Faculty

Hannah M. Linden, MD

Hannah M. Linden, MD FACP

Professor
Department of Medicine
Division of Oncology

Member
Fred Hutch Cancer Research Center
Clinical Research Division

Associate Program Director
Medical Oncology and Hematology Fellowship program UW/FHCRC

Mailing Address

Seattle Cancer Care Alliance
825 Eastlake Avenue W
Seattle WA 98109-1023 G3-630

Admin Contact

Michele Roe
206-606-2053
mroe1@seattlecca.org

Specialty / Expertise

  • Breast Oncology
  • Translational Imaging
  • Clinical trials in breast cancer
  • Patient Navigation

Research Interests

  • Understanding resistance and sensitivity to endocrine therapy of breast cancer, and identification of methods to overcome resistance
  • Pharmacodynamic imaging
  • Improving access to clinical trials
  • Improving outcomes for vulnerable populations

Current Research Projects

Title: A Trial of Endocrine Response in Women With Invasive Lobular Breast Cancer
Funding Source: TBCRC
To determine the change from baseline to post-treatment Ki67 values in ER-positive, HER2-negative ILC tissue derived from postmenopausal women awaiting definitive surgery or further neoadjuvant treatment who are randomized to 21-24 days of neoadjuvant endocrine treatments with fulvestrant (two 250 mg IM injections given on day 1), anastrozole (1mg given orally daily), or tamoxifen (20mg given orally daily)..

Title: A Phase 1/2 study for the safety, efficacy, pharmacokinetic and pharmacodynamics evaluation of SAR439859, administered orally as monotherapy, then in combination with palbociclib in postmenopausal women with estrogen receptor-positive advanced breast.
Funding Source: Sanofi-Aventis U.S.
Primary objective Dose escalation: PART A (SAR439859 monotherapy); PART C (combination of SAR439859 with palbociclib) • To assess the incidence rate of dose-limiting toxicity (DLT) and to determine the maximum tolerated dose (MTD) as well as the recommended dose (RD) of SAR439859 administered as monotherapy (Part A), then in combination with palbociclib (Part C), to postmenopausal women with estrogen receptor (ER) positive and human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. Dose expansion: PART B (SAR439859 monotherapy); PART D (combination SAR439859 with palbociclib)
• To assess antitumor activity using objective response rate (ORR) according to response evaluation criteria in solid tumors (RECIST) v1.1 at the SAR439859 RD administered as monotherapy (Part B), then in combination with palbociclib (Part D), to postmenopausal women with ER-positive and HER2-negative advanced breast cancer.

Title: EAI142 – [18F] Fluoroestradiol (FES) as a Predictive Measure for Endocrine Therapy in Women with Newly Diagnosed Metastatic Breast Cancer
Funding Source: ECOG-ACRIN Medical Research Foundation, Inc.
The purpose is to provide funding for Dr. Linden’s Scope of Work for this trial which is to ensure 1) the protocol scientific aims are consistent with scientific strategy of the related disease site as determined by each disease site committee and 2) compliance with the protocol. She will coordinate with the protocol team to oversee the study conduct and address questions from sites concerning protocol eligibility.

Title: Metronomic Eribulin (Halaven) in Pretreated Metastatic Breast Cancer (MBC)
Funding Source: Eisai Inc.
We believe that the optimal schedule of eribulin has yet to be defined and that an approach similar to that used with vinorelbine could improve the tolerability of the agent without sacrificing efficacy. A lower dose metronomic schedule would allow responding patients to remain on treatment resulting in a longer time to progression and greater use of the drug in practice.

Title: A Phase 2 Open Label, Multi-Center, Multinational, Randomized, Parallel Design Study Investigating the Efficacy and Safety of GTx-024 on Metastatic or Locally Advanced ER+/AR+ Breast Cancer (BC) in Postmenopausal Women
Funding Source: GTx Inc.
The primary efficacy objective of this trial is to estimate the clinical benefit rate at 24 weeks of GTx-024 9 mg and of GTx-024 18 mg given PO daily in subjects with ER+/AR+ breast cancer who have centrally confirmed AR+ status.

Training

Dr. Linden received her BA from Yale University, New Haven, CT and her MD from University of Massachusetts Medical School, Worcester, MA. She completed her Internal Medicine Residency at the University of Arizona, Tucson, AZ, and completed her fellowship and postdoctoral training in Hematology and Oncology at the University of Washington, Seattle, WA.

