International Journal of Radiation Oncology*Biology*Physics
Clinical InvestigationInfluence of Lymphatic Invasion on Locoregional Recurrence Following Mastectomy: Indication for Postmastectomy Radiotherapy for Breast Cancer Patients With One to Three Positive Nodes
Introduction
In many cases in the 1960s, postmastectomy radiotherapy (PMRT) was delivered mainly to regional lymph nodes, not the chest wall (1). This procedure reduced locoregional recurrence rates (LRR) but did not contribute to improvement of survival rates of patients. It gradually came to be shown thereafter that addition of chest wall irradiation resulted in better treatment outcomes including survival rates.
In and after 1997, large-scale clinical trials began to reveal the fact that in primary breast cancer patients with positive lymph nodes, PMRT, as provided in current clinical practice, not only reduced locoregional recurrences but also improved overall survival 2, 3, 4, 5, 6, 7, 8. Recently issued clinical practice guidelines, including those of the American Society of Clinical Oncology (9), the National Comprehensive Cancer Network (10), and the Japanese Breast Cancer Society, recommend PMRT for cases of primary breast cancer with four or more positive axillary lymph nodes. Then, questions arise as to whether PMRT is needed for such cases with one to three positive nodes, and if it is, for what patient subgroups. Those questions remain unanswered 11, 12, 13, 14.
In the present study, we focused on lymphatic invasion (ly), which is regarded as an independent prognostic factor in cases of negative lymph nodes (15). The term ly reflects migration of intralymphatic tumor cells into regional lymph nodes; we considered the possibility of lymphatic obstruction being caused by tumor cells in cases of extensively.
Depending on ly status, LRR for patients with one to three positive nodes may be comparable to those of patients with four or more positive nodes. On the other hand, depending on ly status, LRR may be low even in the presence of four or more positive nodes. Following the hypothesis that PMRT targets and eradicates or decreases residual tumor cells in regional lymphatics, it is deemed critical to consider the indication for PMRT based on LRR.
The purpose of the present study was, focusing on the ly factor, to identify postmastectomy patient subgroups with one to three positive lymph nodes for whom PMRT might be indicated.
Section snippets
Methods and Materials
Retrospective analysis of 1,994 patients with histologically tumor-positive lymph nodes, including micrometastases but not isolated tumor cells, who had undergone mastectomy without postoperative radiotherapy between January 1990 and December 2000 at our hospital was performed; at that time, PMRT was performed on a limited basis to high-risk patients with 10 or more positive nodes because it was thought that the LRR of postmastectomy patients was low. Clinical data including age, T stage,
Results
The median follow-up period for the 1,994 patients was 112 months, with locoregional recurrence in 306 (15.3%) patients. Larger tumor size, more extensive ly, and greater number of positive lymph nodes were associated with higher LRRs, with LRR surpassing 30% in patients with ly++ or 10 or more positive nodes. Univariate analysis revealed that T stage, ly status, and number of positive nodes were particularly strong risk factors (p < 0.001) (Table 1). Although significant difference was
Discussion
The utility of PMRT has been established, including evidence of the Danish clinical trial in 1997 (2) and meta-analysis by the Early Breast Cancer Trialists’ Collaborative Group in 2005 (7). In the United States and Europe, the value of PMRT is a time-proven treatment. In Japan, postoperative irradiation tended to remain uncommon for some time, in response to very low LRRs reported in the US 12, 18. In the 1990s at our hospital, PMRT was not a standard therapy; therefore, we had a number of
Conclusions
Postmastectomy patients with one to three positive lymph nodes showed a particularly high LRR in the presence of extensive ly. This subgroup seems to require local therapy regimens similar to those for patients with four or more positive nodes and should be considered for the indication of PMRT. In postmastectomy patients with one to three positive lymph nodes, because the risk of locoregional recurrence is low even if it is T3, not ly++, PMRT could be considered negatively.
Acknowledgment
The authors thank Drs. Yoshinori. Ito, S. Takahashi, N. Tokudome, R. Yoshida, A. Kuwayama, N. Uehiro, K. Masumura, K. Inoue, Yuko Ito, R. Hashimoto, I. Fukada, Y. Chihara, M. Higa, Y. Fukami, H. Shima, H. Sai, A. Okada, R. Yonekura, and R. Gokan from the Breast Oncology Center, Cancer Institute Hospital of the Japanese Foundation for Cancer Research for their valuable comments and support.
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Postmastectomy Radiotherapy: An American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology Focused Guideline Update
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Postmastectomy radiotherapy: Indications and implications
2014, SurgeonCitation Excerpt :Although the benefit of radiotherapy for patients with 4 or more positive lymphnodes is clear, its use in patients with 1–3 positive lymphnodes remains controversial. Matsunuma at al11 endeavored to address this issue, in a retrospective analysis of 1994 node positive patients, who had undergone mastectomy. They found that postmastectomy radiotherapy significantly decreased loco-regional recurrence in the patients who had extensive lymphovascular invasion (p < 0.001).
The role of lymphatic and blood vessel invasion in predicting survival and methods of detection in patients with primary operable breast cancer
2014, Critical Reviews in Oncology/HematologyCitation Excerpt :Giving that the weighted average of LBVI rate, using immunostaining, was higher and the range was narrower, immunostaining appears to be more reliable approach for to identify LBVI in patients with primary operable breast cancer. There were 19 published studies (Table 2), comprising data on 12,893 patients, reported that the presence of LVI was associated with reduced survival, primarily relapse free survival, in primary breast cancer [45–63]. Six of these studies reported prognostic value of LVI independent of T stage and LN status [50–52,54,56,59].
Conflict of interest: none.