Prediction of Relapse or Survival in Patients with Node-Negative Breast Cancer by DNA Flow Cytometry

Clark, Gary M.; Dressler, Lynn G.; Owens, Marilyn A.; Pounds, George; Oldaker, Teri; McGuire, William

doi:10.1056/nejm198903093201003

Cited by 520 publications

(207 citation statements)

References 25 publications

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“…In a large study of (Silvestrini et al, 1995). As in our study, SPF has been found to be a significant prognostic factor of distant metastasis in diploid but not in aneuploid tumours (Clark et al, 1989). A similar observation has been made in soft-tissue sarcomas (Huuhtanen et al, 1996).…”

Section: Discussionsupporting

confidence: 91%

Tenascin-C expression in invasion border of early breast cancer: a predictor of local and distant recurrence

Jahkola

Toivonen²,

Virtanen³

et al. 1998

Br J Cancer

101

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Summary We have recently demonstrated an association between distant metastasis and the expression of the extracellular matrix glycoprotein tenascin-C (Tn-C) in the invasion border of small axillary node-negative breast carcinomas. Our purpose was to assess the relationship between the expression of Tn-C in the tumour invasion border and several histopathological and biological variables and to compare their usefulness in predicting local and distant disease recurrences. The original patient group consisted of 143 women with axillary node-negative breast cancer (one bilateral) treated with breast-conserving surgery and post-operative radiotherapy, and followed for a median of 8 years. Because of the small number of recurrences an additional group of 15 similarly treated women with recurrent breast cancer was also studied. The size of the tumour, its histology, including a possible intraductal component, and grade were re-evaluated. The expression of erbB-2, p53, Ki-67 and Tn-C was evaluated by immunohistochemistry. Ploidy and S-phase fraction (SPF) were assessed by flow cytometry. The only statistically significant prognostic factor for local recurrence was Tn-C expression in the invasion border. For metastasis Ki-67 positivity, tumour size and Tn-C expression in the invasion border were statistically significant, but Ki-67 positivity was the only independent prognostic factor. Tn-C expression in the invasion border was associated with a higher proliferation rate measured by Ki-67 and SPF, which is consistent with the suggested growth-promoting activity of Tn-C. Tn-C may be a useful marker in selecting patients for adjuvant therapies to reduce the rate of both local and distant cancer recurrences.

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Section: Discussionsupporting

confidence: 91%

Tenascin-C expression in invasion border of early breast cancer: a predictor of local and distant recurrence

Jahkola

Toivonen²,

Virtanen³

et al. 1998

Br J Cancer

101

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“…Multiple sample statistical tests were performed by the comparing survival in multiple groups module (24) and the Cox proportional hazards statistical tests in the regression models module (44,45). DNA ploidy and S-phase proportional hazards assumption was verified by graphical analysis.…”

Section: Discussionmentioning

confidence: 99%

“…In the 1980s, hundreds of flow cytometry papers demonstrated prognostic significance of DNA ploidy and/or S-phase for many types of solid tumors (16 -22). In particular, many studies showed that S-phase and, in some cases, DNA ploidy could stratify node-negative breast cancer patients into low-and high-risk groups for relapse and death (23)(24)(25), potentially giving oncologists more options in treating this prevalent and deadly disease. Unfortunately, many studies found that S-phase and DNA ploidy were highly correlated.…”

mentioning

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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“…For instance, Lelle et al (1986) described a significant difference in the size of growth fractions -as detected by immunostainingbetween benign and malignant breast lesions. Other authors indicated that breast cancer patients with highly proliferating tumours as assessed by immunostaining (Sahin et al, 1991;Veronese et al, 1993) or S-phase evaluation (Clark et al, 1989;Sigurdsson et al, 1990) have an increased risk of recurrence.…”

mentioning

confidence: 99%

Prognostic impact of proliferation-associated factors MIB1 (Ki-67) and S-phase in node-negative breast cancer

Dettmar¹,

Harbeck²,

Thomssen³

et al. 1997

Br J Cancer

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Summary MIBl proliferation rate (MIBl-PR) and total S-phase fraction (SPF) were retrospectively determined in formalin-fixed, paraffinembedded sections of 90 primary node-negative breast carcinomas. None of the patients had received adjuvant systemic therapy. Median follow-up in patients still alive at the time of analysis was 37.5 months (1 6-72 months). lmmuno6taining of Ki-67 antigen was performed using the monoclonal antibody MIBl and the APAAP technique. An adjacent 50-gm paraffin section was used for flow cytometric S-phase determination. Results were compared to established clinicopathological prognostic factors. MIBl -PR was significantly correlated to grading (P = 0.018); SPF was significantly correlated with tumour size (P = 0.041) and inversely with steroid hormone receptor status (P = 0.03). A significant correlation between MIBl -PR and SPF was found in aneuploid (P = 0.025) but not in diploid tumours (P = 0.164). In univariate analysis, both MIBl -PR (optimized cut-off of 25%) and SPF (optimized cut-off of 8%) were significant prognostic factors for disease-free survival (DFS) (MIBl -PR, P = 0.0224; SPF, P = 0.0028). In multivariate analysis, however, only SPF remained significant; it was the strongest prognostic factor for DFS (P = 0.0073), stronger than MIBl -PR or established clinicopathological prognostic factors. We thus conclude that MIBl-PR and SPF provide additional prognostic information in node-negative breast cancer. However, in our study, flow cytometrically determined SPF had the greater prognostic impact.

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Prediction of Relapse or Survival in Patients with Node-Negative Breast Cancer by DNA Flow Cytometry

Cited by 520 publications

References 25 publications

Tenascin-C expression in invasion border of early breast cancer: a predictor of local and distant recurrence

Tenascin-C expression in invasion border of early breast cancer: a predictor of local and distant recurrence

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

Prognostic impact of proliferation-associated factors MIB1 (Ki-67) and S-phase in node-negative breast cancer

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