What Factors Affect Breast Cancer Neoadjuvant Chemotherapy Efficacy?

NCT03501394 | Unknown

• 3 other identifiers: 2/108/723479417/LO/1777
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

Breast cancer is the most prevalent cancer affecting women. To treat locally advanced breast cancers, neoadjuvant chemotherapy (NACT) is often carried out before surgery to reduce the tumour size to allow breast conservation surgery. However, treatment response for individual patients varies, where the tumour may not respond to treatment and the quality of patient care is compromised if the NACT treatment plan is not optimised. Therefore, the assessment of NACT efficacy is beneficial for the early identification of these patients and appropriate management of treatment. Breast tumours have unique features compared to healthy tissue, including abnormal tissue structure and biochemical composition. With NACT there are specific changes to such tumour features indicating tumour treatment response. The purpose of this study is to establish how the changes to breast tumour features following NACT treatment are seen in non-invasive imaging. This study will look at scans of breast tumours using magnetic resonance imaging (MRI). Changes to tissue structure will be measured by advanced diffusion MRI techniques and changes to tumour related biochemical substances will be measured by advanced magnetic resonance spectroscopy techniques. The investigators aim to assess if these techniques can provide information on the tumour treatment response following subsequent rounds of NACT treatment. In this longitudinal study, 25 patients undergoing NACT will be recruited for four repeated MRI investigations over the course of NACT treatment. Magnetic resonance (MR) measurements of tissue microstructure and biochemical composition will be compared against histological measurements and radiological assessments of treatment response. The study will recruit patients undergoing treatment at the NHS Grampian. This research is funded by Friends of ANCHOR, Tenovus Scotland Grampian and the NHS Grampian Endowment Research Fund.

Conditions

Breast Neoplasm Malignant Breast Tissue

Keywords

Magnetic Resonance Imaging; Neoadjuvant Chemotherapy

Outcome Measures

Primary Outcomes (20)

• Baseline: Water diffusion probability density function (Full-Width-At-Half-Maximum, FWHM, units of micrometre)

  The water diffusion probability density function will be quantified by the Full-Width-At-Half-Maximum with units of micrometre

  Scan at pre-treatment baseline (Prior to start of Cycle 1, each cycle is 21 days)

• Post Cycle 1: Water diffusion probability density function (Full-Width-At-Half-Maximum, FWHM, units of micrometre)

  The water diffusion probability density function will be quantified by the Full-Width-At-Half-Maximum with units of micrometre

  Scan at the end of Cycle 1 (Each cycle is 21 days)

• Post Cycle 3: Water diffusion probability density function (Full-Width-At-Half-Maximum, FWHM, units of micrometre)

  The water diffusion probability density function will be quantified by the Full-Width-At-Half-Maximum with units of micrometre

  Scan at the end of Cycle 3 (Each cycle is 21 days)

• Post Treatment: Water diffusion probability density function (Full-Width-At-Half-Maximum, FWHM, units of micrometre)

  The water diffusion probability density function will be quantified by the Full-Width-At-Half-Maximum with units of micrometre

  Scan at the end of Cycle 6 (Each cycle is 21 days)

• Baseline: Water diffusivity (units of mm^2 /s)

  Water diffusivity with units of mm\^2 /s

  Scan at pre-treatment baseline (Prior to start of Cycle 1, each cycle is 21 days)

• Post Cycle 1: Water diffusivity (units of mm^2 /s)

  Water diffusivity with units of mm\^2 /s

  Scan at the end of Cycle 1 (Each cycle is 21 days)

• Post Cycle 3: Water diffusivity (units of mm^2 /s)

  Water diffusivity with units of mm\^2 /s

  Scan at the end of Cycle 3 (Each cycle is 21 days)

• Post Treatment: Water diffusivity (units of mm^2 /s)

  Water diffusivity with units of mm\^2 /s

  Scan at the end of Cycle 6 (Each cycle is 21 days)

