.7). Of the 29 pts with BM progression, additional radiation therapy (RT) (vs. no RT) was associated with improved survival (21.7 vs. 7.0 mo, p&lt;0.0001). Conclusions TNBC pts with BM treated with SRS had an OS of 13.1 mo and FFBMP of 7.4 mo. Good KPS was an independent prognostic factor for OS. Further studies with more pts or conducted prospectively are needed to better understand and to improve treatment outcomes in this pt population.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22214-e22214
Author(s):  
M. Dioca ◽  
M. Savignano ◽  
L. Gimenez ◽  
L. Marino ◽  
C. Delfino ◽  
...  

e22214 Background: Triple negative breast cancer (BC) is a distinct group of tumors that show common but heterogeneous morphologic, genetic, and immunophenotypic features. Despite differences in the definition and prevalence, it comprises 8% to 20% of all breast cancers and is associated with an aggressive clinical course with significant risk of either local or systemic relapse and subsequent increased risk of death on short term follow up (particularly in the first 5 years).We study the pathological characteristics and the clinical outcome of a cohort of 77 triple negative BC patients (pts) diagnosed at our Institution. Methods: Between January 1999 and September 2008, 77 (stage I to III) triple negative BC pts. were retrospectively analyzed. All pts had their receptor status, Her neu, ck-5, ck-6 and staining for EGFR by the same pathologist. Pathological parameters (Pp) analyzed were: status of axilary lymph nodes (LN), nuclear grade, histologic grade, mitotic index and vascular invasion and the use of antraciclins in the adjuvant setting. Univariate and multivariate analysis (proporcional hazard regression Cox model) for the Pp associated with relapse, and the log rank test to compare two curves of each Pp for disease free survival (DFS), and overall survival (OS) were performed. Results: The median age was 57.8 years (range 30–86 years).The median follow up time was 57.7 months (range, 4- 241). From 77 Pts. analized, 65 (84.4%) were basal-like and 43 (64.6%) of those were GH3. Stage at the time of presentation was: 16 (20,7%) stage I; 40 (51,9%) stage II; 21 (27,7%) stage III. Pre-menopausal status was 29,48% (23 pts.), and 61% (47 pts) were LN negative. Overall, relapse rate was 38.5 % (n= 30), 63 Pts (81.8%) are still alive. Median DFS was not reached. Global DFS and OS were 59% and 79% respectively, and status of LN was the only prognostic factor. LN- vs LN+ DFS (p< 00.02) and OS p (< 0.02).All others Pp analyzed were not statistically significative. Conclusions: Despite previous studies have demonstrated that triple negative is an independent marker of poor prognosis in BC as a whole, in the LN-negative, and LN-positive groups, in this basal like population only positive LN was an independent poor prognostic factor for DFS and OS. No significant financial relationships to disclose.


2011 ◽  
Vol 29 (27_suppl) ◽  
pp. 36-36 ◽  
Author(s):  
A. Mathew ◽  
M. Q. Rosenzweig ◽  
A. Brufsky

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.


Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 6059
Author(s):  
William Jacot ◽  
Aurélie Maran-Gonzalez ◽  
Océane Massol ◽  
Charlotte Sorbs ◽  
Caroline Mollevi ◽  
...  

HER2-low breast cancer (i.e., HER 1+ or 2+, without gene amplification) is an emerging subtype for which very few data are available, especially within the triple-negative breast cancer (TNBC) group. Our aim was to evaluate HER2 expression and its prognostic value in a large retrospective series of patients with non-metastatic TNBC (median age: 57.7 years; range: 28.5–98.6). Among the 296 TNBC samples, 83.8% were HER2 0, 13.5% were HER2 1+, and 2.7% were HER2 2+ (HercepTestTM and 2018 ASCO/CAP guidelines for HER2 scoring). CK5/6 and/or EGFR-expressing androgen receptors and FOXA1-expressing tumors were classified as basal-like (63.8%) and molecular apocrine-like (MA, 40.2%), respectively. Compared with HER2 0 tumors, HER2 1+/2+ tumors exhibited a lower histological grade (1/2) (35.4% vs. 18.2%, p = 0.007) and MA profile (57.5% vs. 36.7%, p = 0.008). Moreover, patients with HER2 1+/2+ tumors were older (p = 0.047). After a median follow-up of 9.7 years, HER2 2+ tumors (compared with HER2 0/1+ tumors) were associated with worse relapse-free survival (RFS) (HR = 3.16, 95% CI [1.27; 7.85], p = 0.034) in a univariate analysis. Overall survival (OS) and RFS were not different in the HER2 0 and 1+/2+ groups. HER2 levels were not significantly associated with OS or RFS in a multivariate analysis.


2019 ◽  
Author(s):  
Hua-Ren Cherng ◽  
Stephanie R Rice ◽  
Muhammad Hamza ◽  
Shruti Murali ◽  
Paula Rosenblatt ◽  
...  

