W.J.M. Hrushesky's research while affiliated with Medical University of South Carolina and other places
What is this page?
This page lists the scientific contributions of an author, who either does not have a ResearchGate profile, or has not yet added these contributions to their profile.
It was automatically created by ResearchGate to create a record of this author's body of work. We create such pages to advance our goal of creating and maintaining the most comprehensive scientific repository possible. In doing so, we process publicly available (personal) data relating to the author as a member of the scientific community.
If you're a ResearchGate member, you can follow this page to keep up with this author's work.
If you are this author, and you don't want us to display this page anymore, please let us know.
It was automatically created by ResearchGate to create a record of this author's body of work. We create such pages to advance our goal of creating and maintaining the most comprehensive scientific repository possible. In doing so, we process publicly available (personal) data relating to the author as a member of the scientific community.
If you're a ResearchGate member, you can follow this page to keep up with this author's work.
If you are this author, and you don't want us to display this page anymore, please let us know.
Publications (288)
Introduction:
Nuclear reactor incidents and bioterrorism outbreaks are concerning public health disasters. Little is known about US Food and Drug Administration (FDA)-approved agents that can mitigate consequences of these events. We review FDA data supporting regulatory approvals of these agents.
Areas covered:
We reviewed pharmaceutical produc...
Background
We previously described experiences of clinicians who published adverse drug reaction reports. We now report on threats and intimidations leveled against clinicians and scientists who received publicly documented threats after communicating safety, efficacy, or data integrity findings contrary to corporate interests.
Methods
Data on thr...
Objectives
Cancer patients routinely exhibit dysfunctional circadian organization. Indeed, a dysfunctional circadian organization is a hallmark of advanced cancer. A cohort of advanced cancer patients undergoing chemotherapy was recruited to investigate whether manipulating exposure to blue light could restore or ameliorate their circadian organiza...
Progressive multifocal leukoencephalopathy (PML) is a serious and usually fatal CNS infection caused by the John Cunningham virus. CD4⁺ and CD8⁺ T-cell lymphopenia, resulting from HIV infection, chemotherapy, or immunosuppressive therapy, are primary risk factors for PML. Following its introduction in 1997, the immunomodulatory anti-CD20 monoclonal...
Cancer patients show the signs and symptoms of a failing circadian organization. Melatonin, secreted only during nightly darkness, promotes nightly sleep and synchronizes daily molecular and physiologic clocks. Using a placebo-controlled randomized double-blind clinical trial, we determined whether the hypothesized proper physiologic daily timing,...
Biosimilars are biologic drug products that are highly similar to reference products in analytic features, pharmacokinetics and pharmacodynamics, immunogenicity, safety, and efficacy. Biosimilar epoetin received Food and Drug Administration (FDA) approval in 2018. The manufacturer received an FDA nonapproval letter in 2017, despite receiving a favo...
The EU, the USA, and Japan account for the majority of biological pharmacotherapy use worldwide. Biosimilar regulatory approval pathways were authorised in the EU (2006), in Japan (2009), and in the USA (2015), to facilitate approval of biological drugs that are highly similar to reference products and to encourage market competition. Between 2007...
Background:
Adverse drug/device reactions (ADRs) can result in severe patient harm. We define very serious ADRs as being associated with severe toxicity, as measured on the Common Toxicity Criteria Adverse Events (CTCAE)) scale, following use of drugs or devices with large sales, large financial settlements, and large numbers of injured persons. W...
The report addresses the role of the hazard function in the analysis of disease-free survival data in breast cancer. An investigation on local recurrences after mastectomy provided evidence that uninterrupted growth is inconsistent with clinical findings and that tumor dormancy could be assumed as working hypothesis to understand the clinical cours...
Erythropoisis stimulating agent (ESA) use was addressed in Food and Drug Administration (FDA) Oncology Drug Advisory Committee (ODAC) meetings between 2004 and 2008. FDA safety-focused regulatory actions occurred in 2007 and 2008. In 2007, black box warnings advised of early death and venous thromboembolism (VTE) risks with ESAs in oncology. In 201...
Most current research in cancer is attempting to find ways of preventing patients from dying after metastatic relapse. Driven by data and analysis, this project is an approach to solve the problem upstream, i.e., to prevent relapse.
