Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer

Breast Cancer Clinical Trial

— LABC  

Official title:

Gene Expression Signature and Immunohistochemical Markers Associated With Response to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00820690
• Other study ID #: 135/2008
• Status: Active, not recruiting
• Phase: N/A
• First received: January 9, 2009
• Last updated: August 3, 2015
• Start date: July 2008
• Est. completion date: September 2017

Study information

• Verified date: August 2015
• Source: Barretos Cancer Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Brazil: Ethics Committee
• Study type: Observational

Clinical Trial Summary

The purpose of this study is to analyze gene expression signature and immunohistochemical markers associated with clinical and pathological response to neoadjuvant chemotherapy in locally advanced breast cancer.

Description:

Locally advanced breast cancer is a common condition in development countries. Neoadjuvant chemotherapy gives the opportunity to identify genetic signatures associated with objective clinical and pathological complete responses.

Patients will receive doxorubicin/cyclophosphamide with paclitaxel. Tumor samples collected before and after chemotherapy will be analyzed.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 80
• Est. completion date: September 2017
• Est. primary completion date: April 2012
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Women with locally advanced women breast cancer

• Histology: ductal ou lobular invasive histology

• Agreement to take part in the study and signature of the informed consent

• Clinical condition to receive doxorubicin/cyclophosphamide and paclitaxel

• ECOG 0 or I

Exclusion Criteria:

• Not clinical stage III

• Inflammatory breast cancer

• Previous treatment

• Previous diagnosis of cancer (except basal cell or squamous cell skin carcinoma and non-invasive cervical carcinoma)

• Pregnancy

• Absence of clinical condition to receive chemotherapy

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• doxorubicin
4 cycles AC: doxorubicin 60mg/m2
• cyclophosphamide
4 cycles AC: cyclophosphamide 600mg/m2
• paclitaxel
4 cycles T: paclitaxel 175mg/m2 after 4 AC

Procedure:
• Surgery
The surgery will be performed 30 days after the chemotherapy. The correlation between clinical, radiologic and pathologic response will be reported. The oncoplastic surgery rate will be reported

Locations

Country	Name	City	State
Brazil	Barretos Cancer Hospital	Barretos	São Paulo

Sponsors (2)

Lead Sponsor	Collaborator
Barretos Cancer Hospital	University of Sao Paulo

Country where clinical trial is conducted

Brazil, 

References & Publications (20)

Andre F, Mazouni C, Hortobagyi GN, Pusztai L. DNA arrays as predictors of efficacy of adjuvant/neoadjuvant chemotherapy in breast cancer patients: current data and issues on study design. Biochim Biophys Acta. 2006 Dec;1766(2):197-204. Epub 2006 Aug 9. Review. — View Citation

Apple SK, Suthar F. How do we measure a residual tumor size in histopathology (the gold standard) after neoadjuvant chemotherapy? Breast. 2006 Jun;15(3):370-6. Epub 2005 Sep 26. — View Citation

Carey LA, Dees EC, Sawyer L, Gatti L, Moore DT, Collichio F, Ollila DW, Sartor CI, Graham ML, Perou CM. The triple negative paradox: primary tumor chemosensitivity of breast cancer subtypes. Clin Cancer Res. 2007 Apr 15;13(8):2329-34. — View Citation

Eltahir A, Heys SD, Hutcheon AW, Sarkar TK, Smith I, Walker LG, Ah-See AK, Eremin O. Treatment of large and locally advanced breast cancers using neoadjuvant chemotherapy. Am J Surg. 1998 Feb;175(2):127-32. — View Citation

Faneyte IF, Schrama JG, Peterse JL, Remijnse PL, Rodenhuis S, van de Vijver MJ. Breast cancer response to neoadjuvant chemotherapy: predictive markers and relation with outcome. Br J Cancer. 2003 Feb 10;88(3):406-12. — View Citation

Fernández-Sánchez M, Gamboa-Dominguez A, Uribe N, García-Ulloa AC, Flores-Estrada D, Candelaria M, Arrieta O. Clinical and pathological predictors of the response to neoadjuvant anthracycline chemotherapy in locally advanced breast cancer. Med Oncol. 2006;23(2):171-83. — View Citation

Fisher B, Bryant J, Wolmark N, Mamounas E, Brown A, Fisher ER, Wickerham DL, Begovic M, DeCillis A, Robidoux A, Margolese RG, Cruz AB Jr, Hoehn JL, Lees AW, Dimitrov NV, Bear HD. Effect of preoperative chemotherapy on the outcome of women with operable breast cancer. J Clin Oncol. 1998 Aug;16(8):2672-85. — View Citation

Folgueira MA, Carraro DM, Brentani H, Patrão DF, Barbosa EM, Netto MM, Caldeira JR, Katayama ML, Soares FA, Oliveira CT, Reis LF, Kaiano JH, Camargo LP, Vêncio RZ, Snitcovsky IM, Makdissi FB, e Silva PJ, Góes JC, Brentani MM. Gene expression profile associated with response to doxorubicin-based therapy in breast cancer. Clin Cancer Res. 2005 Oct 15;11(20):7434-43. — View Citation

