The lymph node ratio as prognostic factor in node-positive breast cancer

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Abstract

Background and purpose

The clinical records of the node-positive breast cancer patients treated at our department were reviewed, to evaluate if there is a correlation between the ratio of involved axillary lymph nodes and the overall and cause specific survival.

Patients and methods

From 1984 until July 2001, 2073 files from patients with an invasive breast carcinoma were submitted to retrospective analyses. In 810 cases, a node positive status was diagnosed. All pT-stages were included. The total number of dissected nodes (pNtot) and the number of involved nodes (pN+) were available for 741 patients. The ratio of nodal involvement (pN+%) was categorized into three groups, pN+%≤10% (n=212), between 11 and 50% (n=346) and between 51 and 100% (n=183).

Results

The actuarial overall survival (OS) at 5 and 10 years was, respectively, 78.2 and 59.1%. Cause specific survival (CSS) rates were, respectively, 83.6 and 69.1%. In univariate analyses, age (P=0.01), grade (P=0.02), pT-stage (P<0.0001), chemotherapy (P=0.0002), the number of involved nodes ≤3 versus >3 (pN+) (P<0.0001) and ratio pN+% (P<0.0001) were associated significantly with overall survival. A multivariate analysis using the Cox proportional hazards model found that pN+% was the most significant prognostic factor; pN+lost significance when pN+% was taken into account.

Conclusions

The percentage of positive lymph nodes in an axillary lymph node dissection appears to be an important prognostic factor for survival. The nodes ratio improved on the absolute numbers of involved axillary lymph nodes for assessment of prognosis.

Introduction

For operable primary breast cancer, the standard treatment is surgery, followed by radiotherapy and/or systemic treatment, if indicated. Surgery can be breast conserving or mastectomy with an axillary lymph node dissection. As already known, a negative axillary lymph node status is the most important favorable prognostic factor for breast cancer survival. There is a clear increase of mortality associated with a node positive status. Patients with four or more positive axillary lymph nodes have a worse prognosis compared with those with ≤3 positive nodes [1], [2]. According to the guidelines of the American Society of Clinical Oncology, this cutoff of four or more nodes involved is accepted to define a subgroup of patients for whom postoperative radiotherapy is recommended [12].

However, the biological rationale of this ‘4 nodes cutoff’ is unclear. In a multivariate modeling approach, Vinh-Hung et al. found that the most dramatic change of prognosis occurred between 0 and 1 nodes involved (i.e. from a node negative to a node positive status) [18], [19]. They also noted that the prognosis deteriorates further with each additional involved node, but this effect had no comparable magnitude as the change from 0 to 1 nodes involved. They concluded that no cutoff could be found and that the absolute number of involved nodes was insufficient as prognostic indicator. It was suggested that the lymph node ratio should be considered [18], [19]. The concept of this ratio suggests that breast carcinoma is a disease of progressively increasing severity. This issue has rarely been investigated [8], [16], [18]. Yet, it is important: if the concept of nodes ratio holds, then there is no reason to limit adjuvant radiotherapy to patients with more than four pathologically involved nodes.

The study of Vinh-Hung et al. was based on the Surveillance, Epidemiology and End Results (SEER) registry data. The SEER reports data on very heterogeneous groups of patients, who were treated in different centers, by different surgeons, and no information on systemic treatment was available. The question is: can these findings be confirmed or not by a single institution analysis. At our center (AZ-VUB), the same oncological team managed all patients throughout the years 1984–2001. The axillary surgery was performed consistently, using the same surgical approach [17]. All patients received the same post-operative treatment (according to the treatment guidelines of that moment). Information on the adjuvant systemic treatment is available. For these reasons, we believe that analysis of our patient data might provide a different perspective on the prognostic role of the ratio of nodal involvement.

Section snippets

Patient characteristics

From 1984 until July 2001, 2767 breast cancer patients were treated at our department. Of these files, 2073 records were available for retrospective analyses. In 810 cases, a node positive status was diagnosed. TNM status according to the UICC TNM classification (1997) is used [14]. All T-stages are included: pT1 (n=235), pT2 (n=428), pT3 (n=72), pT4 (n=75). None of the patients had distant metastasis at the time of diagnosis. All patients underwent local surgery (breast conserving surgery:

Results

The actuarial overall survival (OS) at 5 and 10 years was, respectively, 78.2 and 59.1%. Cause specific survival (CSS) rates were, respectively, 83.6 and 69.1%.

In univariate analyses, age (P=0.01), pT-stage (P<0.0001), histological grading (P=0.02), the ratio pN+% (P<0.0001), the number of involved lymph nodes (pN+) (P<0.0001), chemotherapy (P=0.0002), and radiotherapy (P=0.003) were associated significantly with overall survival rates (Table 3). The number of nodes removed (P=0.91) and

Discussion

In the present analyses, we considered the effect of treatments, chemotherapy, hormonotherapy, and radiotherapy [5]. This is a retrospective study, treatment results might have been biased by the selection of patients. It appeared, however, that chemotherapy had a favorable effect on survival. Hormonotherapy and radiotherapy showed a favorable trend but not statistically significant. Radiotherapy was omitted in only a small percentage of patients (2.5%), which might explain the apparent lack of

Conclusion

The percentage of positive lymph nodes in an axillary lymph node dissection appears to be an important prognostic factor. Studies to investigate its use as a prognostic index are warranted.

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