The lymph node status is regarded as one of the most important prognostic factors for the overall survival and disease-free survival of patients with breast cancer. While morphological features and contrast enhancement kinetics of breast cancer shown on dynamic contrast enhanced MRI (DCE-MRI) have been correlated with tumor histological type, grade, and biomarkers [1-4], there were only a few studies reporting the association with nodal status, also results were controversial [5-7]. In this study we investigated the MR imaging features of the primary tumor between patients who had early recurrence vs. those who remained cancer-free, and also between node positive and negative patients.
We analyzed 62 patients (30-83 years old, median 58) with histologically confirmed breast cancer who were enrolled into a breast MRI study during years 2000-2003. A telephone survey was conducted in 2006 to follow-up all patients regarding their disease status. Of the 62 patients, 6 had confirmed cancer recurrence in the previously treated breast. Three had positive nodes (sentinel and/or axillary) at the time of first cancer diagnosis, and 3 had negative nodes. Of the 56 patients who were cancer-free, 28 had positive node and the other 28 had negative nodes. The MRI features of all 62 patients were retrospectively reviewed, and compared between the 6 with early recurrence vs. those who were cancer-free.
Breast MRI was performed on a 1.5T MR scanner. The protocol included pre-contrast images and dynamic contrast enhanced imaging. The characteristics of primary tumor were analyzed. The longest and perpendicular dimension of the tumor size was measured on contrast-enhanced MRI, and then converted to 1-D size. The morphological appearances were characterized using features described in BI-RADS MRI lexicon , separated into mass lesions and non-mass like enhancements. The following enhancement kinetic parameters were analyzed: the enhancement percentage at 1-min (E1), 2-min (E2), 7-min (E3), and the washout slope between 7-min and 2-min. Furthermore pharmacokinetic parameters, including transfer constant (Ktrans) and exchange rate constant (kep), were also analyzed with the Toft's 2-compartmental model .
The comparison of lesion morphology, size, and enhancement kinetic parameters in 3 groups is summarized in Table 1. LN (+) group has more irregular mass lesion (19/28, 68%) compared to LN (−) group (12/28, 43%), fewer round mass (4/28, 14% vs. 10/28, 36%), and more non-mass like lesions (3/28 vs. 0/28). The tumor size in the LN(+) group (0.7 - 4.0 cm, mean 1.8 cm) is bigger compared to that in the LN(−) group (0.5 - 3.0 cm, mean 1.5 cm), but not significant (p = 0.12). The % enhancements at 1-min (E1) and 2-min (E2) are about the same, but the washout slope is significantly faster in the LN (+) group (p = 0.02). The pharmacokinetic parameter Ktrans is higher in the LN(+) group, with borderline significance (p=0.07). Similar as the washout slope, the kep is faster in the LN(+) group (0.48 vs. 0.38 1/min, p= 0.01), indicating significant differences between the two groups. The mean values of these parameters in the recurrence group are also listed in the table. Since there are only 6 cases in the recurrence group, none of the parameters show significant difference compared to the other two groups. Thus the MRI morphology or enhancement kinetics cannot predict recurrence.
Non-invasive MR imaging may evaluate the tumor angiogenic activity. Based on the fact that angiogenesis is required to support cancer growth and metastasis, it may be hypothesized that a tumor with higher angiogenesis may facilitate the spread of cancer cells, thus is more likely to show lymph node metastasis and earlier recurrence. We found that LN(+) group had a stronger washout and faster kep than the LN(−) cohort, suggesting that invasive breast cancers with higher angiogenesis are more likely to have positive nodes. Our results were consistent with that of Tuncbilek et al., which showed correlation between lymph nodes metastasis and washout slope of the primary tumor .
In 6 recurrent patients, three had positive and three had negative nodes at the time of first diagnosis. Three patients with negative lymph nodes developed early recurrence within 4 years were uncommon, which was more likely due to substandard treatment (one patient refused radiation and hormonal therapy after lumpectomy), or the primary tumor expressing highly aggressive biomarkers or genetic markers. The development in oncogene profiling in the last decade has slowly been established as clinical tools. For example, Oncotype DX® based on 21-genes has been shown to predict 10-year distant recurrence in patients with estrogen receptor-positive, axillary lymph node-negative breast cancer [10, 11]. The wide spread use of these tools is expected to provide additional prognostic predictors other than the traditional tumor staging and nodal status to determine the optimal management for each patient. In addition to help deciding which node negative patients should receive chemotherapy and who can be spared, these genomic assays may also predict the response to chemotherapy and endocrine therapy and help to select the optimal treatment [12, 13].
In summary, although the angiogenic activity of breast cancer evaluated by DCE-MRI was significantly higher in node positive compared to node negative patients, it could not predict the nodal status accurately. In our cohort of 62 subjects, the angiogenic activity could not predict which patient would have early recurrence. Further development of genetic profile, biomarkers and imaging markers may be combined to evaluate each specific cancer from different aspects, and to develop the most accurate prognostic predictors . Such predictors will further impact on selection of optimal management plan, contributing to “personalized medicine” for each individual patient.