Local Recurrence After Mastectomy or Breast-Conserving Surgery and Radiation

The article by Freedman and Fowble nicely summarizes the available clinical literature on local relapses after breast-conserving surgery or mastectomy. This comprehensive article outlines the major prognostic factors that are predictive of local relapse in each setting, and further defines some of the prognostic factors that are predictive of outcome once a local relapse has been diagnosed.

Clearly, ipsilateral breast tumor relapses and chest wall relapses represent different entities, with different prognostic and therapeutic implications. Understanding the clinical and pathologic factors that predict for each type of event, and assessing prognosis following each type of event, are critical issues that are a common source of confusion and misunderstanding among patients, as well as clinicians. This article highlights similarities, as well as differences, between ipsilateral breast relapses following breast-conserving therapy and chest wall relapses following mastectomy, providing the reader with a clearer understanding of the risk factors and natural history of the disease in each setting.

Since there is a paucity of prospective data regarding the appropriate management of locally recurrent breast cancer, the clinician must rely on retrospective data, prognostic factors, and extrapolation from prospective trials in the primary management of disease to make rational treatment decisions. Although prospective trials are desirable, the available retrospective studies, combined with extrapolation from available prospective trials in the primary management of disease, can provide significant insight into appropriate management. In this regard, the article by Freedman and Fowble provides the practicing clinician with a comprehensive summary of the available literature addressing these issues. It also lends some meaningful clinical guidance in management at the time of local relapse following breast-conserving therapy or mastectomy.

Areas for Future Study

Since little can be added to this excellent and thorough review of the available clinical literature, I will take this opportunity to highlight avenues worthy of future investigations. There is no formal “staging” for locally recurrent breast cancer, and nodal status is often not available due to nodal dissection at initial diagnosis. Therefore, one must rely on other clinical criteria, including dermal invasion, lymphovascular invasion, time to relapse, and extent of relapse, to estimate the patient’s prognosis and metastatic potential. While the clinical factors outlined in the authors’ Table 5 are valuable and clinically useful prognostic indicators, molecular markers at the time of local relapse may help to further refine prognosis and identify subsets of patients who will benefit from more intensive therapy.

Given the wide variety of molecular markers currently available and under development, it is likely that we can identify a combination of molecular markers and clinical factors with which to stratify locally recurrent patients into clinically meaningful risk groups. Furthermore, molecular markers measured at the time of initial diagnosis may serve to identify patients who are at higher risk for local relapse following conservative surgery or mastectomy and to aid in decision-making regarding locoregional treatment.

The paper by Freedman and Fowble sites some of these preliminary studies, but larger studies with longer follow-up will clearly be required before these factors are routinely applied to clinical decision-making. Hopefully, such data can be used to better define appropriate treatment strategies at the time of diagnosis and at the time of local relapse.

Conclusions

Finally, I would like to make a point regarding the paucity of prospective clinical trials in locally recurrent breast cancer. This is clearly an area worth pursuing. The number of patients with breast cancer who experience locoregional relapse annually is a significant oncologic problem. To put the magnitude of the problem into perspective, the number of locally recurrent breast cancer cases annually exceeds the number of newly diagnosed patients with Hodgkin’s lymphomas or newly diagnosed patients with carcinoma of the larynx. Clearly, there are sufficient clinical cases of locally recurrent breast cancer to consider a clinical trial in this important area.

While it is unlikely that a single institution will be able to conduct a clinical trial, the cooperative groups could carry out a reasonable and clinically meaningful prospective trial addressing systemic therapy and management at the time of local relapse. As a complementary and parallel component of such a trial, obtaining tissue for processing of molecular markers could significantly contribute to our understanding and management of patients with locally recurrent disease.

Until such prospective trials and/or molecular studies are completed, the comprehensive review article by Freedman and Fowble is a practical and concise review for oncologists in training. It is also a valuable resource for the practicing surgical, medical, and radiation oncologist.