Goldstein NS, Decker D, Severson D, Schell S, Vicini F, Margolis J, Dekhne NS. Molecular classification system identifies invasive breast carcinoma patients who are most likely and those who are least likely to achieve a complete pathologic response after neoadjuvant chemotherapy. Cancer. 2007 Oct 15;110(8):1687-96. — View Citation

Keam B, Im SA, Kim HJ, Oh DY, Kim JH, Lee SH, Chie EK, Han W, Kim DW, Moon WK, Kim TY, Park IA, Noh DY, Heo DS, Ha SW, Bang YJ. Prognostic impact of clinicopathologic parameters in stage II/III breast cancer treated with neoadjuvant docetaxel and doxorubicin chemotherapy: paradoxical features of the triple negative breast cancer. BMC Cancer. 2007 Nov 1;7:203. — View Citation

Kuerer HM, Newman LA, Smith TL, Ames FC, Hunt KK, Dhingra K, Theriault RL, Singh G, Binkley SM, Sneige N, Buchholz TA, Ross MI, McNeese MD, Buzdar AU, Hortobagyi GN, Singletary SE. Clinical course of breast cancer patients with complete pathologic primary tumor and axillary lymph node response to doxorubicin-based neoadjuvant chemotherapy. J Clin Oncol. 1999 Feb;17(2):460-9. — View Citation

Kurosumi M. Significance and problems in evaluations of pathological responses to neoadjuvant therapy for breast cancer. Breast Cancer. 2006;13(3):254-9. Review. — View Citation

Mamounas EP, Bryant J, Lembersky B, Fehrenbacher L, Sedlacek SM, Fisher B, Wickerham DL, Yothers G, Soran A, Wolmark N. Paclitaxel after doxorubicin plus cyclophosphamide as adjuvant chemotherapy for node-positive breast cancer: results from NSABP B-28. J Clin Oncol. 2005 Jun 1;23(16):3686-96. Epub 2005 May 16. — View Citation

Molina R, Filella X, Zanon G, Pahisa J, Alicarte J, Munoz M, Farrus B, Ballesta AM. Prospective evaluation of tumor markers (c-erbB-2 oncoprotein, CEA and CA 15.3) in patients with locoregional breast cancer. Anticancer Res. 2003 Mar-Apr;23(2A):1043-50. — View Citation

Prisack HB, Karreman C, Modlich O, Audretsch W, Danae M, Rezai M, Bojar H. Predictive biological markers for response of invasive breast cancer to anthracycline/cyclophosphamide-based primary (radio-)chemotherapy. Anticancer Res. 2005 Nov-Dec;25(6C):4615-21. — View Citation

Rouzier R, Mathieu MC, Sideris L, Youmsi E, Rajan R, Garbay JR, André F, Marsiglia H, Spielmann M, Delaloge S. Breast-conserving surgery after neoadjuvant anthracycline-based chemotherapy for large breast tumors. Cancer. 2004 Sep 1;101(5):918-25. — View Citation

Schott AF, Roubidoux MA, Helvie MA, Hayes DF, Kleer CG, Newman LA, Pierce LJ, Griffith KA, Murray S, Hunt KA, Paramagul C, Baker LH. Clinical and radiologic assessments to predict breast cancer pathologic complete response to neoadjuvant chemotherapy. Breast Cancer Res Treat. 2005 Aug;92(3):231-8. — View Citation

Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000 Feb 2;92(3):205-16. — View Citation

van der Hage JA, van de Velde CJ, Julien JP, Floiras JL, Delozier T, Vandervelden C, Duchateau L. Improved survival after one course of perioperative chemotherapy in early breast cancer patients. long-term results from the European Organization for Research and Treatment of Cancer (EORTC) Trial 10854. Eur J Cancer. 2001 Nov;37(17):2184-93. — View Citation

van der Hage JA, van de Velde CJ, Julien JP, Tubiana-Hulin M, Vandervelden C, Duchateau L. Preoperative chemotherapy in primary operable breast cancer: results from the European Organization for Research and Treatment of Cancer trial 10902. J Clin Oncol. 2001 Nov 15;19(22):4224-37. — View Citation

* Note: There are 20 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical objective and pathological responses to chemotherapy	Clinical and radiological examinations to be performed before chemotherapy, after the 4 cycle of AC and before surgery.; Pathologic evaluation to be performed 30 days after the last cycle of chemotherapy, i.g. after surgery.	8 months	Yes
Secondary	Clinical, radiologic and pathologic correlation	tumor concordance measurement among pre-operative physical examination (PE), mammography (MG), ultrasound (US), breast MRI and post-operative pathologic measurement concordance with PE, MG, US and MRI	3 years	Yes
Secondary	Surgery	The use and security of oncoplastic surgery after neoadjuvant chemotherapy	5 years	Yes
Secondary	Overall actuarial survival		5 years	Yes
Secondary	Pathologic complete response	Pathologic complete response after neoadjuvant chemotherapy	9 months	Yes