Abstract YR02: Clinical – Early breast cancer
Authors: JA Sparano
Journal: Cancer Research (2013)

Abstract The past year has brought several major changes in the management of early stage breast cancer. First was evidence from two randomized phase III trials, including ATLAS (Lancet. 2013: 9; 381) and aTTom (ASCO 2013; abstract 5), that extending the duration of adjuvant tamoxifen therapy from 5 to 10 years reduced the risk of breast cancer recurrence, breast cancer mortality, and overall mortality. A pooled analysis of the 17,477 patients enrolled both trials showed that for patients who took tamoxifen for 10 years, although there was no benefit in years 5-9 during tamoxifen therapy, there was a 25% reduction in breast cancer mortality beginning at year 10 (hazard ratio [HR] 0.75, 95% CI 0.65-0.86; p = 0.00004) and a 16% reduction overall mortality (HR 0.84, 95% CI 0.77-0.93; p = 0.0007). Although there was an increase in the risk of endometrial cancer in ATLAS (2.20, p&amp;lt;0.0001) and aTTom (1.83, p = 0.02), there were far fewer excess endometrial cancers and deaths than breast cancer recurrences and deaths that were prevented. In other news regarding adjuvant endocrine therapy, an analysis of the BIG1-98 trial comparing letrozole with tamoxifen demonstrated that letrozole improved was superior in lobular carcinoma and luminal B ductal carcinoma, indicating that the benefits of letrozole over tamoxifen overall were driven by the benefits seen in these groups (SABCS 2012, abstract S1-1). Regarding other forms of systemic therapy, the GeparSixto trial showed that the additional of carboplatin significantly improved the pathologic complete response rate in patients with triple negative breast cancer when added to an anthracyclines-taxane neoadjuvant regimen (ASCO 2013, abstract 1004), the S0221 trial showed that standard dose biweekly paclitaxel was associated with more neurotoxicity when compared with adjuvant weekly paclitaxel without a reduction in the risk of recurrence (ASCO 2013, CRA1008), and the BEATRICE trial showed no benefit from adding bevacizumab to adjuvant chemotherapy (Lancet Oncol 2013;14:933). Regarding surgical therapy, two studies evaluated the role of sentinel node biopsy after neoadjuvant chemotherapy, including the SENTINA trial (Lancet Oncol 2013; 14: 609) and the Z1071 trial (SABCS 2012, abstract S2-1), revealing lower sentinel node detection rates (80% and 92%, respectively) and higher false negative rates (14.2% and 12.6%, respectively) than typically observed in patients not previously treated with neoadjuvant chemotherapy. Another trial (AMAROS 2013, LBA 1001) showed similar locoregional control rates when axillary radiation was compared with axillary dissection following a positive positive sentinel node biopsy, with less lymphedema associated with axillary dissection. Finally, the U.S. Food and Drug Administration (FDA) granted accelerated approval for the use of pertuzumab in combination with trastuzumab and docetaxel for neoadjuvant therapy based upon the results of the NeoSPHERE trial (Lancet Oncol 2012;13:25), the first drug to receive approval under the FDA's new guidance accepting pathologic complete response rate as an endpoint supporting accelerated approval, with full approval conditional on improved event free survival being demonstrated with additional followup in the same trial, or in other trials (N Eng J Med 2012:366;2438). Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr YR02.