The emerging role of immune checkpoint inhibitors for the treatment of breast cancer

Howard, Frederick M.; Villamar, Dario Martin; He, Guangbin; Pearson, Alexander T.; Nanda, Rita

doi:10.1080/13543784.2022.1986002

Cited by 24 publications

(31 citation statements)

References 111 publications

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“…Indeed, no vascular or immune biomarker has been sufficiently established to permit bedside decision-making to direct ICIs or anti-angiogenic agents for early breast cancer [ 7 , 11 , 24 , 25 , 26 , 27 ]. For example, randomized phase III trials with pembrolizumab (KEYNOTE-522 number, NCT03036488) and atezolizumab (Impassion031 number, NCT03197935) showed the consistent benefits of immunotherapy in early triple-negative breast cancer across subgroups, with or without biomarker expression and programmed death receptor 1 or its ligand positivity, respectively [ 24 , 25 ].…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Usefulness of Hounsfield Units and the Serum Neutrophil-to-Lymphocyte Ratio as Prognostic Factors in Patients with Breast Cancer

Hahn

Kim

et al. 2022

Cancers

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Breast cancer is a leading cause of death worldwide. Tumor vascularity and immune disturbances are hallmarks of cancer. This study aimed to investigate the reciprocal effect of tumor vascularity, assessed by the tumor-to-aorta ratio (TAR) of Hounsfield units (HU) on computed tomography (CT), and host immunity, represented by the serum neutrophil-to-lymphocyte ratio (NLR) from peripheral, complete blood cell counts and its impact on patient survival. Female patients with breast cancer who received primary treatment between 2003 and 2018 at Wonju Severance Hospital, Korea, were included. The final cohort included 740 patients with a mean age of 54.3 ± 11.3 (22–89) years. The TAR was 0.347 ± 0.108 (range, 0.062–1.114) and the NLR was 2.29 ± 1.53 (0.61–10.47). The cut-off value for the TAR and NLR were 0.27 and 1.61, respectively. The patients with a TAR > 0.27 showed a poor recurrence free-interval (RFI) only when their NLR was larger than 1.61, and vice versa. The patients showed worse RFI when they had both high TAR and NLR. Our results suggest a dynamic reciprocal communication between tumor vascularity and systemic immunity.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Usefulness of Hounsfield Units and the Serum Neutrophil-to-Lymphocyte Ratio as Prognostic Factors in Patients with Breast Cancer

Hahn

Kim

et al. 2022

Cancers

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“…Similarly, the GeparNuevo trial, looking at a combination of nab-paclitaxel chemotherapy and durvalumab, showed better pCR rates only in the subgroup that received a window period of durvalumab before combined therapy; however, PD-L1 positivity was associated pCR throughout the entire cohort. 100 Based on the above, close partnership between oncologists and pathologists is vital to perform the correct PD-L1 test for the optimal immunotherapy drug for the required indication. Pembroluzimab is currently the only ICI approved for use in the neoadjuvant setting in the United States but not the United Kingdom.…”

Section: P D -L 1 I M M U N O H I S T O C H E M I S T R Ymentioning

confidence: 99%

Pathology of neoadjuvant therapy and immunotherapy testing for breast cancer

Provenzano

Shaaban

2022

Histopathology

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Neoadjuvant chemotherapy (NACT) has become the standard of care for high-risk breast cancer, including triple-negative (TNBC) and HER2positive disease. As a result, handling and reporting of breast specimens post-NACT is part of routine practice, and it is important for pathologists to recognise the changes in tumour cells, tumour-associated stroma and background breast tissue induced by NACT. Familiarity with characteristic stromal features enables identification of the pre-treatment tumour site and allows confident diagnosis of pathological complete response (pCR) which is important for decisions concerning adjuvant therapy. Neoadjuvant endocrine therapy (NAET) is used less frequently than NACT; however, the SARS-COVID-19 pandemic has changed practice, with increased use as bridging therapy if surgery is delayed. NAET also induces characteristic changes in the tumour and stroma. Changes in the tumour microenvironment following NACT and NAET are also described. Immunotherapy is approved for use in advanced TNBC, and there are several trials exploring its role in early TNBC in the neoadjuvant setting. The current biomarker to determine eligibility for treatment with immune checkpoint inhibitors is programmed death ligand-1 (PD-L1) immunohistochemistry; however, this is complicated by lack of standardisation with different drugs linked to tests using different antibodies with different scoring systems. The situation in the neoadjuvant setting is further complicated by improved pCR rates for PD-L1positive tumours in both immune therapy and placebo arms. Alternative biomarkers are urgently needed to identify which patients will derive benefit from immunotherapy and key candidates are discussed.