Abstract Background: We sought to evaluate the comprehensive patterns of failure associated with treatment for triple negative breast cancer (TNBC) at a single urban institution. Methods: A retrospective review of TNBC patients treated from 2005-2015 was conducted. Detailed patient, tumor and treatment characteristics were included. Information on patterns of treatment failure, including local, regional, distant and combinations of these three were collected. Chi-square testing was used to compare variables, while logistic regression with Kaplan-Meier estimate was used to calculate overall survival (OS) and freedom from recurrence (FFR). Results: With a median follow-up of 46 months, 32 (16%) documented failures occurred. Locoregional failures comprised 84% of failure patterns whether isolated or in combination with distant failure. 5-year OS and FFR were 76.4% and 83.8%, respectively. On univariate analysis, treatment failure was associated with insurance type, smoking status, presence of LVSI, clinical detection of tumor, increasing clinical tumor size (>2 cm), and increasing pathologic tumor stage, nodal stage, and overall staging. On multivariate analysis, pathologic nodal staging was the most significant predictor of treatment failure. Conclusion: Our work shows that with modern therapies, treatment outcomes for patients with TNBC are very good. 53% of patients failed in distant and locoregional sites simultaneously, with an additional 34% failing locally only. These results highlight the need for aggressive local therapies in high-risk patients as well as suggest a need for improved follow up care focusing on detecting locoregional failures. Integrated multidisciplinary care is essential in the management of these patients at time of failure. Keywords: Triple negative, breast cancer, failure, patterns, predictors


2021 ◽  
Vol 8 (18) ◽  
pp. 1287-1292
Author(s):  
Binitha Tresa Thomas ◽  
Preeya Vasanthakumary ◽  
Ancy Joseph

BACKGROUND Breast cancer is now the most common cancer in Indian women, having recently surpassed cervical cancer in incidence. Triple negative breast cancer (TNBC), which accounts for 15 % of all the breast cancers is an aggressive type seen in younger women with early signs of metastasis, has a poor prognosis due to systemic recurrence and its refractoriness to conventional adjuvant therapy. The purpose of this study was to look into the various prognostic factors associated with 5 years disease-free survival (DFS) and overall survival (OS) in TNBC. METHODS This retrospective study included 67 patients with complete treatment and followup (median 57 months) presented and treated in the Department of Radiotherapy, Kottayam, between January 2011 and December 2012. The Kaplan-Meier approach was used to analyse survival. Using the log-rank test, univariate analysis of prognostic factors was completed. Using the Cox regression process, multivariate analysis was performed on IBM SPSS version 20. RESULTS The average age was 51.36 ± 11.393 (median, 51.36 years; range 30.0 – 80.0 years), with a median of 50 months, the five-year OS was 65.7 % and DFS was found to be 59.7 % with a median of 45 months, suggesting aggressive nature and poor TNBC survival. Univariate analysis of prognostic factor, clinical stage (cN) and positive nodes (pN) status, clinical tumour size, lympho-vascular invasion (LVI), grade, and nodal density were found to have a significant impact on DFS. Except tumour grade and LVI all were found to be associated with OS. Multivariate analysis, clinical tumour size and pathological nodal status had a significant impact on OS and DFS. CONCLUSIONS TNBC is an aggressive subtype of breast cancer in younger patients with a high risk of metastasis to visceral organs with inherent molecular subtypes and immunological heterogeneity. For treatment of TNBC, targeted estimated glomerular filtration rate (EGFR), fibroblast growth factor receptor 2 (FGFR2), vascular endothelial growth factor (VEGF), and mechanistic target of rapamycin (mTOR) receptor based initial treatment setting will improve the outcome dramatically and will fill the unmet clinical needs. KEYWORDS TNBC, Recurrence, OS, DFS, Nodal Density


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10555-10555
Author(s):  
R. Gutt ◽  
S. Yovino ◽  
L. Chin ◽  
W. Regine ◽  
P. Amin ◽  
...  

