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Breast cancer subtype and stage are prognostic of time from breast cancer diagnosis to brain metastasis development

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Abstract

Breast cancer brain metastasis (BCBM) is associated with high morbidity and mortality. Patients with breast cancer risk factors associated with rapid development of BCBM could potentially benefit from early brain metastasis screening. We retrospectively reviewed all BCBM patients treated with brain radiotherapy at our institution from 1997 to 2015. Interval time to BCBM was defined as date of pathologic breast cancer diagnosis to date of radiographic evidence of brain metastasis. Patients were stratified by breast cancer molecular subtype and stage at diagnosis. Kaplan Meier analysis was conducted on time to development of BCBM. Breast cancer risk factors were correlated with time to BCBM on Cox proportion hazard analysis. The study cohort comprised 121 BCBM patients, with median interval time to BCBM of 46 months. Times to BCBM for Her2+/2HR+, Her2+, Her2−/HR+, and triple-negative (TNBC) subtypes were 70, 44, 42, and 28 months respectively (p = 0.002). Time to BCBM for stages I, II, III, and IV were 70, 54, 29, and 24 months, respectively (p = 0.000). BCBM patients were further stratified by both molecular subtype (TNBC vs. non-TNBC) and stage (I, II vs. III, IV). Median times to BCBM for non-TNBC/stage I–II, TNBC/stage I–II, non-TNBC stage III–IV, and TNBC/stage III–IV were 68, 47, 29, and 6 months respectively (p = 0.000). Subtype and stage were associated with shorter time to BCBM on multivariate analysis. Subtype and initial stage are independently correlated with decreased time to development of BCBM. Patients with advanced high stage and triple negative breast cancer develop brain metastases significantly earlier.

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T. J. C. W. reports consulting fees for AstraZeneca and travel expenses from Abbvie and Novocure outside the submitted work.

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    Authors and Affiliations

    1. Department of Radiation Oncology, Columbia University Medical Center, CHONY North Basement Room 11, 622 West 168 Street, New York, NY, 10032, USA

      Anurag Saraf, Christopher S. Grubb, Mark E. Hwang, Cheng-Hung Tai, Cheng-Chia Wu, Ashish Jani, Matthew E. Lapa, Jacquelyn I. S. Andrews, Sierra Vanderkelen, Steven R. Isaacson, Simon K. Cheng, Eileen P. Connolly & Tony J. C. Wang

    2. Department of Neurological Surgery, The Neurological Institute, Columbia University Medical Center, 710 West 168 Street, New York, NY, USA

      Steven R. Isaacson, Adam M. Sonabend, Sameer A. Sheth, Guy M. McKhann, Michael B. Sisti, Jeffrey N. Bruce & Tony J. C. Wang

    3. Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, 1130 St Nicholas Avenue, New York, NY, 10032, USA

      Adam M. Sonabend, Sameer A. Sheth, Guy M. McKhann, Michael B. Sisti, Jeffrey N. Bruce, Simon K. Cheng, Eileen P. Connolly & Tony J. C. Wang

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    1. Anurag Saraf
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    Correspondence to Tony J. C. Wang.

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    For this type of study formal consent including for procedures is not required. This article does not contain any studies with animals performed by any of the authors.

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    All patients were retrospectively reviewed on an IRB approved database IRB-AAAM2358, Comprehensive Brain Malignancy and Brain Tumor Clinical Database. This article does not contain any studies with animals performed by any of the authors.

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    Anurag Saraf and Christopher S. Grubb have contributed equally to this study.

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    Saraf, A., Grubb, C.S., Hwang, M.E. et al. Breast cancer subtype and stage are prognostic of time from breast cancer diagnosis to brain metastasis development. J Neurooncol 134, 453–463 (2017). https://doi.org/10.1007/s11060-017-2549-y

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