Nanomedicine: A Promising Avenue for the Development of Effective Therapy for Breast Cancer

2020 ◽  
Vol 20 (8) ◽  
pp. 603-615
Author(s):  
Ali Sartaj ◽  
Sanjula Baboota ◽  
Javed Ali

Purpose: Breast cancer is the most probable cancer among women. However, the available treatment is based on targeting different stages of breast cancer viz., radiation therapy, hormonal therapy, chemotherapy, and surgical interventions, which have some limitations. The available chemotherapeutics are associated with problems like low solubility, low permeability, high first-pass metabolism, and P-glycoprotein efflux. Hence, the aforementioned restrictions lead to ineffective treatment. Multiple chemotherapeutics can also cause resistance in tumors. So, the purpose is to develop an effective therapeutic regimen for the treatment of breast cancer by applying a nanomedicinal approach. Methods: This review has been conducted on a systematic search strategy, based on relevant literature available on Pub Med, MedlinePlus, Google Scholar, and Sciencedirect up to November 2019 using keywords present in abstract and title of the review. As per our inclusion and exclusion criteria, 226 articles were screened. Among 226, a total of 40 articles were selected for this review. Results: The significant findings with the currently available treatment is that the drug, besides its distribution to the target-specific site, also distributes to healthy cells, which results in severe side effects. Moreover, the drug is less bioavailable at the site of action; therefore, to overcome this, a high dose is required, which again causes side effects and lower the benefits. Nanomedicinal approaches give an alternative approach to avoid the associated problems of available chemotherapeutics treatment of breast cancer. Conclusion: The nanomedicinal strategies are useful over the conventional treatment of breast cancer and deliver a target-specific drug-using different novel drug delivery approaches.

2021 ◽  
Vol 27 ◽  
Author(s):  
Ali Sartaj ◽  
Sanjula Baboota ◽  
Javed Ali

Purpose: The available conventional treatment for breast cancer, like surgery, hormonal, radiation, and chemotherapy, given alone or in combination, is commonly used. Due to broad and diverse side effects, toxicity, and multi-drug resistance, chemotherapy has limited use and less effective treatment. In this review, anti-cancer drugs used in combination with phytoconstituents approaches have been summarised. It has been anticipated that this could be a promising and effective strategy for breast cancer treatment. Methods: This review is conducted based on relevant literature using the keywords presented in the title, abstract, and keywords. The available literature search in PubMed, ScienceDirect, MedlinePlus, and Google scholar up to May 2021. A total of 47 articles were selected out of 168 articles based on inclusion and exclusion criteria. Results: The significant drawbacks of available conventional treatment, especially chemotherapy, are low bioavailability for absorption at the specific site of tumor cells, development of multi-drug resistance, and high dose-related to various side effects. The phytoconstituents have anticancerous properties and chemotherapeutic agents that find a promising and potential therapeutics modality. Many in vitro and in vivo studies showed that phytoconstituents could enhance the effectiveness of chemotherapy drugs for breast cancer treatment. Conclusion: The combination approaches of phytoconstituents with chemotherapeutic drugs give less toxicity to normal cells, reduce side effects, and overcome the multi-drug resistance, making the combination approaches an effective strategy.


2019 ◽  
Vol 13 ◽  
pp. 117822341984419 ◽  
Author(s):  
Wei Yue ◽  
Carole Verhoeven ◽  
Herjan Coelingh Bernnink ◽  
Ji-ping Wang ◽  
Richard J Santen

Purpose: Postmenopausal women with estrogen receptor-positive breast cancers often respond initially to tamoxifen or aromatase inhibitor therapy. Resistance to these treatments usually develops within 12 to 18 months. Clinical studies have demonstrated that high-dose estrogen can induce regression of these endocrine-resistant tumors. However, side-effects of high-dose estradiol (E2) or diethylstilbestrol (DES) limit their usage. Estetrol (E4) is the most abundant estrogen during pregnancy and has a long half-life and a low potential for side-effects. Estetrol might then provide benefits similar to DES on tumor regression but with lesser toxicity. Methods: In this study, we systematically evaluated the effects of E4 on cell proliferation and apoptosis in wild-type MCF-7 and long-term estrogen-deprived (LTED) MCF-7 cells and compared its effects with E2 and estriol (E3). Results: Estetrol induced apoptosis in LTED cells but stimulated growth of MCF-7 cells at concentrations from 10−11 to 10−8 M. These effects of E4 are similar to those of E2 but require much higher doses. Differing from E2, E4 at 10−12 M induced apoptosis in MCF-7 cells and another pregnancy estrogen, E3, acted similarly. No antagonistic effect of E4 or E3 against E2 occurred when they were combined. Conclusions: The pro-apoptotic effects of E4 and E3 on LTED cells and at low doses on MCF-7 cells indicate that these steroids could be used as therapeutic agents for endocrine-resistant or sensitive breast cancer.


Breast Care ◽  
2016 ◽  
Vol 11 (1) ◽  
pp. 57-59 ◽  
Author(s):  
Angela A. García-Ruano ◽  
Esther Deleyto ◽  
Jose Maria Lasso

Background: Pyoderma gangrenosum (PG) is a rare cutaneous ulcerative disease that does not respond to antibiotics and worsens with surgical manipulation. This is the first report in the literature revealing that this disease complicates total microsurgical breast reconstruction associated with the transfer of free lymph nodes. Case Report: We report the case of a female patient who underwent left-breast microsurgical reconstruction with a deep inferior epigastric perforator (DIEP) flap and simultaneous transfer of vascularized free lymph nodes for the surgical treatment of secondary left upper-limb lymphedema, and who developed a severe PG of both the skin of the flap and the donor zone on postoperative day 7. After exclusion of other etiologies, treatment with high-dose corticosteroids and topical zinc sulfate was initiated. The flap was salvaged and breast cancer-related lymphedema (BCRL) surgery was definitively effective despite the PG. Conclusions: PG should be considered in the differential diagnosis of progressive cutaneous ulcers following surgical interventions, once infectious and ischemic etiologies have been excluded. Early initiation of immunosuppressive treatment can lead to preservation of the initial flap and function of the transferred lymph nodes in the case of microsurgical breast reconstruction with associated lymph node transfer.


2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A1041-A1041
Author(s):  
David T Zava ◽  
David W Kimball ◽  
Rebecca L Glaser

Abstract Introduction: High dose testosterone (T) has been used for treating hormone-sensitive breast cancers for many years. However, a drawback to T therapy is its propensity to convert to estradiol (E2) via aromatase, which can override the growth inhibitory effects of T and stimulate estrogen sensitive tumors. Aromatase is higher in some women than others, particularly those with active tumors, truncal obesity, and inflammatory conditions contributing to and caused by cancer. Oral aromatase inhibitors (AI) have been used to prevent conversion of T to E2. While this effectively reduces E2 burden, systemic oral AI require higher dosing, which often leads to severe side effects. As an alternative to oral AI therapy, researchers have found that T combined with a much lower dose of AI in a solitary pellet implant placed in the subcutaneous (SC) tissue, or alternatively, into the breast adjacent to a primary tumor, is effective in reducing tumor burden and maintaining a low systemic level of E2, while reducing the adverse side effects of very low E2. Study Design: In this case study we report on the use of an LC-MS/MS method to monitor salivary levels of E2, Estrone (E1), T, and the AIs Letrozole (LET) and Anastrozole (ANZ) following T + AI therapy in a breast cancer patient (intolerant of oral LET) with active (measurable) tumor in the breast and metastatic disease. Steroids and AIs were measured in saliva at baseline, 1 week, and 4 weeks after insertion of subcutaneous pellets containing ‘60 mg T + 4 mg ANZ’ and ‘60 mg T + 6 mg LET’. Results: LC-MS/MS (range values-pg/ml) for postmenopausal women, and baseline, week 1 and week 4 post treatment values for each steroid and AI were: E2: (range 0.3-0.9), 0.4, < 0.3, < 0.3; E1: (range 0.9-3.1), 1.0, <0.4, <0.4; T: (range 7-22), 6, 96, 48; ANZ: (range <4), < 4, 2063, 24; LET: (range <4), < 4, 744, 175. Self-reported (Pre/Post Therapy) estrogen deficiency symptoms such as hot flashes, night sweats, vaginal dryness, joint pain, and sleep disturbances were significantly improved post T+AI therapy. In addition, the intramammary tumor decreased in size > 95% by month 5. Summary: These results show that low-dose SC AI therapy (4-6 mg/2-3 months = 0.1 mg/day) with T (120 mg/2-3 months = 1-2 mg/day) increases T to supra-physiological levels, prevents T metabolism to estrogens E2 and E1, reduces estrogen deficiency symptoms, and has beneficial effects on tumor growth inhibition. Simultaneous testing of sex-steroids E2, E1, T, and aromatase inhibitors LET and ANZ by LC-MS/MS provides a convenient means to monitor the bioavailable levels of these analytes and adjust them as necessary to optimize therapeutic efficacy and reduce adverse side effects.


2001 ◽  
Vol 28 (4) ◽  
pp. 377-388 ◽  
Author(s):  
Roy D. Baynes ◽  
Roger D. Dansey ◽  
Jared L. Klein ◽  
Caroline Hamm ◽  
Mark Campbell ◽  
...  

2002 ◽  
Vol 97 ◽  
pp. 663-665 ◽  
Author(s):  
Kenneth J. Levin ◽  
Emad F. Youssef ◽  
Andrew E. Sloan ◽  
Rajiv Patel ◽  
Rana K. Zabad ◽  
...  

Object. Recent studies have suggested a high incidence of cognitive deficits in patients undergoing high-dose chemotherapy, which appears to be dose related. Whole-brain radiotherapy (WBRT) has previously been associated with cognitive impairment. The authors attempted to use gamma knife radiosurgery (GKS) to delay or avoid WBRT in patients with advanced breast cancer treated with high-dose chemotherapy and autologous bone marrow transplantation (HDC/ABMT) in whom brain metastases were diagnosed. Methods. A retrospective review of our experience from 1996 to 2001 was performed to identify patients who underwent HDC/ABMT for advanced breast cancer and brain metastasis. They were able to conduct GKS as initial management to avoid or delay WBRT in 12 patients following HDC/ABMT. All patients were women. The median age was 48 years (range 30–58 years). The Karnofsky Performance Scale score was 70 (range 60–90). All lesions were treated with a median prescription dose of 17 Gy (range 15–18 Gy) prescribed to the 50% isodose. Median survival was 11.5 months. Five patients (42%) had no evidence of central nervous system disease progression and no further treatment was given. Four patients were retreated with GKS and three of them eventually received WBRT as well. Two patients were treated with WBRT as the primary salvage therapy. The median time to retreatment with WBRT was 8 months after the initial GKS. Conclusions. Gamma knife radiosurgery can be effectively used for the initial management of brain metastases to avoid or delay WBRT in patients treated previously with HDC, with acceptable survival and preserved cognitive function.


2016 ◽  
pp. 74-80
Author(s):  
Phuong Phung ◽  
Thi Thuy Nguyen

ackground and Objectives: Nowadays, the incidence of cancer is constantly increasing in the world as well as in Vietnam. The treatment of cancer is based on multimodality principle. Among those principal modalities, chemotherapy is widely used for different purposes such as neoadjuvant, andjuvant and palliation. However, chemotherapy can induce activation of latent infections, including hepatitis B. Vietnam is in the endemic region of hepatitis B so the reactivation of hepatitis B on cancer patients with chemotherapy has emerged a concerned problem. However, few interests were gained on this problem in the aspect of clinical setting or researching. Aims: to determine the prevalence of hepatitis B reactivation (HBV) in cancer patients treating with chemotherapy and to detect some risks factors of this situation. Subjects and methods: descriptive prospective. The study included 33 cancer patients with inactive HBV infection who are treating with chemotherapy. We define HBV reactivation by ALT > 3 ULN and HBV DNA copies > 10 positive control limit. Results: We found 6 patients with reactivated HBV, accounting for 18.18 %. Among reactivated HBV patients, age less than 60 accounts 83,33%. Rate of reactivated HBV in males was 25,00% while this rate in females was 14,28%. Rate of reactivated HBV in lymphoma, lung cancer and breast cancer was 33,33%, 25% và 22,22% respectively. Clinial manifestation of reactivated HBV includes jaundice (33,33%), fulminant hepatic failure (6%) and death (5%). The reactivated rate was higher in patients got high dose of corticoid (28,57%) vs low dose (15,38%). This rate was 29,41% in patients treated with anthracyclines which was higher than in group without anthracyclines. The reactivated rate of HBV was dramatically higher in patients treated with rituximab (75%). Conclusion: the reactivation of hepatitis B on cancer patients with chemotherapy is common. We found 6 patients with reactivated HBV of 33 subjects of the study which accounts 18.18 %. We recognized that reactivated HBV rate was higher subgroups of age < 60 years old, males, patients with lymphoma, lung cancer, breast cancer. Reactivated HBV may be more prevalent in patients with high-dose corticotherapy, anthracyclines and Rituximab. Key words: HBV reactivation, chemotherapy, cancer, hepatitis B


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