Node-negative breast cancer: prognostic subgroups defined by tumor size and flow cytometry.

O’Reilly, Susan; Camplejohn, R. S.; Barnes, David J.; Millis, R R; Rubens, R. D.; Richards, MA

doi:10.1200/jco.1990.8.12.2040

Cited by 118 publications

(64 citation statements)

References 10 publications

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“…Does a low SPF alone identify node-negative patients at low risk? In other studies of early breast cancer, tumour size has been taken into account in addition to SPF (O'Reilly et al, 1990a;Sigurdsson et al, 1990). In the present study of young patients, however, tumour size showed no additional value, which may be due to its correlation with SPF (Table I).…”

Section: Resultscontrasting

confidence: 48%

Significance of S-phase fraction and hormone receptor content in the management of young breast cancer patients

Stål

Carstensen²,

Hatschek³

et al. 1992

Br J Cancer

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Section: Resultscontrasting

confidence: 48%

Significance of S-phase fraction and hormone receptor content in the management of young breast cancer patients

Stål

Carstensen²,

Hatschek³

et al. 1992

Br J Cancer

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“…In the literature there are conflicting reports about the importance of ploidy in breast cancer. Some authors saw significantly worse survival in patients with aneuploid tumours (Kallioniemi et 1995), while others felt that ploidy did not yield additional prognostic information on survival (O'Reilly et al, 1990;Sigurdsson et al, 1990). Both MIB1-PR and SPF were significant prognostic factors for DFS in our univariate analysis.…”

Section: Discussionmentioning

confidence: 63%

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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“…The higher prognostic value of SPF compared to Ki-67 might be due to the longer follow up time (median 8 years). The SPF value is also higher in aneuploid tumours than in diploid tumours (O'Reilly, et al, 1990) which might give SPF a better discriminatory power than Ki-67. On the other hand, the Ki-67 scores are much higher in aneuploid carcinomas than in diploid ones (Gasparini et al, 1991).…”

Section: Discussionmentioning

confidence: 93%

“…In stage II tumours, including also node negative patients, there was a significant difference in disease free survival between Ki-67 positive/ER negative and ER positive/Ki-67 negative (P <0.005). O'Reilly has described an even more specific subdivision of patients with different prognosis using the S-phase fraction (SPF) and tumour size (O'Reilly et al, 1990). According to these results patients with tumour greater than 1 cm with an SPF < 10% have a 5-year relapse-free survival of 78%, compared to 52% in tumours of the same size with an SPF> 10%.…”

Section: Discussionmentioning

confidence: 99%

Prognostic value of Ki-67 immunolabelling in primary operable breast cancer

Railo

Nordling²,

Boguslawsky³

et al. 1993

Br J Cancer

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Summary The prognostic value of Ki-67 immunohistochemical labelling was evaluated in 327 operable primary carcinomas of the breast. The follow-up time was up to 4 years (mean 2.7 years). The disease-free survival in Ki-67 positive patients was shorter than in Ki-67 negative patients (P<0.005). By combining the Ki-67 expression with ER receptors and stage, subgroups with a different disease-free survival were identified. In stage II patients there was a significant difference (P <0.005) in disease-free survival between Ki-67 positive/ER negative and Ki-67 negative/ER positive patients. In node negative patients there was no such difference. The disease-free survival according to different prognostic factors, stage, ER and node status, were separately examined using a Cox's proportional hazards model. ER (P <0.0001), the Ki-67 (P <0.02), tumour size (P<0.0001) and nodal status (P<0.006) were independent prognostic factors. We conclude that the potential value of Ki-67 labelling for prognostic evaluation of patients with breast carcinoma is good.The increasing number of options for the treatment of breast carcinoma has made the prognostic evaluation of the disease even more important. The histologic criteria for grading of the carcinoma into poorly differentiated and well differentiated ones was established already in 1957 (Bloom & Richardson, 1957). Patients with poorly differentiated tumours have a shorter relapse-free survival than those with differentiated ones. Node positivity also decreases the disease-free survival time (Du-Toit et al., 1990;Fisher et al., 1983). Methods of 3H Thymidine incorporation (Silvestrini et al., 1974) and flow cytometry (Kallioniemi et al., 1987) are well established but complex procedures giving prognostic information. It is desirable to find easier methods for the prognostic evaluation of breast carcinoma. In this respect the introduction of a mouse monoclonal antibody Ki-67 by Gerdes et al. (1983) simplified the measurement of proliferative activity in breast carcinoma tissue. The monoclonal antibody labels a still unknown nuclear antigen in proliferating cells. Cell nuclei in the resting stage (GO) are not stained. Ki-67 immunoreactivity has been studied in several types of carcinoma, e.g. in breast carcinoma (Barnard et al., 1987;Gasparini et al., 1992;Locker et al., 1992), in bladder carcinoma (Fontana et al., 1992), in carcinoma of the prostate (Thompson et al., 1992) and in colon carcinoma (Porschen et al., 1991 Tissue preparation The breast specimens were laid on ice and frozen in liquid nitrogen within 45 min. Sections for Ki-67 labelling, were stored at -20°. The acetone-fixed, air-dried sections were incubated for 60 min at room temperature with the primary Ki-67-antiserum (DakopattsO) diluted 1:10. The rest of the staining procedure was performed using the avidin-biotin method (ABC-Kit, Vector Laboratories@, Burlingame, California). The result was visualised using AEC as chromogen. Finally the sections were lightly counterstained with Mayer's haematoxylin. For the immu...

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Node-negative breast cancer: prognostic subgroups defined by tumor size and flow cytometry.

Cited by 118 publications

References 10 publications

Significance of S-phase fraction and hormone receptor content in the management of young breast cancer patients

Significance of S-phase fraction and hormone receptor content in the management of young breast cancer patients

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

Prognostic value of Ki-67 immunolabelling in primary operable breast cancer

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