• Oncology Clinical Trials
• Breast Cancer

Invasive lobular carcinoma (ILC) is the second most common breast cancer histologic subtype, accounting for 10% to 15% of all breast cancers, with classic lobular carcinoma being the most common variant. Most classic ILCs are hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative. Aromatase inhibitors and tamoxifen are established therapies used for the adjuvant treatment of estrogen receptor (ER)-positive breast cancer, but the relative benefits in invasive ductal carcinomas (IDCs) and ILCs has not been extensively studied. The authors previously presented data from a gene expression profiling study (n=174) that showed the majority of ILCs were low proliferative tumors (76%; luminal A), with a minority that had high proliferation markers (20%; luminal B) [Metzger O et al. SABCS 2011 (abstr P1–02–05)]. A previous analysis of the Letrozole or Tamoxifen in Treating Postmenopausal Women with Breast Cancer [BIG 1–98] trial (n=4922) demonstrated that letrozole resulted in improved disease-free survival (DFS) compared with tamoxifen in patients with tumors that had a higher Ki67 proliferative index [Viale G et al. J Clin Oncol 2008].

Otto Metzger Filho, MD, Dana-Farber Cancer Institute, Boston, Massachusetts, USA, presented an unplanned analysis of data from the BIG 1–98 trial comparing the outcomes of patients with IDC and ILC treated with adjuvant letrozole or tamoxifen. The analysis was also made to adjust for the distribution of luminal A and B subtypes, with a Ki67 of 14% used as a cutoff to separate the 2 subtypes. Among the patients analyzed, 2599 had IDCs (1436 [44%] luminal A and 1163 [36%] luminal B) and 324 had classic ILCs (237 [59%] luminal A and 87 [22%] luminal B) that were HR-positive and HER2-negative.

In patients with IDC, the 5-year DFS with letrozole compared with tamoxifen was 88% versus 84% (HR, 0.80; 95% CI, 0.68 to 0.94; no p value given). In patients with ILC, the 5-year DFS with letrozole compared with tamoxifen was 89% versus 75% (HR, 0.48; 95% CI, 0.31 to 0.74; interaction p=0.03). Multivariate analysis of DFS showed that letrozole was better compared with tamoxifen for treatment by histology (ductal/lobular; interaction p=0.006) and subtype (luminal A/ B; interaction p=0.01).

The 5-year overall survival (OS) rate in patients with IDC treated with letrozole compared with tamoxifen was 94% versus 92% (HR, 0.73; 95% CI, 0.60 to 0.89; no p value given). In patients with ILC, this comparison was 96% versus 86%, favoring letrozole (HR, 0.40; 95% CI, 0.23 to 0.69; interaction p=0.045). Multivariate analysis showed that OS was improved with letrozole compared with tamoxifen in patients with IDC (HR, 0.69; 95% CI, 0.57 to 0.85), and the relative benefit of letrozole was even greater in patients with ILC (HR, 0.39; 95% CI, 0.22 to 0.68; interaction p=0.035).

This analysis showed that letrozole is associated with statistically significant reductions in DFS and OS events for both IDC and ILC. In addition, the magnitude of benefit of adjuvant letrozole was higher among patients with luminal B compared with luminal A tumors for both histologic subtypes, with patients with ILC deriving greater benefit from adjuvant letrozole compared with those with IDC. Dr. Metzger Filho suggested that clinicians might consider letrozole over tamoxifen for the upfront treatment of patients diagnosed with ILC. However, these results are retrospective in nature and need to be confirmed in other adjuvant aromatase inhibitor trials.

• © 2013 MD Conference Express®