title: Measurement of S-phase fraction and ploidy in sequential fine-needle aspirates from primary human breast tumours treated with tamoxifen.
abstract: Sequential fine-needle aspirates (FNAs) for cytodiagnosis and flow cytometry were taken from 21 patients with primary breast carcinoma at intervals ranging from 1 to 3 months after the commencement of first-line tamoxifen therapy. Nine patients achieved a sustained complete or near complete response over a 3-9 month period. The tumour cells from seven out of nine of these patients were initially aneuploid, while the remaining two patients had diploid tumours. An analysis of sequential FNAs showed that, in three out of the seven aneuploid tumours, only benign epithelial cells could be detected by cytology in the post-tamoxifen sample. In the remaining six cases, including the two diploid tumours, there was no change in ploidy but a reduction in S-phase fraction (SPF) to approximately 50% of the pretreatment level. In all cases, these changes in ploidy or SPF were seen with a mean lead time of 4 months before the tumour had reached clinical complete remission. None of these patients have relapsed after a mean follow-up period of 18 months. The tumours of 12 patients achieved no more than a temporary partial response to primary tamoxifen therapy. In seven out of eight of these cases, which were all initially aneuploid, sequential FNAs during tamoxifen therapy revealed either an increase or no change in the SPF with the tumour remaining aneuploid. In the remaining four cases the tumours were all recorded as being diploid in the pretreatment sample. However, although three of these cases had a temporary partial response to tamoxifen, an aneuploid component was picked up in repeat sequential FNAs with a mean lead time of 5 months before clinical confirmation of eventual disease progression. We conclude that changes in ploidy and SPF detected by flow cytometry may predict initial response and the likelihood of relapse of breast tumours to tamoxifen before clinical changes become evident. These data justify a larger study.
authors.affiliation: Department of Radiotherapy and Oncology, Royal Marsden Hospital, Surrey, UK.
authors.forename: I N
authors.initials: IN
authors.lastname: Fernando
authors.forename: J C
authors.initials: JC
authors.lastname: Titley
authors.forename: T J
authors.initials: TJ
authors.lastname: Powles
authors.forename: M
authors.initials: M
authors.lastname: Dowsett
authors.forename: P A
authors.initials: PA
authors.lastname: Trott
authors.forename: S E
authors.initials: SE
authors.lastname: Ashley
authors.forename: H T
authors.initials: HT
authors.lastname: Ford
authors.forename: M G
authors.initials: MG
authors.lastname: Ormerod
mesh_terms: D015415:Biomarkers; D001707:Biopsy, Needle / Q000379:methods; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000188:drug therapy; D002455:Cell Division; D004273:DNA, Neoplasm / Q000032:analysis; D006801:Humans; D011003:Ploidies; D016196:S Phase; D013629:Tamoxifen / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D015415:Biomarkers; D004273:DNA, Neoplasm; D013629:Tamoxifen