• Baseline: Lactate Concentration (units of mM)

  Lactate concentration with units of mM

  Scan at pre-treatment baseline (Prior to start of Cycle 1, each cycle is 21 days)

• Post Cycle 1: Lactate Concentration (units of mM)

  Lactate concentration with units of mM

  Scan at the end of Cycle 1 (Each cycle is 21 days)

• Post Cycle 3: Lactate Concentration (units of mM)

  Lactate concentration with units of mM

  Scan at the end of Cycle 3 (Each cycle is 21 days)

• Post Treatment: Lactate Concentration (units of mM)

  Lactate concentration with units of mM

  Scan at the end of Cycle 6 (Each cycle is 21 days)

• Baseline: Lipid Peak Volume Ratio (Ratio Units)

  Lipid peak volume ratio value with units of ratio

  Scan at pre-treatment baseline (Prior to start of Cycle 1, each cycle is 21 days)

• Post Cycle 1: Lipid Peak Volume Ratio (Ratio Units)

  Lipid peak volume ratio value with units of ratio

  Scan at the end of Cycle 1 (Each cycle is 21 days)

• Post Cycle 3: Lipid Peak Volume Ratio (Ratio Units)

  Lipid peak volume ratio value with units of ratio

  Scan at the end of Cycle 3 (Each cycle is 21 days)

• Post Treatment: Lipid Peak Volume Ratio (Ratio Units)

  Lipid peak volume ratio value with units of ratio

  Scan at the end of Cycle 6 (Each cycle is 21 days)

• Baseline: Fat Fraction (units of %)

  Fat Fraction with units of %

  Scan at pre-treatment baseline (Prior to start of Cycle 1, each cycle is 21 days)

• Post Cycle 1: Fat Fraction (units of %)

  Fat Fraction with units of %

  Scan at the end of Cycle 1 (Each cycle is 21 days)

• Post Cycle 3: Fat Fraction (units of %)

  Fat Fraction with units of %

  Scan at the end of Cycle 3 (Each cycle is 21 days)

• Post Treatment: Fat Fraction (units of %)

  Fat Fraction with units of %

  Scan at the end of Cycle 6 (Each cycle is 21 days)

Secondary Outcomes (6)

• Core Biopsy Tumour Tissue: Ki-67 Staining Percentage (units of %)

  Pre-treatment baseline biopsy (Taken prior to start of Cycle 1, each cycle is 21 days). Assessed following completion of treatment cycles and the routine reporting of core biopsy and excised tissue samples.

• Excised Tumour Tissue: Ki-67 Staining Percentage (units of %)

  Post-treatment surgery excision (Post Cycle 6, each cycle is 21 days). Assessed following the completion of routine pathological reporting of the excised tissue.

• Core Biopsy Tumour Tissue: Serotonin Staining Score (arbitrary units)

  Pre-treatment baseline biopsy (Taken prior to start of Cycle 1, each cycle is 21 days). Assessed following completion of treatment cycles and the routine reporting of core biopsy and excised tissue samples.

• Excised Tumour Tissue: Serotonin Staining Score (arbitrary units)

  Post-treatment surgery excision (Post Cycle 6, each cycle is 21 days). Assessed following the completion of routine pathological reporting of the excised tissue.

• Core Biopsy Tumour Tissue: Cellularity (units of %)

  Pre-treatment baseline biopsy (Taken prior to start of Cycle 1, each cycle is 21 days). Assessed following completion of treatment cycles and the routine reporting of core biopsy and excised tissue samples.

Study Arms (1)

Single Arm

EXPERIMENTAL

25 patients with pathologically confirmed invasive breast cancer who will undergo neoadjuvant chemotherapy treatment (NACT) and surgery will be recruited. During the study, patients will receive the standard care and the current study will not alter the care plan offered to them. All patients in the single arm will undergo 4 magnetic resonance imaging scan sessions. Histopathological analysis will be performed on the core biopsy and tumour tissue removed in surgery. Health questionnaire will be completed by each patient.

