Study of Breast Cancer Shrinkage Modes After Neoadjuvant Chemotherapy With Whole-mount Serial Sections and Three-dimensional Pathological and MRI Reconstruction

NCT01917578 | Unknown Phase 3 DMC

• 1 other identifier: BCSMANC001
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

The main clinical goal of NAC is to down-stage the primary tumor for BCS,yet BCS after NAC has been associated with significantly higher ipsilateral breast tumor recurrences.The accuracy of breast tumor excision in BCS can dramatically reduce IBTR.The main reseason of IBTR might be the uncertain shrinkage modes of the breast cancer after NAC.This clinical trial is firstly carried out to make clear the shrinkage modes of the primary tumor after 3 cycles and whole cycles of NAC,respectively,with whole-mount serial section(WMSS) and three-dimensional(3D) pathological reconstruction of the residual tumor.The second objective is to investigate the predictive value of 3D MRI reconstruction for the shrinkage modes of the primary tumor after NAC.

Conditions

Breast Cancer

Keywords

Breast Cancer; shrinkage modes; three-dimensional reconstruction; neoadjuvant chemotherapy; Magnetic Resonance Imaging

Outcome Measures

Primary Outcomes (1)

• The shrinkage modes of breast tumor after NAC.

  The tumor shrinkage modes of the primary tumor in patients with locally advanced breast cancer after 3 cycles and whole cycles of neoadjuvant chemotherapy(NAC).

  6 year

Secondary Outcomes (1)

• The WMSS and 3D pathological reconstruction of the residual tumors after NAC.

  6 year

Other Outcomes (1)

• The predictive value of 3D MRI reconstruction for the shrinkage modes of primary tumor after NAC.

  4 year

Study Arms (2)

Half Cycles Group

EXPERIMENTAL

Patients complete half of the whole cycles of neoadjuvant chemotherapy.

Device: Ultrasound; Procedure: CNB; Procedure: BCS, Modified Radical Mastectomy; Device: Pathologic Large Tissue Selected Table; Device: Leica TP1020; Device: Pathologic Large Tissue Embedded Table; Device: Leica SM2000 R; Procedure: HE Stain; Device: CX22; Device: Epson V600; Procedure: Three-Dimensional Reconstruction; Device: Mammography; Drug: TAC,TC,TA,CAF,CEF

Whole Cycles Group

EXPERIMENTAL

Patients complete whole cycles of neoadjuvant chemotherapy.

Device: Ultrasound; Procedure: CNB; Procedure: BCS, Modified Radical Mastectomy; Device: Pathologic Large Tissue Selected Table; Device: Leica TP1020; Device: Pathologic Large Tissue Embedded Table; Device: Leica SM2000 R; Procedure: HE Stain; Device: CX22; Device: Epson V600; Device: MRI; Procedure: Three-Dimensional Reconstruction; Device: Mammography; Drug: AC-P,TEC,AC,TC,TCH,CEF,TAC,CAF

Interventions

Ultrasound DEVICE

1. Evaluation of the tumor size by sonography is performed before neoadjuvant chemotherapy and prior to surgery. 2. Measurement of tumor size refers to WHO standards.

Also known as: GE LOGIQ C5

Half Cycles Group; Whole Cycles Group

CNB PROCEDURE

Typically, the pretreatment tumor specimen will be a core needle biopsy. Because 15% to 28% of patients will have no residual tumor after NAT, it is important to have an adequate pretreatment sample in which an unequivocal diagnosis of invasive carcinoma is established and evaluation of hormone receptors and HER2/ neu status is completed before treatment.

Also known as: core needle biopsy

Half Cycles Group; Whole Cycles Group

BCS, Modified Radical Mastectomy PROCEDURE

All patients after neoadjuvant chemotherapy are performed BCS and modified radical mastectomy.

Also known as: BCS: breast conservative surgery

Half Cycles Group; Whole Cycles Group

Pathologic Large Tissue Selected Table DEVICE

1. Pathologic large tissue selected table has obtained Chinese patent.Its license ID is CN101261200. 2. Each piece of breast tissues by cutting with the table has 3mm thickness.