This project started with the unexpected observation of bimodal relapse patterns in breast and a number of other canc...
Oncology-associated adverse drug/device reactions can be fatal. Some clinicians who treat single patients with severe oncology-associated toxicities have researched case series and published this information. We investigated motivations and experiences of select individuals leading such efforts. Clinicians treating individual patients who developed...
Biosimilar filgrastims are primarily indicated for chemotherapy-induced neutropenia prevention. They are less expensive formulations of branded filgrastim, and biosimilar filgrastim was the first biosimilar oncology drug administered in European Union (EU) countries, Japan, and the U.S. Fourteen biosimilar filgrastims have been marketed in EU count...
A bimodal pattern of hazard of relapse among early stage breast cancer patients has been identified in multiple databases from US, Europe and Asia. We have been studying these data to determine if this can lead to new ideas on how to prevent relapse in breast cancer. Using computer simulation and access to a very high quality database from Milan fo...
A 43-year-old female with multiple sclerosis developed urethral melanoma. The only potential risk factor was treatment with natalizumab, a humanized monoclonal antibody against α4 integrins. To investigate the risk-exposure relationship, we reviewed this case, all other published cases, and cases of natalizumab-associated melanoma reported to regul...
e21650
Background: Cancer patients develop symptoms that are pathognomonic of a failing circadian organization [CO]. Our concurrent study of 84 advanced cancer patients on randomly timed chemotherapy revealed that each suffered more disrupted circadian rhythms, sleep disorders, anxiety/depression, and quality of life scores compared to healthy age-...
Purpose:
The US Food and Drug Administration (FDA) has approved epoetin and darbepoetin for chemotherapy-induced anemia (CIA). Approved epoetin and darbepoetin dosing schedules were three times per week and weekly, respectively, although off-label, less frequent scheduling was common. In 2004, 2007, and 2008, a US Food and Drug Administration Advi...
Although the availability of generic oncology drugs allows access to contemporary care and reduces costs, there is international variability in the safety of this class of drugs. In this Series paper, we review clinical, policy, safety, and regulatory considerations for generic oncology drugs focusing on the USA, Canada, the European Union (EU), Ja...
130
Background: Oncology Analytics is a cancer care decision support group recently entering the Puerto Rican cancer care marketplace. Bone agents are used in metastatic cancer management to delay the progression of lytic bone metastases. These agents are also used for the treatment of demonstrated osteoporosis with bone densitometry (DEXA scan). O...
248
Background: The National Comprehensive Cancer Network (NCCN) invites petitions to its scientific panels. Most ( > 95%) are from the pharmaceutical industry lobbying to include their products in the NCCN Guidelines. Rarely, physicians request scientific scrutiny of the guidelines. We report the experience of Oncology Analytics (OA) with petition...
128 Background: Growth factor use is the largest single category of drug expenditure for US cancer patients. Oncology Analytics is a decision support company that assists physicians in determining the appropriate use of GF based on the NCCN, ASCO, and ASH guidelines and the level one data that underlies these guidelines. We hypothesized that there...
126
Background: Oncology Analytics (OA) reviewed drug pre-authorization requests amongst populations with similar demographic features. Small stage I, node-negative, margin-free BC may be treated by observation, hormone therapy or adjuvant chemotherapy. If chemo is used, either standard or DD schedules may be requested. Patient age, HER2 status, an...
William Hrushesky,1–5 James F Grutsch,6 Dinah Faith Q Huff,1 Linda Tavolacci,7 Thomas Kazlausky7 1Oncology Analytics, Inc., Plantation, FL, USA; 2South Carolina College of Pharmacy, 3Arnold School of Public Health, University of South Carolina, Columbia, SC, USA; 4Hollings Cancer Center, 5Department of Public Health Science, Medical University of S...
Academic scientists and scientists employed by manufacturers of erythropoiesis-stimulating agents report opposite findings in studies of the existence of functional erythropoietin receptors on cancer cells.Even when the US Food and Drug Administration approved erythropoietin to treat chemotherapy-induced anemia in 1993, concern was raised that admi...
