Special Issue "Neoadjuvant Therapy in Breast Cancer"

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: closed (31 October 2021).

Special Issue Editor

Dr. Theodoros Foukakis
E-Mail Website
Guest Editor
Department of Oncology-Pathology, Karolinska Institutet, 17164 Stockholm, Sweden
Interests: breast cancer; genomics; tumor microenvironment; predictive biomarkers; neoadjuvant therapy

Special Issue Information

Neoadjuvant therapy in breast cancer has recently expanded beyond its traditional indication of downstaging to make breast-conserving surgery possible. Large patient level meta-analyses show that neoadjuvant chemotherapy has equivalent efficacy compared with adjuvant therapy and that pathologic complete response (pCR) in the surgical specimen correlates with long-term outcomes. The association between pCR and survival is particularly apparent for the HER2-positive and triple-negative subtypes and more recent data show that following failure to achieve pCR, further adjuvant therapy significantly improves prognosis in these subtypes.

In addition to the demonstrated clinical value, neoadjuvant therapy has emerged as a platform for studying the biology of breast cancer and the dynamic evolution of both the tumor (e.g., by genomics) and the host response (tumor microenvironment) under the selection pressure of therapy. Furthermore, clinical trials of neoadjuvant therapy have used pCR as an endpoint for the rapid assessment of the efficacy of novel drugs before proceeding with large phase 3 trials.

However, several questions remain unanswered. High-throughput multi-omics methods and deep-learning approaches have the potential to further dissect the complexity of the disease, exploiting the opportunity provided by neoadjuvant therapy to study the tumor in situ during the course of treatment. Therapeutic algorithms, including the agents to be used, the duration of treatment, the incorporation of novel drugs and the optimization of local treatment (surgery, radiotherapy), vary between different countries and no universal standards of care exist. Prognostication after neoadjuvant treatment is mainly based on the presence or not of residual disease at surgery, which is suboptimal, especially for luminal tumors. This Special Issue will highlight the current state-of-the-art in neoadjuvant treatment and future prospects for improving our understanding of the biology and optimizing patient care.

Dr. Theodoros Foukakis
Guest Editor

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2400 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • breast cancer
  • neoadjuvant treatment
  • residual disease
  • tumor microenvironment
  • prognosis
  • chemotherapy
  • immunotherapy
  • tumor heterogeneity
  • genomics
  • gene expression

Published Papers (6 papers)

