Abstract P3-10-03: Different pCR rates according PAM50 defined subtypes in HER2 positive early breast cancer treated with neoadjuvant pertuzumab and trastuzumab
Authors: T Díaz-Redondo, R Lavado-Valenzuela, N Ribelles, T Pascual, F Galvez, A Falcón, MC Alamo, C Morales, M Amerigo, A Prat, E Alba
Journal: Cancer Research (2019)

Abstract BACKGROUND We aim to compare the benefit of adding pertuzumab (P) to the standard neoadjuvant treatment with trastuzumab (T) in patients (pt) with early immunohistochemically (IHC) defined HER2+ breast cancer (BC) in the different intrinsic molecular subtypes defined by PAM50 gene expression analysis. METHODS Two hundred forty-four pt. with IHC HER2 positive BC, stage I-IIIC, diagnosed in 8 Spanish hospitals were consecutively treated with neoadjuvant chemotherapy (NAC) plus antitargeted HER2 therapy. Cohort A (n=128) received NAC+T and Cohort B (n=116) received NAC+T+P. All the patients were classified into intrinsic molecular subtypes based on the PAM50® signature made in the diagnostic biopsies. Rate of pathologic complete response in breast and axilla (pCR) in the different PAM50 subtypes was compared by ChiSquared and Fisher test. A multivariate logistic regression model was used to analyze the potential effects of the covariates over the pCR rates. RESULTS Characteristics of the patients and intrinsic molecular subtypes are shown in. The overall pCR rate was significantly higher in cohort B vs A (61% vs 39%,p=0,0009). The pCR rate in the HER2E was 50% for T and 75% for T+P (p=0,003) and 11% for T and 42% for T+P (p=0.004) in Luminal subtype. In the multivariate analysis, the improvement pCR rates was highly associated with type of treatment (cohort) (p=0.0015,OR:2.44) and were not related to clinicopathologic covariates (tumor stage, hystological grade, HR) (p&amp;gt;0.05). These results were confirmed for the HER2enriched subtype (p=0.00398,OR:2.94) and even more strongly for Luminals (p=0.0026,OR:13.41). Clinicopathologic and treatment characteristics of patients Trastuzumab+NCT ( groupA, n128)Trastuzumab+pertuzumab+NCT ( groupB, n116)Median age years (range)52 (29-83)50 (30-77)Menopausal Statusn (%)n (%)Pre-menopausal54 (42)54 (47)Post-menupausal49 (38)49 (42)Missing25 (20)13 (11)Histological graden (%)n (%)Grade 12 (2)3 (2)Grade 258 (45)30 (26)Grade 343 (34)44 (38)Grade unknown25 (19)39 834)Ki 67n (%)n (%)&amp;lt;14%11 (9)10 (9)15-50%58 (45)80 (69)&amp;gt;50%24 (19)23 (20)Unknown35 (27)3 (2)Hormone receptor statusn (%)n (%)Positive89 (70)71 (61)Negative39 (30)45 (39)Tumor stagen (%)n (%)T123 (18)13 (11)T275 (59)64 (55)T312 (9)26 (22)T410 (8)12 (11)Tx8 (6)1 (1)Clinical node statusn (%)n (%)Negative54 (42)73 (63)Positive74 (58)43 (37)Chemotherapyn (%)n (%)Taxanes9 (7)16 (14)Taxanes and anthracyclines119 (93)100 (86)PAM50 Subtypesn (%)n (%)HER2E88 (69)64 (55)Luminal A16 (12)17 (15)Luminal B19 (15)21 (18)Basal like2 (2)14 (12)Normal like3 (2)0NCT:neoadjuvant chemotherapy CONCLUSIONS: 1.The highest pCR was reached by the PAM50HER2E patients treated with T+P. 2.In Luminal subtype the improvement of pCR is strongly associated with the used of P and this association is independent of clinical covariates. Citation Format: Díaz-Redondo T, Lavado-Valenzuela R, Ribelles N, Pascual T, Galvez F, Falcón A, Alamo MC, Morales C, Amerigo M, Prat A, Alba E. Different pCR rates according PAM50 defined subtypes in HER2 positive early breast cancer treated with neoadjuvant pertuzumab and trastuzumab [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-10-03.