New technologies for diagnosis and treatment of breast cancer: meeting highlights from the Fourth Milan Breast Cancer Conference (Milan, June 5-7, 2002).
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Biomedical Technology↗
Biomedical subjects
A Goldhirsch
Publications and source records attributed to A Goldhirsch.
Preoperative systemic treatment: prediction of responsiveness.
The use of predictive factors allows a more effective use of available therapies by enabling clinicians to distinguish patients likely to obtain substantial benefit from treatment from those for whom the same therapy is less likely to be effective. A most relevant aspect of clinical research is thus to develop alternative therapeutic approaches which are more efficacious for this latter group, particularly important since treatment effects are likely to be small. In the preoperative setting several predictors of response were identified. They include: diameter of the lesion (larger lesions respond less than smaller lesions), MIB-1 increased expression associated with increased response to chemotherapy, and estrogen receptor (ER) and progesterone receptor (PgR) expression in the tumor typically associated with increased response to endocrine therapies. Other factors include HER-2/neu overexpression, which is a target for treatment with the humanized monoclonal antibody against its extracellular domain, is hypothesized to increase response to anthracycline combination chemotherapy and to lead to an improved response to some endocrine agents (e.g. letrozole) rather than to others. Although primary endocrine therapy demonstrated activity and low profile of side effects in selected populations of older patients, it is infrequently used. On the other hand, chemotherapy remains the mainstay of treatment being considered to be a more active and better documented option. Experience at the European Institute of Oncology on 399 patients with large or locally advanced breast cancer (cT2-T4, N0-2, M0) treated with primary chemotherapy, indicated that a proper selection of primary treatment should be based on tumor characteristics such as ER and PgR status. In particular, patients with tumors with no ER and PgR expression (endocrine-unresponsive disease) at the baseline core-biopsy had a significantly higher response rate to chemotherapy if compared with tumors with some ER/PgR expression. In fact, the absence of ER and PgR expression was the strongest predictors of pCR at the multivariate analysis (P<0.0001). Information on endocrine responsiveness before primary systemic therapy will lead to better tailoring of treatment modalities, thus avoiding chemotherapy in selected populations where other approaches (e.g. endocrine primary therapy) might be more useful.
Animals↗
Tailoring adjuvant treatments for the individual breast cancer patient.
BACKGROUND: Chemotherapy, tamoxifen and ovarian function suppression have all demonstrated their effectiveness for treating women with early breast cancer. Treatment selection for individual patients, however, requires estimates on the magnitude of treatment effects to be achieved from the application of each modality. Unfortunately, information currently available is insufficient to properly tailor adjuvant treatments. METHODS: We consider predictive factors to improve our understanding about selection of adjuvant therapies, reassessment of data from previous clinical trials and design of future studies. RESULTS: Estrogen receptor (ER) and progesterone receptor (PgR) are the primary measures available today to tailor adjuvant therapies. Patient age/menopausal status (ability to obtain treatment effects via ovarian function suppression), measures of the metastatic potential of the tumor (such as number of positive axillary lymph nodes), and concurrent use of chemotherapy and tamoxifen are other factors that modify the magnitude of relative effect associated with chemotherapy and endocrine therapies. The Subpopulation Treatment Effect Pattern Plots (STEPP) method displays the patterns of treatment effects within randomized clinical trials or datasets from meta-analyses to identify features that predict responsiveness to the treatments under study without relying on retrospective subset analysis. Confirmation of hypotheses using independent clinical trial databases is recommended. DISCUSSION: All findings from clinical trials and meta-analyses should be presented primarily according to steroid hormone receptor status and patient age. Future studies should be designed as tailored treatment investigations, with endocrine therapies evaluated within populations of patients with endocrine responsive tumors, and chemotherapy questions focused within populations of patients with endocrine nonresponsive disease.
Antineoplastic Agents, Hormonal↗
Breast and ovarian metastatic localization of signet-ring cell gastric carcinoma.
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Adult↗
Adjuvant systemic therapies in women with breast cancer: an audit of clinical practice in Italy.
