Current Breast Cancer Treatment Research Articles

Shared genetics between breast cancer and predisposing diseases identifies novel breast cancer treatment candidates.

Current effective breast cancer treatment options have severe side effects, highlighting a need for new therapies. Drug repurposing can accelerate improvements to care, as FDA-approved drugs have known safety and pharmacological profiles. Some drugs for other conditions, such as metformin, an antidiabetic, have been tested in clinical trials for repurposing for breast cancer. Here, we exploit the genetics of breast cancer and linked predisposing diseases to propose novel drug repurposing. We hypothesize that if a predisposing disease contributes to breast cancer pathology, identifying the pleiotropic genes related to the risk of cancer could prioritize drug targets, among all drugs treating a predisposing disease. We aim to develop a method to not only prioritize drug repurposing, but also to highlight shared etiology explaining repurposing. We compile breast cancer's predisposing diseases from literature. For each predisposing disease, we use GWAS summary statistics to identify genes in loci showing genetic correlation with breast cancer. Then, we use a network approach to link these shared genes to canonical pathways, and similarly for all drugs treating the predisposing disease, we link their targets to pathways. In this manner, we are able to prioritize a list of drugs based on each predisposing disease, with each drug linked to a set of implicating pathways. Finally, we evaluate our recommendations against drugs currently under investigation for breast cancer. We identify 84 loci harboring mutations with positively correlated effects between breast cancer and its predisposing diseases; these contain 194 identified shared genes. Out of the 112 drugs indicated for the predisposing diseases, 76 drugs can be linked to shared genes via pathways (candidate drugs for repurposing). Fifteen out of these candidate drugs are already in advanced clinical trial phases or approved for breast cancer (OR = 9.28, p = 7.99e-03, one-sided Fisher's exact test), highlighting the ability of our approach to identify likely successful candidate drugs for repurposing. Our novel approach accelerates drug repurposing for breast cancer by leveraging shared genetics with its known risk factors. The result provides 59 novel candidate drugs alongside biological insights supporting each recommendation.

Targeting Cardiomyocytes with Adeno Associated Viruses to Protect Hearts from Trastuzumab-induced Cardiotoxicity

Amplification of HER2 occurs in 20% of breast cancers. HER2 (known as ErbB2 in mouse) belongs to the Epidermal Growth Factor Receptor (EGFR) family that is responsible for cell growth and survival. While HER2 does not bind ligands, it forms heterodimers with HER1 (also known as EGFR) in the presence of its ligand EGF, and HER4 following stimulation with Neuregulin. In HER2-positive breast cancer where HER2 expression is high, HER2 homodimerizes leading to excessive activation of downstream signalling and cell proliferation. Current HER2-positive breast cancer treatment involves chemotherapy with drugs called anthracyclines, such as Doxorubicin, and an antibody targeting HER2 called Trastuzumab. This combination is effective in killing HER2-positive breast tumours, however, Trastuzumab alone or in combination with anthracyclines leads to severe cardiotoxicity and heart failure in 2.6-11% of cases, making it a dose-limiting side effect. We hypothesise that cardiac toxicity can be mitigated by targeting cardiomyocytes exclusively to express a mutated (but functional) version of HER2 that is not recognised by trastuzumab. We designed 3 HER2 variants wherein the trastuzumab binding domain was mutated to disrupt binding. These HER2 mutants were transfected into HEK293T cells, and we confirmed that all 3 successfully localised to the cell membrane, and did not bind trastuzumab. We have used bioluminescence resonance energy transfer to examine the capacity of all 3 mutants to activate recruitment of Grb2 to the HER2 as part of HER1/HER2 and HER4/HER2 heterodimers; Western blotting also confirming mutants were capable of stimulating ERK and Akt phosphorylation. Future studies will evaluate the effcacy of using AAVs to instruct cardiomyocytes to express these HER2 mutants in a murine model of breast cancer. We predict that this new therapy would not only mitigate cardiac toxicity, but would also permit higher doses of trastuzumab to be used to treat breast cancer. This work is supported by Australia's National Health and Medical Research Council and the Australian Research Council. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Analysis of Different Treatment Methods for Breast Cancer

