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Current State of Breast Cancer Diagnosis, Treatment, and Theranostics

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Current State of Breast Cancer Diagnosis, Treatment, and Theranostics pharmaceutics Review Current State of Breast Cancer Diagnosis, Treatment, and Theranostics Arya Bhushan 1,2,†, Andrea Gonsalves 2,† and Jyothi U. Menon 2,* 1 Ladue Horton Watkins High School, St. Louis, MO 63124, USA; [email protected] 2 Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, USA; [email protected] * Correspondence: [email protected]; Tel.: +1-401-874-4914 † These authors have contributed equally to this work. Abstract: Breast cancer is one of the leading causes of cancer-related morbidity and mortality in women worldwide. Early diagnosis and effective treatment of all types of cancers are crucial for a positive prognosis. Patients with small tumor sizes at the time of their diagnosis have a significantly higher survival rate and a significantly reduced probability of the cancer being fatal. Therefore, many novel technologies are being developed for early detection of primary tumors, as well as distant metastases and recurrent disease, for effective breast cancer management. Theranostics has emerged as a new paradigm for the simultaneous diagnosis, imaging, and treatment of cancers. It has the potential to provide timely and improved patient care via personalized therapy. In nanotheranostics, cell-specific targeting moieties, imaging agents, and therapeutic agents can be embedded within a single formulation for effective treatment. In this review, we will highlight the different diagnosis techniques and treatment strategies for breast cancer management and explore recent advances in breast cancer theranostics. Our main focus will be to summarize recent trends and technologies in breast cancer diagnosis and treatment as reported in recent research papers and patents and discuss Citation: Bhushan, A.; Gonsalves, A.; future perspectives for effective breast cancer therapy. Menon, J.U. Current State of Breast Cancer Diagnosis, Treatment, and Keywords: breast cancer; imaging modalities; mammography; breast specific gamma imaging; Theranostics. Pharmaceutics 2021, 13, triple-negative breast cancer; theranostics 723. https://doi.org/10.3390/ pharmaceutics13050723 Academic Editor: Carlotta Marianecci 1. Introduction Breast cancer has a very long history as it was first reported by the ancient Egyptians Received: 19 February 2021 more than 3500 years ago in about 1500 B.C [1]. Today, breast cancer is the second most Accepted: 10 May 2021 Published: 14 May 2021 prevalent type of cancer and is a leading cause of most cancer-related deaths in women in the United States [2]. Around 281,550 women are projected to be diagnosed with breast Publisher’s Note: MDPI stays neutral cancer in 2021, and 43,600 women are predicted to die due to breast cancer in the US, with regard to jurisdictional claims in according to the American Cancer Society. Early diagnosis of the disease is crucial for published maps and institutional affil- effective treatment and positive prognosis, as significantly lower probability of dying and iations. higher survival rate is observed in patients with smaller tumors at the time of diagnosis [3]. Early detection of breast cancer and accurate lesion assessment are, therefore, the primary focus of all imaging modalities. At present the two major pillars to be addressed for effective management of breast cancer disease include: (i) diagnosis of breast cancer in its earliest stages and (ii) providing timely treatment after diagnosis to save lives. Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. Imaging of the breast is utilized almost exclusively for detection, diagnosis, and This article is an open access article clinical management of cancers and for the assessment of the integrity of breast implants distributed under the terms and (Figure1)[ 4]. As a conventional medical imaging modality, ultrasound has played a conditions of the Creative Commons key role in breast cancer detection, image-guided biopsy, and lymph-node diagnosis Attribution (CC BY) license (https:// for many years. Mammography, ultrasonography, magnetic resonance imaging (MRI), creativecommons.org/licenses/by/ scintimammography, single photon emission computed tomography (SPECT), and positron 4.0/). emission tomography (PET) are other commonly used imaging modalities [5–7]. Based Pharmaceutics 2021, 13, 723. https://doi.org/10.3390/pharmaceutics13050723 https://www.mdpi.com/journal/pharmaceutics Pharmaceutics 2021, 13, 723 2 of 24 on the diagnosis and assessment of the extent of breast cancer, the need for preoperative (neoadjuvant) systemic therapy is determined. Targeted and effective therapies with minimal off-target side effects are needed for breast cancer treatment. As breast cancer is a