Biological oncology products are integral to cancer treatment, but their high costs pose challenges to patients, families, providers, and insurers. The introduction of biosimilar agents-molecules that are similar in structure, function, activity, immunogenicity, and safety to the original biological drugs-provide opportunities both to improve healt...
248 Background: Among patients with early stage non-small cell lung cancer (NSCLC), appropriate use of adjuvant chemotherapy is an important determinant of survival. Existing level 1 data, which includes analysis of five cisplatin-based phase III trials (IALT, BLT, ALPI, ANITA, NCIC-CTG-JBR.10), two carboplatin-based phase III trials (CALGB 9633 an...
36 Background: Rituximab maintenance for indolent, incurable non-Hodgkin lymphoma (NHL) remains controversial. NCCN supports maintenance rituximab for a span of up to two years as an alternative to watchful waiting following induction therapy. At least a dozen scientific papers have been published describing rituximab maintenance results; none has...
249 Background: Oxaliplatin-containing regimens are among the most efficacious adjuvant treatments for locally-advanced colon cancer, although significant toxicity can occur. Because of relevant level I data, the NCCN revised its guidelines in 2012, recommending omission of oxaliplatin from combination adjuvant chemotherapy regimens for older patie...
246
Background: Albumin-bound paclitaxel is FDA approved as single agent for breast cancer, in combination with carboplatin for non-small cell lung cancer (NSCLC), and with gemcitabine for pancreatic cancer. Oncology Analytics (OA) is a cancer care decision support group comprised of board-certified oncologists, interacting with more than 2,800 can...
33
Background: The Wall Street Journal recently identified that the highest rates of use of erythropoietin to Medicare-covered persons with cancer in the United States was by 11 oncologists who practiced in Florida (WSJ, June 20, 2014). We asked a related, but similar question: Could chemotherapy claims databases be used to identify individual phys...
212
Background: Oncology Analytics, Inc. (OA) promotes evidence-based, guidelines-compliant cancer therapeutic decision-making on behalf of healthcare payers. The OA web-based 1,300 protocol treatment request system screens several hundred applications each month. Evidence-based requests are automatically approvable within seconds (Auto); those nee...
1080
Background: For decades, anthracyclines have been among the most useful treatments for women with MBC. Though recent publications have confirmed an overall decline in the use of anthracyclines in BC, most of that decline was felt to be due to its diminished utilization in the adjuvant management of BC. Current community anthracycline usage pat...
e20672
Background: Bone modifying agents have been shown to delay and/or prevent skeletal-related events for a range of cancers metastatic to the bone. Various studies have identified pamidronate, zoledronic acid, and denosumab as bone modifying agents, each of which confers clinical benefit. The convenience of administration and costs of these age...
e20697
Background: Circadian, seasonal and annual temporal organization characterizes earth-evolved life forms. Cellular proliferation in human bone marrow shares this temporal organization. Careful clinical trials have documented that bone marrow damage from a range of cytotoxic anti-cancer drugs is predictably greater and lesser when these drugs...
e19130
Background: Oncology Analytics (OA) promotes evidence-based treatments, based upon objective assessments of efficacy and safety. ASCO guidelines and FDA approval recommend bevacizumab only in combination with carboplatin/paclitaxel, based on E4599 which showed improved OS. NCCN guidelines allow bevacizumab with virtually any approved 1st lin...
e11609
Background: Anthracyclines remain among the most active agents for the treatment of BC. NSABP B-31, NCCTG N9831 and HERA, each employing anthracyclines followed by trastuzumab in adjuvant HER2+ BC, demonstrated significant reduction in the risk of recurrence and improvement in survival . A fourth study, BCIRG-006, compared a non-anthracyclin...
e14646
Background: The addition of oxaliplatin in adjuvant chemotherapy for stage II CRC and for elderly (≥ 70) patients with stage II or III CRC requires careful consideration. Most patients with stage II or III CRC receive oxaliplatin-based adjuvant regimens (Abrams. J Clin Oncol 2011). Mature results of the adjuvant MOSAIC and C-07 trials, howev...
Purpose: In the United States, public and private payer misincentivization of medical care and the invisibility of costs to the consumers of that care have conspired to create unsustainable growth in health care expenditure that undermines our economy, diminishes our productivity, and limits our international competitiveness. Cancer medicine provid...