Half Cycles Group; Whole Cycles Group

Leica TP1020 DEVICE

Procedure: 1. Alcohol 70 % 1h 2. Alcohol 80 % 1h 3. Alcohol 85 % 1h 4. Alcohol 90 % 1h 5. Alcohol 95 % 1h 6. Alcohol Ⅰ 100 % 1h 7. Alcohol Ⅱ 100 % 1h 8. Xylene Ⅰ 2h 9. Xylene Ⅱ 2h 10. Xylene Ⅲ 2h 11. Paraffin 6h 12. Paraffin 6h

Also known as: Semi-enclosed Benchtop Tissue Processor Leica TP1020

Half Cycles Group; Whole Cycles Group

Pathologic Large Tissue Embedded Table DEVICE

1. The table is made of brass .It is applying for a chinese patent. 2. The table can simultaneously embed 8 piece of breast tissues.

Half Cycles Group; Whole Cycles Group

Leica SM2000 R DEVICE

Each of paraffin section has 4 um thickness.

Also known as: Sliding microtome Leica SM2000 R

Half Cycles Group; Whole Cycles Group

HE Stain PROCEDURE

Procedure: 1. Xylene Ⅰ 60℃ 15-20 minutes 2. Xylene Ⅱ 60℃ 15-20 minutes 3. Alcohol 100% Ⅰ 3-5 minutes 4. Alcohol 100% Ⅱ 3-5 minutes 5. Alcohol 95% Ⅱ 3-5 minutes 6. Alcohol 90% Ⅱ 3-5 minutes 7. Wash in running tap water for 3 minutes 8. Hematoxylin 5-10 minutes 9. Wash in running tap water for 3 minutes 10. Differentiate in 1% acid alcohol for 30 seconds 11. Wash in running tap water for 1 minute 12. Bluing in 0.2% ammonia water for 30-60 seconds 13. Wash in running tap water for 3 minutes 14. Counterstain in eosin Y solution for 30-60 seconds 15. Wash in running tap water for 1 minute 16. Alcohol 90% Ⅱ 2-3 minutes 17. Alcohol 95% Ⅱ 2-3 minutes 18. Alcohol 100% Ⅱ 3-5 minutes 19. Alcohol 100% Ⅱ 3-5 minutes 20. Xylene Ⅲ 5-10 minutes 21. Xylene Ⅳ 5-10 minutes 22. Mounting with neutral resin

Half Cycles Group; Whole Cycles Group

CX22 DEVICE

The residual tumor areas are microscopically outlined on each slice by pathologist.

Also known as: Biological Microscope CX22（Olympus）

Half Cycles Group; Whole Cycles Group

Epson V600 DEVICE

1. Each slice that has been microscopically outlined is scanned by Epson V600. 2. Every image by scanning should be saved as JPG.

Also known as: Epson Perfection V600 Photo Scanner

Half Cycles Group; Whole Cycles Group

MRI DEVICE

1. Evaluation of the tumor size by MRI was performed before neoadjuvant chemotherapy and prior to surgery. 2. Measurement of tumor size refers to WHO standards. 3. The images of patients which were scanned by MRI should be burned onto disc for 3d reconstruction.

Also known as: Philips Achieva 3.0T MRI System

Whole Cycles Group

Three-Dimensional Reconstruction PROCEDURE

A.Pathological images three-dimensional reconstruction: 1. Pathological images registration is based on skin and shear mark by Photoshop 13.0 software. 2. Residual tumor boundary on Pathological images after registration are outlined and taken three-dimensional reconstruction by 3D-doctor 4.0 software. 3. Observe the shrinkage modes in three-dimensional space. 4. According to WHO standard,the boundaries of all residual tumor images are displayed in one plane and the longest diameter and its longest perpendicular diameter of boundaries are measured in one-dimensional space. 5. According to RECIST standard,the longest diameter of boundaries of residual tumor images in three-dimensional space. B.MRI images three-dimensional reconstruction:the procedure is similar to Pathological images three-dimensional reconstruction

Half Cycles Group; Whole Cycles Group

Mammography DEVICE

1. Evaluation of the tumor size by mammography is performed before neoadjuvant chemotherapy and prior to surgery. 2. Measurement of tumor size and calcification extent refers to WHO standards. 3. Calcification extent is not only measured in mammography image but also under microscope.