Other: Magnetic Resonance Imaging; Other: Histopathological Analysis; Other: Health Questionnaire

Interventions

Magnetic Resonance Imaging OTHER

Patients will undergo 4 MRI sessions during NACT treatment. The first scan will take place at treatment baseline before their first cycle of NACT treatment. The second scan will take place following the first treatment cycle prior to the second treatment cycle. Likewise, the third and last scan will take place after the third treatment cycle and sixth (final) treatment cycle prior to surgery. MRI scan sessions will be composed of research scans including diffusion and lipid profiling MR imaging methods and MR spectroscopy (MRS) methods.

Single Arm

Histopathological Analysis OTHER

Study specific analysis will be performed on the core biopsy and tissue removed in surgery following the completion of NACT treatment. Standard routine histological analysis will be performed, as well as study specific analysis for immunostaining, grading and slide scan imaging for measurement of cellularity markers.

Single Arm

Health Questionnaire OTHER

Health and demographic information will be collected.

Single Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with pathologically confirmed invasive breast cancer undergoing neoadjuvant chemotherapy and surgery.

You may not qualify if:

• Condition to contradictive to MRI investigation with contrast agent (poor renal function, contrast agent allergy, metal implants or pace maker).
• Started hormone or chemotherapy treatment before recruitment.
• Undergoing treatment for concurrent cancer diagnosis.
• Marker coil contradictive to MRI investigation.

Sponsors & Collaborators

• University of Aberdeen: lead
• NHS Grampian: collaborator

Study Sites (1)

NHS Grampian

Aberdeen, Aberdeenshire, AB25 2ZD, United Kingdom

RECRUITING

Related Publications (13)

• Lee MC, Newman LA. Management of patients with locally advanced breast cancer. Surg Clin North Am. 2007 Apr;87(2):379-98, ix. doi: 10.1016/j.suc.2007.01.012.

  PMID: 17498533 BACKGROUND

• Luangdilok S, Samarnthai N, Korphaisarn K. Association between Pathological Complete Response and Outcome Following Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer Patients. J Breast Cancer. 2014 Dec;17(4):376-85. doi: 10.4048/jbc.2014.17.4.376. Epub 2014 Dec 26.

  PMID: 25548587 BACKGROUND

• Graham LJ, Shupe MP, Schneble EJ, Flynt FL, Clemenshaw MN, Kirkpatrick AD, Gallagher C, Nissan A, Henry L, Stojadinovic A, Peoples GE, Shumway NM. Current approaches and challenges in monitoring treatment responses in breast cancer. J Cancer. 2014 Jan 5;5(1):58-68. doi: 10.7150/jca.7047.

  PMID: 24396498 BACKGROUND

• Danishad KK, Sharma U, Sah RG, Seenu V, Parshad R, Jagannathan NR. Assessment of therapeutic response of locally advanced breast cancer (LABC) patients undergoing neoadjuvant chemotherapy (NACT) monitored using sequential magnetic resonance spectroscopic imaging (MRSI). NMR Biomed. 2010 Apr;23(3):233-41. doi: 10.1002/nbm.1436.

  PMID: 20175134 BACKGROUND

• Woodhams R, Kakita S, Hata H, Iwabuchi K, Kuranami M, Gautam S, Hatabu H, Kan S, Mountford C. Identification of residual breast carcinoma following neoadjuvant chemotherapy: diffusion-weighted imaging--comparison with contrast-enhanced MR imaging and pathologic findings. Radiology. 2010 Feb;254(2):357-66. doi: 10.1148/radiol.2542090405.

  PMID: 20093508 BACKGROUND

• Walenta S, Mueller-Klieser WF. Lactate: mirror and motor of tumor malignancy. Semin Radiat Oncol. 2004 Jul;14(3):267-74. doi: 10.1016/j.semradonc.2004.04.004.

