Prognostic value of positive human epidermal growth factor receptor 2 status and negative hormone status in patients with T1a/T1b, lymph node-negative breast cancer

Department of Radiation-Oncology, University of Florence, Florence, Italy.
Cancer (Impact Factor: 4.89). 07/2012; 118(13):3236-43. DOI: 10.1002/cncr.26647
Source: PubMed


The objective of this study was to evaluate prognostic factors of local and distant recurrence in patients diagnosed with T1a and T1b, lymph node-negative breast carcinoma (BC) with emphasis on human epidermal growth factor receptor 2 (HER2) status.
The authors reviewed 704 women with T1aT1bN0M0 BC who received treatment at the Radiation-Oncology Center of Florence University between November 2002 and December 2008. Patients with ductal carcinoma in situ or recurrent BC at presentation and patients who received adjuvant chemotherapy were excluded from the analysis.
In total, 75 patients had HER2-positive BC (10.7%). At a mean follow-up of 4.9 years (standard deviation, 2.6 years; range, 0.5-10.8 years), 19 events were identified, including 10 distant recurrences. Patients with HER2-positive BC had worse distant recurrence-free survival (DRFS) than patients with HER2-negative BC (hazard ratio, 3.66; 95% confidence interval, 0.94-14.69; P = .045). Negative hormone receptor (HR) status was associated significantly with worse DRFS (hazard ratio, 0.26; 95% confidence interval, 0.07-0.93; P = .026). In multivariate analysis, younger age was the only significant risk factor for an event of recurrence (hazard ratio, 0.61;95% confidence interval, 0.20-1.82; P = .029).
The current results indicated that patients with T1a/T1b, lymph node-negative BC have a low risk of distant and local recurrence, but younger age is a significant risk factor for events occurrence. Young women with HER2-positive and HR-negative status have a significant risk of distant recurrence and should be considered for future clinical trials with anti-HER2 adjuvant therapy.

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Available from: Icro Meattini, Dec 27, 2014
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    • "Based on the search strategy, eight eligible studies were identified and included in our analysis [2], [3], [8], [10], [20]–[23]. Four of these studies were used to assess the prognosis of different subtypes in pT1a-bN0M0 breast cancer patients, with 351 HER2+,1852 HR+/HER2-, 313 triple negative [2], [3], [8], [10]. "
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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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    • "Tumor proliferation status was another relevant prognostic factor evaluated in the literature series in small, node-negative, breast cancers (Hanrahan et al. 2007; Colleoni et al. 2004; Railo et al. 2007), resulting a high proliferative index a significant negative prognostic factor; in our casistic, Ki-67 was confirmed to be an independent prognostic factor at multivariate Cox analysis. As young age at diagnosis concerns, it was frequently associated with a higher rate of recurrence (Kwon et al. 2010; Livi et al. 2012); in our series, only 18 patients were younger than 35 years, and as expected, this issue resulted frequently related with Her-2 positivity or triple negative status, but the limited sample size does not allow a correct analysis. "
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