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The shifting landscape of metastatic breast cancer to the CNS

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Abstract

The improved survival following the diagnosis of breast cancer has potentially altered the characteristics and course of patients presenting with CNS involvement. We therefore sought to define our current cohort of breast cancer patients with metastatic disease to the CNS in regard to modern biomarkers and clinical outcome. Review of clinical and radiographic records of women presenting to a tertiary medical center with the new diagnosis of CNS metastatic disease from breast cancer. This was a retrospective review from patients identities obtained from two prospective databases. There were 88 women analyzed who were treated over the period of January 2003 to February 2010, average age 56.9 years. At the time of initial presentation of CNS disease, 68 % of patients had multiple brain metastases, 17 % had a solitary metastasis, and 15 % had only leptomeningeal disease (LMD). The median survival for all patients from the time of diagnosis of breast disease was 50.0 months, and 9.7 months from diagnosis of CNS involvement. The only factor related to overall survival was estrogen receptor-positive pathology (57.6 v. 38.2 months, p = .02 log-rank); those related to survival post CNS diagnosis were presentation with LMD (p = .004, HR = 3.1, Cox regression) and triple-negative hormonal/HER2 status (p = .02, HR = 2.3, Cox regression). Patients with either had a median survival of 3.1 months (no patients in common). Of the 75 patients who initially presented with metastatic brain lesions, 20 (26 %) subsequently developed LMD in the course of their disease (median 10.4 months), following which survival was grim (1.8 months median). Symptoms of LMD were most commonly lower extremity weakness (14/33), followed by cranial nerve deficits (11/33). The recently described Graded Prognostic Assessment (GPA) tumor index stratified median survival at 2.5, 5.9, 13.1, and 21.7 months, respectively, for indices of 1–4 (p = .004, log-rank), which contrasted with the nonsignificant survival difference between Radiation Therapy Oncology Group Recursive Partitioning Analysis classes one and two. (13.1 v. 13.2, p = .8, log-rank). Treatment of patients with metastatic brain disease from breast cancer should be tailored to the patient’s hormonal status and GPA index. Practitioners must be vigilant for the development of LMD, especially as it often presents with nondescript complaints such as back pain.

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Conflict of interest

The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

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Authors and Affiliations

  1. Department of Neurosurgery, Allegheny General Hospital, 420 East North Ave, Pittsburgh, PA, 15212, USA

    Matthew R. Quigley, Olivia Fukui & Brandon Chew

  2. Department of Radiation Oncology, Allegheny General Hospital, 420 East North Ave, Pittsburgh, PA, 15212, USA

    Steven Karlovits

  3. Department of Neurosurgery, West Virginia University, Morgantown, WV, USA

    Sanjay Bhatia

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  1. Matthew R. Quigley
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  2. Olivia Fukui
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  3. Brandon Chew
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  4. Sanjay Bhatia
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Correspondence to Matthew R. Quigley.

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Comments

Moshe Hadani, Zvi R Cohen, Tel Aviv, Israel

In this article, Quigley et al. present a retrospective review of 88 patients with CNS involvement of breast cancer. The authors conclude that the treatment should be tailored to the patient hormonal status and GPA index. Their conclusion support previous publications. Their findings of the increased likelihood of active metastatic disease elsewhere in the body as well as frequent development of LMD in triple-negative disease are novel. The finding that there was no increase in LMD in patients that underwent SRS with or without surgery for oligometastases when WBXRT was initially withheld is of significant importance.

Andreas M. Stark, Kiel, Germany

Survival of breast cancer patients has significantly improved during the past decades. As a consequence, it is appropriate to evaluate a current cohort of patients with breast cancer brain metastases in the light of actual classifications, biomarkers, and clinical characteristics. Quigley and colleagues have reviewed the clinical data of 88 female patients with breast cancer brain metastases treated between 2003 and 2010. They included hormonal markers/HER2 status and presented survival data according to the LUMINAL classification [Geyer et al. 2012]. They found prognostic impact of estrogen receptor status on overall survival as well as prognostic impact of triple-negative hormonal/HER2 status on survival post central nervous system affection. Additionally, they evaluated their data based on the recently described Graded Prognostic Assessment Tumor Index [Sperduto et al. 2012]. This retrospective study is a solid basis for further prospective trials concerning patients with breast cancer brain lesions including endocrine and molecular data.

References

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Sperduto PW, Kased N, Roberge D, Xu Z, Shanley R, Luo X, Sneed PK, Chao ST, Weil RJ, Suh J, Bhatt A, Jensen AW, Brown PD, Shih HA, Kirkpatrick J, Gaspar LE, Fiveash JB, Chiang V, Knisely JP, Sperduto CM, Lin N, Mehta M. Summary report on the graded prognostic assessment: an accurate and facile diagnosis-specific tool to estimate survival for patients with brain metastases. J Clin Oncol. 2012 Feb 1;30(4):419–25. doi: 10.1200/JCO.2011.38.0527

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Quigley, M.R., Fukui, O., Chew, B. et al. The shifting landscape of metastatic breast cancer to the CNS. Neurosurg Rev 36, 377–382 (2013). https://doi.org/10.1007/s10143-012-0446-6

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