title: A phase II study of sequential neoadjuvant gemcitabine plus doxorubicin followed by gemcitabine plus cisplatin in patients with operable breast cancer: prediction of response using molecular profiling.
abstract: This study examined the pathological complete response (pCR) rate and safety of sequential gemcitabine-based combinations in breast cancer. We also examined gene expression profiles from tumour biopsies to identify biomarkers predictive of response. Indian women with large or locally advanced breast cancer received 4 cycles of gemcitabine 1200 mg m(-2) plus doxorubicin 60 mg m(-2) (Gem+Dox), then 4 cycles of gemcitabine 1000 mg m(-2) plus cisplatin 70 mg m(-2) (Gem+Cis), and surgery. Three alternate dosing sequences were used during cycle 1 to examine dynamic changes in molecular profiles. Of 65 women treated, 13 (24.5% of 53 patients with surgery) had a pCR and 22 (33.8%) had a complete clinical response. Patients administered Gem d1, 8 and Dox d2 in cycle 1 (20 of 65) reported more toxicities, with G3/4 neutropenic infection/febrile neutropenia (7 of 20) as the most common cycle-1 event. Four drug-related deaths occurred. In 46 of 65 patients, 10-fold cross validated supervised analyses identified gene expression patterns that predicted with >or=73% accuracy (1) clinical complete response after eight cycles, (2) overall clinical complete response, and (3) pCR. This regimen shows strong activity. Patients receiving Gem d1, 8 and Dox d2 experienced unacceptable toxicity, whereas patients on other sequences had manageable safety profiles. Gene expression patterns may predict benefit from gemcitabine-containing neoadjuvant therapy.
authors.affiliation: Department of Radiotherapy and Oncology, AIIMS, New Delhi 110029, India. drjulka@rediffmail.com
authors.forename: P K
authors.initials: PK
authors.lastname: Julka
authors.forename: R T
authors.initials: RT
authors.lastname: Chacko
authors.forename: S
authors.initials: S
authors.lastname: Nag
authors.forename: R
authors.initials: R
authors.lastname: Parshad
authors.forename: A
authors.initials: A
authors.lastname: Nair
authors.forename: D S
authors.initials: DS
authors.lastname: Oh
authors.forename: Z
authors.initials: Z
authors.lastname: Hu
authors.forename: C B
authors.initials: CB
authors.lastname: Koppiker
authors.forename: S
authors.initials: S
authors.lastname: Nair
authors.forename: R
authors.initials: R
authors.lastname: Dawar
authors.forename: N
authors.initials: N
authors.lastname: Dhindsa
authors.forename: I D
authors.initials: ID
authors.lastname: Miller
authors.forename: D
authors.initials: D
authors.lastname: Ma
authors.forename: B
authors.initials: B
authors.lastname: Lin
authors.forename: B
authors.initials: B
authors.lastname: Awasthy
authors.forename: C M
authors.initials: CM
authors.lastname: Perou
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008875:Middle Aged; D011379:Prognosis; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D004317:Doxorubicin; D002945:Cisplatin; D000093542:Gemcitabine