Selected Publications

Agoff SN, Swanson PE, Linden HM, Hawes SE, Lawton TJ.  Androgen receptor expression in estrogen receptor negative breast cancer:  Immunohistochemical, Clinical, and Prognostic Associations.  Am J Clin Pathl 120(5):725-31, 2003.

Linden HM, Ramsey S, Anderson N: An ounce of prevention or a pound of cure? Investing to Improve Breast Cancer Outcomes for African American Women. J Clin Oncology 22(13):2517-2518, 2004, Invited editorial

Dunnwald LK, Gralow JR, Ellis GK, Livingston RB, Linden HM, Lawton TJ, Barlow WE Schubert EK, Mankoff DA.  Residual tumor uptake of [99mTc]-sestamibi after neoadjuvant chemotherapy for locally advanced breast carcinoma predicts survival. Cancer 103(4):680-688, 2005.

Oestreicher N, Veenstra DL, Linden HM, McCune JS, Ramsey SD:  The cost of adjuvant chemotherapy in early stage breast carcinoma. Cancer. 2005, 104(10):2054-62.

Oestreicher N, Ramsey SD, Linden HM, McCune JS, Van’t Veer LJ, Burke W, Veenstra DL. Gene Expression Profiling and Breast Cancer Care: What are the potential benefits and policy implications? Genet Med 2005 Jul-Aug; 7(6):380-9.

Specht JM, Tam SL, Kurland BF, Gralow JR, Livingston RB, Linden HM, Ellis GK, Schubert EK, Dunwald LK, Mankoff DA.  Serial 2-[18F] flouro-2-deoxy-d-glucose positron emission tomography (FDG-PET) to monitor treatment of bone-dominant metastatic breast cancer predicts time to progression (TTP).  Published on line, February 1st, 2006, Breast Cancer Res Treatment.

Linden HM, Krohn KA, Livingston RB, Mankoff D.  Monitoring targeted therapy:  Is fluorodeoxylucose (FDG) uptake a marker of early response?  Invited editorial.  Clin Cancer Res. 2006 Oct 1;12(19):5608-5610.

Linden HM, Stekhova SA, Link JM, Gralow JR, Livingston RB, Ellis GK, Petra P, Peterson LM, Schubert E, Dunnwald LK, Krohn KA, Mankoff DA.  Quantitative fluoroestradiol positron emission tomography imaging predicts response to endocrine treatment.  J Clin Oncol 2006 24(18): 2793-2799.

Mankoff DA, Dunnwald LK, Gralow JR, Ellis GK, Livingston RB, Linden HM, Specht JM, Doot RK, Lawton TJ, Barlow WE, Kurland BF, Schubert EK.  Tumor Metabolism and Blood Flow Changes by PET – Relation to Survival among a Prospective Cohort of Neoadjuvantly Treated Locally Advanced Breast Cancer Patients.  J Clin Oncol 2007, #154385. 

Linden HM, Haskell CM, Green SJ, Osborne CK, Sledge, Jr. GW, Shapiro CL, Ingle JN, Lew D, Hutchins LF, Livingston RB, Martino S. Sequenced compared with simultaneous anthracycline and cyclophosphamide in high-risk stage I and II breast cancer: final analysis from INT-0137 (S9313). J Clin Oncol 2007 Feb 20; 25(6):656-661.
[PubMed Abstract]

Linden HM, Reisch LM, Nakano C, Harrington M, Jackson C, Hart A, Elmore JG.   Attitudes toward participation in breast cancer screening and randomized clinical trials in the African American community: a focus group study. Cancer Nursing 2007 30(2):1-10.

Krohn KA. O’Sullivan F, Crowley J, Eary JF, Linden HM, Link JM, Mankoff DA, Muzi M, Rajendran JG, Spence AM, Swanson KR. Challenges in Clinical Studies with Multiple Imaging Probes. Nucl Med Bio. 2007 Oct,34(7):879-85 Review

Ramsey SD, Zeliadt SB, Richardson LC, Pollack L, Linden HM, Blough D, Anderson N.  Disenrollment from Medicaid after recent cancer diagnosis?  Medical Care.  2008 Jan;46(1):49-57.

Linden HM, Jackson C.  Ending cancer treatment disparities.  Seattle Post-Intelligencer NW Source/guest editorial 349983.  February 4, 2008.