BACKGROUND: Evidence-based guidelines, consensus conferences and experts' opinion are rarely promptly transferred to patient care. We audited prescriptions of adjuvant systemic therapies for Italian breast cancer patients and compared them with recommendations of an International Consensus Panel. PATIENTS AND METHODS: Disease characteristics and adjuvant therapies for 768 breast cancer patients referred to 87 Italian centers from 16 to 23 March 2000 were evaluated for adherence to the published recommendations. RESULTS: Endocrine therapy was not prescribed for 102 of 541 patients (19%) with endocrine-responsive disease and for 22 of 45 patients (49%) with unknown hormonal receptor status. Instead, endocrine therapy was prescribed for 22 of 182 patients (12%) with endocrine-unresponsive disease. Adjuvant chemotherapy was prescribed for 98% of the patients. The type of chemotherapy was the cyclophosphamide, methotrexate, 5-fluorouracil regimen for 453 of 754 (60%), while 253 of 754 (34%) received an anthracycline-based regimen. The proportion of patients with anthracyclines increased with the number of involved axillary nodes and grading, and decreased with age. Endocrine therapy was administered to 482 of 768 (63%) and was mainly represented by an antiestrogen. CONCLUSIONS: Lack of adherence to evidence-based guidelines for adjuvant treatment of Italian breast cancer patients was as high as 19%. It might be wise for national health authorities to promote education on life-saving procedures, like adjuvant systemic treatments, in cancer medicine.
Adult↗
Systemic treatments for women with breast cancer: outcome with relation to screening for the disease.
Early detection and proper care of breast cancer are currently the best available approaches to the treatment of patients with the disease. In countries with a breast cancer screening programme, there has been a demonstrated reduction in breast cancer-related mortality. Such reduction has also been observed in Switzerland, a country in which no national programme of screening is available. Although there is no doubt that early diagnosis might have had a major role in reducing breast cancer mortality the magnitude of this effect is unknown. Research with tailored approaches on alternative imaging for early detection of breast cancer in high-risk women and on treatments offered according to proper criteria of responsiveness to therapies is warranted.
Adult↗
Adjuvant therapy after excision and radiation of isolated postmastectomy locoregional breast cancer recurrence: definitive results of a phase III randomized trial (SAKK 23/82) comparing tamoxifen with observation.
BACKGROUND: Adjuvant systemic treatment for patients with isolated locoregional recurrence (ILRR) of breast cancer is based on a single reported randomized trial. The trial, conducted by the Swiss Group for Clinical Cancer Research, compared tamoxifen (TAM) with observation after complete excision of the ILRR and proper radiotherapy. We performed a definitive analysis of treatment outcome at >11 years of follow-up, after the majority of the patients had a subsequent event of interest. Patient and methods One hundred and sixty-seven patients with 'good-risk' characteristics of disease were randomized. 'Good-risk' was defined as estrogen receptor expression in the ILRR, or having a disease-free interval of >12 months and a recurrence consisting of three or less tumor nodules, each </=3 cm in diameter. Seventy-nine percent of the patients were postmenopausal at randomization. RESULTS: The median follow-up time of the surviving patients was 11.6 years. The median post ILRR disease-free survival (DFS) was 6.5 years with TAM and 2.7 years with observation (P = 0.053). The difference was mainly due to reduction of further local relapses (P = 0.011). In postmenopausal patients, TAM led to an increase of DFS from 33% to 61% (P = 0.006). In premenopausal women, 5-year DFS was 60%, independent of TAM medication. For the whole study population, the median post-recurrence overall survival (OS) was 11.2 and 11.5 years in the observation and the TAM group, respectively; premenopausal patients experienced a 5-year OS of 90% for observation compared with 67% for TAM (P = 0.175), while the respective figures for postmenopausal patients were both 75%. CONCLUSIONS: These definitive results confirmed that TAM significantly improves the post-recurrence DFS of patients after local treatment for ILRR. This beneficial effect does not translate into a detectable OS advantage.
Adult↗
Preoperative and perioperative chemotherapy with 5-fluorouracil as continuous infusion in operable breast cancer expressing a high proliferation fraction: cytotoxic treatment during the surgical phase.
