A clinical perspective on escalating or de-escalating adjuvant therapy in HER2+ breast cancer

Introduction: Patients with early HER2-positive breast cancer (BC) benefit from HER2-targeted systemic therapy. The endorsed standard adjuvant treatment for patients with early HER2-positive breast cancer is chemotherapy plus trastuzumab administered for 1 year. Areas covered: Several trials have investigated modifications of the standard treatment in terms of de-escalation by either shortening the duration or giving less resource-demanding regimens and in terms of escalation by either adding a second anti-HER2 agent or extending the duration of HER2-targeted treatment for more than 12\ua0months. In this perspective, we would offer a comprehensive view of these trials and discuss their findings. Expert commentary: At the current state of knowledge, there are still open questions regarding the management of HER2+ BC patients, such as the most adequate duration of trastuzumab therapy, the optimal chemotherapy regimen that should be combined with trastuzumab, and the addition of a second anti-HER2 agent. Growing evidences suggest that some HER2+ BC patients may not need chemotherapy. If these patients could be recognized upfront, optimal response could potentially be reached with HER2-targeted therapy alone

TILs in ER+/HER2- breast cancer

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Early triple negative breast cancer: Conventional treatment and emerging therapeutic landscapes

Triple negative breast cancers (TNBCs) are characterized by worse prognosis, higher propensity to earlier metastases, and shorter survival after recurrence compared with other breast cancer subtypes. Anthracycline-and taxane-based chemotherapy is still the mainstay of treatment in early stages, although several escalation approaches have been evaluated to improve survival outcomes. The addition of platinum salts to standard neoadjuvant chemotherapy (NACT) remains controversial due to the lack of clear survival advantage, and the use of adjuvant capecitabine represents a valid treatment option in TNBC patients with residual disease after NACT. Recently, several clinical trials showed promising results through the use of poly ADP-ribose polymerase (PARP) inhibitors and by incorporating immunotherapy with chemotherapy, enriching treatment options beyond conventional cytotoxic agents. In this review, we provided an overview on the current standard of care and a comprehensive update of the recent advances in the management of early stage TNBC and focused on the latest emerging biomarkers and their clinical application to select the best therapeutic strategy in this hard-to-treat population

Barriers to the use of trastuzumab for HER2+ breast cancer and the potential impact of biosimilars : a physician survey in the united states and emerging markets

Trastuzumab in combination with chemotherapy has become a standard of care for patients with HER2+ breast cancer. The cost of therapy, however, can limit patient access to trastuzumab in areas with limited financial resources for treatment reimbursement. This study examined access to trastuzumab and identified potential barriers to its use in the United States, Mexico, Turkey, Russia and Brazil via physician survey. The study also investigated if the availability of a biosimilar to trastuzumab would improve access to and use of HER2 monoclonal antibody therapy. Across all countries, a subset of oncologists reported barriers to the use of trastuzumab in a neoadjuvant, adjuvant or metastatic setting. Common barriers to the use of trastuzumab included issues related to insurance coverage, drug availability and cost to the patient. Overall, nearly half of oncologists reported that they would increase the use of HER2 monoclonal antibody therapy across all treatment settings if a lower cost biosimilar to trastuzumab were available. We conclude that the introduction of a biosimilar to trastuzumab may alleviate cost-related barriers to treatment and could increase patient access to HER2-directed therapy in all countries examined

Profile of buparlisib and its potential in the treatment of breast cancer: evidence to date.

Alteration of the phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin signaling pathway is key for the growth and survival of several cancers, including breast cancer. In addition, dysregulation of PI3K signaling may contribute to resistance to several anticancer agents. PI3K inhibitors may, therefore, be effective as antineoplastic therapy. Buparlisib is a potent and highly specific oral inhibitor of the pan-class I PI3K family. Buparlisib specifically inhibits class I PIK3 in the PI3K/AKT kinase signaling pathway in an ATP-competitive manner, thus inhibiting the production of the secondary messenger phosphatidylinositol (3,4,5)-trisphosphate and activation of the PI3K signaling pathway. This may induce inhibition of tumor cell growth and survival in susceptible tumor cell populations. Buparlisib is currently under investigation in patients with a variety of solid tumors, including breast cancer. Buparlisib has been validated as a promising anticancer agent, and tremendous efforts have been taken to develop it. However, buparlisib monotherapy has resulted in humble benefit so far. Results from studies combining buparlisib with different anticancer agents - namely, endocrine therapy, anti-HER2 therapy, and chemotherapy - have showed variable efficacy with consistent substantial toxicity

Cardiovascular toxicity induced by chemotherapy, targeted agents and radiotherapy: ESMO Clinical Practice Guidelines

Cardiovascular (CV) toxicity is a potential short- or long-term complication of various anticancer therapies. Some drugs, such as anthracyclines or other biological agents, have been implicated in causing potentially irreversible clinically important cardiac dysfunction. Although targeted therapies are considered less toxic and better tolerated by patients compared with classic chemotherapy agents, rare but serious complications have been described, and longer follow-up is needed to determine the exact profile and outcomes of related cardiac side-effects. Some of these side-effects are irreversible, leading to progressive CV disease, and some others induce reversible dysfunction with no long-term cardiac damage to the patient. Assessment of the prevalence, type and severity of cardiac toxicity caused by various cancer treatments is a breakthrough topic for patient management. Guidelines for preventing, monitoring and treating cardiac side-effects are a major medical need. Efforts are needed to promote strategies for cardiac risk prevention, detection and management, avoiding unintended consequences that can impede development, regulatory approval and patient access to novel therapy. These new ESMO Clinical Practice Guidelines are the result of a multidisciplinary cardio-oncology review of current evidence with the ultimate goal of providing strict criteria-based recommendations on CV risk prevention, assessment, monitoring and management during anticancer treatmen

Pten alterations and their role in cancer management: Are we making headway on precision medicine?