Mankoff DA, Link JM, Linden HM, Sundararajan L, Krohn KA.  Tumor Receptor Imaging.  J Nucl Med.  2008 June; 49(6):149S-163S

Dunnwald LK, Gralow JR, Ellis GK, Livingston RB, Linden HM, Specht JM, Doot RK, Lawton TJ, Barlow WE, Kurland BF, Schubert EK, Mankoff DA.  Tumor metabolism and blood flow changes by positron emission tomography: relation to survival in patients treated with neoadjuvant chemotherapy for locally advanced breast cancer. J Clin Oncol. 2008 Sep 20;26(27):4449-57.
[PubMed Abstract]

Ramsey SD, Zeliadt SB, Richardson LC, Pollack LA, Linden HM, Blough DK, Keitheri Cheteri M, Tock L, Nagy K, Anderson N. Discontinuation of Radiation Treatment among Medicaid-Enrolled Women with Local and Regional Stage Breast Cancer. The Breast Journal (in press).

Specht JM, Kurland BF, Montgomery S, Dunnwald L, Doot R, Gralow JR, Ellis GK, Linden HM, Livingston RB, Allison K, Schubert E, Mankoff DA.  Tumor metabolism and blood flow as assessed by PET varies by tumor subtype in locally advanced breast cancer. Clin Cancer Res May 15, 2010 16:2803-2810.

Modi S, Stopeck A, Linden H, Solit D, Chandarlapaty S, Rosen N, D’Andrea G, Dickler M, Moynahan M, Sugarman S, Ma W, Patil S, Norton L, Hannah A, Hudis C. HSP90 Inhibition is Effective in Breast Cancer: A Phase 2 Trial of Tanespimycin (17AAG) plus Trastuzumab in Patients with HER2-Positive Metastatic Breast Cancer Progressing on Trastuzumab. Clinical Cancer Research. August 2011. 1;17(15): 5132-5139.

*Linden H, Kurland B, Peterson L, Schubert E, Gralow J, Specht J, Ellis G, Lawton T, Livingston R, Petra P, Link J, Krohn K, Mankoff D. Fluoroestradiol (FES) Positron Emission Tomography (PET) Reveals Differences In Pharmacodynamics of Aromatase Inhibitors, Tamoxifen, And Fulvestrant In Patients With Metastatic Breast Cancer. Clinical Cancer Research. July 2011. 15;17(14): 4799-4805.

Chew H, Somlo G, Mack P, Gitlitz B, Gandour-Edwards R, Christensen S, Linden H, Solis LJ, Yang X, Davies A. Phase I Study of Continuous and Intermittent Schedules of Lapatinib in Combination with Vinorelbine in Solid Tumors. Ann Oncol. July 2011.

Kurland B, Peterson L, Lee J, Linden H, Schubert E, Dunnwald L, Link J, Krohn K, Mankoff D. Between-patient and Within-patient (Site-to-Site) Variability in Estrogen Receptor Binding, Measured in Vivo by 18F-fluoroestradiol PET. Journal of Nuclear Medicine. October 2011. 52(10): 1541-1549.

Peterson L, Kurland B, Link J, Schubert E, Stekhova S, Linden H, Mankoff D. Factors Influencing the Uptake of 18F-fluoroestradiol in Patients with Estrogen Receptor Positive Breast Cancer. Nucl Med Biol. October 2011. 38(7) 969-978.

Muzi M, O’Sullivan F, Mankoff D, Doot R, Pierce L, Kurland B, Linden H, Kinahan P. Quantitative assessment of dynamic PET imaging data in cancer imaging. Magn Reson Imaging. 2012 Nov;30(9):1203-15. doi:10.1016/j.mri.2012.05.008. Epub 2012 Jul 21. Review. PubMed PMID: 22819579;PubMed Central PMCID: PMC3466344.

Doot R, Thompson T, Greer B, Allberg K, Linden H, Mankoff D, Kinahan P. QIN. Early Experiences in Establishing a Regional Quantitative Imaging Network for PET/CT Clinical Trials. Magn Reson Imaging. 2012 Nov;30(9):1291-300. doi:10.1016/j.mri.2012.06.002. Epub 2012 Jul 15. PubMed PMID: 22795929; PubMed Central PMCID: PMC3466345.

Kurland B, Gadi V, Specht J, Allison K, Livingston R, Rodler E, Peterson L, Schubert E, Chai X, Mankoff D, Linden H. Feasibility study of FDG PET as an indicator or early response to aromatase inhibitors and trastuzumab in a heterogeneous group of breast cancer patients. EJNMMI Res. 2012 Jun 25;2(1):34. doi: 10.1186/2191-219X-2-34. PubMed PMID: 22731662; PubMed Central PMCID: PMC3444390.

