PURPOSE: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) combined with endocrine therapy (ET) are the standard first-line treatment for hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2–) advanced breast cancer (ABC); however, disease progression occurs in almost all patients and additional treatment options are needed. Herein, we report outcomes of the postMONARCH trial investigating a switch in ET with/without CDK4/6 inhibition with abemaciclib after disease progression on CDK4/6i. METHODS: This double-blind, randomized phase III study enrolled patients with disease progression on previous CDK4/6i plus aromatase inhibitor as initial therapy for advanced disease or recurrence on/after adjuvant CDK4/6i + ET. Patients were randomly assigned (1:1) to abemaciclib + fulvestrant or placebo + fulvestrant. The primary end point was investigator-assessed progression-free survival (PFS). Secondary end points included PFS by blinded independent central review, objective response rate (ORR), and safety. RESULTS: This study randomly assigned 368 patients (abemaciclib + fulvestrant, n = 182 placebo + fulvestrant, n = 186). At the primary analysis (258 events), the hazard ratio (HR) was 0.73 (95% CI, 0.57 to 0.95; nominal P = .017), with median PFS 6.0 (95% CI, 5.6 to 8.6) versus 5.3 (95% CI, 3.7 to 5.6) months and 6-month PFS rates of 50% and 37% in the abemaciclib + fulvestrant and placebo + fulvestrant arms, respectively. These results were supported by BICR-assessed PFS (HR, 0.55 [95% CI, 0.39 to 0.77]; nominal P < .001). A consistent treatment effect was seen across major clinical and genomic subgroups, including with/without ESR1 or PIK3CA mutations. Among patients with measurable disease, investigator-assessed ORR was improved with abemaciclib + fulvestrant versus placebo + fulvestrant (17% v 7%; nominal P = .015). No new safety signals were observed, with findings consistent with the known safety profile of abemaciclib. CONCLUSION: Abemaciclib + fulvestrant significantly improved PFS after disease progression on previous CDK4/6i + ET in patients with HR+, HER2– ABC, offering an additional targeted therapy option for these patients.

Introduction: There is much literature about the role of 2-[¹⁸F]FDG PET/CT in patients with breast cancer (BC). However, there exists no international guideline with involvement of the nuclear medicine societies about this subject. Purpose: To provide an organized, international, state-of-the-art, and multidisciplinary guideline, led by experts of two nuclear medicine societies (EANM and SNMMI) and representation of important societies in the field of BC (ACR, ESSO, ESTRO, EUSOBI/ESR, and EUSOMA). Methods: Literature review and expert discussion were performed with the aim of collecting updated information regarding the role of 2-[¹⁸F]FDG PET/CT in patients with no special type (NST) BC and summarizing its indications according to scientific evidence. Recommendations were scored according to the National Institute for Health and Care Excellence (NICE) criteria. Results: Quantitative PET features (SUV, MTV, TLG) are valuable prognostic parameters. In baseline staging, 2-[¹⁸F]FDG PET/CT plays a role from stage IIB through stage IV. When assessing response to therapy, 2-[¹⁸F]FDG PET/CT should be performed on certified scanners, and reported either according to PERCIST, EORTC PET, or EANM immunotherapy response criteria, as appropriate. 2-[¹⁸F]FDG PET/CT may be useful to assess early metabolic response, particularly in non-metastatic triple-negative and HER2+ tumours. 2-[¹⁸F]FDG PET/CT is useful to detect the site and extent of recurrence when conventional imaging methods are equivocal and when there is clinical and/or laboratorial suspicion of relapse. Recent developments are promising. Conclusion: 2-[¹⁸F]FDG PET/CT is extremely useful in BC management, as supported by extensive evidence of its utility compared to other imaging modalities in several clinical scenarios.

