PURPOSE: Testing for germline BRCA1 and/or BRCA2 mutations (gBRCAm) is recommended for patients with human epidermal growth factor receptor 2–negative (HER2–) breast cancer (BC) to guide treatment selection with poly (ADP-ribose) polymerase inhibitors (PARPis). However, real-world data on germline BRCA1 and/or BRCA2 (gBRCA) testing and PARPi treatment patterns in metastatic BC (mBC) are limited. METHODS: Deidentified patient data from adults diagnosed with HER2– mBC between 2014 and 2022 were captured from electronic health records in the US Flatiron Health database. gBRCA testing patterns and prevalence were examined by tumor subtype (hormone receptor–positive [HR+]/triple-negative) and disease stage at diagnosis. Demographic and clinical characteristics were described by receipt of gBRCA testing and PARPi. PARPi treatment patterns were assessed, and real-word overall survival (OS) was estimated in patients with gBRCAm diagnosed with mBC after January 1, 2018. RESULTS: Of the 15,006 total patients, 4,654 (31.0%) received a gBRCA test. gBRCA testing rates mostly increased from 2014 to 2022 and were lower in patients with HR+ than triple-negative tumors. Of the patients who underwent gBRCA testing, 337 (7.2%) had gBRCAm. From 2018 to 2022, PARPi was initiated in 94 (45.6%) of 206 patients with gBRCAm. With a median follow-up of 22.8 months across patients with available first-line treatment start dates, real-world OS was numerically longer among 94 patients with gBRCAm who received PARPi (32.3 months [95% CI, 22.7 to 47.4]) than among 99 patients who did not (21.9 months [95% CI, 18.4 to not reached]). CONCLUSION: Although gBRCA testing increased over time, testing and PARPi utilization rates remained suboptimal in potentially eligible patients with HER2– mBC. Exploratory analysis showed numerically longer OS in patients who received PARPi. Wider and timelier gBRCA testing is warranted to inform potentially optimal treatment decisions.

Breast cancer (BC) is the most prevalent malignancy in women worldwide. Despite most cases being diagnosed in the early stages, patients typically require a multimodal treatment approach. This typically involves a combination of surgery, radiotherapy, systemic treatments (including chemotherapy or immunotherapy), targeted therapy, and endocrine therapy, depending on the disease subtype and the risk of recurrence. Moreover, patients with BC and germline mutations in the breast cancer genes 1 or 2 (BRCA1/BRCA2), (gBRCAm), who are typically young women, often require more aggressive therapeutic interventions. These mutations present unique characteristics that necessitate a distinct treatment approach, potentially influencing the side effect profiles of patients with BC. Regardless of the clear benefit observed with these treatments in terms of reduced recurrence and mortality rates, long-term, treatment-related adverse events occur that negatively affect the health-related quality of life (HRQoL) of BC survivors. Thus, long-term adverse events need to be factored into the treatment decision algorithm of patients with early BC (eBC). Physical, functional, emotional, and psychosocial adverse events can occur and represent a significant concern and a challenge for clinicians, patients, and their families. This review article provides an overview of the various long-term adverse events that patients with eBC may experience, including their associated risk factors, as well as management and prevention strategies. We also explore the evidence of the long-term impact of treatment on the HRQoL of patients with gBRCAm. By providing a comprehensive overview of current evidence and recommendations regarding patients’ HRQoL, we aim to equip clinicians with scientific and clinical knowledge and provide guidance to optimize care and improve long-term outcomes.

Introduction Poly(ADP-ribose) polymerase inhibitors (PARPi) have survival benefits for patients with high-risk (High-risk disease is defined per the phase III OlympiA trial as follows: for triple-negative breast cancer, residual disease after neoadjuvant chemotherapy or node-positive or ≥ 2 cm tumors after adjuvant chemotherapy; for hormone receptor-positive disease, four or more positive nodes after adjuvant chemotherapy or a CPS + EG score ≥ 3 after incomplete response to neoadjuvant chemotherapy. The CPS + EG score accounts for clinical/pathologic stage, ER status, and grade (Giaquinto et al. in CA Cancer J Clin 72:524–541, 2022)), human epidermal growth factor receptor 2 (HER2)-negative early breast cancer (eBC) with germline BReast CAncer gene mutations (gBRCAm). However, many patients are unaware of their gBRCA status; this can impact eligibility for targeted treatment. We sought to evaluate patient preferences for BRCA testing and treatment decision-making as they relate to HER2-negative eBC. Methods We conducted an online survey, including a best–worst scaling exercise (BWS) and discrete-choice experiment (DCE), among patients with self-reported HER2-negative eBC residing in the USA who were either untested, unsure if they were tested, or tested positive for the gBRCAm. The BWS generated a rank ordering of 16 barriers and facilitators to BRCA testing. The DCE evaluated patient preferences for adjuvant therapies versus no treatment based on seven treatment attributes: invasive disease-free survival, targeted treatment, nausea risk, risk of serious side effects, regimen, treatment duration, and cost. BWS and DCE exercises were analyzed using hierarchical Bayesian models. Results Among the 359 women included in our sample, the top facilitators for BRCA testing were determining eligibility for targeted therapy that may prevent or delay metastasis, a physician’s recommendation, and absence of out-of-pocket costs (OOPC). In contrast, the top barriers were an OOPC of $250, potential anxiety from test results, and the possibility of a 3- to 4-week delay in treatment. The DCE showed that most participants preferred adjuvant treatment (77.6%) over no treatment, and reducing treatment OOPC from $900 to $0, reducing the risk of serious side effects from 77 to 24%, and having a BRCA-targeted treatment influenced treatment choice most. Conclusions Individuals reported that a key benefit of BRCA testing was the insight it provided into their treatment options, allowing for more personalized care. However, OOPC was a barrier to testing. Their choice to receive adjuvant therapy was most influenced by OOPC, followed by the tolerability of the treatment and the ability to receive a targeted therapy.

