High recurrence risk and use of adjuvant trastuzumab in patients with small, HER2-positive, node-negative breast cancers

Department of Breast Oncology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan.
International Journal of Clinical Oncology (Impact Factor: 2.13). 06/2011; 17(2):131-6. DOI: 10.1007/s10147-011-0269-4
Source: PubMed


Five randomized trials of adjuvant trastuzumab have reported significant improvements in recurrence-free survival (RFS) and overall survival. However, patients with node-negative tumors 1 cm or smaller were excluded from these trials. We assessed the recurrence risk and benefit of adjuvant therapy in such patients with small tumors.
We identified patients with node-negative breast tumors 1 cm or smaller between April 2003 and December 2007. Patients were categorized according to HER2 status and pathological tumor size (pT <5 mm vs. 5-10 mm), hormone receptor (HR) status and adjuvant chemotherapy. The primary endpoint was RFS.
Of 267 patients included in the analysis, 42 had HER2-positive tumors. The median follow-up was 4.3 years. RFS was worse in patients with HER2-positive tumors than HER2-negative tumors (90.5 vs. 97.7% at 5 years; P = 0.031). In the group with HER2-positive tumors, there were no recurrences in patients with pT<5 mm, but 4 recurrences in those with pT 5-10 mm. RFS was worse in patients with pT 5-10 mm than pT <5 mm (79.0 vs. 100%, P = 0.025). Furthermore 3 recurrences occurred in patients without adjuvant trastuzumab, and 1 recurrence occurred as soon as adjuvant trastuzumab was finished. Our results appear to establish the efficacy of adjuvant trastuzumab therapy. HR status and use of adjuvant chemotherapy were not significantly associated with RFS.
Patients with HER2-positive, node-negative breast tumors 1 cm or smaller (especially 0.5-1.0 cm) have a significant recurrence risk and the decision to employ adjuvant trastuzumab therapy should be discussed with patients based on our results and those of other studies.

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    • "A further analysis on 267 node-negative, 1 cm or smaller tumors, revealed that patients with Her-2 positive, (particularly 0.5–1.0 cm) have a significant recurrence risk if not treated (Horio et al. 2012). In contrast, a recent evaluation on 194 node-negative pT1a, b breast cancer, 58 % treated with adjuvant chemotherapy, showed an excellent 5-year outcome irrespective of chemotherapy (Ho et al. 2012). "
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    ABSTRACT: Purpose Recurrences and deaths are known to occur, even if less frequently, in small, node-negative breast cancer patients, and decision on adjuvant treatments remains controversial. In the present analysis, we evaluate recurrence risk in patients with pT1 a, b, c, node-negative, breast cancer, accordingly with some prognostic biological factors. Methods We retrospectively evaluated 900 node-negative patients (pT1a, b, c) surgery treated between 2000 and 2009 in four Italian oncologic centers. We defined 3 different cohorts: ER positive (ER+); Her-2 positive (Her-2+); and triple negative (TN). Results pT1a was seen in 7.6% of patients, 37.7 % pT1b, 54.8 % pT1c. Concerning the 3 different cohorts, 58.2 % were ER+; 10.8 % were Her-2+; 8.2 % were TN. Overall, chemotherapy was given to 3.0 %, 27.2 %, 69.8 % of pT1a, b, c, respectively, and to 22.7 %, 58.8 %, 68.9 % of ER+, Her-2+, TN subgroups. At a median follow-up of 67 months, 5-year DFS was 96.3 %, 89.2 %, 89.4 % in pT1a, b, c, respectively (100 %, 93.6 %, 89.8 % in ER+; 100 %, 78.7 %, 85.0 % in Her-2+; 100 %, 76.8 %, 85.2 % in TN) (p = ns). At multivariate analysis, histologic grade and Ki-67 resulted independent prognostic factors. Overall, 5-year OS was 98 %, without differences among pT1a, b, c, or among the 3 cohorts. Conclusions Overall, 5-year DFS was very favorable in this series of small, node-negative breast cancers, but Her-2+ and TN cohorts have a higher recurrence rate than ER+ cohort (p < 0.0001); pT1c, but also pT1b, in Her-2+ and TN subgroups, have a worse outcome, and effective chemotherapy treatment should be considered in these unfavorable subgroups.
    Full-text · Article · Feb 2013 · Journal of Cancer Research and Clinical Oncology

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    ABSTRACT: Although the prognosis of patients with small (≤1cm) tumors is generally favorable, emerging data suggests that biological behavior varies between intrinsic subtypes in such patients. Furthermore, it still remains unclear whether HER2-positive pT1a-bN0M0 patients could benefit from adjuvant trastuzumab. For further evaluation, we sought to conduct a meta-analysis so as to get a better understanding of the prognosis for HER2-positive pT1a-bN0M0 patients and their survival benefit from adjuvant trastuzumab, accordingly, offering the implications for current practice. The PubMed database, the online proceedings of the American Society of Clinical Oncology (ASCO) Annual Meetings, the online proceedings of the San Antonio Breast Cancer Symposium, and the CD proceedings of the International St. Gallen Breast Cancer Conference were searched for all relevant studies published before September 2012. Relative risks (RRs) were used to compare the prognosis of different intrinsic subtypes for pT1a-bN0M0 breast cancer. Analyses were also performed to estimate the association between adjuvant trastuzumab and various survival outcomes. With eight eligible studies identified, this meta-analysis demonstrated a deleterious effect of HER2+ phenotype on disease-free survival (DFS; RR = 3.677, 95% CI 2.606-5.189, p <0.001) and distant disease-free survival (DDFS; RR = 3.824, 95% CI 2.249-6.501, p<0.001) as compared to HR+/HER2- subgroup. However, significant difference failed to be achieved in terms of any endpoint between HER2+ and triple negative breast cancer (TNBC). Besides, a marked improvement in DFS was observed with the addition of trastuzumab for HER2-positive pT1a-bN0M0 patients (RR = 0.323, 95% CI 0.191-0.547, p<0.001). This meta-analysis clarifies that intrinsic subtypes might be a reliable marker to predict the prognosis in pT1a-bN0M0 breast cancer. Besides, even for such early stage HER2-positive patients, adjuvant trastuzumab might bring significant survival benefit.
    Full-text · Article · Jan 2014 · PLoS ONE
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