Linden H, Dehdashi F. Novel Methods and Tracers for Breast Cancer Imaging. Semin Nucl Med. 2013 Jul;43(4):324-9. doi: 10.1053/j.semnuclmed.2013.02.003. Review. PubMed PMID: 23725994.

Kurland B, Doot R, Linden H, Mankoff D, Kinahan P. Multicenter trials using FDG PET to predict chemotherapy response: Effects of differential measurement error and bias on power calculations for unselected and enrichment designs. Clin Trials. 2013;10(6):886-95. doi:10.1177/1740774513506618. Epub 2013 Oct 29. PubMed PMID: 24169628.

Goss P, Hershman D, Cheung A, Ingle J, Khosla S, Stearns V, Chalchal H, Rowland K, Muss H, Linden H, Scher J, Elliott C, Crnjevic T, Chapman A, Shepherd L. Effects of Adjuvant Exemestane versus Anastrozole on Bone Mineral Density in Women with Early Breast Cancer. A Companion Study to NCIC CTG MA.27. Lancet Oncol. 2014 Apr;15(4):474-82. doi: 10.1016/S1470-2045(14)70035-X. Epub 2014 Mar 11. PubMed PMID: 24636210.

Peterson LM, Kurland BF, Schubert EK, Link JM, Gadi VK, Specht JM, Eary JF, Porter P, Shankar LK, Mankoff DA, Linden HM. A Phase 2 Study of 16α-[18F]-fluoro-17β-estradiol Positron Emission Tomography (FES-PET) as a Marker of Hormone Sensitivity in Metastatic Breast Cancer (MBC). (MBC). Mol Imaging Biol. 2014 Jun; 16(3):431-401. DOI: 10.1007/s11307-013-0699-7. PubMed PMID: 24170452.

Byrd D, Linden H, Kinahan P. Efforts Addressing SUV Accuracy for PET Quantitation and Standardization. SNMMI PET Center of Excellence newsletter. 2014 Volume 10, Issue 4.

Mountz JM, Tankeelov TE, Rubin DL, Buatti JM, Chenevert TL, Erikson BJ, Fennessy FM, Gillies RJ, Huang W, Kinahan PE, Linden HM, Mankoff DA, Schawrtz LH, Shim H, Wahl RL. Letter to Cancer Center Directors: Progress in Quantitative Imaging as a Means to Predict and/or Measure Tumor Response in Cancer Therapy Trials. J Clin Oncol. 2014 Jul 1;32(19):2115-6. doi: 10.1200/JCO.2014.55.8866. Epub 2014 May 27. PubMed PMID: 24868025.

Chen L, Linden H, Anderson B, Li, C. Trend in 5-year survival rates among breast cancer patients by hormone receptor status and stage. Breast Cancer Res Treat. 2014 Aug 28. [Epub ahead of print] PubMed PMID: 25164974.

Cho E, Rubinstein L, Stevenson P, Gooley T, Philips M, Halasz LM, Gensheimer MF, Linden HM, Rockhill JK, Gadi VK. The use of stereotactic radiosurgery for brain metastases from breast cancer: Who benefits most? Breast Cancer Res Treat. 2015 Feb 1. [Epub ahead of print] PubMed PMID: 25638395

Cho E, Schwemm AK, Rubinstein LM, Stevenson PA, Gooley TA, Ellis GK, Specht JM, Livingston RB, Linden HM, Gadi VK. Adjuvant Metronomic CMF in a Contemporary Breast Cancer Cohort: What's Old Is New. Clin Breast Cancer. 2015 Oct;15(5):e277-85. doi: 10.1016/j.clbc.2015.04.002. Epub 2015 Apr 24. PMID: 26025883

Kinahan PE, Mankoff DA, Linden HM. The Value of Establishing the uantitative Accuracy of PET/CT Imaging. J Nucl Med. 2015 Aug;56(8):1133-4. doi: 10.2967/jnumed.115.159178. Epub 2015 Jun 18. PubMed PMID: 26089552.

Williams JM, Rani SD, Li X, Arlinghaus LR, Lee TC, MacDonald LR, Partridge SC, Kang H, Whisenant JG, Abramson RG, Linden HM, Kinahan PE, Yankeelov TE. Comparison of prone versus supine 18F-FDG-PET of locally advanced breast cancer: Phantom and preliminary clinical studies. Med Phys. 2015 Jul;42(7):3801. doi: 10.1118/1.4921363. PubMed PMID: 26133582; PubMed Central PMCID: PMC4464063.

