S-phase fraction is a prognostic factor in stage I breast carcinoma.

Stål, Olle; Dufmats, Monika; Hatschek, Thomas; Carstensen, John; Klintenberg, Claes; Rutqvist, Lars Erik; Skoog, Lambert; Sullivan, S.; Wingren, Sten; Nordenskjöld, Bo

doi:10.1200/jco.1993.11.9.1717

Cited by 61 publications

(33 citation statements)

References 36 publications

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“…In this view, it is promising that a high proportion of relapses in systemically untreated premenopausal patients seems to be identified by S-phase fraction (Stal et al, 1992). Recently, we also reported results suggesting that SPF is a long-term prognostic factor in small node-negative tumours (T1NO) (Stal et al, 1993). These results, together with the present data, suggest that estimation of proliferative activity could facilitate the identification of early breast cancer patients suitable for adjuvant chemotherapy.…”

Section: Discussionsupporting

confidence: 66%

S-phase fraction and survival benefit from adjuvant chemotherapy or radiotherapy of breast cancer

Stål

Skoog²,

Rutqvist³

et al. 1994

Br J Cancer

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Summary Cancer chemotherapy interacts with cell proliferation, but data on the relationship between cancer cell replication and the effect of adjuvant chemotherapy are scarce. We have investigated the S-phase fractions of the primary tumour from premenopausal breast cancer patients who participated in a randomised trial comparing 12 cycles of polychemotherapy (CMF) with post-operative radiotherapy. DNA flow cytometry was performed on frozen tissues from 208 primary breast carcinomas, of which the S-phase fraction was estimated in 176 cases. There was a significantly higher benefit from CMF among patients with a high S-phase fraction (P = 0.0033). The relative risk of distant recurrence or death in the chemotherapy group as compared with the radiotherapy group was 0.19 for patients whose tumours had an S-phase fraction of 10% or over (95% CI 0.07-0.51) and 1.55 (0.88-2.73) for patients whose tumours showed lower S-phase levels. The interaction was still significant in multivariate analysis (P = 0.0057), including lymph node metastases, tumour size and oestrogen receptor content. We conclude that the benefit from adjuvant chemotherapy compared with radiotherapy is largely confined to patients with highly proliferative tumours.

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Section: Discussionsupporting

confidence: 66%

S-phase fraction and survival benefit from adjuvant chemotherapy or radiotherapy of breast cancer

Stål

Skoog²,

Rutqvist³

et al. 1994

Br J Cancer

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“…Several studies in which cell kinetics have been determined using the in vitro (3H) thymidine labeling index [1,2] or flow cytometric evaluation of the S-phase fraction (SPF) of the cell cycle [3,4], demonstrated that these markers have an independent prognostic val-ue in series of node-negative breast cancer (NNBC) patients. However, both these methods present some technical difficulties, are complex, and timeconsuming, and have not yet been completely standardized [5,6].…”

Section: Introductionmentioning

confidence: 99%

Lack of prognostic significance of the monoclonal antibody Ki-S1, a novel marker of proliferative activity, in node-negative breast carcinoma