BACKGROUND: Experimental data on perioperative chemotherapy (PeCT) indicate that its initiation might be most useful if administered as close as possible to the time of first 'disturbance of the tumour'. Regimens including 5-fluorouracil (5-FU) as continuous infusion are commonly used in the preoperative setting, especially for large tumours and locally advanced disease. We therefore evaluated the role of PeCT with 5-FU as continuous infusion after preoperative chemotherapy (PreCT), covering the surgical phase and acute wound healing period, in patients with breast cancer too large to attempt breast-conserving surgery upon diagnosis. PATIENTS AND METHODS: Breast cancer patients, clinical stages T2-T3, N0-N2, M0, and Ki-67 labelling index >/= 20%, were treated every 3 weeks with a maximum of six courses of vinorelbine 20 mg total dose intravenously (i.v.) on days 1 and 3, cisplatin 60 mg/ m(2) i.v. on day 1 and 5-FU 200 mg/m(2)/day as a continuous infusion (ViFuP regimen). Patients who achieved a clinical and radiological objective remission with PreCT were also treated with perioperative 5-FU that was continued until 30 min before, and restarted immediately after surgery, prolonging infusion until 15 days after surgery. RESULTS: Following preoperative treatment, 39 of 49 evaluable patients [80%; 95% confidence interval (CI) 70% to 90%] had an objective response. Pathological complete remission (pCR) was achieved in 14 (29%) patients. No relevant clinical or haematological toxicity due to PeCT was observed. In 36 patients submitted to PeCT the rate of pCR was 33% (95% CI 18% to 48%). The highest response of the primary tumour to PreCT and PeCT was observed in women with tumours not expressing estrogen and progesterone receptors (pCR 46%; 95% CI 19% to 73%). CONCLUSIONS: Preoperative therapy can be protracted into the surgical (and wound healing) period without significant additional short-term toxicity. Proper selection of patients according to biological features might improve the therapeutic yield of preoperative therapies.
Adult↗
Duration of adjuvant chemotherapy for breast cancer: a joint analysis of two randomised trials investigating three versus six courses of CMF.
Cyclophosphamide, methotrexate and fluorouracil adjuvant combination chemotherapy for breast cancer is currently used for the duration of six monthly courses. We performed a joint analysis of two studies on the duration of adjuvant cyclophosphamide, methotrexate and fluorouracil in patients with node-positive breast cancer to investigate whether three courses of cyclophosphamide, methotrexate and fluorouracil might suffice. The International Breast Cancer Study Group Trial VI randomly assigned 735 pre- and perimenopausal patients to receive 'classical' cyclophosphamide, methotrexate and fluorouracil for three consecutive cycles, or the same chemotherapy for six consecutive cycles. The German Breast Cancer Study Group randomised 289 patients to receive either three or six cycles of i.v. cyclophosphamide, methotrexate and fluorouracil day 1, 8. Treatment effects were estimated using Cox regression analysis stratified by clinical trial without further adjustment for covariates. The 5-year disease-free survival per cents (+/-s.e.) were 54+/-2% for three cycles and 55+/-2% for six cycles (n=1024; risk ratio (risk ratio: CMFx3/CMFx6), 1.00; 95% confidence interval, 0.85 to 1.18; P=0.99). Use of three rather than six cycles was demonstrated to be adequate in both studies for patients at least 40-years-old with oestrogen-receptor-positive tumours (n=594; risk ratio, 0.86; 95% confidence interval, 0.68 to 1.08; P=0.19). In fact, results slightly favoured three cycles over six for this subgroup, and the 95% confidence interval excluded an adverse effect of more than 2% with respect to absolute 5-year survival. In contrast, three cycles appeared to be possibly inferior to six cycles for women less than 40-years-old (n=190; risk ratio, 1.25; 95% confidence interval, 0.87 to 1.80; P=0.22) and for women with oestrogen-receptor-negative tumours (n=302; risk ratio, 1.15; 95% confidence interval, 0.85 to 1.57; P=0.37). Thus, three initial cycles of adjuvant cyclophosphamide, methotrexate and fluorouracil chemotherapy were as effective as six cycles for older patients (40-years-old) with oestrogen-receptor-positive tumours, while six cycles of adjuvant cyclophosphamide, methotrexate and fluorouracil might still be required for other cohorts. Because endocrine therapy with tamoxifen and GnRH analogues is now available for younger women with oestrogen-receptor-positive tumours, the need for six cycles of cyclophosphamide, methotrexate and fluorouracil is unclear and requires further investigation.
Adult↗
Low-dose oral methotrexate and cyclophosphamide in metastatic breast cancer: antitumor activity and correlation with vascular endothelial growth factor levels.
