Abstract PS4-40: Her2 low status and response to neoadjuvant chemotherapy in Her2 negative early breast cancer
Authors: Mattos Bruna RaphaeliSilva , Cesca Marcelle Goldner , de Moura Leite Luciana , Tavares Monique Celeste , Silva Sinara Figueiredo , Pirolli Rafaela , Fogassa Camilla AlbinaZanco , Silva Erick Figueiredo , Rocha Francisca Giselle , Loose Simone Klug , Campos Fernando AugustoBatista , Sanches Solange Moraes , de Lima Vladmir ClaudioCordeiro , Pondé Noam Falbel 
Published: February 2021

Background: HER2-positive status has for 20 years defined a subgroup of breast cancer (BC) patients who benefit from anti-HER2 therapies. Studies testing trastuzumab in HER2-low patients – defined as IHC 1+ or 2+/ISH non-amplified have not shown an improvement in outcomes. Recently, the results of Phase I studies with novel antibody drug conjugates targeting HER2 (Trastuzumab-deruxtecan and trastuzumab-duocarmazine) have suggested a benefit in HER2-low patients with advanced breast cancer. Little is known about HER2-low BC and data on early stage disease and the prognostic value of HER2-low is scarce. More data on this population is urgently needed in order to prepare the integration of these new drugs into treatment guidelines. Most large Phase 3 trials conducted in the past in luminal or triple negative (TNBC) disease did not collect detailed HER2 status data, rendering retrospective cohorts of particular value Patients and Methods: This is a retrospective cohort of all early breast cancer patients treated with neoadjuvant chemotherapy (2007 – 2018) in a single cancer center. HER2 positive (IHC +3 or IHC +2 FISH/SISH amplified) patients were excluded. HER2-low status was defined as HER2 IHC 1+ or 2+/ISH non-amplified. Other patients were classified as HER2-0. Our primary objective was to investigate whether HER2-low status impacts on efficacy outcomes, including pathologic complete response (pCR), relapse free survival (RFS) for patients undergoing neoadjuvant chemotherapy. Secondary objectives include describing this novel population from a demographical and pathological perspective. Categorial variables were compared by Fisher’s exact test. Survival was estimated by the Kaplan-Maier method. Prognostic factors were adjusted by Cox regression model and logistic regression.

Results: 478 non-HER2-positive patients were eligible, with a median follow-up of 59 months. 315 pts had luminal (65.9%) and 163 TNBC subtypes (34.1%). HER2-0 in 330 pts (69%), +1 in 87 (18.2%) and +2/ISH non-amplified in 61 (12.8%). Among luminal tumors, 70 patients had HER2 IHC +1 (22.2%) and 56 IHC +2/ISH non-amplified (17.8%). This proportion was lower in TNBC, with only 17 HER2 IHC +1 (10.4%) and 5 IHC +2 (3.1%). The baseline characteristics and outcomes of this population stratified by the presence/absence of the her2 low status is described in Table 1. Most pts had T3/4 , node positive, grade II/III and stage III tumors, irrespectively of her2-low status or subtype. pCR was achieved in 10.7% of the luminal pts and in 49.4% of TNBC, with no impact of HER2-low status. Five-year relapse-free survival (RFS) was also not affected by this factor. HER2-low was not associated with pCR or RFS in univariate and multivariate analysis. Conclusion: In this cohort, 31% of patients were HER2-low. There were no substantial differences in demographic/pathologic terms between HER2-low and HER2-0 patients. HER2-low status did not impact pCR rates or RFS of luminal and triple negative tumors treated with neoadjuvant chemotherapy. Larger studies are urgently needed to better characterize this subpopulation and determine whether focused phase 3 trials will be warranted.

Table 1: Baseline characteristics stratified by Her2-low statusCharacteristicsTNBCLuminalHER2-0HER2-LowHER2-0HER2-LowN 141N 22N 189N 126Mean age (range)45 (27-90)44 (26-65)46 (27-72)48 (27-77)cTT19 (6.5%)3 (13.6%)8 (4.3%)7 (5.5%)T261 (43.9%)6 (27.3%)54 (28.7%)38 (30.2%)T337 (26.6%)3 (13.6%)61 (32.4%)34 (27%)T431 (22.3%)10 (45.5%)64 (34%)47 (37.3%)missing3 (0.7%)2 (0.6%)cNN positive92 (65.2%)17 (77.3%)119 (62.9%)86 (68.3%)N negative47 (33.3%)5 (34.7%)69 (36.5%)40 (31.7%)missing2 (0.5%)1 (0.6%)StageI-II64 (47.0%)6 (27.3%)70 (38.0%)41 (32.5%)III72 (52.9%)16 (72.7%)114 (62.0%)85 (67.5%)Histologic gradeI1 (0.7%)013 (6.9%)17 (13.5%)II31 (22.0%)4 (18.2%)114 (60.6%)69 (54.8%)III94 (66.7%)16 (72.7%)51 (27.1%)36 (28.6%)Missing15 (10.6%)2 (9.1%)11 (5.3%)4 (3.2%)pCR68 (48.6%)12 (54.5%)19 (10.1%)15 (11.9%)p 0.65p 0.715y RFS (%)74.6%75.3%75.4%75.4%

Citation Format: Bruna RaphaeliSilva Mattos, Marcelle Goldner Cesca, Luciana de Moura Leite, Monique Celeste Tavares, Sinara Figueiredo Silva, Rafaela Pirolli, Camilla AlbinaZanco Fogassa, Erick Figueiredo Silva, Francisca Giselle Rocha, Simone Klug Loose, Fernando AugustoBatista Campos, Solange Moraes Sanches, Vladmir ClaudioCordeiro de Lima, Noam Falbel Pondé. Her2 low status and response to neoadjuvant chemotherapy in Her2 negative early breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS4-40.