Bevilacqua¹,

Verderio

Barbareschi

et al. 1996

Breast Cancer Res Tr

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In a series of 205 node-negative breast cancers (NNBC), we determined staining by the novel antibody Ki-S1, a marker of tumor cell proliferation, in order to test its association with other prognostic variables and its prognostic significance. Ki-S1 was determined in routinely formalin-fixed paraffin-embedded tumor samples. Ki-S1 gave a nuclear staining in the majority of the carcinomas (188 of 205), with percentages of reacting nuclei ranging from 2% to 90% (median value of 7%). In 107 tumors frozen sections were available to also assess the Ki-67 antibody. Among these, 94 had a nuclear staining of cancer cells ranging from 5% to 80% (median value of 7%). In 46 tumors we also determined the MIB-1 antibody. The percentage of MIB-1 nuclear staining ranged from 1% to 50% (median value of 20%). There was no significant relationship between Ki-S1 and the other two cell kinetic markers. Ki-S1 labeling was significantly associated only with tumor size (p = 0.03). With a median follow-up of 6 years, Ki-S1 had no significant prognostic value for either relapse-free survival (RFS) or overall survival (OS) (Ki-S1 as continuous logarithmic variable; p = 0.86 and p = 0.23, respectively). For RFS the following variables had a significant prognostic value: Ki-67 (< or = 10% vs > 10%; p = 0.037); progesterone receptor (PgR) expression (- vs+/++; p = 0.041); tumor size (pT1 vs pT2-3; p = 0.042) and grading (GI vs GII-III; p = 0.047). For OS, tumor size (p = 0.0044), age (continuous variable; p = 0.0060), and Ki-67 (p = 0.043) were significantly prognostic. In multivariate analysis (final model), only tumor size retained a significant and independent prognostic value for RFS (p = 0.0042). For OS, both tumor size (p = 0.0029) and age (< or = 55 years vs > 55 years; p = 0.041) retained significance in the multivariate model. In conclusion, Ki-S1 does not seem to have prognostic relevance in this series of NNBC. Possible hypotheses to explain this observation are discussed.

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“…Unfortunately, many studies found that S-phase and DNA ploidy were highly correlated. When tested in multivariate analysis strategies, DNA ploidy failed to be an independent prognostic variable (26,27). Also, some investigators presented data that failed to show any prognostic significance of either S-phase (28 -30) or DNA ploidy (28,30,31).…”

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confidence: 99%

Optimizing flow cytometric DNA ploidy and S‐phase fraction as independent prognostic markers for node‐negative breast cancer specimens

Bagwell¹,

Spyratos

et al. 2001

Cytometry

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Developing a reliable and quantitative assessment of the potential virulence of a malignancy has been a long-standing goal in clinical cytometry. DNA histogram analysis provides valuable information on the cycling activity of a tumor population through S-phase estimates; it also identifies nondiploid populations, a possible indicator of genetic instability and subsequent predisposition to metastasis. Because of conflicting studies in the literature, the clinical relevance of both of these potential prognostic markers has been questioned for the management of breast cancer patients. The purposes of this study are to present a set of 10 adjustments derived from a single large study that optimizes the prognostic strength of both DNA ploidy and S-phase and to test the validity of this approach on two other large multicenter studies. Ten adjustments to both DNA ploidy and S-phase were developed from a single node-negative breast cancer database from Baylor College (n ‫؍‬ 961 cases). Seven of the adjustments were used to reclassify histograms into low-risk and high-risk ploidy patterns based on aneuploid fraction and DNA index optimum thresholds resulting in prognostic P values changing from little (P < 0.02) or no significance to P < 0.000005. Other databases from Sweden (n ‫؍‬ 210 cases) and France (n ‫؍‬ 220 cases) demonstrated similar improvement of DNA ploidy prognostic significance, P < 0.02 to P < 0.0009 and P < 0.12 to P < 0.002, respectively. Three other adjustments were applied to diploid and aneuploid S-phases. These adjustments eliminated a spurious correlation between DNA ploidy and S-phase and enabled them to combine independently into a powerful prognostic model capable of stratifying patients into low, intermediate, and high-risk groups (P < 0.000005). When the Baylor prognostic model was applied to the Sweden and French databases, similar significant patient stratifications were observed (P < 0.0003 and P < 0.00001, respectively). The successful transference of the Baylor prognostic model to other studies suggests that the proposed adjustments may play an important role in standardizing this test and provide valuable prognostic information to those involved in the management of breast cancer patients. Cytometry (Comm. Clin. Cytometry) 46: 121-135, 2001.

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S-phase fraction is a prognostic factor in stage I breast carcinoma.

Abstract: This study suggests that cytometric SPF has prognostic significance in stage I breast carcinoma.

Cited by 61 publications

References 36 publications

S-phase fraction and survival benefit from adjuvant chemotherapy or radiotherapy of breast cancer

S-phase fraction and survival benefit from adjuvant chemotherapy or radiotherapy of breast cancer

Lack of prognostic significance of the monoclonal antibody Ki-S1, a novel marker of proliferative activity, in node-negative breast carcinoma

Optimizing flow cytometric DNA ploidy and S‐phase fraction as independent prognostic markers for node‐negative breast cancer specimens

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