Kinetics of human mammary carcinomas and their correlation with the cancer and the host characteristics

Silvestrini, Rosella; Sanfilippo, Ornella; Tedesco, Graziella

doi:10.1002/1097-0142(197410)34:4<1252::aid-cncr2820340435>3.0.co;2-l

Cited by 56 publications

(17 citation statements)

References 23 publications

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“…Another possible clinical application may be as indicators of the need for initiating early treatment. Several studies reported a duplication time of about 2 months in mammary tumours (Silvestrini et al, 1974;Goldie, 1989). A mean lead time of 4.9 months for early diagnosis of recurrence indicates, at least in theory, a 4-fold smaller tumour mass at detection and therefore also a higher possibility of response to treatment (Silvestrini et al, 1974;De Vita et al, 1983;Goldie, 1989).…”

Section: Discussionmentioning

confidence: 99%

“…Several studies reported a duplication time of about 2 months in mammary tumours (Silvestrini et al, 1974;Goldie, 1989). A mean lead time of 4.9 months for early diagnosis of recurrence indicates, at least in theory, a 4-fold smaller tumour mass at detection and therefore also a higher possibility of response to treatment (Silvestrini et al, 1974;De Vita et al, 1983;Goldie, 1989). The use of tumour marker serial determinations may allow the initiation of systemic treatment with a theoretically higher probability of response in 76.4% of the patients with distant recurrence.…”

Section: Discussionmentioning

confidence: 99%

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Utility of C-erbB-2 in tissue and in serum in the early diagnosis of recurrence in breast cancer patients: comparison with carcinoembryonic antigen and CA 15.3

Molina

Jo²,

Zanón³

et al. 1996

Br J Cancer

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Summary To evaluate the utility of c-erbB-2, carcinoembryonic antigen (CEA) and CA 15.3 in the early diagnosis of recurrence, serial serum determinations of these antigens were performed in 200 patients (followup 1-4 years, mean 2.2 years) with primary breast cancer and no evidence of residual disease (NED) after radical treatment (radical mastectomy or simple mastectomy and radiotherapy). Eighty-nine patients developed metastases during follow-up. C-erbB-2, CEA and CA 15.3 were elevated (>20 U ml -, > 0 ng ml-or >60 U ml-1 respectively) before diagnosis in 28%, 30% and 47% of the 89 patients with recurrence, with a lead time of 4.5 + 2.4, 4.9+2.4 and 4.8 + 2.4 months respectively. Tumour marker sensitivity was clearly related to the site of recurrence, with the lowest sensitivity found in locoregional relapse and the highest in patients with liver metastases. When patients with locoregional recurrences were excluded, sensitivity improved: 31 % (cerbB-2), 33% (CEA) and 56% (CA 15.3), with 76% having at least one of the three tumour markers. C-erbB-2 sensitivity in early diagnosis was significantly higher in patients with c-erbB-2 overexpression in tissue (8/10, 80%) than in those without overexpression (1/30, 3.3%) (P=0.0001). Likewise, higher levels of both, c-erbB-2 and CA 15.3 at diagnosis of recurrence, higher sensitivity in early diagnosis of relapse and a higher lead time were found in PR+ patients (CA 15.3, P<0.0001) or in PR-patients (c-erbB-2, P=0.009). Specificity of the tumour markers was 100% for all three markers (111 NED patients). In conclusion, c-erbB-2 is a useful tool for early diagnosis of metastases, mainly in those patients with c-erbB-2 overexpression in tissue. Using all three markers simultaneously it is possible to increase the sensitivity in the early diagnosis of recurrence by 11.2%.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Utility of C-erbB-2 in tissue and in serum in the early diagnosis of recurrence in breast cancer patients: comparison with carcinoembryonic antigen and CA 15.3

Molina

Jo²,

Zanón³

et al. 1996

Br J Cancer

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“…[35][36][37] Increased proliferation rates are associated with a decreased time to relapse [38][39][40] and decreased overall survival. 41 Furthermore, the benefits of chemotherapy in terms of survival or response appear to be greatest for high growth rate tumors, 42,43 although results from some studies do not support this relationship. 22,44 Since paclitaxel inhibits the mitotic spindle, causing a G 2 /M block and apoptosis, [45][46][47] the cytotoxic action of paclitaxel is highly (probably completely) cell cycle dependent.…”

Section: Introductionmentioning

confidence: 99%

Estrogen Receptor Expression and Sensitivity to Paclitaxel in Breast Cancer

Dougherty¹,

Schumaker²,

Jordan³

et al. 2004

Cancer Biology & Therapy

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ACKNOWLEDGEMENTS Research Paper Estrogen Receptor Expression and Sensitivity to Paclitaxel in Breast Cancer ABSTRACTA retrospective analysis of CALGB trial 9344 suggested paclitaxel administration following cyclophosphamide and doxorubicin adjuvant chemotherapy is most beneficial for patients with ERα negative (ERα-) breast cancer. Since the cytotoxic effects of paclitaxel are cell cycle dependent, we postulated that the relationship between ERα and the effectiveness of adjuvant paclitaxel reflects the observation that ERα positive (ERα+) breast cancers proliferate more slowly than ERα-breast cancers. Three in vitro models (MCF-7, T47D and ZR-75) were examined to compare growth rates and paclitaxelinduced apoptosis in ERα+ and ERα-clones of the same, originally ERα+ cell line. For the T47D and ZR-75 cell lines, loss of ERα was associated with a decrease in doubling time and an increase in paclitaxel sensitivity. However, when cell culture conditions were altered to achieve equivalent cell proliferation rates, no difference in paclitaxel sensitivity was observed. Similarly, an ERα-clone of MCF-7 cells that did not exhibit an enhanced growth rate compared to its ERα+ counterpart also did not show increased paclitaxel sensitivity. The combined apoptotic effects of tamoxifen and paclitaxel on MCF-7 cells were not synergistic or even clearly additive. In these in vitro models, the effectiveness of paclitaxel correlated more closely with growth rate than ERα expression. These data suggest that measurements of tumor proliferation may provide more accurate predictive markers for the benefits of adjuvant paclitaxel than ERα analysis.

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“…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.…”

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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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Kinetics of human mammary carcinomas and their correlation with the cancer and the host characteristics

Cited by 56 publications

References 23 publications

Utility of C-erbB-2 in tissue and in serum in the early diagnosis of recurrence in breast cancer patients: comparison with carcinoembryonic antigen and CA 15.3

Utility of C-erbB-2 in tissue and in serum in the early diagnosis of recurrence in breast cancer patients: comparison with carcinoembryonic antigen and CA 15.3

Estrogen Receptor Expression and Sensitivity to Paclitaxel in Breast Cancer

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

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