HER2 Overexpression Is a Major Risk Factor for Recurrence in pT1a-b, N0 Breast Cancer: A French Regional Population-Based Study of 671 Patients
Frederic Bibeau, Florence Boissiere-Michot, Amelie Denouel, Vanessa Szablewski, Helene Perrocchia, Christine Pignodel, Amelie Gudin de Vallerin, Christina Leaha, Marie-Christine Chateau, Gilbert Barneon, Patrice Vic, Agnes Garnier, Mireille Granier, Pascal Roger. CRLCC Val d'Aurelle, Montpellier, Herault, France; Hôpital Gui de Chauliac, Montpellier, Herault, France; Groupe Hospitalo-Universitaire, Nîmes, Gard, France; Centre de Pathologie, Montpellier, Herault, France; CACP Les Tonnelles, Montpellier, Herault, France
Background: Only very few studies have been performed about HER 2 status in small breast cancer. We aimed to evaluate the prognostic impact of HER2 overexpression (3+) in patients with pT1a-b, node negative (N0), breast cancers.
Design: From 1999 to 2004, 1127 pT1a-b, pN0 breast cancer patients were identified, thanks to the ONCO LR Southern French regional network. Treatments were: conservative (95%), tamoxifen (80%), chemotherapy (5%). HER2 status was retrospectively assessed in 671 samples (121 pT1a/549 pT1b) by immunohistochemistry (IHC) (HER-2/neu (4B5) Primary Antibody, Ventana®). Amplification was tested by dual in situ hybridization (Inform HER2 Dual ISH assay or DISH, Ventana®).
Results: HER2 3+ was observed in 5.2% of the patients and most frequently identified in : pT1a lesions (12.3% vs 3.6%; p 0.0001), mastectomies (14% vs 4.4%; p 0.023), grades 2-3 (91% vs 50%; p<0.0001), estrogen receptor (ER) negative (–) tumors (57% vs 30%; p<0.0001), progesteron receptor (PR) negative (–) tumors (74% vs 42%; p 0.0002).). 33 relapses (5%) were observed (median follow-up: 6.4 years (range, 0.3 to 9.9 years). The 5-year DFS rates were 78% and 95% in HER2 3+ and HER2 non overexpressed (-) tumors, respectively (p 0.017). According to the IHC phenotype, 5-year DFS, were 95%, 94%, 85% and 73,6% for ER+PR+/HER2 - (n= 502, 75%), ER-/PR-/HER2 - (n=134, 20%), ER+/PR+/HER2 3+ (n=15, 2%) and ER-/PR-/HER2 3+ tumors (n=20, 3%), respectively (p 0.02). In univariate analysis, HER2 3+ tumors (p 0.017), phenotype classification (p 0.02) and adjuvant treatment (p 0.013) were significant prognostic factors. In multivariate analysis, HER2 3+ patients had higher risks of recurrence than HER2 - tumors ([HR], 2.41; 95% CI: [1.06-5.53]; p<0.05). DISH interpretation is ongoing and results will be presented at the meeting.
Conclusions: pT1a-b, pN0 HER 2 3 + breast cancer patients have a significant risk of recurrence. In ER+/PR+ patients, HER2 3+ status is associated with a worse DFS than patients with triple negative tumors, in spite of tamoxifen. HER family pathway might be the cause of prognostic variability within these ER + tumors. In the light of the worse prognosis of HER2 3+ pT1a-b, pN0 tumors, HER2 testing is necessary and further investigation of a potential benefit from an HER2 treatment is warranted.
Tuesday, March 20, 2012 9:30 AM
Poster Session III # 28, Tuesday Morning