BACKGROUND: Anticancer chemotherapy is thought to be effective by means of direct cytotoxicity on tumor cells. Alternative mechanisms of efficacy have been ascribed to several common anticancer agents, including cyclophosphamide (CTX), methotrexate (MTX), anthracyclines and taxanes, postulating an antiangiogenic activity. PATIENTS AND METHODS: We evaluated the clinical efficacy and impact on serum vascular endothelial growth factor (VEGF) levels of low-dose oral MTX and CTX in patients with metastatic breast cancer. MTX was administered 2.5 mg bd on days 1 and 2 each week and CTX 50 mg/day administered continuously. RESULTS: Sixty-four patients were enrolled, 63 were evaluable: Eastern Cooperative Oncology Group (ECOG) performance status 0-1, > or =2 sites of metastatic disease (n = 50 patients), progressive disease at study entry (n = 51), 1 regimen for metastatic disease (n = 32) and > or =2 regimens (n = 20). Among the 63 evaluable patients, there were two complete remissions (CR), 10 partial remissions (PR) for an overall response rate of 19.0% (95% CI 10.2% to 30.9%) and an overall clinical benefit (CR+ PR+ stable disease >24 weeks) of 31.7% (95% CI 20.6% to 44.7%). Grade > or =2 leucopenia was registered in only 13 patients. The median serum VEGF level for the subgroup of patients on treatment for at least 2 months decreased with treatment from 315 pg/ml (95% CI 245 to 435) at baseline to 248 pg/ml (95% CI 205 to 311) at 2 months (P <0.001). Both responders and non-responders showed similar reductions in serum VEGF (P = 0.78). After 6 months patients still on treatment had a median VEGF level of 195 pg/ml (95% CI 96 to 355), which was significantly lower than the median baseline values (P = 0.001). CONCLUSIONS: Continuously low-dose CTX and MTX is minimally toxic and effective in heavily pretreated breast cancer patients. A drop in VEGF was associated with the treatment and so alternative hypotheses, other than that of direct toxicity on tumor cells, must be favored when trying to explain the anticancer effect.
Administration, Oral↗
Very young women (<35 years) with operable breast cancer: features of disease at presentation.
BACKGROUND: Breast cancer rarely occurs in young women. Our knowledge about disease presentation, prognosis and treatment effects are largely dependent upon older series. MATERIALS AND METHODS: We evaluated biological features and stage at presentation for 1427 consecutive premenopausal patients aged < or = 50 years with first diagnosis of invasive breast cancer referred to surgery at the European Institute of Oncology from April 1997 to August 2000. A total of 185 patients (13%) were aged < 35 years ('very young') and 1242 (87%) were aged 35-50 years ('less young'). The expression of estrogen receptors (ER), progesterone receptors (PgR), presence of vascular invasion (VI), grading (G), expression of Ki-67, HER2/neu overexpression, pathological stage according to TNM staging system (pTNM), pathological tumor size and number of axillary lymph node involvement were evaluated. RESULTS: Compared with less young patients, the very young patient group had a higher percentage of tumors classified as ER negative (P < 0.001), PgR negative (P = 0.001), higher expression of Ki-67 > or = 20% of cells stained; 62.2% versus 53%, (P < 0.001), vascular or lymphatic invasion (48.6% versus 37.3%, P = 0.006), and pathological grade 3 (P < 0.0001). There was no difference between the two groups for pT, pathological tumor size (pN) and number of positive lymph nodes. CONCLUSIONS: We conclude that compared with less young premenopausal patients, very young women have a greater chance of having an endocrine-unresponsive tumor, and are more likely to present with a higher grade, more extensively proliferating and vessel invading disease. Pathological tumor size, nodal status and number of positive axillary lymph-nodes have a similar distribution among the younger and the older cohorts, thus not supporting previous data indicating more advanced disease in younger patients at diagnosis of operable disease.
Adult↗
Recognizing features that are dissimilar in male and female breast cancer: expression of p21Waf1 and p27Kip1 using an immunohistochemical assay.