Alterations in the tumor suppressor phosphatase and tensin homolog (PTEN) occur in a substantial proportion of solid tumors. These events drive tumorigenesis and tumor progression. Given its central role as a downregulator of the phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway, PTEN is deeply involved in cell growth, proliferation, and survival. This gene is also implicated in the modulation of the DNA damage response and in tumor immune microenvironment modeling. Despite the actionability of PTEN alterations, their role as biomarkers remains controversial in clinical practice. To date, there is still a substantial lack of validated guidelines and/or recommendations for PTEN testing. Here, we provide an update on the current state of knowledge on biologic and genetic alterations of PTEN across the most frequent solid tumors, as well as on their actual and/or possible clinical applications. We focus on possible tailored schemes for cancer patients\u2019 clinical management, including risk assessment, diagnosis, prognostication, and treatment

Immunotherapy for HER2-Positive Breast Cancer: Clinical Evidence and Future Perspectives

Breast cancer is the most common malignancy among women worldwide, and HER2-positive breast cancer accounts for approximately 15% of all breast cancer diagnoses. The advent of HER2-targeting therapies has dramatically improved the survival of these patients, significantly reducing their risk of recurrence and death. However, as a significant proportion of patients ultimately develop resistance to these therapies, it is extremely important to identify new treatments to further improve their clinical outcomes. Immunotherapy has revolutionized the treatment and history of several cancer types, and it has already been approved as a standard of care for patients with triple-negative breast cancer. Based on a strong preclinical rationale, immunotherapy in HER2-positive breast cancer represents an intriguing field that is currently under clinical investigation. There is a close interplay between HER2-targeting therapies (both approved and under investigation) and the immune system, and several new immunotherapeutic strategies, including immune checkpoint inhibitors, CAR-T cells and therapeutic vaccines, are being studied in this disease. In this narrative review, we discuss the clinical evidence and the future perspectives of immunotherapy for patients with HER2-positive breast cancer

Impact of Rehabilitation on Breast Cancer Related Fatigue: A Pilot Study

Breast cancer fatigue (BCF) is a complex and multidimensional condition characterized by a persistent sense of physical and/or mental stiffness, resulting in a substantial impairment of health-related quality of life in breast cancer survivors. Aim of this prospective cohort study was to evaluate the feasibility and the effectiveness of a 4-week rehabilitation protocol on BCF, muscle mass, strength, physical performance, and quality of life in breast cancer (BC) survivors. We recruited adult BC women with a diagnosis of BCF, according to the International Classification of Diseases 10 criteria, referred to the Outpatient Service for Oncological Rehabilitation of a University Hospital. All participants performed a specific physical exercise rehabilitative protocol consisting of 60-min sessions repeated 2 times/week for 4 weeks. All outcomes were evaluated at the baseline (T0), at the end of the 4-week rehabilitation treatment (T1), and at 2 months follow up (T2). The primary outcome measure was the Brief Fatigue Inventory (BFI); secondary outcomes included: Fat-Free Mass and Fat Mass, assessed by Bioelectrical Impedance Analysis (BIA); Hand Grip Strength Test (HGS); Short Physical Performance Battery (SPPB); 10-meter walking test (10 MWT); 6-min walking test (6 MWT); European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ–C30). Thirty-six women (mean age: 55.17 ± 7.76 years) were enrolled in the study. Significant reduction of BCF was observed both after the 4-week rehabilitation treatment (T1) (BFI: 5.4 ± 1.6 vs. 4.2 ± 1.7; p = 0.004) and at the follow-up visit (T2) (BFI: 5.4 ± 1.6 vs. 4.4 ± 1.6; p = 0.004). Moreover, significant differences (p < 0.001) HGS, SPPB, 10 MWT, 6 MWT, and EORTC QLQ-C30 were found at T1, while at T2 all the outcome measures were significantly different (p < 0.05) from the baseline. The rehabilitation protocol seemed to be feasible, safe, and effective in reducing BCF, improving muscle mass and function, and improving HRQoL in a cohort of BC survivors. The results of this study could improve awareness of this underestimated disease, suggesting the definition of a specific therapeutic exercise protocol to reduce BCF

Immune checkpoint blockade in cancer treatment : a double-edged sword cross-targeting the host as an "innocent bystander"

Targeted immune checkpoint blockade augments anti-tumor immunity and induces durable responses in patients with melanoma and other solid tumors. It also induces specific "immune-related adverse events" (irAEs). IrAEs mainly include gastrointestinal, dermatological, hepatic and endocrinological toxicities. Off-target effects that arise appear to account for much of the toxicity of the immune checkpoint blockade. These unique "innocent bystander" effects are likely a direct result of breaking immune tolerance upon immune check point blockade and require specific treatment guidelines that include symptomatic therapies or systemic corticosteroids. What do we need going forward to limit immune checkpoint blockade-induced toxicity? Most importantly, we need a better understanding of the roles played by these agents in normal tissues, so that we can begin to predict potentially problematic side effects on the basis of their selectivity profile. Second, we need to focus on the predictive factors of the response and toxicity of the host rather than serially focusing on individual agents. Third, rigorous biomarker-driven clinical trials are needed to further elucidate the mechanisms of both the benefit and toxicity. We will summarize the double-edged sword effect of immunotherapeutics in cancer treatment