10555 Background: Outcomes of gamma knife stereotactic radiosurgery (GK-SRS) for patients with brain metastases specifically from breast cancer have not been well-defined. This study was undertaken to report the long-term experience with GK-SRS in this subset of patients. Methods: From 1995 to 2005, 75 patients with 162 brain lesions were treated with GK-SRS at the University of Maryland Medical Center. Complete follow-up data were available in 65 patients. Additional whole brain radiation therapy (WBRT) was administered to 53 (81.5%) patients. The median WBRT dose was 36.75 Gy (30.0–45.0 Gy). The median number of lesions treated with GK-SRS was 2 (1–8 lesions). The median follow-up, age, and KPS were 7.2 months (0.4–75.7 months), 53.5 years (23–81 years), and 90 (40–100), respectively. The factors included in the univariate and multivariate analyses for overall survival (OS) and progression free survival (PFS) were age, Karnofsky Performance Status (KPS), tumor histology, estrogen receptor status, Her-2-neu status, number of intracranial lesions, and presence of systemic disease. Results: Median PFS and OS from GK-SRS were 5.3 months (0.4–33.2 months) and 8.1 months (0.4–75.7 months), respectively. The 6, 12, and 24 month actuarial PFS were 47.8%, 24.9%, and 9.6% respectively. The 6, 12, and 24 month actuarial OS were 60.7%, 39.1%, and 18.1% respectively. The tumor local control after WBRT and GK-SRS was 87.7%. Radiation necrosis was a complication in 10.8% of patients. Forty-seven (72.3%) patients had neurological symptoms prior to gamma knife treatment. Seven (14.9%) and 9 (19.1%) of these patients experienced symptom resolution and significant symptomatic improvement, respectively. Multivariate and univariate analysis did not reveal any of the prognostic factors in question to be significantly associated with OS nor PFS. Conclusions: This relatively large cohort of patients experienced poor survival outcomes despite aggressive therapy with WBRT and GK-SRS. However, GK-SRS can provide significant symptomatic relief, with acceptable complication rates. More research is required to improve the survival of breast cancer patients with intracranial metastases. No significant financial relationships to disclose.


2021 ◽  
Author(s):  
Jan Sieluk ◽  
Lingfeng Yang ◽  
Amin Haiderali ◽  
Min Huang ◽  
Kim M Hirshfield

Aim: To analyze therapy for metastatic triple-negative breast cancer (mTNBC), factors contributing to survival and costs. Patients & methods: Using 2010–2016 SEER-Medicare data, we identified women (≥65 years) with mTNBC. Results: Of 302 eligible patients, 152 (50%) received systemic therapy. In multivariable regression analyses, only age <75 years was associated with therapy receipt (odds ratio: 2.91; 95% CI: 1.79–4.74); and only systemic therapy significantly reduced risk of death (hazard ratio: 0.34; 95% CI: 0.26–0.44). Median overall survival was 13.4 (95% CI: 11.3–15.1) vs 3.3 months (95% CI: 2.7–3.9) in therapy vs no-therapy cohorts. Mean per-patient-per-month costs <30 days before end-of-life/follow-up were $14,100 and $15,600 (2019 USD), respectively. Conclusion: Poor outcomes and high costs indicate need for more effective mTNBC therapy.


Author(s):  
Ankita Gupta ◽  
Budhi Singh Yadav ◽  
Nagarjun Ballari ◽  
Namrata Das ◽  
Ngangom Robert

Abstract Background: Brain metastases (BM) are common in patients with HER2-positive and triple-negative breast cancer. In this study we aim to report clinical outcomes with LINAC-based stereotactic radiosurgery/radiotherapy (SRS/SRT) for BM in patients of breast cancer. Methods: Clinical and dosimetric records of breast cancer patients treated for BM at our institute between May, 2015 and December, 2019 were retrospectively reviewed. Patients of previously treated or newly diagnosed breast cancer with at least a radiological diagnosis of BM; 1–4 in number, ≤3·5 cm in maximum dimension, with a Karnofsky Performance Score of ≥60 were taken up for treatment with SRS. SRT was generally considered if a tumour was >3·5 cm in diameter, near a critical or eloquent structure, or if the proximity of moderately sized tumours would lead to dose bridging in a single-fraction SRS plan. The median prescribed SRS dose was 15 Gy (range 7–24 Gy) and SRT dose was 27 Gy in 3 fractions. Clinical assessment and MR imaging was done at 6 weeks post-SRS and then every 3 months thereafter. Intracranial progression-free survival (PFS) and overall survival (OS) were calculated using Kaplan–Meier method and subgroups were compared using log rank test. Results: Total, 40 tumours were treated in 31 patients. The median tumour diameter was 2·3 cm (range 1·0–4·6 cm). SRS and SRT were delivered in 27 and 4 patients, respectively. SRS/SRT was given as a boost to whole brain radiotherapy (WBRT) in four patients and as salvage for progression after WBRT in six patients. In general, nine patients underwent prior surgery. The median follow-up was 7·9 months (0·2–34 months). Twenty (64·5%) patients developed local recurrence, 10 (32·3%) patients developed distant intracranial relapse and 7 patients had both local and distant intracranial relapse. The estimated local control at 6 months and 1 year was 48 and 35%, respectively. Median intracranial progression free survival (PFS) was 3·73 months (range 0·2–25 months). Median intracranial PFS was 3·02 months in patients who received SRS alone or as boost after WBRT, while it was 4·27 months in those who received SRS as salvage after WBRT (p = 0·793). No difference in intracranial PFS was observed with or without prior surgery (p = 0·410). Median overall survival (OS) was 21·7 months (range 0·2–34 months) for the entire cohort. Patients who received prior WBRT had a poor OS (13·31 months) as compared to SRS alone (21·4 months; p = 0·699). Conclusion: In patients with BM after breast cancer SRS alone, WBRT + SRS and surgery + SRS had comparable PFS and OS.


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