Also known as: GE Mammography

Half Cycles Group; Whole Cycles Group

TAC,TC,TA,CAF,CEF DRUG

1. TAC:Docetaxel 75 mg/㎡ iv day 1 + Doxorubicin 50 mg/㎡ in day 1 + Cyclophosphamide 500 mg/㎡ iv day 1(Cycled every 21 days for 3 cycles) 2. TC:Docetaxel 75 mg/㎡ iv day 1 + Cyclophosphamide 600 mg/㎡in day 1(Cycled every 21 days for 2 cycles) 3. TA:Docetaxel 75 mg/㎡ iv day 1 + Doxorubicin 50 mg/㎡ in day 1(Cycled every 21 days for 2 cycles) 4. CAF:Cyclophosphamide 100 mg/㎡ po days 1-14 + Doxorubicin 30 mg/㎡ iv days 1,8 +5-fluorouracil 500 mg/㎡ iv days 1,8(cycled every 28 days for 3 cycles) 5. CEF:Cyclophosphamide 75 mg/㎡ po day 1-14 + Epirubicin 60 mg/㎡ iv days 1,8 + 5-fluorouracil 500mg/㎡ iv days 1,8(cycled every 28 days for 3 cycles)

Also known as: 1.TAC(docetaxel/doxorubicin/cyclophosphamide), 2.TC(docetaxel/cyclophosphamide), 3.TA(paclitaxel/doxorubicin), 4.CAF(fluorouracil/doxorubicin/cyclophosphamide), 5.CEF(cyclophosphamide/epirubicin//fluorouracil)

Half Cycles Group

AC-P,TEC,AC,TC,TCH,CEF,TAC,CAF DRUG

1. AC-P:Doxorubicin 60 mg/㎡ iv day 1 +Cyclophosphamide 600 mg/㎡ iv day 1(Cycled every 14 days for 4 cycles)→ Paclitaxel 175mg/㎡ by 3h iv infusion day 1(Cycled every 14 days for 4 cycles) or Paclitaxel 80mg/㎡ by 1h iv infusion weekly for 12 wks. 2. TEC:Docetaxel 75 mg/㎡ iv day 1 + Epirubicin 75 mg/㎡ in day 1 + Cyclophosphamide 500 mg/㎡ iv day 1(Cycled every 21 days for 6 cycles) 3. AC:Doxorubicin 60 mg/㎡ in day 1 + Cyclophosphamide 600 mg/㎡ iv day 1(Cycled every 21 days for 4 cycles) 4. TC:Docetaxel 75 mg/㎡ iv day 1 + Cyclophosphamide 600 mg/㎡in day 1(Cycled every 21 days for 4 cycles) 5. TCH:Docetaxel 75 mg/㎡ iv day 1 + Carboplatin AUC 6 iv day1(Cycled every 21 days for 6 cycles) + Trastuzumab 4 mg/kg iv wk 1 → Trastuzumab 2 mg/kg iv for 17 wks → Trastuzumab 6 mg/kg iv every 3 wks to complete 1 year. 6. CEF:Cyclophosphamide 75 mg/㎡ po day 1-14 + Epirubicin 60 mg/㎡ iv days 1,8 + 5-fluorouracil 500mg/㎡ iv days 1,8(cycled every 28 days for 6 cycles)

Also known as: 1.AC(doxorubicin/cyclophosphamide)-P(paclitaxel), 2.TEC(docetaxel/epirubicin/cyclophosphamide), 3.AC(doxorubicin/cyclophosphamide)-T(docetaxel), 4.TC(docetaxel/cyclophosphamide), 5.TCH(docetaxel/carboplatin/trastuzumab), 6.CEF(cyclophosphamide/epirubicin/fluorouracil), 7.TAC(docetaxel/doxorubicin/cyclophosphamide), 8.CAF(fluorouracil/doxorubicin/cyclophosphamide)