  PMID: 15254870 BACKGROUND

• Carmona-Fontaine C, Bucci V, Akkari L, Deforet M, Joyce JA, Xavier JB. Emergence of spatial structure in the tumor microenvironment due to the Warburg effect. Proc Natl Acad Sci U S A. 2013 Nov 26;110(48):19402-7. doi: 10.1073/pnas.1311939110. Epub 2013 Nov 11.

  PMID: 24218566 BACKGROUND

• Bolan PJ, Meisamy S, Baker EH, Lin J, Emory T, Nelson M, Everson LI, Yee D, Garwood M. In vivo quantification of choline compounds in the breast with 1H MR spectroscopy. Magn Reson Med. 2003 Dec;50(6):1134-43. doi: 10.1002/mrm.10654.

  PMID: 14648561 BACKGROUND

• Baik HM, Su MY, Yu H, Mehta R, Nalcioglu O. Quantification of choline-containing compounds in malignant breast tumors by 1H MR spectroscopy using water as an internal reference at 1.5 T. MAGMA. 2006 May;19(2):96-104. doi: 10.1007/s10334-006-0032-4. Epub 2006 May 9.

  PMID: 16779565 BACKGROUND

• He Q, Shkarin P, Hooley RJ, Lannin DR, Weinreb JC, Bossuyt VI. In vivo MR spectroscopic imaging of polyunsaturated fatty acids (PUFA) in healthy and cancerous breast tissues by selective multiple-quantum coherence transfer (Sel-MQC): a preliminary study. Magn Reson Med. 2007 Dec;58(6):1079-85. doi: 10.1002/mrm.21335.

  PMID: 17969083 BACKGROUND

• Naressi A, Couturier C, Castang I, de Beer R, Graveron-Demilly D. Java-based graphical user interface for MRUI, a software package for quantitation of in vivo/medical magnetic resonance spectroscopy signals. Comput Biol Med. 2001 Jul;31(4):269-86. doi: 10.1016/s0010-4825(01)00006-3.

  PMID: 11334636 BACKGROUND

• Yamada I, Hikishima K, Miyasaka N, Tokairin Y, Ito E, Kawano T, Kobayashi D, Eishi Y, Okano H. Esophageal carcinoma: Evaluation with q-space diffusion-weighted MR imaging ex vivo. Magn Reson Med. 2015 Jun;73(6):2262-73. doi: 10.1002/mrm.25334. Epub 2014 Jun 19.

  PMID: 24947492 BACKGROUND

• Cheung SM, Wu WS, Senn N, Sharma R, McGoldrick T, Gagliardi T, Husain E, Masannat Y, He J. Towards detection of early response in neoadjuvant chemotherapy of breast cancer using Bayesian intravoxel incoherent motion. Front Oncol. 2023 Dec 6;13:1277556. doi: 10.3389/fonc.2023.1277556. eCollection 2023.

  PMID: 38125950 DERIVED

MeSH Terms

Interventions

Magnetic Resonance Spectroscopy; Patient Health Questionnaire

Intervention Hierarchy (Ancestors)

Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques; Surveys and Questionnaires; Data Collection; Epidemiologic Methods; Psychological Tests; Behavioral Disciplines and Activities; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health

Study Officials

• Jiabao He, PhD

  University of Aberdeen

  STUDY CHAIR

• Nicholas Senn, MPhys

  University of Aberdeen

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nicholas Senn, MPhys

CONTACT

+44 (0)1224 438351; r03ns15@abdn.ac.uk

Jiabao He, PhD

CONTACT

+44 (0)1224 437321; jiabao.he@abdn.ac.uk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Masking Details: Single group with one arm and no masking.
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Single group longitudinal study.

Study Record Dates

• First Submitted: March 28, 2018
• First Posted: April 18, 2018
• Study Start: May 2, 2018
• Primary Completion: June 1, 2019
• Study Completion: June 1, 2019
• Last Updated: May 3, 2018

Record last verified: 2018-04

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)