BACKGROUND: Male breast cancer (MBC) is an uncommon disease, and most of our current knowledge of its biology, natural history and treatment has been extrapolated from data on the disease in women. Information is still needed on the molecular biological properties of male breast tumors and their predictive relevance. Kinase inhibitor proteins (KIPs) p27Kip1 and p21Waf1 negatively regulate cell cycle progression by preventing the passage of cycling cells from G1 to S phase through G1 cyclin-dependent kinase activation. No studies exist on the role of these factors in male breast carcinoma. PATIENTS AND METHODS: We have retrospectively analyzed the immunohistochemical expression of p21Waf1 and p27Kip1 protein in 27 primary MBC and in 101 female breast cancers (FBC) treated at the European Institute of Oncology between 1997 and 2000. We also assessed sex hormone receptors status, p53, bcl-2 and c-erb-B2 protein expression, and Ki-67 labeling index. RESULTS: We observed a statistically significant difference in the immunostaining of KIPs p27Kip1 and p21Waf1 in male patients compared with females. Expression of p21Waf1 was observed in 19 of the 27 (70.3%) primary MBCs versus 29 of 101 FBC (29%). Fourteen of 22 negative c-erbB-2 MBCs cases expressed immunostaining for p21Waf1 (P = 0.05). p27Kip1 immunoreactivity was been detected in 26 of 27 (96.2%) male breast patients versus 39 of 101 FBC (39.3%) (P = 0.000). Highly positive staining for P27Kip1 was found in 21 of 25 androgen receptor-expressing samples. Higher levels of p27Kip1 were expressed in bcl-2-positive samples (17 of 20). Eighteen of 22 c-erbB-2-negative cases were strongly immunoreactive for p27Kip1. CONCLUSIONS: p27Kip1 and p21Waf1 immunoreactivity is higher in MBCs compared with FBCs. The findings of higher p27Kip1 and p21Waf1 immunostaining may be an additional predictive factor in MBC. These biological features could be possible indicators for different biological pathways in the tumorigenesis of MBCs.
Adult↗
Endocrine therapy of breast cancer.
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Antineoplastic Agents, Hormonal↗
Influence of endocrine-related factors on response to perioperative chemotherapy for patients with node-negative breast cancer.
PURPOSE: We investigated tumor- and patient-related features that might influence the response to perioperative chemotherapy (PeCT) compared with no adjuvant therapy for patients with node-negative breast cancer. PATIENTS AND METHODS: A total of 1,275 patients were randomized to either no adjuvant treatment (427 patients) or PeCT (848 patients). The following variables thought to have prognostic significance were evaluated: grade, tumor size, estrogen (ER) and progesterone receptor (PgR) content (absent; low, 1 to 9 fmol/mg cytosol protein; or positive, > or = 10 fmol/mg cytosol protein), c-erbB-2 overexpression, menopausal status, and age. Cox proportional hazards regression models were used to assess the relative influence of these factors to predict the effect of PeCT on disease-free survival (DFS). Median follow-up was 13.5 years. RESULTS: The 10-year DFS percentage for 692 premenopausal patients did not significantly differ between the PeCT and no-adjuvant-treatment groups: 61% and 59%, respectively (relative risk [RR], 0.95; 95% confidence interval [CI], 0.75 to 1.20; P = .70). No predictive factors were identified. For 583 postmenopausal patients, 10-year DFS percentages for the groups were 63% and 58%, respectively (RR, 0.75; 95% CI, 0.58 to 0.93; P = .03). The absence of expression of ER, PgR, or both ER and PgR was the most important factor predicting improved outcome with PeCT among postmenopausal patients. The 10-year DFS percentages were 85% and 53% for the steroid hormone receptor-absent cohort of treated and untreated patients, respectively (RR, 0.18; 95% CI, 0.06 to 0.49; P = .0009). CONCLUSION: The role of PeCT should be explored for patients whose primary tumors do not express steroid hormone receptors, because it is likely that early initiation of treatment is exclusively relevant for such patients.
Adult↗
Meeting highlights: International Consensus Panel on the Treatment of Primary Breast Cancer. Seventh International Conference on Adjuvant Therapy of Primary Breast Cancer.
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Breast Neoplasms↗
A randomized, prospective trial of central venous ports connected to standard open-ended or Groshong catheters in adult oncology patients.