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Research

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Article
Dynamics of Serum Thymidine Kinase 1 at the First Cycle of Neoadjuvant Chemotherapy Predicts Outcome of Disease in Estrogen-Receptor-Positive Breast Cancer
Cancers 2021, 13(21), 5442; https://doi.org/10.3390/cancers13215442 - 29 Oct 2021
Viewed by 671
Abstract
Pathologic complete response (pCR) predicts the long-term outcome of neoadjuvantly treated (NAC) breast cancer (BC) but is reached in <10% of hormone-receptor-positive patients. Biomarkers enabling adjustment or interruption of an ineffective therapy are desired. Here, we evaluated whether changes in the serum concentration [...] Read more.
Pathologic complete response (pCR) predicts the long-term outcome of neoadjuvantly treated (NAC) breast cancer (BC) but is reached in <10% of hormone-receptor-positive patients. Biomarkers enabling adjustment or interruption of an ineffective therapy are desired. Here, we evaluated whether changes in the serum concentration of thymidine kinase 1 (sTK1) during NAC could be utilized as a biomarker. In the PROMIX trial, women with localized HER2- BC received neoadjuvant epirubicin/docetaxel in six cycles. sTK1 was measured with an ELISA in 54 patients at cycles 1–4 and in an additional 77 patients before and 48 h after treatment 1. Treatment resulted in a 2-fold increase of sTK1 before and a 3-fold increase 48 h after the cycles, except for the first cycle, where half of the patients reacted with a significant decrease and the other half with an increase of sTK1. In Kaplan–Meier estimates of ER+ patients divided by the median of the post/pre-treatment sTK1 ratio at the first treatment cycle, OS was 97.7% and 78% (p = 0.005), and DFS was 90.7% and 68% (p = 0.006), respectively. Thus, the response of sTK1 at the first cycle of chemotherapy could be used both as an early biomarker for the guidance of chemotherapy and for the study of inherent tumor chemo-sensitivity, which could predict long-term outcome prior to therapy. Full article
(This article belongs to the Special Issue Neoadjuvant Therapy in Breast Cancer)
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Article
A Novel Immunomodulatory 27-Gene Signature to Predict Response to Neoadjuvant Immunochemotherapy for Primary Triple-Negative Breast Cancer
Cancers 2021, 13(19), 4839; https://doi.org/10.3390/cancers13194839 - 28 Sep 2021
Viewed by 1767
Abstract
A precise predictive biomarker for TNBC response to immunochemotherapy is urgently needed. We previously established a 27-gene IO signature for TNBC derived from a previously established 101-gene model for classifying TNBC. Here we report a pilot study to assess the performance of a [...] Read more.
A precise predictive biomarker for TNBC response to immunochemotherapy is urgently needed. We previously established a 27-gene IO signature for TNBC derived from a previously established 101-gene model for classifying TNBC. Here we report a pilot study to assess the performance of a 27-gene IO signature in predicting the pCR of TNBC to preoperative immunochemotherapy. We obtained RNA sequencing data from the primary tumors of 55 patients with TNBC, who received neoadjuvant immunochemotherapy with the PD-L1 blocker durvalumab. We determined the power and accuracy in predicting pCR for the immunomodulatory (IM) subtype identified by the 101-gene model, the 27-gene IO signature, and PD-L1 expression by immunohistochemistry (IHC). The pCR rate was 45% (25/55). The odds ratios for pCR were as follows: IM subtype by 101-gene model, 3.14 (p = 0.054); 27-gene IO signature, 4.13 (p = 0.012); PD-L1 expression by IHC, 2.63 (p = 0.106); 27-gene IO signature in combination with PD-L1 expression by IHC, 6.53 (p = 0.003). The 27-gene IO signature has the potential to predict the pCR of primary TNBC to neoadjuvant immunochemotherapy. Further analysis in a large cohort is needed. Full article
(This article belongs to the Special Issue Neoadjuvant Therapy in Breast Cancer)
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Article
Hypnosis Sedation Reduces the Duration of Different Side Effects of Cancer Treatments in Breast Cancer Patients Receiving Neoadjuvant Chemotherapy
Cancers 2021, 13(16), 4147; https://doi.org/10.3390/cancers13164147 - 18 Aug 2021
Viewed by 541
Abstract
Background: Reducing side effects of cancer treatments is a major challenge for clinicians involved in the management of breast cancer patients. Methods: We analyzed data from 63 patients (32 in the general anesthesia group and 31 in the hypnosis sedation group) who were [...] Read more.
Background: Reducing side effects of cancer treatments is a major challenge for clinicians involved in the management of breast cancer patients. Methods: We analyzed data from 63 patients (32 in the general anesthesia group and 31 in the hypnosis sedation group) who were included in 1 prospective non-randomized trial evaluating hypnosis sedation in breast cancer treatment. The patients were followed every 3 months for 2 years. All patients received neoadjuvant chemotherapy with 4 cycles of epirubicin and cyclophosphamide followed by taxanes. Thereafter, patients underwent surgery while on general anesthesia or while on hypnosis sedation. Radiotherapy was administered according to institutional guidelines. Endocrine therapy was prescribed if tumors expressed hormone receptors. Prevalence, intensity and duration of polyneuropathy, musculoskeletal pain, postoperative pain and cancer-related fatigue were assessed at each medical visit. Results: Symptoms duration was statistically reduced for polyneuropathy (p < 0.05), musculoskeletal pain (p < 0.05) postoperative pain and cancer-related fatigue (p < 0.05) in the hypnosis group. Conclusion: Despite the limitations of this study (lack of randomization and small size) we conclude that hypnosis sedation may exert a role on different side effects of breast cancer treatment in patients receiving neoadjuvant chemotherapy, mainly by reducing their duration. Full article
(This article belongs to the Special Issue Neoadjuvant Therapy in Breast Cancer)
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Article
A Novel Three-Gene Score as a Predictive Biomarker for Pathologically Complete Response after Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer
Cancers 2021, 13(10), 2401; https://doi.org/10.3390/cancers13102401 - 16 May 2021
Cited by 1 | Viewed by 894
Abstract
Although triple-negative breast cancer (TNBC) typically responds better to neoadjuvant chemotherapy (NAC) compared to the other subtypes, a pathological complete response (pCR) is achieved in less than half of the cases. We established a novel three-gene score using genes based on the E2F [...] Read more.
Although triple-negative breast cancer (TNBC) typically responds better to neoadjuvant chemotherapy (NAC) compared to the other subtypes, a pathological complete response (pCR) is achieved in less than half of the cases. We established a novel three-gene score using genes based on the E2F target gene set that identified pCR after NAC, which showed robust performance in both training and validation cohorts (total of n = 3862 breast cancer patients). We found that the three-gene score was elevated in TNBC compared to the other subtypes. A high score was associated with Nottingham histological grade 3 in TNBC. Across multiple cohorts, high-score TNBC enriched not only E2F targets but also G2M checkpoint and mitotic spindle, which are all cell proliferation-related gene sets. High-score TNBC was associated with homologous recombination deficiency, high mutation load, and high infiltration of Th1, Th2, and gamma-delta T cells. However, the score did not correlate with drug sensitivity for paclitaxel, 5-fluorouracil, cyclophosphamide, and doxorubicin in TNBC human cell lines. High-score TNBC was significantly associated with a high rate of pCR not only in the training cohort but also in the validation cohorts. High-score TNBC was significantly associated with better survival in patients who received chemotherapy but not in patients who did not receive chemotherapy. The three-gene score is associated with a high mutation rate, immune cell infiltration, and predicts response to NAC in TNBC. Full article
(This article belongs to the Special Issue Neoadjuvant Therapy in Breast Cancer)
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Review

