Japanese Journal of Clinical Oncology 33:14-16 (2003)
© 2003 Foundation for Promotion of Cancer Research
Correlation among Intratumoral Blood Flow in Breast Cancer, Clinicopathological Findings and Nottingham Prognostic Index
1 Digestive Surgery and 2 Radiology, Tokyo Medical and Dental University, Graduate School, Tokyo, Japan
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Background: The purpose of this study was to evaluate the correlation among intratumoral blood flow as assessed by color Doppler ultrasonography, clinicopathological findings and the Nottingham Prognostic Index (NPI).
Methods: Twenty-seven patients with breast cancer were examined. All patients received surgical treatment. Color Doppler ultrasonography was performed prior to surgery to detect arterial blood flow signals within the tumors. The lowest resistance index (RI) was recorded. Formalin-fixed, paraffin-embedded slides were reviewed by senior pathologists to evaluate the size of tumor, histological size, lymph node status and histological grade. Estrogen and progesterone receptor levels were measured by enzyme immunoassay. The Nottingham Prognostic Index was calculated using the equation NPI = 0.2 x tumor size (cm) + grade (I–III) + lymph node score (1–3).
Results: The lowest RI correlated well with NPI and histological grade (grade II:III = RI 1.037:0.816, P = 0.0035). Regression analysis revealed a linear relationship between the lowest RI and NPI (correlation coefficient = 0.475; P = 0.0153).
Conclusions: Intratumoral blood flow analysis assessed by color Doppler ultrasonography correlates well with histological grade and NPI. Preoperative assessment using color Doppler ultrasonography provides useful information and may contribute to the determination of prognosis.
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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The incidence of regional lymph node metastasis has important prognostic implications in primary operable breast cancer (1), as does histological grade (2). The Nottingham Prognostic Index (NPI), which is based on invasive tumor size, lymph node stage and histological tumor grade, is a reliable prognostic index used to predict patient survival (3). However, these data can only be obtained postoperatively, while accurate preoperative prediction regarding high-risk patients is required for neoadjuvant chemotherapy. Some authors have reported that the information obtained by color Doppler ultrasonography correlates well with surgical stage, tumor grade, tumor invasion and lymph node status in endometrial carcinoma (4). However, the usefulness of color Doppler ultrasonography for the assessment of high-risk breast cancer patients is controversial. The purposes of the present study were to examine the correlation among preoperative intratumor blood flow assessed by color Doppler ultrasonography, histopathological findings and NPI.
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PATIENTS AND METHODS |
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TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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From January 1998 to August 1999, 27 female patients with breast cancer (aged 41 to 66 years, average 54.2 years) were evaluated. All 27 patients received surgical treatment including mastectomy and partial resection with axillary lymph node resection (level III). Stage was determined according to the General Rules of the Japanese Breast Cancer Society. Four patients were in stage I and 23 in stage IIA.
For all patients, areas representative of the invasive component of the tumor were selected from sections stained with hematoxylin and eosin and reviewed by independent pathologists. The following morphological features were recorded: grade of tumor differentiation (grading), infiltration to surrounding tissue, lymph node involvement and venous and lymphatic infiltration.
Power Doppler ultrasonography was performed prior to surgery to detect the arterial blood flow velocity waveforms within the tumor, using a power Doppler ultrasonography unit (LOGIQ 700MR, Yokogawa GE, Japan). The resistance index (RI) was then calculated as the difference between the systolic and end diastolic frequency shift divided by the systolic frequency shift. As many samplings as possible throughout the tumor were taken and the lowest RI value was used for the analysis.
The Nottingham Prognostic Index (NPI), described by Elston and Ellis in 1991 (2), is an integrated prognostic index used to predict high-risk patients. In the present study, using three histological factors (tumor size, histological grade and lymph node score), the NPI was calculated using the equation NPI = 0.2 x tumor size (cm) + grade (I–III) + lymph node score.
Statistical Analysis
Statistical analysis was performed using Student’s t-test and regression analysis. Regression analysis was performed using Spearman rank correlation. Statistical significance was established at the P < 0.05 level.
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RESULTS |
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TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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For the 27 patients, tumor size ranged from 1.5 to 5.0 cm with an average of 3.33 cm. The histological subtypes in our series included papillotubular carcinoma (n = 12), solid tubular carcinoma (n = 3) and scirrhous carcinoma (n = 12). The sampling number ranged from one to five (mean 2.85 ± 1.17). RI ranged from 0.46 to 1.33 (mean 0.87 ± 0.18) and NPI ranged from 3.40 to 6.20 (mean 4.63 ± 0.80) (Table 1).
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No significant correlation was observed between RI and each clinicopathological finding (lymph node status, estrogen and progesterone receptor, histological type and vessel involvement). However, significant correlation was observed between lower RI values and histological grade (grade 2, 1.037 ± 0.193; grade 3, 0.816 ± 0.142) (Table 2).
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Regression analysis revealed a linear relationship between the lowest RI and NPI (correlation coefficient = 0.475; P = 0.0153) (Fig. 1).
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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In the treatment of breast cancer, it is important to clarify the factors that affect the prognosis, not only to provide appropriate preoperative adjuvant chemotherapy, but also to select appropriate postoperative chemotherapy specifically for the treatment of certain types of cancers such as locally advanced cancers (5,6). The NPI has been reported to be a useful parameter for predicting the prognosis of both large- and small-sized breast cancers (2,3). However, since the NPI is determined based on the size and other parameters of the resected specimen, the NPI of preoperative cases is difficult to determine. In most of these cases, therefore, whether adjuvant chemotherapy is indicated has been determined based on the findings obtained from preoperative diagnostic imaging techniques such as mammography, ultrasonic tomography and computed tomography (CT) (9).
The purpose of the present study was to investigate whether preoperative color Doppler ultrasonography can be used as a diagnostic tool for evaluating the degree of malignancy of breast cancer in individual patients. Our analysis revealed a positive correlation between the NPI and the results of preoperative color Doppler test, suggesting that this method may be used as a tool for evaluating the degree of malignancy of breast cancer. A previous study showed that the results of the preoperative color Doppler test were related to the degree of malignancy and the degree of neovascularization in patients with uterine and ovarian cancer (4,8). The use of the color Doppler test in patients with breast cancer has been reported to be useful for distinguishing whether a tumor is malignant or benign (9). However, there has been no report on the usefulness of this method for determining the degree of malignancy of breast cancer, which has been shown to be positively correlated with the degree of neovascularization in the tumor (10). Since the color Doppler test result represents the degree of blood circulation in the inner part of the tumor, this value can be considered to reflect the degree of neovascularization in the tumor. In general, several influx vessels enter a tumor. Using color Doppler ultrasonography, we determined that the RI of these influx vessels varies. Therefore, we decided to use the lowest RI in a tumor as the parameter for evaluating the degree of neovascularization of the tumor, because the blood vessel with the lowest RI would be the main supplier of blood to the tumor and the greater the blood supply, the greater is the degree of neovascularization. We confirmed that preoperative color Doppler ultrasonography is useful for evaluating the degree of malignancy of breast cancer, although further investigation is necessary.
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FOOTNOTES |
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+ For reprints and all correspondence: Takayuki Osanai, Digestive Surgery, Tokyo Medical and Dental University, Graduate School, 1–5–45, Yushima, Bunkyo-ku, Tokyo 113-8519, Japan
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REFERENCES |
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Received April 11, 2002; accepted September 25, 2002
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