Nan Chen

Background: Over the past few decades, the gonadotropin-releasing hormone agonist goserelin has been evaluated in ovarian function suppression (OFS) with adjuvant endocrine therapy and ovarian function preservation (OFP) during chemotherapy. Objective: The goal of this systematic literature review was to assess the efficacy of goserelin in OFS and OFP in combination with endocrine therapies and chemotherapy, respectively, in pre- and perimenopausal women with early-stage breast cancer. Design: This study is a systematic review. Data sources and methods: The literature search was conducted using PubMed. Prospective clinical studies evaluating the efficacy of goserelin in OFS or OFP in pre- or perimenopausal breast cancer were identified by four reviewers working in teams of two. Results: Twenty-nine studies were included in this systematic review. The addition of goserelin as OFS to adjuvant endocrine therapy generally resulted in significant benefits in disease-free survival. Studies have shown better OFP results among women 40 years or younger compared with older patients. Chemotherapy in association with goserelin for OFP resulted in a higher recovery rate of menses within 6–24 months, a shorter time for menstrual recovery, and significantly higher pregnancy rates when compared with cytotoxic therapy without goserelin. Hormonal recovery with higher anti-Müllerian hormone and estradiol levels, and lower follicle-stimulating hormone and luteinizing hormone levels occurred more frequently among women who received goserelin during chemotherapy as compared with those receiving cytotoxic therapy alone. The benefits of goserelin in OFP were more substantial among women 40 years or younger than in older patients. Conclusion: The findings of this systematic review highlight the benefits of adding goserelin to endocrine therapies for OFS and chemotherapy for OFP in early-stage breast cancer. Additionally, scientific data supporting OFS (including goserelin) in combination with newer agents such as cyclin-dependent kinase 4 and 6 inhibitors and bone-modifying agents are emerging.

PURPOSE: Human epidermal growth factor receptor 2 (HER2)–targeted therapy improves outcomes in HER2+ breast cancer, but efficacy in cases with discordant immunohistochemistry (IHC) and in situ hybridization (ISH) results or with ASCO/College of American Pathologists (CAP) group 2-4 ISH results remains uncertain. METHODS: This retrospective study included patients from the National Cancer Database diagnosed from 2013 to 2021. Cases were classified as classically HER2+ (HER2/centromeric region of chromosome 17 [CEP17] ratio ≥2 with HER2 copy number ≥4, IHC 2-3+), HER2– (ratio <2, copy number <4, IHC 0-2+), discordant ISH/IHC, or HER2+ with ISH group 2 (ratio ≥2, copy number <4), group 3 (ratio <2, copy number ≥6), or group 4 (ratio <2, copy number ≥4 and <6) per ASCO/CAP guidelines. Adjusted odds ratio (aOR) for pathologic complete response (pCR) for these subgroups receiving HER2-targeted therapy was calculated compared with HER2– controls. RESULTS: We identified N = 144,013 patients with IHC and dual-probe ISH. Of HER2 IHC 3+ cases (n = 8,579), 8.2%, 2.8%, 4.2%, and 8.8% had ISH categorized as groups 2, 3, 4, and 5 (discordant negative), respectively. Classically, HER2+ (aOR, 2.9 [95% CI, 2.65 to 3.18], P < .001) and group 2 (aOR, 2.38 [95% CI, 1.42 to 3.96], P < .001) treated with HER2-targeted therapy had higher pCR than HER2– controls. Benefit was also seen in group 3 (aOR, 1.63 [95% CI, 1.24 to 2.13], P < .001) and cases with discordant ISH+/IHC– (aOR, 1.61 [95% CI, 1.13 to 2.30], P = .008)—but this was only significant in group 3 cases with copy number ≥8 and discordant ISH+/IHC– cases with HER2/CEP17 ratio ≥3. Group 4 ISH cases and cases with ISH–/IHC+ did not benefit. CONCLUSION: Patients with ASCO/CAP group 4, discordant ISH–/IHC+ results, and weakly amplified group 3 and discordant ISH+/IHC– have low benefit from HER2 therapy, and alternative approaches for such patients are needed.

Best overall response. A, ORR data for all patients and by disease category for patients treated with either ICI monotherapy or chemo/ICI combination therapy. B, ORR data for all patients and by disease category for patients treated with ICI monotherapy. C, ORR data for patients with NSCLC stratified by PD-L1 status treated with ICI monotherapy. Only patients for whom PD-L1 was known were included.

Best overall response. A, ORR data for all patients and by disease category for patients treated with either ICI monotherapy or chemo/ICI combination therapy. B, ORR data for all patients and by disease category for patients treated with ICI monotherapy. C, ORR data for patients with NSCLC stratified by PD-L1 status treated with ICI monotherapy. Only patients for whom PD-L1 was known were included.

Immune-related adverse events (irAE) within the entire treatment cohort. A, Overall irAE rate as a function of race/ethnic group. B, ORR as a function of irAE for the ICI monotherapy cohort. PR, partial response; SD, stable disease; PD, progressive disease.

Immune-related adverse events (irAE) within the entire treatment cohort. A, Overall irAE rate as a function of race/ethnic group. B, ORR as a function of irAE for the ICI monotherapy cohort. PR, partial response; SD, stable disease; PD, progressive disease.

Best overall response by PD-L1. ORR data by race/ethnic group for patients with NSCLC treated with ICI monotherapy stratified by PD-L1 e50% (A), 1%–49% (B), and 0% (C). PR, partial response; SD, stable disease; PD, progressive disease.

Patient and treatment characteristics

Patient and treatment characteristics