Whole Cycles Group

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female patients,locally advanced breast cancer,age ≥18 years.
• Histologically confirmed invasive adenocarcinoma of the breast.
• Primary palpable disease confined to a breast and axilla on physical examination. For patients without clinically suspicious axillary adenopathy, the primary tumor must be larger than 2 cm in diameter by physical exam or imaging studies (clinical T2-T3, N0-N1, M0). For patients with clinically suspicious axillary adenopathy, the primary breast tumor can be any size (clinical T1-3, N1-2, M0). (T1N0M0 lesions are excluded.)
• Patients without clearly defined palpable breast mass or axillary lymph nodes but radiographically measurable tumor masses are acceptable. Accepted procedures for measuring breast disease are mammography, MRI, and breast ultrasound. This will need to be re-evaluated after 3 cycles and prior to surgery.
• ECOG 0 or 2
• No distant metastasis, as documented by complete staging workup ≤6 weeks prior to initiation of study treatment.
• No previous treatment for breast cancer.
• Adequate hematologic function with:
• Absolute neutrophil count (ANC) \>1500/μL. Platelets ≥100,000/μL. Hemoglobin ≥10 g/dL.
• Adequate hepatic function with:
• Serum bilirubin ≤ the institutional upper limit of normal (ULN). Aspartate aminotransferase (AST) ≤2.5 x institutional ULN. Alanine aminotransferase (ALT) ≤2.5 x institutional ULN.
• Adequate renal function with serum creatinine ≤1.5 x ULN.
• Planned primary systemic (neoadjuvant) chemotherapy and surgical resection of residual primary tumor (mastectomy or lumpectomy/breast conservation) following completion of neoadjuvant chemotherapy

You may not qualify if:

• inflammatory breast cancer
• Pregnancy or breast-feeding.A negative serum pregnancy test within 7 days prior to first study treatment (Day 1, Cycle 1) for all women of childbearing potential is required. Patients of childbearing potential must agree to use a birth control method that is approved by their study physician while receiving study treatment and for 3 weeks after their last dose of study treatment. Patients must agree to not breast-feed while receiving study treatment.
• Concurrent treatment with an ovarian hormonal replacement therapy or with hormonal agents such as raloxifene, tamoxifen or other selective estrogen receptor modulator (SERM). Patients must have discontinued use of such agents prior to beginning study treatment.
• Uncontrolled intercurrent illness including (but not limited to) ongoing or active infection.
• Concurrent treatment with any anti-cancer therapy other than those agents used in this study.
• Mental condition or psychiatric disorder that would prevent patient comprehension of the nature, scope, and possible consequences of the study or that would limit compliance with study requirements.

Sponsors & Collaborators

• Shandong Cancer Hospital and Institute: lead

Study Sites (1)

Shandong Cancer Hospital

Jinan, Shandong, 250117, China

RECRUITING

Related Publications (1)

• Y-S Wang, Z-P Zhang, G Liu, D-B Mu, and X-Y Sun.Study of Breast Cancer Shrinkage Modes After Neoadjuvant Chemotherapy With Whole-mount Serial Sections and Three-dimensional Pathological and MRI Reconstruction. Cancer Res 2012;72(24 Suppl):Abstract nr P1-14-17.

  RESULT

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Ultrasonography; Biopsy, Large-Core Needle; Mastectomy, Segmental; Mastectomy, Modified Radical; Mammography; AC protocol; Cyclophosphamide; Doxorubicin; EC regimen

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Biopsy, Needle; Biopsy; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Punctures; Investigative Techniques; Mastectomy; Mastectomy, Radical; Radiography; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Yong-sheng Wang, MD

  Shandong Cancer Hospital and Institute

  STUDY CHAIR

• Tao Yang, MD

  Shandong Cancer Hospital and Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yong-sheng Wang, MD

CONTACT

+8613505409989; wangysh2008@aliyun.com

Tao Yang, MD

CONTACT

+8618264190568; yangtao133252@aliyun.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Head of Breast Cancer Center, Principal Investigator, Clinical Professor

Study Record Dates

• First Submitted: August 4, 2013
• First Posted: August 6, 2013
• Study Start: August 1, 2008
• Primary Completion: March 1, 2014
• Study Completion: July 1, 2014
• Last Updated: August 6, 2013

Record last verified: 2013-08

Locations

CN (1)