The Effect of Molecular Subtype and Residual Disease on Locoregional Recurrence in Breast Cancer Patients Treated with Neoadjuvant Chemotherapy and Postmastectomy Radiation

Abstract

Background The relative contribution of biologic subtype to locoregional recurrence (LRR) in patients who have been treated with neoadjuvant chemotherapy (NAC), mastectomy and postmastectomy radiotherapy (PMRT) is not clearly defined. Methods 233 patients with Stage II-III breast cancer received NAC, mastectomy and PMRT between 2000-2009: 53% (n=123) had HR+ (ER or PR+/HER2−), 23% (n=53) had HER2+ (HER2+/HR+ or HR−), and 24% (n=57) had triple negative disease (TN: HR−/HER2−). The 5-year LRR rates were estimated by Kaplan-Meier methods. Cox regression analysis was performed to evaluate covariates associated with LRR. Results Median follow-up was 62 months. A pathologic complete response (pCR) was seen in 14% of patients. The 5-year LRR rate was 8% in the entire cohort. The LRR rate was 0% in patients with a pCR versus 9% in patients without a pCR (p=0.05). TN disease (HR=4.4, p=0.003) and pathologic node positivity (HR=9.8, p=0.03) were associated with LRR. Patients with TN disease had a higher LRR rate compared to patients with HER2+ and HR+ disease (20% versus 6% and 4%, p=0.005). In patients without a pCR, TN subtype was associated with increased LRR (26% versus 7% HER+ and 4% HR+, p<0.001). Conclusions Patients with TN breast cancer had the highest LRR rate after NAC, mastectomy and PMRT. While no LRR was observed in TN patients with pCR, TN patients with residual disease had significantly higher LRR risk. Patients with HR+ and HER2+ breast cancer had favorable LRR rates, regardless of NAC response, likely due to receipt of adjuvant systemic targeted therapies.

Tumor Biology and Response to Chemotherapy Impact Breast Cancer-specific Survival in Node-positive Breast Cancer Patients Treated With Neoadjuvant Chemotherapy

“…A prior small study that included 53 patients with HER2-positive disease demonstrated favorable locoregional recurrence rates regardless of response to neoadjuvant chemotherapy. [26] The findings from this study and the current study are in contrast to multiple previous studies which have shown that in patients with HER2-positive disease pCR is associated with improved survival compared to those with residual disease. [7, 11, 13, 33, 35] A meta-analysis of studies by Cortazar et al which included 1989 patients with HER2-positive disease showed a significant difference in event-free survival between the 586 patients who achieved a pCR and the 1403 patients with residual disease.…”

“…Consistent with other studies, we found that patients with TNBC that achieved a pCR had a significantly better BCSS and OS compared with those with residual disease. [26] In fact, patients with TNBC who experienced a pCR had 5-year BCSS and OS in keeping with the other tumor subtypes. It is reassuring that such patients with “chemosensitive” TNBC, have an excellent outcome, such that additional systemic therapy may not be necessary.…”

Breast Cancer Biology: Clinical Implications for Breast Radiation Therapy

“…The relationship between LRR, response to NAC, and breast cancer subtype has been described in a few large single-institution studies and a meta-analysis (17,(72)(73)(74). A large study of 751 breast cancer patients (219 with TNBC) by the MD Anderson Cancer Center group showed that TNBC patients treated with NAC not only had a high pCR rate compared with the HRþ/HER2À patients (42% vs 16.5%, respectively) but also that survival outcomes differed among TNBC patients according to chemotherapy response (17).…”

Higher Locoregional Recurrence in Hormone Receptor-Negative Breast Cancer Patients with Residual Disease after Neoadjuvant Treatment Undergoing Breast Conservation Surgery

“…Another large analysis of the European Organisation for Research and Treatment of Cancer (EORTC) 10994/BIG 1 − 00 study of patients with locally advanced breast cancer receiving NAC showed that pCR was a favorable factor with regards to the prediction of LRR after NAC [16]. Several retrospective series also demonstrated that achieving pCR after NAC can result in better local control following surgery [1][2][17][18]. Therefore, achieving pCR was an important factor not only for distant disease control but also for local control.…”