Incidence of Brain Metastases in Nonmetastatic and Metastatic Breast Cancer: Is There a Role for Screening?

Komorowski, Adam S; Warner, Ellen; Mackay, Helen; Sahgal, Arjun; Pritchard, Kathleen I.; Jerzak, Katarzyna J.

doi:10.1016/j.clbc.2019.06.007

Cited by 49 publications

(61 citation statements)

References 60 publications

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“…Our analysis is of clinical relevance in the context of prospective trials examining the benefit of early detection in breast cancer patients with a high risk for BM development. Considering the low time-dependent incidence of BM in early breast cancer patients [ 26 , 27 ], we suggest a prospective trial evaluating BM screening in patients with metastatic disease. It is estimated that almost a quarter of such patients develop BM [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

Characteristics and Clinical Outcome of Breast Cancer Patients with Asymptomatic Brain Metastases

Laakmann

Witzel

Neunhöffer³

et al. 2020

Cancers

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Background: Brain metastases (BM) have become a major challenge in patients with metastatic breast cancer. Methods: The aim of this analysis was to characterize patients with asymptomatic BM (n = 580) in the overall cohort of 2589 patients with BM from our Brain Metastases in Breast Cancer Network Germany (BMBC) registry. Results: Compared to symptomatic patients, asymptomatic patients were slightly younger at diagnosis (median age: 55.5 vs. 57.0 years, p = 0.01), had a better performance status at diagnosis (Karnofsky index 80–100%: 68.4% vs. 57%, p < 0.001), a lower number of BM (>1 BM: 56% vs. 70%, p = 0.027), and a slightly smaller diameter of BM (median: 1.5 vs. 2.2 cm, p < 0.001). Asymptomatic patients were more likely to have extracranial metastases (86.7% vs. 81.5%, p = 0.003) but were less likely to have leptomeningeal metastasis (6.3% vs. 10.9%, p < 0.001). Asymptomatic patients underwent less intensive BM therapy but had a longer median overall survival (statistically significant for a cohort of HER2-positive patients) compared to symptomatic patients (10.4 vs. 6.9 months, p < 0.001). Conclusions: These analyses show a trend that asymptomatic patients have less severe metastatic brain disease and despite less intensive local BM therapy still have a better outcome (statistically significant for a cohort of HER2-positive patients) than patients who present with symptomatic BM, although a lead time bias of the earlier diagnosis cannot be ruled out. Our analysis is of clinical relevance in the context of potential trials examining the benefit of early detection and treatment of BM.

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Section: Discussionmentioning

confidence: 99%

Characteristics and Clinical Outcome of Breast Cancer Patients with Asymptomatic Brain Metastases

Laakmann

Witzel

Neunhöffer³

et al. 2020

Cancers

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“…Approximately 40% to 50% of patients with advanced, HER2‐positive BC develop BCBM, a devastating diagnosis associated with significant morbidity and mortality and requiring skilled multidisciplinary input 15 . A major issue relates to the suboptimal ability of several HER2‐directed therapies and chemotherapy to penetrate the blood‐brain barrier (BBB) and the presence of efflux pumps along with resistance to HER2‐directed therapies 96 . Despite advances in systemic therapy overall, the incidence of CNS relapses was similar in both arms of the KATHERINE trial (40% of relapses); the prevention of these relapses remains an unmet clinical need.…”

Section: Therapeutic Advances and Challenges In The Treatment Of Advamentioning

confidence: 99%

“…Many clinical trials historically excluded patients with active (or even stable) BCBM; the HER2CLIMB study established an important precedent by including patients with active BCBM when clinically appropriate 15 . Treatment for HER2‐positive CNS disease typically includes surgery for solitary lesions, stereotactic radiosurgery for patients with ≤4 BCBMs, whole‐brain radiation for multiple lesions, or a combined approach 15,96‐98 . Over the last decade, there has been increasing use of systemic therapy either in place of, or as an adjunct to, local therapy.…”

Section: Therapeutic Advances and Challenges In The Treatment Of Advamentioning

confidence: 99%

Evolving standards of care and new challenges in the management of HER2‐positive breast cancer

Choong

Cullen

O’Sullivan

2020

CA A Cancer J Clinicians

118

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The management of human epidermal growth factor receptor (HER2)positive breast cancer (BC) has rapidly evolved over the last 20 years. Major advances have led to US Food and Drug Administration approval of 7 HER2-targeted therapies for the treatment of early-stage and/or advanced-stage disease. Although oncologic outcomes continue to improve, most patients with advanced HER2-positive BC ultimately die of their disease because of primary or acquired resistance to therapy, and patients with HER2-positive early BC who have residual invasive disease after preoperative systemic therapy are at a higher risk of distant recurrence and death. The concept of treatment de-escalation and escalation is increasingly important to optimally tailor therapy for patients with HER2-positive BC and is a major focus of the current review. Research efforts in this regard are discussed as well as updates regarding the evolving standard of care in the (neo)adjuvant and metastatic settings, including the use of novel combination therapies. The authors also briefly discuss ongoing challenges in the management of HER2-positive BC (eg, intrinsic vs acquired drug resistance, the identification of predictive biomarkers, the integration of imaging techniques to guide clinical practice), and the treatment of HER2-positive brain metastases. Research aimed at superseding these challenges will be imperative to ensure continued progress in the management of HER2-positive BC going forward.

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“…[3][4][5][6][7] In patients with metastatic HER2positive and TNBC, the incidence of BM is 11-48% and 25-46%, respectively, while in patients with luminal A and B, incidences are 8-15% and 11%, respectively. [7][8][9][10][11][12][13] Patients with BM experience neurological dysfunction 14 and have worse prognoses by molecular subtypes. 15,16 The reported median overall survival (OS) for patients with luminal and HER2-positive disease was 7.1-18.9 and 13.1-16.5 months, respectively, while for patients with TNBC, OS was 4.4-4.9 months.…”

Section: Introductionmentioning

confidence: 99%

Evolving treatment strategies of brain metastases from breast cancer: current status and future direction

Kim

2020

Ther Adv Med Oncol

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Remarkable progress in breast cancer treatment has improved patient survival, resulting in an increased incidence of brain metastasis (BM). Current treatment options for BM are limited and are generally used for palliative purposes. Historically, local treatment, consisting of radiotherapy and surgery, is the standard of care due to delivery limitations of systemic treatments through the blood–brain barrier. However, as novel biological mechanisms for tumors and BM have been discovered, several innovative systemic agents, such as small-molecular-targeted therapy and immunotherapy, have begun to change the treatment paradigm. In addition, efforts to maximize antitumor effects have been attempted using combination therapy, informed by tumor biology. In this comprehensive review, we will highlight various clinical trials investigating the treatment of BM in breast cancer patients, discuss presently available treatment options, and suggest potential directions of future therapeutic targets.

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Incidence of Brain Metastases in Nonmetastatic and Metastatic Breast Cancer: Is There a Role for Screening?

Cited by 49 publications

References 60 publications

Characteristics and Clinical Outcome of Breast Cancer Patients with Asymptomatic Brain Metastases

Characteristics and Clinical Outcome of Breast Cancer Patients with Asymptomatic Brain Metastases

Evolving standards of care and new challenges in the management of HER2‐positive breast cancer

Evolving treatment strategies of brain metastases from breast cancer: current status and future direction

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