BACKGROUND: Implanted central venous access is practiced extensively in oncology; however, information on the relevance of using the device with a valved catheter (Groshong), compared with an open-ended catheter, is scarce. The authors investigated the two types of catheters in a randomized trial using the same type of subcutaneous port and evaluated efficacy as well as early and late complications. METHODS: Three hundred four patients with malignant disease (solid tumors) who were eligible to receive intravenous chemotherapy were accrued during a 15-month period. After providing informed consent, the patients were assigned randomly to implantation of a titanium and silicone, rubber port (Dome Port; Bard Inc., Salt Lake City, UT) attached either to an 8.0-F silastic Groshongtrade mark catheter tube (experimental group) or to a 9.6-F silastic open-ended catheter tube (control group). Both catheters were manufactured by Bard Inc. Implantation, care, and follow-up followed the same protocol guidelines until removal of the device, death, or ending of the study. Power and color Doppler ultrasound examinations of internal jugular and subclavian veins were performed at 1 month and at 4 months or at anytime when a venous thrombosis was suspected. RESULTS: Three hundred two patients (99.3%) were evaluable, 150 patients in the control group and 152 in the experimental group. The median follow-up was 237 days. There was a trend toward more early complications in the experimental group (5.9%; 95% confidence interval [95% CI], 2.7-10.9%) than in the control group (2.7%; 95% CI, 0.7-6.7%), although the difference was not statistically significant (P = 0.26). There was also a trend toward more late complications in the experimental group (17.1%; 95% CI, 11.5-24.1%) compared with the control group (10.7%; 95% CI, 6.2-16.7%; P = 0.13), although the difference, again, was not statistically significant. The most frequent late complication was the inability to draw blood samples (12.5% in the experimental group and 2% in the control group; P < 0.001). Sepsis was observed in 1 patient and in 3 patients and venous thrombosis was observed in 6 patients and in 11 patients in the experimental and control treatment groups, respectively (P value not significant). CONCLUSIONS: In the tested clinical setting, the use of a Groshong catheter was not superior to a traditional, open-ended device in terms of early and late complications of the implant and its use. The theoretical justification for its superiority for more efficient use of the implantable device could not be substantiated.
Adult↗
Polychemotherapy for early breast cancer: an overview of the randomised clinical trials with quality-adjusted survival analysis.
BACKGROUND: Overview analysis involving 18000 women with breast cancer in 47 randomised trials showed that prolonged chemotherapy significantly reduces the risk of relapse and death compared with no chemotherapy. Here we express the size of the benefit in terms of quality-adjusted survival time gained. METHODS: We used the Q-TWiST method (Quality-adjusted Time Without Symptoms of disease and Toxicity of treatment) to provide treatment comparisons within 10 years' follow-up, incorporating differences in quality of life associated with times patients spend with chemotherapy toxic effects, after relapse, and without symptoms of relapse or toxicity. FINDINGS: Within 10 years' follow-up the benefit of increased relapse-free and overall survival for younger women (<50 years old) who received polychemotherapy balanced the burdens in terms of acute toxic side-effects, especially among women enrolled in trials that did not include tamoxifen. Overall, chemotherapy-treated younger women gained an average of 10.3 months of relapse-free survival and 5.4 months of overall survival within 10 years (p<0.0001 for both) compared with the no-chemotherapy group. Polychemotherapy provided more quality-adjusted time than control across nearly all values of utility weights for time spent undergoing chemotherapy and time after relapse. The range of benefit was from -0.6 to 10.3 months. For older women (50-69 years) overall, polychemotherapy also provided significant benefit compared with no chemotherapy but, compared with younger women, the size of benefit was less and the range of utility-weight values favouring polychemotherapy was smaller. Average gains for older women treated with polychemotherapy (with or without tamoxifen) were 6.8 months of relapse-free survival (p<0.0001) and 2.9 months of overall survival (p=0.0001) within 10 years. The range of quality-adjusted benefit was -3.1 to 6.8 months. For older women with oestrogen-receptor-poor tumours who did not receive tamoxifen (9% of the total), the benefit of polychemotherapy was significant and similar to that observed for younger women. INTERPRETATION: The benefits of adjuvant chemotherapy within 10 years outweigh the burdens especially for younger women (<50 years old) and among older women (50-69 years) to a lesser degree. Additional studies to compare the quality-adjusted survival of chemotherapy plus endocrine therapy versus endocrine therapy alone are required for younger patients with tumours that express steroid-hormone receptors.
Aged↗
Resting and activated endothelial cells are increased in the peripheral blood of cancer patients.
Circulating endothelial cells (CECs) were enumerated in 20 healthy controls and 76 newly diagnosed cancer patients by means of 4-color flow cytometry. In breast cancer (n = 46) and lymphoma (n = 30) patients, both resting and activated CECs were increased by 5-fold (P <.0008 vs control). CECs significantly correlated with plasma levels of vascular cell adhesion molecule-1 and vascular endothelial growth factor. Resting and activated CECs were similar to healthy controls in 7 lymphoma patients achieving complete remission after chemotherapy, and activated CECs were found to decrease in 13 breast cancer patients evaluated before and 24 hours after quadrantectomy. (Blood. 2001;97:3658-3661)
Breast Neoplasms↗