PURPOSE: The aim of this work is to update key recommendations of the ASCO guideline adaptation of the Cancer Care Ontario guideline on the selection of optimal adjuvant chemotherapy regimens for early breast cancer and adjuvant targeted therapy for breast cancer. METHODS: An Expert Panel conducted a targeted systematic literature review guided by a signals approach to identify new, potentially practice-changing data that might translate into revised guideline recommendations. RESULTS: The Expert Panel reviewed abstracts from the literature review and identified one article for inclusion that reported results of the phase III, open-label KATHERINE trial. In the KATHERINE trial, patients with stage I to III human epidermal growth factor receptor 2 (HER2)–positive breast cancer with residual invasive disease in the breast or axilla after completing neoadjuvant chemotherapy and HER2-targeted therapy were allocated to adjuvant trastuzumab emtansine (T-DM1; n = 743) or to trastuzumab (n = 743). Invasive disease–free survival was significantly higher in the T-DM1 group than in the trastuzumab arm (hazard ratio, 0.50; 95% CI, 0.39 to 0.64; P < .001), and risk of distant recurrence was lower in patients who received T-DM1 than in patients who received trastuzumab (hazard ratio, 0.60; 95% CI, 0.45 to 0.79). Grade 3 or higher adverse events occurred in 190 patients (25.7%) who received T-DM1 and in 111 patients (15.4%) who received trastuzumab. RECOMMENDATIONS: Patients with HER2-positive breast cancer with pathologic invasive residual disease at surgery after standard preoperative chemotherapy and HER2-targeted therapy should be offered 14 cycles of adjuvant T-DM1, unless there is disease recurrence or unmanageable toxicity. Clinicians may offer any of the available and approved formulations of trastuzumab, including trastuzumab, trastuzumab and hyaluronidase-oysk, and available biosimilars. Additional information can be found at www.asco.org/breast-cancer-guidelines

PURPOSE: Patients who have cancer have leveraged the Internet to gain a better understanding of their disease and connect across geographic boundaries with others facing the same challenges. Online cancer communities have developed into resources that highlight new research and evolving care pathways. Combined with increasing health literacy and social media, they have enabled some patients to become experts in their cancer. This combination of empowerment and expertise describes the new “e-patients.” METHODS: We reviewed the literature to identify key areas where expert e-patients have directly participated in advancing cancer medicine, as well as opportunities available to those who wish to become more involved in research advocacy. RESULTS: E-patients are widely acknowledged as key stakeholders in oncology by clinicians, researchers, cancer centers, government agencies, and nonprofits. Their input is vital for informing cancer care delivery, developing and launching research initiatives, creating care guidelines and pathways, and formulating policy. CONCLUSION: Expert e-patients play an expanded role in their own care and in larger conversations regarding practice, research, and policy. Clinicians can engage e-patients as partners in cancer care as we work together towards improving health care access and outcomes for people with cancer.

Antibody drug conjugates (ADCs) have emerged as a highly effective treatment strategy across breast cancer (BC) subtypes, including human epidermal growth factor receptor 2-positive (HER2+), hormone-receptor positive (ER/PR+), and triple-negative breast cancer (TNBC). Over the past twenty years, ADCs have undergone relevant evolutions, from target diversity to payload ratio, to linker design, allowing for a progressive increase in their efficacy. From the first-generation ADC, trastuzumab emtansine (T-DM1), approved in 2013 for HER2+ breast cancer, to next generation ADCs such as sacituzumab govitecan and trastuzumab deruxtecan, to emerging ADCs on the horizon, we continue to see unparalleled efficacy compared to traditional chemotherapy. However, each ADC has brought a new cadre of adverse events for clinicians and patients to manage. Importantly, with the development and approval of several ADCs to treat metastatic breast cancer, there are unanswered clinical questions surrounding how to optimally sequence treatment for patients who may be candidates for more than one ADC and, in general, how to treat patients beyond progression on ADCs. From bench to bedside, in this review, we will discuss the pharmacology and current indications for the novel ADCs trastuzumab deruxtecan and sacituzumab govitecan. Highlighting emerging ADCs and ongoing clinical trials, we will anticipate the changes in the breast cancer treatment paradigm. Lastly, we will outline the available data and current approaches for adverse event management and sequencing strategies for ADCs in clinical practice, including proposed mechanisms of resistance.

In hormone receptor-positive and HER2-negative breast cancers, a growing number of revolutionary personalized therapies are in clinical use or trials, such as CDK4/6 inhibitors, immune checkpoint inhibitors, and PIK3CA inhibitors. Those treatment options are largely driven by the presence or absence of genomic alterations in the tumor. Therefore, molecular profiling is often performed during disease progression. The most encountered genomic alterations are in the PI3K/AKT/mTOR/PTEN pathway. This review discusses the genetic alterations associated with the PI3K/AKT/mTOR/PTEN pathway to help clinicians understand drug selection, resistance, or interaction from a molecular pathologist’s perspective.