High Risk of Recurrence for Patients With Breast Cancer Who Have Human Epidermal Growth Factor Receptor 2–Positive, Node-Negative Tumors 1 cm or Smaller

Abstract

A B S T R A C T PurposeTo evaluate the risk of recurrence in women diagnosed with T1a and T1b, node-negative, human epidermal growth factor receptor 2 (HER2) -positive breast cancer. MethodsWe reviewed 965 T1a,bN0M0 breast cancers diagnosed at our institution between 1990 and 2002. Dedicated breast pathologists confirmed HER2 positivity if 3ϩ by immunohistochemistry or if it had a ratio of 2.0 or greater by fluorescence in situ hybridization (FISH). Patients who received adjuvant chemotherapy or trastuzumab were excluded. Kaplan-Meier product was used to calculate recurrence-free survival (RFS) and distant recurrence-free survival (DRFS). Cox proportional hazard models were fit to determine associations between HER2 status and survival after adjustment for patient and disease characteristics. Additionally, 350 breast cancers from two other institutions were used for validation. ResultsTen percent of patients had HER2-positive tumors. At a median follow-up of 74 months, there were 72 recurrences. The 5-year RFS rates were 77.1% and 93.7% in patients with HER2-positive and HER2-negative tumors, respectively (P Ͻ .001). The 5-year DRFS rates were 86.4% and 97.2% in patients with HER2-positive and HER2-negative tumors, respectively (P Ͻ .001). In multivariate analysis, patients with HER2-positive tumors had higher risks of recurrence (hazard ratio [HR], 2.68; 95% CI, 1.44 to 5.0; P ϭ .002) and distant recurrence (HR, 5.3; 95% CI, 2.23 to 12.62; P Ͻ .001) than those with HER2-negative tumors. Patients with HER2-positive tumors had 5.09 times (95% CI, 2.56 to 10.14; P Ͻ .0001) the rate of recurrences and 7.81 times (95% CI, 3.17 to 19.22; P Ͻ .0001) the rate of distant recurrences at 5 years compared with patients who had hormone receptor-positive tumors. ConclusionPatients with HER2-positive T1abN0M0 tumors have a significant risk of relapse and should be considered for systemic, anti-HER2, adjuvant therapy.

From tumor size andHER2status to systems oncology for very early breast cancer treatment

“…Overall, the incidence of HER2-positive disease was low, approximately 10%, which is significantly lower than the 25% incidence in more advanced stages. Although inconsistent, the results of these two new studies [10,11] and those of a few previous studies [12][13][14] demonstrate the prognostic significance of HER2 status even at the early stage pT1a,bN0M0 and raise the question of the use of chemotherapy-trastuzumab treatment to reduce the substantial recurrence risk in these women with HER2-overexpressing tumors. The absolute risk of recurrence in these patients with HER2-positive, pT1a,bN0 tumor reached up to 23% [10].…”

“…More recently, the results from two highly specialized institutions in the USA [10] and Europe [11] have been reported. Can these reports from the MD Anderson Cancer Center (MDACC study [10]) and Instituto Europeo di Oncologia Milano (IEOM study [11]) be considered as treatment-changing studies for pT1a,bN0M0 disease?…”

“…Can these reports from the MD Anderson Cancer Center (MDACC study [10]) and Instituto Europeo di Oncologia Milano (IEOM study [11]) be considered as treatment-changing studies for pT1a,bN0M0 disease?…”

Adjuvant Paclitaxel and Trastuzumab for Node-Negative, HER2-Positive Breast Cancer

“…Anderson Cancer Center suggests that among 98 patients with T1a-bN0 HER2-positive tumors, the 5-year rate of recurrence-free survival was 77.1%, and the 5-year rate of survival free from distant recurrence was 86.4%. 11 In a study of 117 node-negative, HER2-positive tumors measuring up to 2 cm in the greatest dimension in a tumor registry in British Columbia, Canada, the 10-year rate of relapse-free survival was 68.3% among patients with hormone-receptor-negative tumors and 77.5% among patients with hormone-receptor-positive tumors. 17 Although recurrence rates vary across these studies, the rates range from approximately 5 to 30%, with distant recurrences occurring in as many as 20% of patients with tumors measuring up to 1 cm in the greatest diameter.…”

“…[10][11][12][13][14] However, given the more limited benefit from adjuvant treatment in these patients, the decision to use trastuzumab and chemotherapy is influenced by the toxicity of the treatment regimen.…”