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Review
The Present and Future of Neoadjuvant Endocrine Therapy for Breast Cancer Treatment
Cancers 2021, 13(11), 2538; https://doi.org/10.3390/cancers13112538 - 21 May 2021
Cited by 2 | Viewed by 760
Abstract
Endocrine therapy (ET) has established itself as an efficacious treatment for estrogen receptor-positive (ER+) breast cancers, with a reduction in recurrence rates and increased survival rates. The pre-surgical approach with chemotherapy (NCT) has become a common form of management for large, locally advanced, [...] Read more.
Endocrine therapy (ET) has established itself as an efficacious treatment for estrogen receptor-positive (ER+) breast cancers, with a reduction in recurrence rates and increased survival rates. The pre-surgical approach with chemotherapy (NCT) has become a common form of management for large, locally advanced, or high-risk tumors. However, a good response to NCT is not usually expected in ER+ tumors. Good results with primary ET, mainly in elderly women, have encouraged studies in other stages of life, and nowadays neoadjuvant endocrine treatment (NET) has become a useful approach to many ER+ breast cancers. The aim of this review is to provide an update on the current state of art regarding the present and the future role of NET. Full article
(This article belongs to the Special Issue Neoadjuvant Therapy in Breast Cancer)

Other

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Commentary
Circulating and Intracellular miRNAs as Prognostic and Predictive Factors in HER2-Positive Early Breast Cancer Treated with Neoadjuvant Chemotherapy: A Review of the Literature
Cancers 2021, 13(19), 4894; https://doi.org/10.3390/cancers13194894 - 29 Sep 2021
Cited by 1 | Viewed by 512
Abstract
MicroRNAs (miRNA) are small noncoding RNAs that can act as both oncogene and tumor suppressors. Deregulated miRNA expression has been detected in human cancers, including breast cancer (BC). Considering their important roles in tumorigenesis, miRNAs have been investigated as potential prognostic and diagnostic [...] Read more.
MicroRNAs (miRNA) are small noncoding RNAs that can act as both oncogene and tumor suppressors. Deregulated miRNA expression has been detected in human cancers, including breast cancer (BC). Considering their important roles in tumorigenesis, miRNAs have been investigated as potential prognostic and diagnostic biomarkers. Neoadjuvant setting is an optimal model to investigate in vivo the mechanism of treatment resistance. In the management of human epidermal growth factor receptor-2 (HER2)-positive early BC, the anti-HER2-targeted therapies have drastically changed the survival outcomes. Despite this, growing drug resistance due to the pressure of therapy is relatively frequent. In the present review, we focused on the main miRNAs involved in HER2-positive BC tumorigenesis and discussed the recent evidence on their predictive and prognostic value. Full article
(This article belongs to the Special Issue Neoadjuvant Therapy in Breast Cancer)
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