global problem, major emphasis also needs to be put on diminishing worldwide disparities in terms of access to diagnosis, multimodal treatment, and novel drugs. Figure 1. Representation of the various imaging techniques that can be used in breast cancer diagnosis. For this review, we conducted a literature search within the Google Scholar and PubMed databases using the keywords: “Breast Cancer”, “Imaging”, and “Treatment” in the title field, with dates from 2000 to 2021. After reading the abstracts, we manually selected the relevant papers for this review. In this review article, we examine various detection techniques for breast cancer, provide an in-depth analysis on the therapies for different subtypes of breast cancer, and investigate recent trends and the future of breast cancer theranostics. 2. Techniques for Diagnosis or Detection of Breast Cancer Early diagnosis is a key to successful breast cancer treatment. T1 tumors measuring less than 2 cm in diameter have a 10-year survival of approximately 85%, while T3 tumors— essentially the result of delayed diagnosis—have a 10-year survival of less than 60% [8]. Imaging techniques commonly used for detection of breast cancer are summarized in Table1. Pharmaceutics 2021, 13, 723 3 of 24 Table 1. Summary of various imaging modalities for screening of breast cancer. Imaging Modality Principle Diagnostic Accuracy Advantages Limitations References Uses ionizing radiation. Sensitivity decreases with increasing breast density. Most cost-effective. Accuracy is low in Mammography Low-dose ionizing Sensitivity: 75–90% Good response with young women. (First-line tool for x-ray creates detailed Specificity: 90–95% high specificity and [9–12] High false-positive breast screening) images of the breast. Spatial Resolution: 50 µm sensitivity. results in young Portable device. women due to dense breasts. Poor contrast compared to MRI. Expensive, Uses low-energy Ability to detect inability to standardize radio waves and Sensitivity: 75–100% breast malignancies the test. Magnetic Resonance strong magnets to Specificity: 83–98.4% that often escape Unnecessary breast [13,14] Imaging obtain detailed Spatial Resolution: from clinical, biopsies due to inability images of structures 25–100 µm mammograms, and to distinguish between within the breast ultrasound detection. malignant and benign lesions. Overcomes limitations of Employs magnetic mammography. Expensive and field on body fluids Sensitivity: 93% Radiation-free time-consuming. Magnetic Resonance and tissue samples to Specificity: 70% imaging technology. Low specificity. [15–18] Spectroscopy obtain chemical Spatial Resolution: up to Excellent Sensitivity. Not portable. information of that 0.25 cm3 Excellent spatial False-positive results in region resolution. some benign tumors. All imaging planes possible. False-negative results Multiple MRI scans Sensitivity: 89–99% Exhibits good Dynamic Contrast observed due to taken post i.v. Specificity: 37–86% performance in Enhanced MRI artifacts based on [14,19–21] injection of contrast Spatial Resolution: monitoring response (DCE-MRI) bleeding and tumor agent 25–100 µm post therapy. structure. Failure to detect high Sensitivity: 83% Employs diffusion of water content Diffusion-Weighted Specificity: 84% Non-radioactive water molecules to malignant lesions due [14,22] Imaging Spatial Resolution: imaging technique generate contrast. to high apparent 25–100 µm diffusion coefficients. Dynamic elasticity imaging technique that combines MRI Sensitivity: 90–100% Non-invasive, Lacking in spatial imaging with low MR Elastography Specificity: 37–80% non-ionizing and resolution and frequency. [14,23,24] (MRE) Spatial Resolution: cross-sectional detection of small focal Employs mechanical 25–100 µm imaging modality lesions. waves to create an elastogram to assess tissue stiffness. Non-invasive. Provides twice the Positron Emission Combines nuclear diagnostic benefits Tomography medicine technique Sensitivity: 90–100% (Elevated activity High-cost. conjugated with and computed Specificity: 75–90% within the body Unable to detect [14,23] computed tomography Spatial Resolution: 2–10 detected by PET scan tumors less than 8 mm. Tomography resulting in high mm and intricate images (PET-CT) detailed images. of tissues and organs by CT scan). Not useful for patients Surgical procedure to Sensitivity: 90.5% Significantly reduces with locally advanced Sentinel lymph node detect spreading of Specificity: 85.7% post-operative cancers and [24,25] biopsy (SLNB) cancer in lymphatic Spatial Resolution: Not complications inflammatory breast system. Applicable cancer. Pharmaceutics 2021, 13, 723 4 of 24 Table 1. Cont. Imaging Modality Principle Diagnostic Accuracy Advantages Limitations References Employs use of a Sensitivity: 90–96% Able to identify High radiation dose. Breast Specific
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