Pattern of Local Recurrence and Distant Metastasis in Breast Cancer By Molecular Subtype

Abstract

Background and Purpose: No longer considered a single disease entity, breast cancer is being classified into several distinct molecular subtypes based on gene expression profiling. These subtypes appear to carry prognostic implications and have the potential to be incorporated into treatment decisions. In this study, we evaluated patterns of local recurrence (LR), distant metastasis (DM), and association of survival with molecular subtype in breast cancer patients in the post–adjuvant radiotherapy setting.Material and Methods: The medical records of 1,088 consecutive, non-metastatic breast cancer patients treated at a single institution between 2004 and 2012 were reviewed. Estrogen/progesterone receptors (ER/PR) and human epidermal growth factor receptor-2 (HER2) enrichment were evaluated by immunohistochemistry. Patients were categorized into one of four subtypes: luminal-A (LA; ER/PR+, HER2-, Grade 1-2), luminal-B (LB; ER/PR+, HER2-, Grade > 2), HER2 over-expression (HER2; ER/PR-, HER2+), and triple negative (TN; ER/PR-, HER2-). Results: The median follow-up time was 6.9 years. During the follow-up, 16% (174/1,088) of patients failed initial treatment and developed either LR (48) or DM (126). The prevalence of LR was the highest in TN (12%) and the lowest in LA (2%). Breast or chest wall relapse was the most frequent site (≈80%) of recurrence in LA, LB, and HER2 subtypes, whereas the regional lymph nodes and chest wall were the common sites of relapse in the TN group (50.0%). DM rates were 6.4% in LA, 12.1% in LB, 19.2% in HER2, and 27.4% in TN subgroups. Five-year survival rates were 84%, 83%, 84%, and 77% in the LA, LB, HER2 and TN subgroups, respectively. There was a statistically significant association between survival and molecular subtypes in an univariate analysis. In the adjusted multivariate analysis, the following variables were independent prognostic factors for survival: T stage, N stage, and molecular subtype.Conclusions: Of the four subtypes, the LA subtype tends to have the best prognosis, fairly high survival, and low recurrent or metastases rates. The TN and HER2 subtypes of breast cancer were associated with significantly poorer overall survival and prone to earlier recurrence and metastases. Our results demonstrate a significant association between molecular subtype and survival. The risk of death and relapse/metastases increases fewfold in TN compared to LA. Future prospective studies are warranted and could ultimately lead to the tailoring of adjuvant radiotherapy treatment fields based on both molecular subtype and the more conventional clinicopathologic characteristics.

Ten‐year recurrence rates for breast cancer subtypes in the Netherlands: A large population‐based study

“…The lowest recurrence rates we found in luminal A breast cancers confirms results from previously published studies . In addition, triple negative and HER2 positive disease were shown to have a worse prognosis compared to the other subtypes, as was also shown before .…”

“…The lowest recurrence rates we found in luminal A breast cancers confirms results from previously published studies . In addition, triple negative and HER2 positive disease were shown to have a worse prognosis compared to the other subtypes, as was also shown before . A Canadian study showed that, after a median follow‐up of 6.9 years, 2% of luminal A breast cancers had a local recurrence, compared to 4% in luminal B, 8% in HER2 positive, and 12% in triple negative .…”

“…In addition, triple negative and HER2 positive disease were shown to have a worse prognosis compared to the other subtypes, as was also shown before . A Canadian study showed that, after a median follow‐up of 6.9 years, 2% of luminal A breast cancers had a local recurrence, compared to 4% in luminal B, 8% in HER2 positive, and 12% in triple negative . Our study showed 10‐year local recurrence rates of 3.7, 5.0, 7.5 and 7.1% for the four subtypes, respectively.…”

“…This highlights the importance of at least 10 years of follow‐up when studying recurrences, as demonstrated in several studies . The same Canadian study showed that distant metastases occurred in 6.4% of luminal A, 12.1% of luminal B, 19.2% of HER2 positive and 27.4% of triple negative breast cancers, while in our study these percentages were 9.5, 20.0, 25.6 and 23.2%. In our study, percentages of distant metastases were higher than in the Canadian study, which may partly be attributed to the fact that not all patients were treated with trastuzumab in our study.…”

Targeted Therapy and Local Control: The Dynamic Duo

“…subtypes are ascribed higher rates of locoregional recurrence (LRR) and distant metastases, shown in a number of studies and a large systematic review. [1][2][3][4][5][6] The development of trastuzumab serves as a premier example of targeting tumor biology for therapeutic gain. Trastuzumab is a humanized monoclonal antibody that binds to and interferes with the HER2-mediated signaling cascade, inhibiting proliferation and resulting in cell death.…”