This research discusses the mechanisms of current medical treatments for breast cancer and a brief analysis of the treatments. The aim of this research is to present the different cancer therapies and to select the most promising and promising therapies for breast cancer based on the performance of each therapy, where chemotherapy, radiotherapy, and immunotherapy for breast cancer are discussed. By analyzing the various therapies, it is concluded that all three therapies selected for discussion have shown a significant increase in efficacy over their traditional counterparts, but at the same time, the risks and potential shortcomings of the newer therapies have been demonstrated in experimental trials. Through the analysis of this research, it is hoped that there will be a combination of techniques and breakthroughs in therapies for breast cancer. Each therapy has its own shortcomings, and the combination of chemotherapy, radiation, and immunotherapy with current cancer therapies will be the future of cancer breakthroughs.

Abstract 5314: Improved breast cancer tumor control with addition of CD40 agonist and Flt3 ligand to pegylated liposomal doxorubicin is only partially mediated by CD8 T cells

Abstract Background: There is a need for improved immunotherapy strategies beyond current FDA approved treatments for triple negative breast cancer. Defective antigen presentation has been shown to play a contributory role in deficient anti-tumor immunity in breast cancers. Flt3 ligand (Flt3L) is a growth factor that increases differentiation into DC1 dendritic cells. CD40 agonist (CD40a) activates all 3 classes of antigen presenting cells - DCs, B cells, and macrophages. Synergy with chemotherapy and CD40a has been seen in other cancers but not explored in breast cancers. Methods: C57BL/6 mice (aged 6-8 weeks) were injected with 150,000 E0771 breast cancer cells within the mammary fat pad. Tumors were allowed to grow to a volume of ~50 mm3 before randomization into treatment groups. Mice were treated with triplet therapy of pegylated liposomal doxorubicin (PLD) via tail vein followed by Flt3L intraperitoneal (IP) daily for 5 days and CD40a IP 1 week later as well as monotherapy and doublet therapy controls. Tumor growth and survival were monitored throughout the experiment. Tumors were harvested for single cell RNA sequencing (scRNAseq) and immunohistochemistry. To further study subset specific effects on efficacy of the immunotherapy, CD8 and CD4 T-cells were systemically depleted with anti-CD8 and anti-CD4 antibodies administered IP every 4 days starting 2 days before PLD treatment. Results: Triplet therapy led to improved tumor control compared to no treatment, monotherapy, and doublet controls (p<0.0001). Increased tumor infiltration with CD8 T cells was observed with triplet therapy via immunohistochemistry. scRNAseq showed increased cDC1 subset with Flt3L treatment. Contrastingly, CD40a decreased DC subsets likely due to activation and emigration out of the tumor, remodeled macrophage populations, and decreased T regulatory cells. CD8 depletion led to faster tumor growth whereas CD4 depletion reduced tumor growth. Triplet therapy maintained efficacy over PLD with both CD8 and CD4 depletion but showed reduced magnitude of benefit with CD8 T cell depletion suggesting a partial CD8 mediated process. CD4 T cell depletion did not hinder triplet therapy efficacy compared to PLD but depletion further enhanced tumor control in combination with triplet therapy, with 20% (2/10) of animals achieving complete regression. Conclusion: Triplet therapy with PLD, Flt3L, and CD40a improved tumor control and survival in syngeneic E0771 breast cancer mouse model. Added benefit of immunotherapy to PLD is partially CD8 T cell mediated. CD4 depletion further enhances tumor control in combination with triplet therapy. Experiments to explore the interactive effect of triplet therapy with other pertinent immune subsets are ongoing. A clinical trial with this combination in metastatic triple negative breast cancer patients is open and recruiting (NCT05029999). Citation Format: Preteesh L. Mylabathula, Shruthi Nooka, Anas Alkhani, James Zhu, Ashley Vu, Riyasat Ali, Varshini Ramasamy Balasubramanian, Isaac Chan, Sangeetha M. Reddy. Improved breast cancer tumor control with addition of CD40 agonist and Flt3 ligand to pegylated liposomal doxorubicin is only partially mediated by CD8 T cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5314.

