Survival Outcomes in Patients With Hormone Receptor–Positive Metastatic Breast Cancer With Low or No ERBB2 Expression Treated With Targeted Therapies Plus Endocrine Therapy

Abstract

ImportanceApproximately 45% to 60% of hormone receptor (HR)–positive metastatic breast cancer (mBC) shows a low-level expression of ERBB2. Low ERBB2 expression is defined as ERBB2 immunohistochemical expression of 1+ or 2+ with a negative ERBB2 amplification by in situ hybridization. The efficacy of the antibody-drug conjugate trastuzumab deruxtecan in low-ERBB2, HR-positive mBC has been practice changing. However, there are conflicting data on the prognostic value of low ERBB2 expression in HR-positive mBC and whether low ERBB2 expression is a separate entity.ObjectiveTo examine whether outcomes differ by immunohistochemical analysis for patients with HR-positive mBC with low ERBB2 expression vs those without ERBB2 expression when treated with targeted therapy (TT) plus endocrine therapy (ET).Design, Setting, and ParticipantsThis single-institution cohort study used prospectively collected electronic data from the MD Anderson Cancer Center for patients with a diagnosis of HR-positive mBC treated with ET in combination with a TT (cyclin-dependent kinase 4/6 inhibitors [CDK4/6is], everolimus, or alpelisib) between January 1, 2010, and December 31, 2021.ExposureHR-positive mBC with either low or no ERBB2 expression.Main Outcome and MeasuresThe main outcomes were median progression-free survival and overall survival. Data on demographic characteristics, estrogen and progesterone receptor status, ERBB2 status, histologic subtype, menopausal status, treatment duration, and survival status were collected.ResultsA total of 1585 women (median [range] age, 51 [24-92] years) were included in the study. Of these women, 1013 (63.9%) had mBC with low ERBB2 expression and 572 (36.1%) had mBC with no ERBB2 expression. A total of 1084 (68.4%) were treated with a CDK4/6i (912 patients were treated in the first line and 172 were treated in the second line); 475 (30.0%) received everolimus and 26 (1.6%) received alpelisib. In the patients who received a first-line CDK4/6i, 618 (67.8%) received an aromatase inhibitor as their ET backbone and 265 (29.1%) received fulvestrant. With a median follow-up time of 17.9 months (range, 1-111 months), progression-free survival and overall survival were not statistically different between the patients with low and no ERBB2 expression treated with TT plus ET.Conclusions and RelevanceIn this cohort study of patients with HR-positive mBC treated with TT plus ET, low ERBB2 expression did not have a significant association with prognosis.

The association between HER2-low status and survival in patients with metastatic breast cancer treated with Cyclin-dependent kinases 4 and 6 inhibitors: a systematic review and meta-analysis

“…Nine studies encompassing a total of 2705 patients were included in the analyses. The four studies were conducted in the first line [ 18 , 23 – 25 ], while mixed cohorts were present in five studies [ 17 , 19 , 26 – 28 ]. Five studies were multicenter, and single-center data were reported in four studies.…”

“…Six of nine studies reported no association between the HER2-low status and PFS with CDK 4/6 inhibitors [ 17 , 23 – 25 , 27 , 28 ]. In the pooled analysis of nine studies, the risk of progression and/or death was higher in patients with the HER2-low tumors compared to HER2 zero (HR: 1.22, 95% CI 1.10–1.35, p < 0.001) (Fig.…”

Multi-gradient Permutation Survival Analysis Identifies Mitosis and Immune Signatures Steadily Associated with Cancer Patient Prognosis

“…Previous studies have highlighted the complexity of this task, which is influenced by various factors including cancer type, clinical stage, therapeutic interventions, nursing care, unexpected comorbidities, and other non-cancer related illnesses that may interplay [3][4][5][6] . Furthermore, the gene expression plays a crucial role in predicting cancer patient prognosis, such as HER2, VEGF, Ki67, etc [7][8][9][10][11][12] . Nevertheless, there is still a need for further improvement in prognostic accuracy to better inform treatment decisions and patient outcomes.…”

Oncotype DX in Breast Cancer Management: Insights and Outcomes From the United Arab Emirates

“…Endocrine therapy is a fundamental component in the management of hormone receptor-positive breast cancer, with the primary objective of inhibiting the proliferative influence of estrogen and progesterone on the cancer cells [22]. Widely utilized pharmaceutical agents such as tamoxifen and aromatase inhibitors have effectively diminished recurrence risk and enhanced survival outcomes [23]. The selection and duration of this therapeutic approach are contingent upon the unique characteristics of the cancer and the menopausal status of the patient, emphasizing the necessity for individualized treatment plans in the comprehensive management of breast cancer [24].…”

“…The Oncotype DX test, a genomic assay, quantifies the expression of 21 genes in tumor tissue, producing a RS that stratifies patients into low (<18), intermediate (18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31), and high (>31) risk of recurrence categories. This RS guides adjuvant therapy decisions, aiming to personalize treatment approaches based on genetic risk profiles.…”