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Breast Cancer Chemotherapy

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Endocrinology and Metabolism".

Deadline for manuscript submissions: closed (31 May 2022) | Viewed by 41811

Special Issue Editor


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Guest Editor
Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY 14642, USA
Interests: breast cancer; HER2; hormone receptor-positive breast cancer; chemotherapy; genomic; translational; circulating tumor DNA
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Breast cancer remains one of the most common cancers in women, and despite improved early diagnosis and treatments, many women will still die from this disease. This Special Issue on "Breast Cancer Chemotherapy" will gather reviews and original research articles highlighting our successes as well as ways we can learn from our failures in breast cancer management.

Topics gathered will emphasize ways to improve personalized breast cancer management using genomics and other biomarkers, improve the selection of patients for specific treatments, underscore CDK4/6 inhibitors' success in advanced disease but conflicting results in early disease, and novel therapeutic approaches, especially for triple-negative and HER2+ breast cancers.

We invite contributions of original research papers, up-to-date review articles, and short commentaries about breast cancer at basic, translational, and clinical levels and anticipate that we will provide a Special Issue with expert insights and perspectives on advances in the field of breast cancer management.

Prof. Dr. Carla I Falkson
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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
  • genomics
  • personalized medicine
  • CDK4/6 inhibitors
  • hormone positive breast cancer
  • triple-negative breast cancer
  • metastatic breast cancer
  • HER2+ targeted therapy
  • novel therapy
  • biomarkers
  • adjuvant therapy
  • adjuvant breast cancer

Published Papers (6 papers)