Fowler AM, Clark AS, Katzenellenbogen JA, Linden HM, Dehdashti F. Imaging Diagnostic and Therapeutic Targets: Steroid Receptors in Breast Cancer. J Nucl Med. 2016 Feb;57 Suppl 1:75S-80S. doi: 10.2967/jnumed.115.157933. PubMed PMID: 26834106.

Currin E, Peterson LM, Schubert EK, Link JM, Krohn KA, Livingston RB, Mankoff DA, Linden HM. Temporal Heterogeneity of Estrogen Receptor Expression in Bone-Dominant Breast Cancer: 18F-Fluoroestradiol PET Imaging Shows Return of ER Expression. J Natl Compr Canc Netw. 2016 Feb;14(2):144-7. PubMed PMID: 26850484.

Kurland BF, Muzi M, Peterson LM, Doot RK, Wangerin KA, Mankoff DA, Linden HM, Kinahan PE. Multicenter Clinical Trials Using 18F-FDG PET to Measure Early Response to Oncologic Therapy: Effects of Injection-to-Acquisition Time Variability on Required Sample Size. J Nucl Med. 2016 Feb;57(2):226-30. doi: 10.2967/jnumed.115.162289. Epub 2015 Oct 22. PubMed PMID: 26493206; PubMed Central PMCID: PMC4749350.

Kurland BF, Peterson LM, Lee JH, Schubert EK, Currin ER, Link JM, Krohn KA, Mankoff DA, Linden HM. Estrogen Receptor Binding (18F-FES PET) and Glycolytic Activity (18F-FDG PET) Predict Progression-Free Survival on Endocrine Therapy in Patients with ER+ Breast Cancer. Clin Cancer Res. 2017 Jan 15;23(2):407-415. doi: 10.1158/1078-0432.CCR-16-0362. PMID: 27342400.

Byrd DW, Doot RK, Allberg KC, MacDonald LR, McDougald WA, Elston BF, Linden HM, Kinahan PE. Evaluation of Cross-Calibrated 68Ge/68Ga Phantoms for Assessing PET/CT Measurement Bias in Oncology Imaging for Single- and Multicenter Trials.Tomography. 2016 Dec;2(4):353-360. doi: 10.18383/j.tom.2016.00205. PMID: 28066807.

Fowler AM, Linden HM. Functional Estrogen Receptor Imaging Prior to Neoadjuvant therapy for Primary Breast Cancer.J Nucl Med. 2017 Apr;58(4):560-562. doi: 10.2967/jnumed.116.183533. Epub 2016 Nov 17.PMID: 27856629.

Kurland BF, Aggarwal S, Yankeelov TE, Gerstner ER, Mountz JM, Linden HM, Jones EF, Bodeker KL, Buatti JM. Accrual Patterns for Clinical Studies Involving Quantitative Imaging: Results of an NCI Quantitative Imaging Network (QIN) Survey.Tomography. 2016 Dec;2(4):276-282. doi: 10.18383/j.tom.2016.00169. PMID: 281275862.

Wangerin KA, Muzi M, Peterson L, Linden H, Novakova A, Mankoff D, Kinahan P. A virtual clinical trial comparing static versus dynamic PET imaging in measuring response to breast cancer therapy.Phys Med Biol. 2017 Feb 13. doi: 10.1088/1361-6560/aa6023. [Epub ahead of print]PMID: 28191877.

Kurland BF, Linden HM, Mankoff DA. FDG PET and FES PET Predict PFS on Endocrine Therapy-Response. Clin Cancer Res. 2017 Jul 1;23(13):3475. doi: 10.1158/1078-0432.CCR-17-0479. PMID: 28674116.

Kurland BF, Peterson LM, Lee JH, Schubert EK, Currin ER, Link JM, Krohn KA, Mankoff DA, Linden HM. Estrogen Receptor Binding (18F-FES PET) and Glycolytic Activity (18F-FDG PET) Predict Progression-Free Survival on Endocrine Therapy in Patients with ER+ Breast Cancer. Clin Cancer Res. 2017 Jan 15;23(2):407-415. doi: 10.1158/1078-0432.CCR-16-0362. PMID: 27342400.

Chang AE, Wu QV, Jenkins IC, Specht JM, Gadi VK, Gralow JR, Salazar LG, Kurland BF, Linden HM. Phase I/II Trial of Combined Pegylated Liposomal Doxorubicin and Cyclophosphamide in Metastatic Breast Cancer. Clin Breast Cancer. 2017 Oct 9. pii: S1526-8209(17)30280-X. doi: 10.1016/j.clbc.2017.10.005. [Epub ahead of print] PMID: 29174203

Last updated: January 2018

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