Periodic episodes of increased sunspot activity (solar electromagnetic storms) occur with 10-11 and 5-6 year periodicities and may be associated with measurable biological events. We investigated whether this sunspot periodicity characterized the incidence of Pap smear-determined cervical epithelial histopathologies and human physiologic functions....
The interactions between a therapeutic protein and the surfaces of a delivery device may play a pivotal role in the efficacy of a recombinant protein-based biologic therapy program. Protein adsorption may induce conformational changes and aggregation, resulting in the inactivation of the protein of interest and even malfunction of the delivery devi...
The study was designed to determine how tumour hormone receptor status affects the subsequent pattern over time (dynamics) of breast cancer recurrence and death following conservative primary breast cancer resection.
Time span from primary resection until both first recurrence and death were considered among 2825 patients undergoing conservative su...
The circadian clock exists in virtually every cell and regulates key biological processes in cells and tissues. Even in cancer cells, DNA synthesis, cell division and tumor growth are gated by the circadian clock. This study examined the gene expression profiles of transplanted mouse breast tumor cells under normal light-dark (LD) as well as consta...
Human breast cancer incidence has seasonal patterns that seem to vary among global populations. The aggregate monthly frequency of breast cancer diagnosis was collected and examined for 2,921,714 breast cancer cases diagnosed across 64 global regions over spans from 2 to 53 years. Breast cancer is consistently diagnosed more often in spring and fal...
The circadian clock controls many cellular processes, some of which are key to tumor suppression, including cell proliferation
and apoptosis, DNA repair, metabolism, hormone signaling, and immune function. The association between altered circadian clock
function and increased risk of colorectal cancer is increasingly evident from epidemiologic, pre...
Melatonin, a small organic molecule synthesized by the pineal gland and the retina, has a variety of physiologic functions such as circadian clock pacemaker and antioxidant. Retinal melatonin is down-regulated by light and is barely detectable during the day. The absence of melatonin in the retina during prolonged light exposure may contribute to l...
Separation of colorectal cancer cells from other biological materials is important for stool-based diagnosis of colorectal cancer. In this paper, we use conventional dielectrophoresis in a microfluidic chip to manipulate and isolate HCT116 colorectal cancer cells. It is noticed that at a particular alternating current frequency band, the HCT116 cel...
We measured subjectively evaluated depression and anxiety, and objectively measured daily sleep-activity patterns in inpatients and outpatients with advanced non-small cell lung cancer (NSCLC) and determined whether cancer-associated depression and anxiety are accompanied by characteristic circadian rhythm abnormalities.
Equal numbers of inpatients...
Period genes ( Per2, Per1) are essential circadian clock genes. They also function as negative growth regulators. Per2 mutant mice show de novo and radiation-induced epithelial hyperplasia, tumors, and an abnormal DNA damage response. Human tumors show Period gene mutations or decreased expression. Other murine clock gene mutations are not associat...
Circadian disruption has been linked with inflammation, an established cancer risk factor. Per3 clock gene polymorphisms have also been associated with circadian disruption and with increased cancer risk. Patients completed a questionnaire and provided a blood sample prior to undergoing a colonoscopy (n = 70). Adjusted mean serum cytokine concentra...
Timeless (Tim), a core circadian clock gene in Drosophila, is retained in mammals but has no apparent mammalian circadian clock function. Mammalian TIM is essential for ATR-dependent
Chk1 activation and S-phase arrest. We report that TIM is likewise essential for ATM-dependent Chk2-mediated signaling of
doxorubicin-induced DNA double strand breaks....
Breast cancer relapse and death occur more often and sooner among young pre-menopausal women. Breast cancer resected during luteal phase cures about a quarter more women than if the operation is performed during follicular phase. We have identified candidate breast cancer gene signatures that may point to the potential mechanisms of cycle stage-dep...
Separation of cancer cells from the other biological cells can be useful
for clinical cancer diagnosis and cancer treatment. In this
presentation, conventional dielectrophoresis (c-DEP) is used in a
microfluidic chip to manipulate and collect colorectal cancer HCT116
cell, which is doped with Human Embryonic Kidney 293 cells (HEK 293). It
is notice...