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Research

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18 pages, 3836 KiB  
Article
Chemotherapy-Induced Changes in the Lung Microenvironment: The Role of MMP-2 in Facilitating Intravascular Arrest of Breast Cancer Cells
by Justin D. Middleton, Subhakeertana Sivakumar and Tsonwin Hai
Int. J. Mol. Sci. 2021, 22(19), 10280; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms221910280 - 24 Sep 2021
Cited by 7 | Viewed by 18437
Abstract
Previously, we showed that mice treated with cyclophosphamide (CTX) 4 days before intravenous injection of breast cancer cells had more cancer cells in the lung at 3 h after cancer injection than control counterparts without CTX. At 4 days after its injection, CTX [...] Read more.
Previously, we showed that mice treated with cyclophosphamide (CTX) 4 days before intravenous injection of breast cancer cells had more cancer cells in the lung at 3 h after cancer injection than control counterparts without CTX. At 4 days after its injection, CTX is already excreted from the mice, allowing this pre-treatment design to reveal how CTX may modify the lung environment to indirectly affect cancer cells. In this study, we tested the hypothesis that the increase in cancer cell abundance at 3 h by CTX is due to an increase in the adhesiveness of vascular wall for cancer cells. Our data from protein array analysis and inhibition approach combined with in vitro and in vivo assays support the following two-prong mechanism. (1) CTX increases vascular permeability, resulting in the exposure of the basement membrane (BM). (2) CTX increases the level of matrix metalloproteinase-2 (MMP-2) in mouse serum, which remodels the BM and is functionally important for CTX to increase cancer abundance at this early stage. The combined effect of these two processes is the increased accessibility of critical protein domains in the BM, resulting in higher vascular adhesiveness for cancer cells to adhere. The critical protein domains in the vascular microenvironment are RGD and YISGR domains, whose known binding partners on cancer cells are integrin dimers and laminin receptor, respectively. Full article
(This article belongs to the Special Issue Breast Cancer Chemotherapy)
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20 pages, 3307 KiB  
Article
Stress-Inducible Gene Atf3 Dictates a Dichotomous Macrophage Activity in Chemotherapy-Enhanced Lung Colonization
by Justin D. Middleton, Jared Fehlman, Subhakeertana Sivakumar, Daniel G. Stover and Tsonwin Hai
Int. J. Mol. Sci. 2021, 22(14), 7356; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22147356 - 08 Jul 2021
Cited by 5 | Viewed by 2436
Abstract
Previously, we showed that chemotherapy paradoxically exacerbated cancer cell colonization at the secondary site in a manner dependent on Atf3, a stress-inducible gene, in the non-cancer host cells. Here, we present evidence that this phenotype is established at an early stage of [...] Read more.
Previously, we showed that chemotherapy paradoxically exacerbated cancer cell colonization at the secondary site in a manner dependent on Atf3, a stress-inducible gene, in the non-cancer host cells. Here, we present evidence that this phenotype is established at an early stage of colonization within days of cancer cell arrival. Using mouse breast cancer models, we showed that, in the wild-type (WT) lung, cyclophosphamide (CTX) increased the ability of the lung to retain cancer cells in the vascular bed. Although CTX did not change the WT lung to affect cancer cell extravasation or proliferation, it changed the lung macrophage to be pro-cancer, protecting cancer cells from death. This, combined with the initial increase in cell retention, resulted in higher lung colonization in CTX-treated than control-treated mice. In the Atf3 knockout (KO) lung, CTX also increased the ability of lung to retain cancer cells. However, the CTX-treated KO macrophage was highly cytotoxic to cancer cells, resulting in no increase in lung colonization—despite the initial increase in cell retention. In summary, the status of Atf3 dictates the dichotomous activity of macrophage: pro-cancer for CTX-treated WT macrophage but anti-cancer for the KO counterpart. This dichotomy provides a mechanistic explanation for CTX to exacerbate lung colonization in the WT but not Atf3 KO lung. Full article
(This article belongs to the Special Issue Breast Cancer Chemotherapy)
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13 pages, 3230 KiB  
Article
Influence of Paclitaxel and Doxorubicin Therapy of ßIII-Tubulin, Carbonic Anhydrase IX, and Survivin in Chemically Induced Breast Cancer in Female Rat
by Alena Pastornická, Silvia Rybárová, Slávka Drahošová, Jozef Mihalik, Andrea Kreheľová, Andriana Pavliuk-Karachevtseva and Ingrid Hodorová
Int. J. Mol. Sci. 2021, 22(12), 6363; https://doi.org/10.3390/ijms22126363 - 14 Jun 2021
Cited by 6 | Viewed by 1759
Abstract
Breast cancer is the most common cancer in females. The aim of this study was to determine the effect of paclitaxel (PTX) and doxorubicin (DOX) therapy on the βIII-tubulin, carbonic anhydrase IX (CA IX), and survivin expression in chemically-induced rat mammary tumors. Animals [...] Read more.
Breast cancer is the most common cancer in females. The aim of this study was to determine the effect of paclitaxel (PTX) and doxorubicin (DOX) therapy on the βIII-tubulin, carbonic anhydrase IX (CA IX), and survivin expression in chemically-induced rat mammary tumors. Animals with induced mammary carcinogenesis were randomly divided into treatment groups and an untreated group. The total proportion of tumors, the proportion of carcinoma in situ (CIS), and invasive carcinoma (IC) were evaluated. Protein expression in tumor tissue was determined using IHC. Statistical analysis of the data, evaluated by Fisher-exact test and unpaired t-test. Significantly increased levels of proteins in the tumor cells were confirmed using the IHC method for all studied proteins. The expression of βIII-tubulin, CA IX, and survivin increased significantly after treatment with both cytostatics (PTX and DOX). Depending on the type of tumor, a significant increase in all proteins was observed in IC samples after PTX treatment, and CA IX expression after DOX treatment. In CIS samples, a significant increase of βIII-tubulin and survivin expression was observed after a DOX treatment. The results suggest that βIII-tubulin, survivin, and CA IX may be significant drug resistance markers and the clinical regulation of their activity may be an effective means of reversing this resistance. Full article
(This article belongs to the Special Issue Breast Cancer Chemotherapy)
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Review

