Abstract PS4-33: Androgen receptors are highly expressed in HER2-positive breast cancers that achieve pCR to anti-HER2 monoclonal antibodies
Authors: Benedetta Pellegrino, Nicoletta Campanini, Daniela Boggiani, Daniele Zanoni, Angelica Sikokis, Gabriele Missale, Giuseppe Maglietta, Antonio Frassoldati, Maria Michiara, Enrico Maria Silini, Antonino Musolino
Journal: Cancer Research (2021)

Abstract BackgroundAlmost 50% of early HER2-positive Breast Cancer (BC) patients achieve pathological complete response (pCR) when treated with pertuzumab and trastuzumab in association with neoadjuvant chemotherapy (TPCT). Novel predictive factors are needed in order to improve the response rate by introducing innovative and less toxic combination regimens. We aimed to address this unmet clinical need by dissecting the role of Androgen Receptor (AR) expression in this subgroup of patients. MethodsWe quantified AR expression by Immunohistochemistry (IHC) in 59 untreated samples of patients enrolled in the ImmunHER trial. This is a non-comparative, phase II, neoadjuvant, randomized study that enrolled previously untreated patients with histologically confirmed, locally advanced, inflammatory, or early-stage HER2-positive BC. Patients were treated with FEC (fluorouracil 500 mg/m2; epirubicin 75 mg/m2; cyclophosphamide 500 mg/m2) q21 x 3 cycles. Then, they were randomly assigned (1:1) to receive: docetaxel (75 mg/m2) plus pertuzumab (840 mg loading dose (LD), then 420 mg) plus IV trastuzumab (8 mg/kg LD, then 6 mg/kg) q21 x 4 cycles (arm A) or, docetaxel plus pertuzumab plus SC trastuzumab (fixed dose of 600 mg) q21 x 4 cycles (arm B). After surgery, patients received trastuzumab q21 x 14 cycles using the same formulation (SC or IV) of the preoperative phase. The primary endpoint was the rate of stromal TILs (sTILs) on residual disease after surgery. ClinicalTrials.gov: NCT03144947. ResultsIn 46 samples (78%), ARs were expressed in more than 10% of tumor cells. The median expression was 90%. ARs were more expressed in women older than 40 yo compared to younger (median expression: 90% vs 40% [P-value not provided for post hoc tests]) and in Estrogen Receptor (ER)-positive tumors compared to ER-negative (median expression: 90% vs 75%). ARs were more expressed in tumors that achieved pCR than in non-responder patients (median expression: 90% vs 60%) and in high sTILs tumors compared to low-intermediate sTILs tumors (median expression: 90% vs 80%). In our series, AR expression did not correlate with Ki67, CD3, CD56, PD1, PD-L1 expression. ConclusionsARs are highly expressed in early HER2-positive BC. The higher AR expression observed in patients with pCR and high-sTILs suggests the combined use of TPCT with Selective Androgen Receptor Modulator (SARM). We are currently testing the in vitro combination of SARM with trastuzumab and pertuzumab, and efficacy results will be presented at the meeting. Citation Format: Benedetta Pellegrino, Nicoletta Campanini, Daniela Boggiani, Daniele Zanoni, Angelica Sikokis, Gabriele Missale, Giuseppe Maglietta, Antonio Frassoldati, Maria Michiara, Enrico Maria Silini, Antonino Musolino. Androgen receptors are highly expressed in HER2-positive breast cancers that achieve pCR to anti-HER2 monoclonal antibodies [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 PS4-33.