S-phase fraction determined on fine needle aspirates is an independent prognostic factor in breast cancer - A multivariate study of 770 patients

Department of Pathology, Institute of Oncology, Ljubljana, Slovenia.
Cytopathology (Impact Factor: 1.48). 10/2008; 19(5):294-302. DOI: 10.1111/j.1365-2303.2007.00528.x
Source: PubMed

ABSTRACT The prognostic significance of DNA ploidy and the S-phase fraction (SPF) have been extensively studied in breast cancer, but their clinical utility remains controversial. The type of tumour material can substantially influence flow cytometric DNA measurements. Material obtained by fine needle aspiration (FNA) biopsy is very suitable for flow cytometric DNA analysis because it contains a low proportion of non-tumour cells and less debris than tissue samples.
The prognostic significance of DNA ploidy and SPF, determined on FNA samples, was analysed in 770 breast cancer patients, diagnosed between 1992 and 1997. DNA ploidy and SPF were determined at the time of diagnosis as part of the diagnostic work-up. The median follow-up was 90 months. Survival analysis included overall cancer specific survival (OS), disease free survival (DFS) and survival after recurrence (SAR). Other variables included in survival analyses were age, histological grade, histological type, lymph node status and tumour size. Disease free interval and the site of recurrence were also included in SAR analysis.
DNA ploidy and SPF correlated with tumour type, size, lymph node involvement and, especially, tumour grade. In a univariate analysis, both aneuploidy and high SPF were associated with shorter OS, DFS and SAR, but only SPF retained its independent prognostic significance in multivariate analyses. Independent prognostic variables for OS were node status, histological grade, SPF and tumour size. Node status, histological grade and SPF were independent predictors of DFS, while the site of recurrence, SPF, histological grade, disease free interval and age were independent predictors of SAR.
DNA ploidy and SPF can be efficiently and routinely determined on FNA samples. High SPF is independently associated with a worse clinical outcome of patients with breast cancer. Although SPF and histological grade share prognostic information to some degree, SPF provides additional, less subjective prognostic information. The prognostic value of SPF determined on FNA samples could be even more relevant in neoadjuvant settings and for patients not amenable for surgical treatment, when histological grade cannot be assessed.

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    • "A relationship between tumor growth and negative PR status has previously been described in the human tumor clonogenic assay (Hug et al., 1986; Gonzalez-Angulo et al., 2007). It is likely that this association is simply a reflection of the lower proliferation rates in hormone receptor positive tumors (Silvestrini et al, 1993; Fisher et al., 2004; Wenger et al., 1993; Gazic et al., 2008) and that may mirror the tumor activity measured in our study. "
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    ABSTRACT: Taxol has anti-tumor properties, polysaccharide peptide (PSP), an active substance of Yunzhi, is an effective immunopotentiator, which is used to supplement the chemotherapy and radiotherapy of cancers patients. The antitumor activity of polysaccharopeptides has been documented. In this study, the in vitro effect of PSP upon the metabolic rate of breast solid tumors was observed and this effect was compared with taxol, which is a well-known chemotherapeutic drug. 117 patients' tissues were treated with 4, 2 and 1 mg/ml of PSP and 4.27 μg/ml of taxol for 24 h. ATP bioluminescence assay was used to measure the in vitro metabolic rate of the breast cancer tissues and SPSS was used for statistical analysis. The estrogen receptor (ER), progesterone receptor (PR), HER-2, tumor grading and the age of patients were all analysed in the study. Taxol was significantly effective on tumors in younger aged, low tumor grade; ER and PR negative group's subjects. PSP demonstrated similar results and also suppresses the activity of breast solid tumor. ATP bioluminescence assay was successfully performed in determining tumor metabolic rate in a timely fashion such that chemotherapeutic treatment could be guided by the results.
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    • "The size of the SPF indicates the percentage of cells in the stage of DNA replication in cell cycle and it is a validated marker for estimating the proliferative rate of tumor cells (Clark et al., 1989). SPF is also recognized as an independent prognostic factor in breast cancer (Bae et al., 2007; Gazic et al., 2008). A complete procedure of SPF measurement is described by Naguib et al. (1999). "
  • Cytopathology 11/2008; 19(5):269-70. DOI:10.1111/j.1365-2303.2008.00613.x · 1.48 Impact Factor
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