Cell cycle progression is tightly regulated. The expressions of cell cycle regulators, the products of which either promote or inhibit cell proliferation, oscillate during each cell cycle. Cellular proliferation and the expression of cell cycle regulators are also controlled by the circadian clock. Disruption of the circadian clock may thereby lead...
Purpose Per2, a core circadian clock gene, has tumor suppressor properties and is mutated or down regulated in human breast cancers. We have manipulated the expression of this gene in vitro and in vivo to more fully understand how the Per2 clock gene product affects cancer growth. Methods We used siRNA and shRNA to down regulate Per2 expression in...
Supplementary Table 1 shows the circadian variation in tumor size
and thymidylate synthase in tumor and normal tissues.
Supplementary Table 2 shows the circadian-dependent 5-FU effects
on host toxicity, anti-tumor efficacy and toxic-therapeutic index.
Supplementary Table 3 shows the circadian variation in tumor
histopathology.
Supplementary Movie 1...
Circadian clocks gate cellular proliferation and, thereby, therapeutically target availability within proliferative pathways. This temporal coordination occurs within both cancerous and noncancerous proliferating tissues. The timing within the circadian cycle of the administration of drugs targeting proliferative pathways necessarily impacts the am...
Erythropoietin (EPO) stimulates red blood cell production, in part by inhibiting apoptosis of the red blood cell precursors. The erythropoietic effects of EPO are circadian stage dependent. Retinal injury due to light occurs through oxidative mechanisms and is manifest by retinal and retinal pigment epithelium (RPE) cells apoptosis. The visual cycl...
At 3-hr intervals over a 24-hr span, 36 systemic, serologic and urinary variables were examined in 7 men in their mid 20's in the Spring of 1969, and again in the same 7 men in the Spring of 1979 under a similar chronobiologic protocol, using the same chemical and numerical analytical procedures. The variables examined for rhythms by cosinor were:...
Proliferation of intestinal epithelial cells is rhythmic throughout the day. This temporal organization occurs through the interaction between the endogenous peripheral circadian clock and pathways controlling cell cycle progression. Per2, a core clock gene with tumour suppresser function, is critical to clock function and to the regulation of cell...
Separation of cancer cells from the other biological cells is important for clinical cancer diagnosis and cancer treatment. In this presentation, we use conventional dielectrophoresis (c-DEP) in a microfluidic chip to manipulate and collect colorectal cancer HCT116 cell. It is noticed that at particular AC frequency band, the HCT116 cell are deflec...
Colorectal cancer risk is increased in shift workers with presumed circadian disruption. Intestinal epithelial cell proliferation is gated throughout each day by the circadian clock. Period 2 (Per2) is a key circadian clock gene. Per2 mutant (Per2(m/m)) mice show an increase in lymphomas and deregulated expression of cyclin D and c-Myc genes that a...
To explain bimodal relapse patterns observed in breast cancer data, we have proposed that metastatic breast cancer growth commonly includes periods of temporary dormancy at both the single cell phase and the avascular micrometastasis phase. The half-lives of these states are 1 and 2 years respectively. We also suggested that surgery to remove the p...
A few clinical investigations suggest that while primary breast cancer surgical removal favorably modifies the natural history for some patients, it may also hasten the metastatic development for others. The concepts underlying this disease paradigm, i.e. tumor homeostasis, tumor dormancy and surgery-driven enhancement of metastasis development, ha...
Oxaliplatin combined with 5-fluorouracil (5-FU), with or without leucovorin (LV), is effective and well tolerated for first-line therapy of advanced colorectal cancer (CRC). However, there is no consensus as to which oxaliplatin/5-FU-containing regimen is superior in the first-line setting. This randomized, multicenter phase II trial was designed t...
Since the 1970s, overall age-adjusted breast cancer mortality rates in the U.S. have been higher among African American (AA) women than among Caucasian American (CA) women. The racial disparity is not fully explainable based on socioeconomic factors. Suspected biologic factors underlying this trend may be interpreted by both epidemiologic and clini...
There is excess breast cancer mortality for African-Americans (AA) compared to European-Americans (EA) of 1.5-2.2 fold that first appeared in 1970s and has been worsening since. This disparity may not be explained solely by reduced access to medical care. We proposed that surgery to remove a primary tumor induces angiogenesis of distant dormant mic...
