title: Prediction of response to neoadjuvant chemoendocrine therapy in primary breast carcinomas.
abstract: Our aim was to determine whether biological molecular markers can predict response to neoadjuvant chemoendocrine therapy in patients with early breast cancer. Ninety patients (median age 56 years; range, 28-69 years) with primary operable breast carcinoma were studied. They were treated with four 3-weekly cycles of chemotherapy with mitozantrone, methotrexate (+/- mitomycin C), and tamoxifen prior to surgery. Fine-needle aspiration was used to obtain samples from patients prior to therapy, and the following parameters were assessed: estrogen receptor (ER), progesterone receptor (PgR), p53, Ki67, Bcl-2, and c-erbB-2 measured by immunocytochemistry, and ploidy and S-phase fraction (SPF) by flow cytometry. The tumors of 78% of the subjects responded (complete response, 9%; partial response, 69%) and 22% did not (no change, 20%; progressive disease, 2%). Response rates according to disease stage and patient age were as follows: T1, 74%; T2, 79%; T3/T4, 78%; age </=50 years, 76%; >50, 79% (P = not significant). Response rates for other parameters were as follows: ER-positive, 82%, and -negative, 70%; PgR-positive, 86%, and -negative, 71%; p53-positive, 74%, and -negative, 81%; Bcl-2-positive, 85%, and -negative 61%; c-erbB-2-positive, 57%, and -negative, 93%; Ki67 high, 77%, and low, 81%; SPF high, 77%, and low, 77%; aneuploid, 71%; and diploid, 85%. Only the difference for c-erbB-2 was statistically significant (P = 0.007). A trend for higher response rates to neoadjuvant chemoendocrine therapy for tumors that were positive for ER, PgR, and Bcl-2 was observed but did not reach statistical significance. Tumors negative for c-erbB-2 had a higher response rate, which was statistically significant. In contrast, Ki67, ploidy, SPF, and p53 failed to predict for response.
authors.affiliation: Breast Unit, Royal Marsden Hospital, Downs Road, Sutton, Surrey SM2 5PT, London, United Kingdom.
authors.forename: A
authors.initials: A
authors.lastname: Makris
authors.forename: T J
authors.initials: TJ
authors.lastname: Powles
authors.forename: M
authors.initials: M
authors.lastname: Dowsett
authors.forename: C K
authors.initials: CK
authors.lastname: Osborne
authors.forename: P A
authors.initials: PA
authors.lastname: Trott
authors.forename: I N
authors.initials: IN
authors.lastname: Fernando
authors.forename: S E
authors.initials: SE
authors.lastname: Ashley
authors.forename: M G
authors.initials: MG
authors.lastname: Ormerod
authors.forename: J C
authors.initials: JC
authors.lastname: Titley
authors.forename: R K
authors.initials: RK
authors.lastname: Gregory
authors.forename: D C
authors.initials: DC
authors.lastname: Allred
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001707:Biopsy, Needle; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery*; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D018450:Disease Progression; D005260:Female; D006801:Humans; D008593:Menopause; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage; D008942:Mitoxantrone / Q000008:administration & dosage; D009367:Neoplasm Staging; D011003:Ploidies; D011237:Predictive Value of Tests; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D016196:S Phase; D013629:Tamoxifen / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D019253:Proto-Oncogene Proteins c-bcl-2; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013629:Tamoxifen; D016685:Mitomycin; D008942:Mitoxantrone