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. 2009 Dec 1;27(34):5700-6.
doi: 10.1200/JCO.2009.23.2025. Epub 2009 Nov 2.

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

Ana M Gonzalez-Angulo  1 , Jennifer K Litton, Kristine R Broglio, Funda Meric-Bernstam, Ronjay Rakkhit, Fatima Cardoso, Florentia Peintinger, Emer O Hanrahan, Aysegul Sahin, Merih Guray, Denis Larsimont, Francesco Feoli, Heidi Stranzl, Thomas A Buchholz, Vicente Valero, Richard Theriault, Martine Piccart-Gebhart, Peter M Ravdin, Donald A Berry, Gabriel N Hortobagyi
Affiliations

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

Ana M Gonzalez-Angulo et al. J Clin Oncol. .

Abstract

Purpose: To evaluate the risk of recurrence in women diagnosed with T1a and T1b, node-negative, human epidermal growth factor receptor 2 (HER2) -positive breast cancer.

Methods: We reviewed 965 T1a,bN0M0 breast cancers diagnosed at our institution between 1990 and 2002. Dedicated breast pathologists confirmed HER2 positivity if 3+ 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.

Results: Ten 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 < .001). The 5-year DRFS rates were 86.4% and 97.2% in patients with HER2-positive and HER2-negative tumors, respectively (P < .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 = .002) and distant recurrence (HR, 5.3; 95% CI, 2.23 to 12.62; P < .001) than those with HER2-negative tumors. Patients with HER2-positive tumors had 5.09 times (95% CI, 2.56 to 10.14; P < .0001) the rate of recurrences and 7.81 times (95% CI, 3.17 to 19.22; P < .0001) the rate of distant recurrences at 5 years compared with patients who had hormone receptor-positive tumors.

Conclusion: Patients with HER2-positive T1abN0M0 tumors have a significant risk of relapse and should be considered for systemic, anti-HER2, adjuvant therapy.

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Conflict of interest statement

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Figures

Fig 1.
Fig 1.
Recurrence-free survival by (A) human epidermal growth factor receptor 2 status and (B) breast cancer subtype.
Fig 2.
Fig 2.
Distant recurrence–free survival by (A) human epidermal growth factor receptor 2 (HER2) status and (B) breast cancer subtype. HR, hormone receptor–positive status; HER2, HER2-positive status; TN, triple-receptor–negative status.
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