Human breast cancer incidence, histopathologic grade, invasiveness, and mortality risk vary significantly throughout each year. In order to better understand this seasonal cancer biology, we investigated the circannual pattern of post-resection breast cancer metastasis, under genetically and environmentally controlled conditions.
Over a span of 14...
Tumor expression of the proliferation antigen Ki67 is widely used to assess the prognosis of cancer patients. A change in the expression of Ki67 after short-term exposure of patients to therapeutic agents is frequently used as a pharmacody- namic marker of efficacy, particularly among breast cancer patients before under- going surgery. To determine...
To determine if high-dose melatonin for Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) Class 2 patients with brain metastases improved survival over historical controls, and to determine if the time of day melatonin was given affected its toxicity or efficacy. RTOG 0119 was a phase II randomized trial for this group o...
Without Abstract
To explain bimodal relapse patterns, we have previously suggested that metastatic breast cancer growth commonly includes periods of temporary dormancy at both the single cell and avascular micrometastasis phases (with 1 year and 2 year half-lives respectively). We further suggested that primary surgery sometimes initiates growth of distant dormant...
To find a quantitative relationship between tumor size and frequency of axillary lymph node involvement.
The frequency of axillary node involvement versus primary tumor volume was analyzed in 10 selected series of patients incorporating a total of 57,244 women with resectable breast cancer. The average number of events per unit volume resulting in...
Dysregulated cellular proliferation is a characteristic property of cancer. We show that, despite this fact, cancers maintain high amplitude, circadian rhythms in their growth, DNA synthesis, and mitosis. These patterns are accompanied by the daily traverse of BMAL-1 protein between the cytoplasm, where it is produced, and nucleus, where it influen...
Germ-line mutation of the Apc gene has been linked to familial adenomatous polyposis (FAP) that predisposes to colon cancer. Apc(Min/+) mice, heterozygous for the Apc gene mutation, progressively develop small intestinal tumours in a manner that is analogous to that observed in the colon of patients with FAP (Su et al. 1992; Fodde et al. 1994; Mose...
Citations
... Depending on total radiation doses, supportive care can range from antacids, antibiotics, hydration, and analgesics to the administration of blood cell transfusions if there is severe bone marrow damage (14). There are currently six FDA-approved drugs for the treatment of hematopoietic ARS (H-ARS) including PEGylated Granulocyte Colony Stimulating Factor (also known as PEG-G-CSF, Neulasta™, or PEG-filgrastim), which is in the SNS (15). Although these therapies can alleviate some H-ARS effects, a poly-pharmacy approach with an SNS resource such as ciprofloxacin (an FDA-approved antimicrobial) could enhance the efficacy of Neulasta which may improve outcomes that have been evident with inhibition of the radiation-induced brain hemorrhage in irradiated mice (16,17). ...
![[object Object]](https://i1.rgstatic.net/ii/profile.image/277258569830401-1443115002237_Q64/Kevin-Knopf.jpg)
... The aforementioned lines of evidence provide some possible explanation for the enhanced susceptibility to PML following treatment with B-cell depleting agents such as rituximab [7,8,32]. Thus, it has been suggested that JCV spreading may occur during the B-cell repopulation phase following their prior drug-induced elimination [33]. ...
![[object Object]](https://i1.rgstatic.net/ii/profile.image/273557859074050-1442232684135_Q64/Daniele-Focosi.jpg)
... An additional component to reflect on is the limiting nature of integrating preclinical data in a clinical setting. Reports suggest that factors such as (1) differences in the circadian rhythms (known to influence cancer incidence and progression), (2) differences in metabolic rates (that should affect the response to anti-cancer drug interventions), (3) immune responses, and (4) genetic variations since humans are diurnal when compared to most experimental animals (rats or mice), known to be nocturnal, must be carefully considered in melatonin-related research [165][166][167][168][169]. ...