Exploring Anti-Breast Cancer Effects of Live Pediococcus acidilactici and Its Cell-Free Supernatant Isolated from Human Breast Milk.

Current breast cancer treatment options are limited by drug resistance and adverse side effects, which calls for the need for alternatives or complementary remedies. Probiotic bacteria isolated from human breast milk have been shown to possess proapoptotic and anti-inflammatory properties against breast mastitis in breastfeeding mothers and are being studied as possible anticancer regimens. Thus, this study aimed at exploring the effect of lactic acid bacteria isolated from human breast milk on MDA-MB 231 breast cancer cells. A total of twenty-two bacteria were isolated from four human breast milk samples. The isolates were characterized and identified using biochemical tests and Sanger sequencing, respectively. For in vitro experiments, we used isolated P. acidilactici to treat MDA-MB-231 cells, and an MTT assay was used to detect proliferation. RT-qPCR and wound healing assays were performed to determine the effect of the isolated P. acidilactici on breast cancer cytokine expression and migration. Exposure of MDA-MB 231 breast cancer cells to live P. acidilactici and its cell-free supernatant (CFS) for 24 h resulted in a reduction in cancer cell viability. Also, the expression of the cytokines IL-6, IL-8, and IL-10 in the breast cancer cells increased following exposure to P. acidilactici and its CFS for 24 and 72 h. Additionally, the levels of the SLUG gene remained unchanged while the TWIST1 gene was upregulated following exposure of the cancer cells to bacteria, indicating that P. acidilactici may promote epithelial-mesenchymal transition in breast cancer. Finally, the CFS significantly inhibited cancer cell mobility. These findings serve as a foundation to further investigate the usefulness of P. acidilactici as a potential therapeutic agent in breast cancer therapy.

Spinosyn A exerts anti-tumorigenic effects on progesterone-sensitive ERα-positive breast cancer cells by modulating multiple signaling pathways

Breast cancer is one of the most common and deadly cancers in women worldwide. Current treatments for breast cancer have limitations, such as toxicity, resistance, and side effects. Therefore, there is a need to develop new and effective anti-cancer agents from natural sources. Spinosyn A (SPA) is a natural product derived from soil bacteria. SPA has been reported to have anti-parasitic, insecticidal, and anti-bacterial activities. However, its anti-cancer effects and mechanisms are not well understood. In this study, we investigated the effects of SPA on T47-D, estrogen receptor-positive breast cancer cells. We found that SPA inhibited cell proliferation and migration and induced apoptosis and cell cycle arrest. Flow cytometry and holographic imaging microscopy revealed that SPA activated MAPK and PI3K signaling pathways and altered cellular morphology. Finally, RNA-Seq analysis revealed that SPA treatment altered the expression of 1380 genes in T47-D cells, which were enriched in various biological processes and signaling pathways related to cell proliferation, cholesterol metabolism, growth factor activity, amino acid transport activity, extracellular matrix, PI3K-Akt signaling pathway, neuroactive ligand-receptor interaction, and PPAR signaling pathway. Our results suggest that SPA exerts multiple anti-cancer effects on T47-D cells by modulating multiple pathways and cellular processes involved in cell growth, survival, and motility. Our findings provide new insights into the molecular mechanisms of SPA action on breast cancer cells and its potential applications as a novel anti-cancer agent.

Cutting-edge approaches for targeted drug delivery in breast cancer: beyond conventional therapies.

Breast cancer is a global health challenge with staggering statistics underscoring its pervasive impact. The burden of this disease is measured in terms of its prevalence and the challenges it poses to healthcare systems, necessitating a closer look at its epidemiology and impact. Current breast cancer treatments, including surgery, chemotherapy, radiation therapy, and targeted therapies, have made significant strides in improving patient outcomes. However, they are not without limitations, often leading to adverse effects and the development of drug resistance. This comprehensive review delves into the complex landscape of breast cancer, including its incidence, current treatment modalities, and the inherent limitations of existing therapeutic approaches. It also sheds light on the promising role of nanotechnology, encompassing both inorganic and organic nanoparticles equipped with the ability to selectively deliver therapeutic agents to tumor sites, in the battle against breast cancer. The review also addresses the emerging therapies, their associated challenges, and the future prospects of targeted drug delivery in breast cancer management.

SERM Therapy for patients of breast cancer and otherwise.

Madam, In Pakistan, the most frequently diagnosed cancer among females is breast cancer, where every year at least 90,000 women suffer from the disease [1]. This incidence is 2.5 times higher than that of Pakistan’s neighbouring countries and the highest in Asia[1]. The current treatments for breast cancer in the country are all invasive forms of therapy and include radiation therapy, chemotherapy, lymph node removal, and mastectomy. This letter aims to draw attention to a newer form of treatment for breast cancer known as selective estrogen receptor modulators (SERMs). Selective estrogen receptor modulators (SERMs) are synthetic molecules that provide a non-invasive therapy for breast cancer patients. Recent studies have proposed that the specificity of SERM’s mechanism of action and antiviral properties yield fruitful outcomes in treating covid-positive breast cancer patients [2], giving SERMs a significant advantage over former treatments such as radiation therapy or chemotherapy which reduce the body’s ability to fight infections. SERMs block the effects of estrogen on breast tissue, preventing cancer cells from dividing. They also act as an adjuvant in breast cancer therapy [3], suppressing secondary tumor formation. A recent study published in the Journal of Clinical Oncology showed significant benefits from two years of tamoxifen therapy in estrogen receptor- positive premenopausal patients of breast cancer [4]. On various other tissues, they act as estrogen, allowing for their use alongside other treatments for postmenopausal women to prevent bone loss and osteoporosis [3]. Despite SERM ‘s wide range of benefits in patients with breast cancer, it is not a fully recognized form of treatment for this population in Pakistan. Such hormonal therapy is only offered by a handful of high-end private-sector hospitals. This is attributed to a lack of research in this area due to various socio-economic factors. A limited choice of treatment for women with breast cancer in Pakistan results from fear of stigmatization and feminine sensitivity [5]. Attention should be brought to alternative therapies for breast cancer treatment to improve prognosis and help patients make the best possible shared decision-making choices.

Protocol of the HISTOTHERM study: assessing the response to hyperthermia and hypofractionated radiotherapy in recurrent breast cancer.

Breast cancer is globally the leading cancer in women, and despite the high 5-year survival rate the most frequent cause of cancer related deaths. Surgery, systemic therapy and radiotherapy are the three pillars of curative breast cancer treatment. However, locoregional recurrences frequently occur after initial treatment and are often challenging to treat, amongst others due to high doses of previous radiotherapy treatments. Radiotherapy can be combined with local hyperthermia to sensitize tumor cells to radiation and thereby significantly reduce the required radiation dose. Therefore, the combination treatment of mild local hyperthermia, i.e. locally heating of the tissue to 39-43°C, and re-irradiation with a reduced total dose is a relevant treatment option for previously irradiated patients. The mechanisms of this effect in the course of the therapy are to date not well understood and will be investigated in the HISTOTHERM study. Patients with local or (loco)regional recurrent breast cancer with macroscopic tumors are included in the study. Local tumor control is evaluated clinically and histologically during the course of a combination treatment of 60 minutes mild superficial hyperthermia (39 - 43°C) using water-filtered infrared A (wIRA) irradiation, immediately followed by hypofractionated re-irradiation with a total dose of 20-24 Gy, administered in weekly doses of 4 Gy. Tumor and tumor stroma biopsies as well as blood samples will be collected prior to treatment, during therapy (at a dose of 12 Gy) and in the follow-up to monitor therapy response. The treatment represents the standard operating procedure for hyperthermia plus re-irradiation. Various tissue and blood-based markers are analyzed. We aim at pinpointing key mechanisms and markers for therapy response which may help guiding treatment decisions in future. In addition, quality of life in the course of treatment will be assessed and survival data will be evaluated. The study is registered at the German Clinical Trials Register, Deutsches Register Klinischer Studien (DRKS00029221).

Chemopreventive approach of Indian spice “Curcumin” in the treatment of breast cancer

One of the primary concerns for women in good health is breast cancer. The most typical hazardous growth is this one. It spreads easily, and the clinical conditions are terrible. Bosom illness is the second‐most common type of malignant tumor that regularly causes women to pass away in the U.S. bosom malignant growth is the most well‐known disease among women worldwide, with 2.1 million cases reported in 2018 and more than 620,000 fatalities per year. Natural components are viewed as promising alternatives for the development of novel anti‐tumor drugs. Curcumin, also termed diferuloylmethane, is a yellow pigment made by the turmeric plant, Curcuma longa Linn. It is the curcuminoid and polyphenol present in the plant’s root that is most abundant. The antioxidant and anti‐inflammatory qualities of curcumin have been demonstrated, and it is frequently utilized in traditional medicine and cuisine. Due to its sophisticated pharmacological capabilities of chemoprevention and anticancer effects, curcumin, the main component of turmeric, has been linked to the treatment of breast cancer. The morbidity or mortality of the disease have not been significantly decreased by current breast cancer treatment options such as surgery, radiation, adjuvant chemotherapy, or hormone therapy. The expansion, estrogen receptor (trauma center), and human epidermal development factor receptor 2 (HER2) pathways are all involved in the activity of curcumin in illness. In breast cancer cells, curcumin is also known to regulate microRNA, cell stage-related characteristics, and apoptosis. This study reviews recent research on the atomic targets and anticancer effects of curcumin in breast cancer.

Bioactive Natural Products for Breast Cancer Chemoprevention and Treatment

Background: In addition to being one of the deadliest tumors, breast cancer is also one of the most difficult to cure. Due to the serious side effects of current breast cancer treatments and the rise in drug resistance, current drugs are losing their effectiveness. Potential Natural Bioactives: Bioactive natural compounds target various pathophysiological pathways involved in the development and progression of cancer and hence have the ability to prevent both the growth of breast cancer and the advancement of metastatic disease concurrently. : Natural anticancer compounds have been shown to be effective, complementary treatment may be of great assistance in this case. Clinical Outcomes: Nutraceuticals and popular folk remedies may provide benefits over manufactured pharmaceuticals since they have fewer side effects and less toxicity in both in vitro and in vivo studies. A variety of natural compounds have been shown to reduce the aggressiveness of breast cancer, inhibit the growth of malignant cells, and alter the pathways involved in cancer development and progression. Either by directly affecting certain biological targets, such genes, or by indirectly stabilising conjugates that have an impact on metabolic processes, natural compounds called phytochemicals can enhance human health. Mechanistic Pathways: There are many promising bioactive natural products that can be used to treat breast cancer, including those that inhibit aromatase activity, target HIF-1 signaling, inhibit cytoplasmic signaling, modulate epigenetic regulation, modulate estrogen signaling pathways, or work in chemosensitivity/adjuvant therapy (such as resveratrol, epigallocatechin-3-gallate, and eugenol).

Real-world evaluation of an acceptance and commitment therapy–based group programme for breast cancer survivors with fear of cancer recurrence

PurposeTo evaluate the effectiveness and acceptability of a 6-week acceptance and commitment therapy (ACT)–based group programme on participants’ fear of cancer recurrence (FCR), quality of life (QoL), psychological distress and psychological flexibility at the end of the programme and 12-week follow-up.MethodsA one-group, post-test service evaluation of a real-world psychological programme was carried out to evaluate collected outcome measures and attendance for a total of 21 groups facilitated between 2017 and 2019. Participants were breast cancer survivors who attended a 6-week group programme led by NHS clinicians. Descriptive statistics and repeated measures ANOVA analyses were carried out for each outcome measure. Attendance levels were examined to assess acceptability.ResultsA total of 97 group participants who had completed curative treatment for breast cancer took part. Of whom, 89% completed at least 4 of the 6 weekly group sessions and 76% attended the 12-week follow-up session. Eighty-four (87%) participants returned outcome measures at all three time points relative to group participation (T1 = pre, T2 = post T3 = 12-week follow-up). Group participants were female, mean age 51.9 years. FCR was highest at T1 (mean 25.2, SD 4.7), reduced T2 (mean 21.2, SD 5.4) and further lowered T3 (mean 19.5, SD 6.2). This difference was statistically significant (p < 0.001). QoL was lowest at T1 (mean 62.4, SD 15.7), increased T2 (mean 71.7, SD 18.1) and further increased at T3 (mean 75.9, SD 17.5). This difference was statistically significant (p < 0.001). Psychological distress measures were shown to reduce, and psychological flexibility increased.ConclusionsThis real-world evaluation of an ACT-based group programme led to improvements in FCR, QoL, psychological distress and psychological flexibility in this population. This evaluation provides basis for further investigation to determine if these results can be replicated by controlled research design across diverse populations.

Successful fat-only whole breast reconstruction using cultured mature adipocytes and conditioned medium containing MCP-1

A mastectomy is a curative treatment for breast cancer. It causes breast and soft tissue deficits, resulting in a chest with poor vascularity. Autologous tissue breast reconstruction is commonly associated with donor site morbidity. Breast implants are another reconstruction alternative, but they are associated with infection, rupture, and the need for replacement. Autologous aspirated fat grafting has appeared as an ideal breast reconstruction method, but low graft viability and high resorption remain as the main shortcomings. We developed a novel method for fat-only grafts using cultured mature adipocytes (CMAs) mixed with their condition medium. Twenty-five mastectomy patients, aged 32–72 years, received a mixed grafting of CMAs, MCP1-containing condition medium, and fat grafts for total breast reconstruction. In follow-up periods of 24–75 months, MRI analysis showed full thickness fat-engraftment. The cell proliferation marker Ki67 was negative in post-transplant biopsy specimens from all patients. Aesthetic full breast morphology was achieved, patient satisfaction was evaluated 1 year and 3–6 years after surgery. All grafts were confirmed safe, demonstrating high reliability and long-term sustainability.

Individualising radiation therapy decisions in breast cancer patients based on tumour infiltrating lymphocytes and genomic biomarkers.

Radiation therapy (RT) has long been fundamental for the curative treatment of breast cancer. While substantial progress has been made in the anatomical and technological precision of RT delivery, and some approaches to de-escalate or omit RT based on clinicopathologic features have been successful, there remain substantial opportunities to refine individualised RT based on tumour biology. A major area of clinical and research interest is to ascertain the individualised risk of loco-regional recurrence to direct treatment decisions regarding escalation and de-escalation of RT. Patient-tailored treatment with RT is considerably lagging behind compared with the massive progress made in the field of personalised medicine that currently mainly applies to decisions on the use of systemic therapy or targeted agents. Herein we review select literature surrounding the use of tumour genomic biomarkers and biomarkers of the immune system, including tumour infiltrating lymphocytes (TILs), within the management of breast cancer, specifically as they relate to progress in moving toward analytically validated and clinically tested biomarkers utilized in RT.

Actively targeted gold-polydopamine (PDA@Au) nanocomplex for sequential drug release and combined synergistic chemo-photothermal therapeutic effects

Multifunctional nanoparticles for treatment in cancer are getting more and more attention recently. In this study, we employed a novel polydopamine (PDA) framework-based gold nanoparticles as a carrier of an antimetabolite drug, 5-Fluorouracil (5-FU). Folic acid (FA) was embellished onto the surface of nanoparticle imparting the nanosystem with remarkable tumor-targeting abilities through its precise binding with FA receptor that is notably overexpressed in breast cancer cells. PDA served as a photothermal treatment (PTT) agent and a gatekeeper to regulate drug release since it is highly pH-sensitive and might lengthen the residency period while simultaneously enhancing water solubility and biological compatibility of nanomaterials. Gold nanoparticles (Au NPs) end up serving as both a drug delivery platform and a source of substantial photothermal effects, culminating in synergistically coupled chemo-photothermal therapy. The PDA@Au@FA nanocomplex, loaded with 5-FU, is biocompatible, features strong NIR absorption and photothermal conversion, and can control drug release in pH/NIR dual response environment. The cell viability in PDA@Au@5-FU-FA group with NIR irradiation in 48 h was only 20.1 ± 2.6%. In addition, apoptosis staining experiments revealed greater cellular uptake of PDA@Au@5-FU-FA by MCF-7 cells. Therefore, PDA@Au@5-FU-FA nanocomplex that we postulated herein may be a potential contender for effective curative treatment for breast cancer.

Breast Cancer in Brazil: Screening Program and Surgical Approach

Breast cancer is the most common female cancer, and Screening mammography is a current strategy that reduces mortality among women. In Brazil, more recent data show an increasing number of mammograms but unequal geographic access to the exam nationwide. Breast surgery is essential to the current oncological treatment and management of breast cancer. Conservative breast techniques have been established as an effective treatment option; however, mastectomies are still widely used in Brazil. The increase in breast cancer screening programs nationwide should increase the number of breast-conserving surgeries over total mastectomies. However, these expectations may be compromised in developing countries such as Brazil, where there are relevant discrepancies in the public health system.

The аntitumor effect of 2-[3-(2-chloroethyl)-3-nitrosoureido]-1,3-propanediol (chlonisol) on the growth of spontaneous mammary tumors in HER-2/neu transgenic mice

Background. Current treatment of HER2-positive metastatic breast cancer (BC) is based on the use of anti-HER2 blockers as pathogenic drugs, as well as the search for the optimal combination of anticancer drugs with different mechanisms of action. The potential activity of chlonisol in HER2+ ВС is of great interesting. The aim of the study was to evaluate the antitumor effect of 2-[3-(2-chloroethyl)-3-nitrosouriedo]-1,3-propanediol (chlonisol) on the growth of spontaneous mammary tumors in HER-2/neu transgenic FVB/N mice. Material and Methods. A prospective study used 5-month-old female mice with HER2-positive mammary tumors. Of these animals, ten pairs with almost the same size of tumors were formed (respectively, for the control group and the chlonisol treatment group). Chlonisol was administered at a dose of 20 mg/kg intraperitoneally, once. The animals were followed up for 30 days. Results. In all ten pairs of mice, chlonisol showed a significant antitumor effect, up to a complete temporary regression of the tumor. When summing the comparative results of all ten pairs of animals, the inhibition of tumor growth (ITG) in the chlonisol treatment group was 90-97 % (p&lt;0.0001), and the area under the kinetic curve of tumor growth was 13.6 times less than in the control group (p&lt;0.0001), thus indicating a significant effect. Conclusion. Chlonisol has a high therapeutic activity by inhibiting the growth of spontaneous HER2-positive breast tumors in FVB/N mice.

Primary care provider attitudes about and tendency to use non-recommended surveillance tests after curative breast cancer treatment.

Little is known about the factors contributing to the receipt of non-recommended surveillance testing among early-stage breast cancer survivors. We assessed primary care providers (PCP) attitudes about and tendency to order non-recommended surveillance testing for asymptomatic early-stage breast cancer survivors post-adjuvant chemotherapy. A stratified random sample of PCPs identified by early-stage breast cancer survivors were surveyed (N = 518, 61% response rate). PCPs were asked how likely they would be to order bone scans, imaging and/or tumor marker testing using a clinical vignette of an early-stage asymptomatic patient where these tests are non-recommended. A composite tendency to order score was created and categorized by tertiles (low, moderate, high). PCP-reported factors associated with high and moderate tendency to order non-recommended testing (vs. low) were estimated using multivariable, multinomial logistic regression. In this sample, 26% reported a high tendency to order non-recommended surveillance tests during survivorship for early-stage breast cancer survivors. PCPs who identified as family practice physicians and PCPs reporting more confidence in ordering surveillance testing were more likely to report a high tendency to order non-recommended testing (vs. low) ((aOR family practice 2.09, CI 1.2, 3.8; aOR more confidence 1.9, CI 1.1, 3.3). In this population-based sample of PCPs caring for breast cancer survivors, over a quarter of PCPs reported they would order non-recommended surveillance testing for asymptomatic early-stage breast cancer survivors. Efforts to better support PCPs and disseminate information about appropriate surveillance for cancer survivors are warranted.

Early-stage CCNG1+ HR+ HER2+ Invasive Breast Carcinoma in Older Women: Current Treatment and Future Perspectives for DeltaRex-G, a CCNG1 Inhibitor.

Women with HR+HER2+ early-stage breast cancer are disadvantaged by the lack of clinical trials focused on women ≥70 years of age. In the past years, there has been increasing controversy on the use of toxic chemotherapy as standard of care treatment for early- stage HR+ HER2+ breast carcinoma in older women. With precision medicine coming of age, molecular profiling of tumors and circulating tumor DNA has identified target oncogenes that could be used in designing an optimal treatment for this group of women. This article reviews the current treatment of early-stage triple receptor positive breast cancer, the risks of chemotherapy in older women, and CCNG1, a novel biomarker in development for the use of DeltaRex-G, a CCNG1 inhibitor. Further, future perspectives for DeltaRex-G in older women with early stage CCNG1+ HR+ HER2+ breast cancer are discussed.

Enhanced Recovery After Surgery and Postoperative Nausea and Length of Stay in Mastectomy Patients With Reconstruction

IntroductionSurgery is a mainstay of curative breast cancer treatment and is associated with postoperative nausea and vomiting (PONV) negatively impacting the patient experience. Enhanced recovery after surgery (ERAS) protocols are a combination of evidence-based strategies applied to traditional perioperative practices with the goal to reduce postoperative complications. ERAS protocols have been traditionally underutilized in breast surgery. We investigated if the implementation of an ERAS protocol was associated with decreased rates of PONV as well as length of stay (LOS) in patients undergoing mastectomy with breast reconstruction. MethodsWe conducted a retrospective chart review case-control study in which we compared PONV and LOS between ERAS cases and non-ERAS controls. Our data set consisted of 138 ERAS cases and 96 non-ERAS controls. All patients were >18 y old and underwent mastectomy with immediate implant or tissue expander-based reconstruction between 2018 and 2020. The non-ERAS group consisted of procedure-matched controls that were treated prior to implementation of the ERAS protocol. ResultsIn univariate comparisons, patients who underwent the ERAS protocol had significantly decreased postoperative nausea (mean 37.5% of controls versus 18.1% of ERAS, P < 0.001) and shorter LOS (1.21 versus 1.49 d, P < 0.001). Using a multivariable regression to control for potential confounders, ERAS protocol was associated with less postoperative nausea (odds ratio [OR] = 0.26, 95% confidence interval [CI] = 0.13-0.5), LOS 1 d versus > 1 d (OR = 0.19, 95% CI = 0.1-0.35), and less postoperative ondansetron use (OR = 0.03, 95% CI = 0.01-0.07). ConclusionsOur results indicate that implementation of the ERAS protocol in women undergoing mastectomy with immediate reconstruction is associated with improved patient outcomes in postoperative nausea and LOS.