Abstract

Introduction

Breast cancer is the most common female malignancy and most women present with early stage disease. Conventionally, routine pretherapy noninvasive investigations including radiological imaging is done to assign a clinical disease stage at diagnosis. Accurate stage determination of breast cancer at presentation is essential to decide on primary loco regional therapy versus systemic therapy. The application of these staging tests in early breast cancer has been questioned as the detection of metastatic disease is low.[1] Several practice guidelines have suggested against the routine use of staging imaging in asymptomatic patients.[2,3] However, despite recommendations reports confirm the continual practice of pursuing routine staging investigations in newly diagnosed breast cancer. Inappropriate imaging in early stage breast cancer may increase treatment expenses and potentially lead to harm by false positive results.[4]

It is difficult to understand the reluctance among oncologist to follow practice guideline recommendations regarding staging investigations in breast cancer. The accuracy of a diagnostic test depends on the pretest probability of detecting disease consequently applying staging investigations to high-risk groups is likely to enhance identification of asymptomatic metastasis.[5] In this study, we sought to reexamine the basis behind the guideline practice recommendations and to recognize predictive factors that could identify disease at high risk of asymptomatic metastasis.

Methods

The oncology records of newly diagnosed breast cancer patients attending our center were reviewed for study inclusion. Patients presenting with symptomatic metastatic breast cancer were excluded from the study. Data from 200 patients in clinical Stages I-III (AJCC Stage 7th edition) and asymptomatic for metastatic disease were retrieved and included in the study. Demographic information, tumor characteristics, and pathological data were collected, molecular typing followed the St. Gallen 2011 recommendations. Our center follows a policy of liver ultra sound examination and chest X-ray (CXR) in addition to routine hematological and liver biochemistry studies in early breast cancer. Isotope bone scan, computed tomography (CT) chest and ultra sound/CT abdomen are done as staging imaging in clinical Stage III breast cancer. The radiological reports of bone scan, CT chest, CXR, and abdominal ultrasound of study patients were examined and included for analysis. The overall prevalence rate of asymptomatic metastatic disease deduced and applied for the positive- and negative-predictive value calculations (PPV and NPV). The study applied a definition of unequivocal radiological report of metastatic disease (multiple) as a true positive result. Solitary or asymmetric tracer uptake in bone scans were confirmed by magnetic resonance imaging/CT scans to confirm metastatic disease. Solitary lesions in liver ultrasound were confirmed by CT abdomen or a biopsy, a similar policy was followed for solitary pulmonary/indeterminate lung lesions. Patients with normal staging imaging results but developed symptomatic metastasis while under therapy were deemed to have had a false negative imaging study.

The prevalence of asymptomatic metastatic disease, sensitivity, specificity, and predictive values of staging imaging investigations were calculated. An analysis of tumor and patient related factors to identify predictive factors for metastatic disease was done. Categorical variables were analyzed using Fisher's exact test or Chi-square test and ordinal data tested for significance using the Student's t-test. A P < 0>

Results

The mean age of the study patients was 50 years, 27 (13.5%) symptomatic metastasis was identified, and this formed the prevalence value for subsequent analysis. Bone lesions (8%) were the most common metastatic site followed by lungs (7%) and liver (1%). Ten patients (37%) had a single system involvement, while axial skeleton and the lungs were the most common combination noted. Sensitivity, specificity, positive- and negative-predictive values (PPV and NPV) of bone scans and CT chest were 100%, 97%, 74%, 100% and 92%, 99%, 87, 3%, 99.4%, respectively. The above values for ultrasound abdomen and CXRs were 100%, 99%, 93%, 100% and 21%, 94%, 20%, 94%, respectively [Table 1]. An analysis of factors predictive of metastatic disease was done and showed age (P = 0.24) and menopausal status (P = 1) had no influence on detection of metastasis. Tumor size (P = 0.001), tumor stage T1/T2 versus T3/T4 (P = 0.0002), nodal stages N0/N1 versus N2/N3 (P = 0.001), and high histological Grade G I versus GII/GIII (P = 0.0001) were strongly predictive of metastatic disease. Among the molecular sub types of breast cancer the luminal A was the least aggressive P = 0.003, but the human epidermal growth factor receptor 2 (HER 2) (P = 0.04) and triple negative (P = 0.02) types significantly predicted higher metastatic disease [Table 2].

Table 1

Discussion

Our study detected a metastatic prevalence of 13.6% in clinical Stage I-III breast cancer. The prevalence of distant disease in breast cancer patients asymptomatic for metastasis varies in literature from 2% to 10%.[1,6,7] Greater proportion of patients presenting in Stage III disease in this study compared to other published series could explain the high prevalence of metastatic disease observed, as Indian women typically present late and metastatic disease show a linear increase with advancing tumor stage.

The incidence of bone metastasis in breast cancer is variable. Radioisotope bone scans are sensitive than skeletal survey in detecting bone metastasis. The reported sensitivity of isotope bone scans varies and false positive rates are high as benign processes are also detected. Asymptomatic bone metastasis was detected in 8% of the study patients with a sensitivity, specificity, PPV, and NPV of 100%, 97%, 74%, and 100%, respectively. The prevalence of bone lesions and accuracy of bone scan in detecting metastasis matches with the results of Puglisi et al.[6] An evidence-based review that included 20 studies reports a sensitivity of 98% but cautions a high false positive rate of 10%–22% and a false negative rate of 10%. The review also noted a declining trend in positive bone scans from 10% to 3%-between studies published earlier and after 1985.[2] In addition, our results also confirm a linear association of bone metastasis with increasing clinical stage.