Is Breast Conservation Therapy Superior to Mastectomy for Women With Triple-Negative Breast Cancers?

Abstract

In the article that accompanies this editorial, Abdulkarim et al report that women with T1-2N0 triple-negative breast cancers (TNBCs) treated with breast-conserving surgery followed by radiation therapy had significantly better locoregional control compared with matched women treated with total mastectomy after a median follow-up of 7.8 years (P .027). Should this observation change practice guidelines? There has been much attention focused on TNBCs since the first identification of basal-like cancers using microarray expression profiling studies in 2005. TNBCs lack the expression of estrogen and progesterone receptors and do not overexpress human epidermal growth factor receptor 2. There is a significant overlap between TNBCs, which are defined by immunohistochemistry, and basaloidlike tumors, which are identified from gene expression profiling, such that those two entities are frequently considered synonymous from a clinical perspective. TNBCs have a poor prognosis and do not respond to therapy directed at known breast cancer growth factor targets, including hormonal therapy and trastuzumab. TNBCs are fast-growing tumors, usually have a high histologic grade, and tend to metastasize earlier compared with breast cancers that express hormone receptors. The predominant sites of metastases for TNBCs differ from the luminal subtype. They are more frequently nodenegative and spread, in 70% of patients, to the lung and brain, whereas luminal cancers tend to metastasize, in 70% of patients, to the bone and liver. TNBC tumors seem to be more sensitive to chemotherapy, and although there is a sharp decrease in survival early after diagnosis, survival plateaus after 8 to 10 years. Although poorer survival and metastatic outcomes of TNBCs are well known, local or regional evolution characteristics of TNBCs remain controversial. Publications that assessed the value of TNBCs as an independent prognostic factor for locoregional recurrence showed mixed results; some articles reported an increased risk of locoregional recurrence, and other articles reported no increase in the locoregional recurrence risk compared with the luminal A phenotype. Most of these series included a small number of TNBCs mixed with other breast cancer subtypes, and the study by Abdulkarim et al adds appreciably to this literature by reporting exclusively on TNBCs. The authors identified 768 patients with TNBCs referred to the sole regional cancer center in northern Alberta, Canada, between 1998 and 2008. As such, this series approximated a population-based experience with its strength and weaknesses. In one way, the series represented a single-institution retrospective study; in contrast, it represented the largest series of TNBCs reported to date, without the drawback of patient selection associated with clinical trials. The investigators analyzed locoregional recurrence and survival outcomes by the type of initial local therapy and found that patients treated with breast-conserving surgery followed by adjuvant radiotherapy had significantly lower rates of locoregional recurrence compared with patients treated with mastectomy alone. An important and valuable analytic approach was to identify a subset of 195 pairs of patients with T1-2N0 TNBCs by matching for T stage individuals treated with breast-conserving surgery followed by adjuvant radiotherapy with patients treated by mastectomy. Among patients with T1-2N0 TNBCs, individuals initially treated with breast-conserving surgery followed by adjuvant radiotherapy had a 5-year actuarial locoregional recurrence rate of 4% compared with 10% after mastectomy (P .027). It would have been useful to have had specific information on the quality of the matching for important prognostic factors such as including the number of nodes removed, margin width/status, BRCA status, type of chemotherapy used, and duration of follow-up between groups; however, these parameters can be inferred to be reasonably equivalent on the basis of the data presented in Table 4 and Figure 2B. As listed in the table and figure, both cohorts had relatively similar clinicopathologic characteristics in regards to age, tumor grade, lymphovascular invasion status, and delivery of adjuvant chemotherapy and had the same proportions of patients accrued over time. Although there was the possibility that confounding factors may not have been perfectly balanced between groups, the data of Abdulkarim et al, together with those of other reports, suggested that local recurrence is an issue and radiotherapy may decrease this risk. There are three messages to take from this study. First, the paradigm in breast cancer that breast-conserving surgery followed by radiation therapy is equivalent to mastectomy alone may not apply to all patients. TNBCs are rapidly growing and locally aggressive cancers that may represent a limit to this principle. Obviously, the role of adjuvant radiotherapy in this population requires additional study. JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L S