Locoregional Recurrence Remains Strong Outcome Predictor 10 Years After Lumpectomy

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Elsevier Global Medical News. 2010 Apr 1, S Freeman

BARCELONA (EGMN) - Locoregional recurrence after breast-conserving therapy remains a very strong, independent risk factor for long-term outcome, even after an extended event-free period.

Research presented at the European Breast Cancer Conference showed that, even in women who were event free 10 years after primary treatment, experiencing a locoregional recurrence was the only independent prognostic indicator of worse outcome, as it was associated with both reduced distant disease-free survival and lower overall survival.

"Although locoregional recurrence after breast-conserving therapy is a well known independent risk factor of unfavorable long-term outcome, controversy exists on the prognostic impact of locoregional recurrence after a long event-free interval," said the presenting author, Dr. Sven Mieog of the department of surgery at Leiden University, the Netherlands.

Dr. Mieog and associates examined individual patient data from four European Organisation for Research and Treatment of Cancer (EORTC) trials, which altogether included 7,751 women who had undergone breast-conserving therapy (J. Natl. Cancer. Inst. 2000;92:1143-50; Eur. J. Cancer 2001;37:2184-93; Breast Cancer Res. Treat. 2009;115:101-13; Cancer Radiother. 2008;12:565-70). They looked at locoregional recurrence as a first event in landmark analyses at three time frames.

The first of these looked at the impact on overall survival in all 7,749 women with available data. At a median follow-up of 10.9 years, 910 women experienced a locoregional recurrence while 6,839 did not, with significantly worse overall survival in those women who experienced locoregional recurrence (P less than .0001).

Dr. Mieog reported that after taking other factors associated with outcome into account (including tumor size, nodal status, age, estrogen receptor [ER] status and use of chemotherapy), locoregional recurrence was an important prognostic indicator of overall survival (hazard ratio 5.1, P less than .01) and distant disease-free survival (HR 5.24, P less than .01).

The second analysis looked at women who experienced an event-free interval of more than 5 years. Locoregional recurrence occurred in 363 of 5,783 women, and was the strongest predictor of both overall survival (HR 3.7, P less than .01) and distant disease-free survival (HR 3.87, P less than .01).


The third and final analysis, involving 3,350 women who had an event-free interval of more than 10 years, showed that 64 women experienced locoregional recurrence, and that this was the only statistically significant predictor of overall survival (HR 8.4, P less than .01) and distant disease-free survival (HR 4.1, P = .02).

"These levels of increased risk need to be treated with caution because, with the longer time interval between the primary cancer and the recurrence, the number of events goes down, making the calculations less certain," Dr. Mieog said. Nevertheless, they remain important for clinicians when deciding on the best treatment approach for their patients, he suggested.

Dr. Mieog hypothesized that the results could suggest that locoregional recurrence is a symptom of disease progression, associated with a high likelihood of simultaneous distant metastases. They also suggest that there could be a "lower threshold for secondary adjuvant treatment for patients with a [locoregional recurrence] even after a long event-free interval."

"It is interesting that, even after a long period of time, these late recurrences are still systemic disease," said Dr. Peter Ravdin, a medical oncologist at the University of Texas Health Science Center at San Antonio. Data are limited on how patients should be treated after very late recurrence, he said, but treatment advances mean that late recurrences are likely to become less frequent in the future.

"Late recurrences tend to be ER positive and as hormonal therapy becomes more prolonged we are getting better at treating that disease," Dr. Ravdin observed. "So I think late recurrences are going to become less common."

The investigators reported no conflicts of interest.

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