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“…Of these, 46 patients were PD-L1+ and had a 15% ORR and a disease control rate of 24% with no response or disease control observed in those who were PD-L1−. In the other trial, in which recruited patients had previously been treated with trastuzumab, pertuzumab, and a taxane, and were then given durvalumab and trastuzumab, no response was recorded [ 133 ]. In the phase II Kate2 trial [ 134 ], patients who were previously treated with trastuzumab and a taxane were randomized to receive atezolizumab or placebo associated with T-DM1.…”

Section: Introductionmentioning

confidence: 99%

“…Other trials investigating NACT combined with ICIs and anti-HER2 therapies are ongoing. In the Impassion 050 trial, patients were randomized to receive atezolizumab or placebo concomitant with NACT, including doxorubiicin + cyclophosphamide, followed by paclitaxel, trastuzumab, and pertuzumab [ 133 , 136 ]. Atezolizumab or placebo was continued in an adjuvant setting together with trastuzumab and pertuzumab for 52 weeks overall.…”

Section: Introductionmentioning

confidence: 99%

Immune Checkpoint Inhibitors and Other Immune Therapies in Breast Cancer: A New Paradigm for Prolonged Adjuvant Immunotherapy

Nicolini

Carpi

2022

Biomedicines

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Breast cancer is the most common form of cancer in women worldwide. Advances in the early diagnosis and treatment of cancer in the last decade have progressively decreased the cancer mortality rate, and in recent years, immunotherapy has emerged as a relevant tool against cancer. HER2+ and triple-negative breast cancers (TNBCs) are considered more immunogenic and suitable for this kind of treatment due to the higher rate of tumor-infiltrating lymphocytes (TILs) and programmed death ligand 1 (PD-L1) expression. In TNBC, genetic aberrations further favor immunogenicity due to more neo-antigens in cancer cells. Methods: This review summarizes the principal ongoing conventional and investigational immunotherapies in breast cancer. Particularly, immune checkpoint inhibitors (ICIs) and their use alone or combined with DNA damage repair inhibitors (DDRis) are described. Then, the issue on immunotherapy with monoclonal antibodies against HER-2 family receptors is updated. Other investigational immunotherapies include a new schedule based on the interferon beta-interleukin-2 sequence that was given in ER+ metastatic breast cancer patients concomitant with anti-estrogen therapy, which surprisingly showed promising results. Results: Based on the scientific literature and our own findings, the current evaluation of tumor immunogenicity and the conventional model of adjuvant chemotherapy (CT) are questioned. Conclusion: A novel strategy based on additional prolonged adjuvant immunotherapy combined with hormone therapy or alternated with CT is proposed.

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The emerging role of immune checkpoint inhibitors for the treatment of breast cancer

Cited by 24 publications

References 111 publications

Usefulness of Hounsfield Units and the Serum Neutrophil-to-Lymphocyte Ratio as Prognostic Factors in Patients with Breast Cancer

Usefulness of Hounsfield Units and the Serum Neutrophil-to-Lymphocyte Ratio as Prognostic Factors in Patients with Breast Cancer

Pathology of neoadjuvant therapy and immunotherapy testing for breast cancer

Immune Checkpoint Inhibitors and Other Immune Therapies in Breast Cancer: A New Paradigm for Prolonged Adjuvant Immunotherapy

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