![[object Object]](https://i1.rgstatic.net/ii/profile.image/278822093115397-1443487775360_Q64/Robert-Levin-2.jpg)
![[object Object]](https://i1.rgstatic.net/ii/profile.image/278829051465741-1443489434437_Q64/David-Blask-2.jpg)
... A reduction in chemotherapy dose could lead to worse outcomes for early-stage patients [34], and chemotherapy dose is highly correlated with serious ADRs. Additionally, serious ADRs can cause financial loss and harm to patients and have a negative effect on manufacturers as well as clinicians [35]. So it is crucial to assess patients' risk of serious ADRs with the aid of web-based tools. ...
![[object Object]](https://i1.rgstatic.net/ii/profile.image/279772862140427-1443714456898_Q64/Shamia-Hoque.jpg)
... Trastuzumab is a drug of great significance in cancer treatment in the sense that it opened up the therapeutic system of HER2-targeted therapy. Along with the widespread use of trastuzumab and the increased demand for cancer treatment, a trastuzumab biosimilar was developed and received FDA approval in 2017 [11,12]. A convenient subcutaneous injection formulation of trastuzumab is also being developed [13,14]. ...
![[object Object]](https://i1.rgstatic.net/ii/profile.image/279883486908424-1443740831452_Q64/Martin-Schoen-4.jpg)
... The results of this paper may also be useful to generate hypotheses about disease progression following a breast cancer diagnosis. Breast cancer metastases have been shown to appear at variable intervals (33), and two hypotheses have been proposed to explain this. The first postulated uninterrupted tumor growth, while the second hypothesized tumor progression as a discontinuous process alternating states of dormancy followed by rapid growth. ...
![[object Object]](https://i1.rgstatic.net/ii/profile.image/1014233210843136-1618823449432_Q64/Romano-Demicheli.jpg)
![[object Object]](https://i1.rgstatic.net/ii/profile.image/273587655409675-1442239791792_Q64/Michael-Retsky.jpg)
![[object Object]](https://i1.rgstatic.net/ii/profile.image/1057519698968576-1629143752990_Q64/Elia-Biganzoli.jpg)
... Titles and abstracts of the 2794 articles were screened; 52 were selected for full-text screening. Of the 52 studies, 40 were excluded at full-text screening or during extraction attempts with the consensus of two coauthors; 12 unique eligible studies were included [32][33][34][35][36][37][38][39][40][41][42][43] (Fig. 1). ...
![[object Object]](https://i1.rgstatic.net/ii/profile.image/277229083873284-1443107972627_Q64/Brian-Chen-13.jpg)
... Pharmaceuticals already on the market have significant safety records and robust drug-drug interaction data compared to natural products and several researchers have looked at the effects of existing pharmaceuticals as it relates to relapse. Retsky (2012, 2020), for example, observed that the perioperative use of the NSAID analgesic ketorolac appears to reduce early relapse following mastectomy in breast cancer [79,80] . Hence, the use of both NHPs and repurposed pharmaceuticals to reach a broad-spectrum of molecular targets could be useful in developing personalized treatment protocols [81] [ Figure 2]. ...
![[object Object]](https://i1.rgstatic.net/ii/profile.image/272333789200433-1441940843800_Q64/Patrice-Forget.jpg)
... Of all the topics we searched, we found the greatest number of studies on treatment patterns in HER2-negative and TN mBC: ten articles [29][30][31][32][33][34][35][36][37][38] and eight conference abstracts (Table 4) [39,40,41,42,43,44,45,46]. Ten of these were retrospective chart reviews [29,30,[32][33][34]37,38,41,44,45], two were physician surveys [31,46] and six were analyses of secondary databases (e.g., Surveillance, Epidemiology and End Results [SEER]-Medicare database, commercial claims) [35,36,39,40,42,43]. ...
... It has been estimated that over 2.2 million people per year in the United States were hospitalized due to adverse drug reactions (ADRs), with approximately 130,000 of those reactions becoming fatal [85]. Prediction and detection of ADRs remains difficult, often relying on time-consuming reporting processes, insufficient data, and professional repercussions [86]. In the last several years, many have proposed utilizing machine learning algorithms to analyze elaborate troves of computerized healthcare data to more successfully predict and prevent future ADRs [87,88]. ...
![[object Object]](https://i1.rgstatic.net/ii/profile.image/272789882011651-1442049584164_Q64/Benjamin-Schooley.jpg)
