Invasive Lobular Carcinoma: Features Associated with Late Recurrence (>5 yrs)
The usual invasive lobular carcinoma (ILC) is low to intermediate grade, ER positive, low to intermediate mitotic index and rarely Her2 positive. More than 80% are
classified as luminal A using gene expression profiling. These biologic characteristics would suggest a very long-lasting risk over time. In a large matched analysis with long follow-up, Pestalozzi et al reported that survival curves for ILC and invasive ductal carcinoma started off more favorably for ILC but crossed overtime (see graph at right).
Several retrospective studies have suggested that tumor size and number of positive nodes were independently associated with the risk of distant recurrence. Similar retrospective studies have suggested that tumor grade and Ki-67 labeling index were prognostic factors during the first 5 years but were of little relevance thereafter. Conforti et al have in this study reported for the first time an evaluation of clinical and pathological characteristics on the risk of late recurrence in women with early stage, ER+ ILC.
Between 1994 and 2010, 1872 patients with ILC fulfilled the inclusion criteria. With 8.7 years median follow-up 530 patients had recurrence, of which 205 were distant metastases (DM). Of the patients with DMs 116 occurred within the first 5 years and 89 occurring beyond 5 years. In the first 5 years, using univariate analysis, all variables tested impacted DM (ER, PR, Her2, Ki-67,Grade, nodal status, T-stage).
Following the first 5 years only T3/4 stage, positive node status and high Ki-67 (>20) remained strongly associated with long-term freedom from DM. The value of Ki-67 in predicting long-term survival was particularly impressive (see graph at left) as it did not change significantly over time and was able to stratify the long-term outlook for both node positive and node negative patients. Positive nodal status had a significantly lower prognostic value in late follow-up.
In conclusion, we are aware that ER+ ILC has a significant risk of late recurrence beyond 5 years. Determining the risk of late recurrence risk is valuable in that it may promote long-term hormonal therapy. Surprisingly, the strength of association between Ki-67 and DM both early and late did not change over time and moreover was able to stratify the outlook of both node negative and node positive patients. Surprisingly, node status alone was unable to predict prognosis beyond the first five years.