PURPOSE: To describe and compare patient characteristics, treatment patterns, and survival outcomes of patients with human epidermal growth factor receptor 2 (HER2)–low and HER2 immunohistochemistry 0 (IHC 0) stage IV breast cancer METHODS: A retrospective study was conducted across three academic centers in the United States. Adult patients diagnosed with stage IV breast cancer between 1-1-2010 and 12-31-2020 and classified as having either HER2-low (immunohistochemistry 1+/2+ with negative fluorescence in situ hybridization) or HER2 IHC 0 disease were followed through 12-31-2021. Patient characteristics, treatments received, and treatment discontinuation were analyzed and survival analyses were conducted using Kaplan-Meier methods. RESULTS: Among 501 eligible patients, 385 were classified as HER2-low (76.8%) and 116 as HER2 IHC 0 (23.2%). No statistically significant differences were found for demographic characteristics, but PTEN mutations (11.6% v 0%, P = .02) were more common, while germline BRCA1 mutations (1.9% v 8.6%, P = .04) were less prevalent in the HER2-low subgroup compared with those with HER2 IHC 0 disease. Treatment patterns in both subgroups were largely similar. In the overall cohort, 20%-30% of patients who discontinued treatment did not proceed to a subsequent line of therapy. Median overall survival trended shorter in the HER2 IHC 0 subgroup than the HER2-low subgroup, but 95% confidence intervals overlapped. For both subgroups, progression-free survival (PFS) decreased substantially at 2L and 3L compared with previous line of therapy. CONCLUSION: Patient characteristics were similar between HER2-low and HER2 IHC 0 subgroups except for some differences in genetic alterations. Deterioration of PFS in later lines of therapy highlights a potential unmet need. Given the high patient attrition, the most effective treatments should be used as early as indicated as some patients may not proceed to subsequent lines of therapy.

Background: Despite recent advances in new therapies for early-stage breast cancer (eBC), the impact of the current treatment landscape on patients’ quality of life remains poorly understood. This study explored the experiences and unmet needs of women with eBC, leading to the development of a patient-informed conceptual disease model (PI-CDM) that summarizes patient priorities. Methods: This qualitative study used a step-wise approach: (1) a targeted literature review; (2) draft CDM development; (3) interview guide development; (4) semi-structured interviews with women in the United States with a diagnosis of eBC; (5) thematic content analysis of interview transcripts; (6) patient steering committee insights; and (7) PI-CDM finalization. Results: Thirty-six women with eBC (stage I, n = 18; stage II, n = 11; stage III, n = 9) were interviewed between December 2023 and May 2024. Key health concepts included signs and symptoms leading to diagnosis and common treatment side effects. Emotional and psychological impacts were prominent, and 28 participants reported moderate to extremely severe anxiety or depression on the EQ-5D-5L. Other impacts included social life, body satisfaction, daily activities, physical functioning, sexual functioning, and finances. Needs for improved communication from healthcare providers about treatment options and better support were emphasized. These insights, combined with patient steering committee recommendations, resulted in a final PI-CDM. Conclusions: This study highlights the substantial burden women with eBC face and provides a framework for future patient-centric research. A CDM developed with patients summarizes the complexity of the eBC experience and can aid discussions between patients and physicians, facilitating shared decision-making to enhance care.

Background and Objectives: As adjuvant treatment for human epidermal growth factor receptor 2 (HER2)-negative early-stage breast cancer (eBC) evolves, real-world data should inform olaparib utilization, sequencing, and combination patterns in clinical practice. Methods: Using Komodo US claims data (1 January 2019–31 December 2023), we retrospectively analyzed HER2-negative eBC patients on adjuvant olaparib. Continuous insurance for 12 months pre- and ≥30 days post-index date (first olaparib prescription), with follow-up through disenrollment or study end, was required. Outcomes, including time on therapy (Kaplan–Meier median persistence), adherence (proportion of days covered), dose reduction, and combination patterns, were stratified by claims-derived hormone-receptor-positive (HR+) and triple-negative BC (TNBC) status. Results: Among 176 olaparib-treated patients (median age, 44 years), the median (95% CI) time on therapy was 11.0 (9.2, 12.2) months; 27.3% (n = 48) discontinued before 12 months without re-initiating, 19.9% experienced a dose reduction, and median adherence was 90%. Olaparib was combined with other therapies in 48.3% (n = 85) (29.6% [32/108] of TNBC and 77.9% [53/68] of HR+ patients), most often with immunotherapy in TNBC (81.3%, n = 26) and endocrine therapy in HR+ (88.7%, n = 47). Conclusions: Real-world data suggest favorable persistence and dosing patterns with adjuvant olaparib. Future research should prioritize olaparib combination regimen safety and effectiveness.