title: Paclitaxel-induced apoptosis and mitotic arrest assessed by serial fine-needle aspiration: implications for early prediction of breast cancer response to neoadjuvant treatment.
abstract: The extent of tumor reduction from neoadjuvant chemotherapy for breast cancer correlates with outcome. We investigated whether the initial cellular responses to paclitaxel are related to the extent of tumor reduction. Eleven women with breast cancer received paclitaxel (every 2 weeks for 4 cycles) as neoadjuvant treatment. Serial fine-needle aspirations (FNA; 25-gauge, 1 pass) were obtained before treatment and at 24, 48, 72, and 96 h after the first paclitaxel dose. Microscopic counts of apoptotic and mitotic indices were performed. The change in cancer volume from treatment was determined using radiological measurements with allowance for change in the histopathological amount of cancer. Apoptotic and mitotic responses usually subsided within 4 days. The duration of the initial apoptotic response was different for women with different treatment results. Cumulative apoptotic response for the first 4 days inversely correlated with the proportion of residual cancer after neoadjuvant treatment. FNA is a versatile clinical method to obtain breast cancer cells for therapy response studies. Apoptotic response to the first dose of paclitaxel is almost complete within 4 days, implying that more frequent (weekly) paclitaxel dosing might be beneficial. The apoptotic response to the first dose of paclitaxel appeared to predict the amount of cancer reduction from this treatment. This is a promising start toward the development of an early chemopredictive assay for paclitaxel treatment of breast cancer.
authors.affiliation: Department of Pathology, and Kaplan Comprehensive Cancer Center, New York University Medical Center, New York 10016, USA. fsymmans@mdanderson.org
authors.forename: W F
authors.initials: WF
authors.lastname: Symmans
authors.forename: M D
authors.initials: MD
authors.lastname: Volm
authors.forename: R L
authors.initials: RL
authors.lastname: Shapiro
authors.forename: A B
authors.initials: AB
authors.lastname: Perkins
authors.forename: A Y
authors.initials: AY
authors.lastname: Kim
authors.forename: S
authors.initials: S
authors.lastname: Demaria
authors.forename: H T
authors.initials: HT
authors.lastname: Yee
authors.forename: H
authors.initials: H
authors.lastname: McMullen
authors.forename: R
authors.initials: R
authors.lastname: Oratz
authors.forename: P
authors.initials: P
authors.lastname: Klein
authors.forename: S C
authors.initials: SC
authors.lastname: Formenti
authors.forename: F
authors.initials: F
authors.lastname: Muggia
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D017209:Apoptosis; D001707:Biopsy, Needle; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000628:therapy*; D017024:Chemotherapy, Adjuvant; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D020287:In Situ Nick-End Labeling; D008938:Mitosis; D017239:Paclitaxel / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel