Best of ASCO 2021: new data from triple-negative breast cancer

SummaryThis year’s ASCO Annual Meeting has been a showcase for the overwhelming success of novel, targeted therapies, particularly in a tumor entity that has – until recently – been felt to be only treatable with chemotherapy. New data are extremely encouraging, but also highlight the need for target identification beyond the classical clinicopathological factors. Both, the Olympia and the Neotala study have been performed in BRCA-mutated tumors, and their results clearly point to the necessity to offer germline testing to HER2-negative high risk early breast cancer. In addition, GeparNuevo once more highlights the fact that immunotherapy is here to stay, not only in the advanced breast cancer setting, but also in early stage breast cancer. The side effect profile is acceptable, and long-term outcome a real improvement to conventional chemotherapy.

Immunotherapy-induced coeliac disease in curative lung cancer

The advent of immunotherapy has revolutionised the treatment of metastatic lung cancer and it has recently been established as the standard of care in the radical treatment of lung cancer. However, immune-related adverse events (IrAEs) frequently occur in patients treated with immunotherapy, and rare IrAEs continue to be identified. We report a case of immunotherapy-induced coeliac disease due to adjuvant durvalumab post-chemoradiotherapy in a patient receiving curative treatment for lung cancer. The patient had raised anti-tissue transglutaminase IgA and histological findings consistent with coeliac disease. This is the first published case report of probable immunotherapy-induced coeliac disease both with the immunotherapy drug durvalumab and in the curative lung cancer setting.

The Role of Post-Translational Modifications of Chemokines by CD26 in Cancer

Chemokines are a large family of small chemotactic cytokines that fulfill a central function in cancer. Both tumor-promoting and -impeding roles have been ascribed to chemokines, which they exert in a direct or indirect manner. An important post-translational modification that regulates chemokine activity is the NH2-terminal truncation by peptidases. CD26 is a dipeptidyl peptidase (DPPIV), which typically clips a NH2-terminal dipeptide from the chemokine. With a certain degree of selectivity in terms of chemokine substrate, CD26 only recognizes chemokines with a penultimate proline or alanine. Chemokines can be protected against CD26 recognition by specific amino acid residues within the chemokine structure, by oligomerization or by binding to cellular glycosaminoglycans (GAGs). Upon truncation, the binding affinity for receptors and GAGs is altered, which influences chemokine function. The consequences of CD26-mediated clipping vary, as unchanged, enhanced, and reduced activities are reported. In tumors, CD26 most likely has the most profound effect on CXCL12 and the interferon (IFN)-inducible CXCR3 ligands, which are converted into receptor antagonists upon truncation. Depending on the tumor type, expression of CD26 is upregulated or downregulated and often results in the preferential generation of the chemokine isoform most favorable for tumor progression. Considering the tight relationship between chemokine sequence and chemokine binding specificity, molecules with the appropriate characteristics can be chemically engineered to provide innovative therapeutic strategies in a cancer setting.

Immunotherapy Treatment for Triple Negative Breast Cancer

Triple-negative breast cancer (TNBC) is considered one of the highest-risk subtypes of breast cancer and has dismal prognosis. Local recurrence rate after standard therapy in the early breast cancer setting can be upwards to 72% in 5 years, and in the metastatic setting, the 5-year overall survival is 12%. Due to the lack of receptor expression, there has been a paucity of targeted therapeutics available, with chemotherapy being the primary option for systemic treatment in both the neoadjuvant and metastatic setting. More recently, immunotherapy has revolutionized the landscape of cancer treatment, particularly immune checkpoint inhibitor (ICI) therapy, with FDA approval in over 20 types of cancer since 2011. Compared to other cancer types, breast cancer has been traditionally thought of as being immunologically cold; however, TNBC has demonstrated the most promise with immunotherapy use, a timely discovery due to its lack of targeted therapy options. In this review, we summarize the trials using checkpoint therapy in early and metastatic TNBC, as well as the development of biomarkers and the importance of immune related adverse events (IRAEs), in this disease process.

Autocrine signaling explains the emergence of Allee effects in cancer cell populations

In many human cancers, the rate of cell growth depends crucially on the size of the tumor cell population. Low, zero, or negative growth at low population densities is known as the Allee effect; this effect has been studied extensively in ecology, but so far lacks a good explanation in the cancer setting. Here, we formulate and analyze an individual-based model of cancer, in which cell division rates are increased by the local concentration of an autocrine growth factor produced by the cancer cells themselves. We show, analytically and by simulation, that autocrine signaling suffices to cause both strong and weak Allee effects. Whether low cell densities lead to negative (strong effect) or reduced (weak effect) growth rate depends directly on the ratio of cell death to proliferation, and indirectly on cellular dispersal. Our model is consistent with experimental observations of brain tumor cells grown at different densities. We propose that further studying and quantifying population-wide feedback, impacting cell growth, will be central for advancing our understanding of cancer dynamics and treatment, potentially exploiting Allee effects for therapy.

Financial distress and its associated burden in couples coping with an advanced cancer

Purpose As the economic burden and financial distress (FD) resulting from cancer care are increasingly recognized, FD remains inadequately understood from the perspective of patients and their spousal caregiver, the relational context where most financial and treatment decisions are navigated. Therefore, we assessed FD in both patients with advanced cancer and their spouses to identify symptom and QOL correlates. We additionally examined if illness communication moderated the association between FD and QOL. Methods Patients undergoing treatment for stage III/IV lung cancer or grade III/IV primary brain tumor and their spouses completed measures of their own FD, QOL, symptoms, perception of their spouse’s symptoms, and overall illness communication. Results Patients (62.7%) and spouses (64.7%) endorsed FD; however, spouses rated FD with greater relative severity. For both, FD was associated with greater anxiety, depression, and poorer physical QOL. For patients, FD was additionally associated with poorer mental QOL. Spousal caregivers accurately perceived patient FD, yet patients underreported spouse’s FD by a clinically meaningful difference. A 3-way interaction (FD X role X illness communication) revealed (b = .40, p = .041) that illness communication moderated the association between FD and physical QOL for spouses only. Conclusion In the advanced cancer setting, FD is prevalent in both patients and their caregivers and associated with psychological distress and poor physical QOL. Results suggest that optimal FD interventions should include patients and spouses. As illness communication appears to buffer the negative association of FD with physical QOL, studies targeting illness communication deficits in couples facing advanced disease are warranted.