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43 pages, 4058 KiB  
Review
The Mammary Gland: Basic Structure and Molecular Signaling during Development
by Swarajit Kumar Biswas, Saswati Banerjee, Ginger Wendolyn Baker, Chieh-Yin Kuo and Indrajit Chowdhury
Int. J. Mol. Sci. 2022, 23(7), 3883; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23073883 - 31 Mar 2022
Cited by 30 | Viewed by 11874
Abstract
The mammary gland is a compound, branched tubuloalveolar structure and a major characteristic of mammals. The mammary gland has evolved from epidermal apocrine glands, the skin glands as an accessory reproductive organ to support postnatal survival of offspring by producing milk as a [...] Read more.
The mammary gland is a compound, branched tubuloalveolar structure and a major characteristic of mammals. The mammary gland has evolved from epidermal apocrine glands, the skin glands as an accessory reproductive organ to support postnatal survival of offspring by producing milk as a source of nutrition. The mammary gland development begins during embryogenesis as a rudimentary structure that grows into an elementary branched ductal tree and is embedded in one end of a larger mammary fat pad at birth. At the onset of ovarian function at puberty, the rudimentary ductal system undergoes dramatic morphogenetic change with ductal elongation and branching. During pregnancy, the alveolar differentiation and tertiary branching are completed, and during lactation, the mature milk-producing glands eventually develop. The early stages of mammary development are hormonal independent, whereas during puberty and pregnancy, mammary gland development is hormonal dependent. We highlight the current understanding of molecular regulators involved during different stages of mammary gland development. Full article
(This article belongs to the Special Issue Breast Cancer Chemotherapy)
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13 pages, 665 KiB  
Review
PI3Kinase Inhibition in Hormone Receptor-Positive Breast Cancer
by Ajay Dhakal, Luna Acharya, Ruth O’Regan, Shipra Gandhi and Carla Falkson
Int. J. Mol. Sci. 2021, 22(21), 11878; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222111878 - 02 Nov 2021
Cited by 1 | Viewed by 2472
Abstract
Derangement of the phosphatidylinositol-3 kinase (PI3K) pathway is implicated in several subtypes of breast cancers. Mutation or upregulation of PI3K enhances cancer cells’ survival, proliferation, and ability to metastasize, making it an attractive molecular target for systemic therapy. PI3K has four isoforms, and [...] Read more.
Derangement of the phosphatidylinositol-3 kinase (PI3K) pathway is implicated in several subtypes of breast cancers. Mutation or upregulation of PI3K enhances cancer cells’ survival, proliferation, and ability to metastasize, making it an attractive molecular target for systemic therapy. PI3K has four isoforms, and several drugs targeting individual isoforms or pan-PI3K have been or are currently being investigated in clinical trials. However, the search for an effective PI3K inhibitor with a robust therapeutic effect and reasonable safety profile for breast cancer treatment remains elusive. This review focuses on the recently completed and ongoing clinical trials involving PI3K inhibitors as mono- or combination therapy in breast cancer. We review the salient findings of clinical trials, the therapeutic efficacy of PI3K inhibitors, and reported adverse effects leading to treatment discontinuation. Lastly, we discuss the challenges and potential opportunities associated with adopting PI3K inhibitors in the clinic. Full article
(This article belongs to the Special Issue Breast Cancer Chemotherapy)
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21 pages, 570 KiB  
Review
MicroRNA Expression Profiles and Breast Cancer Chemotherapy
by Matthew G. Davey, Aoife J. Lowery, Nicola Miller and Michael J. Kerin
Int. J. Mol. Sci. 2021, 22(19), 10812; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms221910812 - 06 Oct 2021
Cited by 31 | Viewed by 3370
Abstract
Breast cancer is the most common malignancy diagnosed in women. Traditionally, radical surgical resection was the cornerstone of breast cancer management, with limited exceptions. In recent times, our enhanced appreciation of the biomolecular characteristics of breast cancer has transformed the treatment paradigm to [...] Read more.
Breast cancer is the most common malignancy diagnosed in women. Traditionally, radical surgical resection was the cornerstone of breast cancer management, with limited exceptions. In recent times, our enhanced appreciation of the biomolecular characteristics of breast cancer has transformed the treatment paradigm to include prescription of chemotherapeutical agents, radiotherapies, targeted therapies, as well as more refined surgical approaches. While treatments with such modalities have enhanced clinico-oncological outcomes for breast cancer patients, the efforts of oncological and translational research have concentrated on the identification of novel biomarkers which may successfully inform prognosis and response to therapies, improve current therapeutic strategies, and enhance prognostication. Mi(cro)RNAs are small, non-coding molecules which are known to play regulatory roles in governing gene expression and cellular activity. Measurement of miRNA expression profiles have been illustrated to inform the response to therapies, such as conventional chemotherapy, and are currently undergoing assessment as means of enhancing treatment strategies with these cytotoxic agents. Herein, this review outlines how chemotherapy prescription has revolutionised breast cancer treatment and illustrates the novel role of miRNAs as biomarkers capable of enhancing current therapeutic strategies using chemotherapy in patients being treated with curative intent for breast cancer. Full article
(This article belongs to the Special Issue Breast Cancer Chemotherapy)
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