Cancer Research and Therapeutics

Comparison of local recurrence after mastectomy for pure ductal carcinoma in situ with close or positive margins: A meta-analysis Donghyun Kim, Yongkan Ki, Wontaek Kim, Dahl Park, Jihyeon Joo, Hosang Jeon, Jiho Nam Journal of Cancer Research and Therapeutics 2020 16(6):1197-1202 Background: There is controversy regarding the relationship between margin status and risk of local recurrence (LR) in patients with Ductal carcinoma in situ(DCIS) treated by mastectomy. Purpose: We sought to assess the LR rates for patients with DCIS breast cancer treated by mastectomy with respect to the resection margin (RM) status. Materials and Methods: Systematic search of MEDLINE, EMBASE, and Cochrane library published was performed. Studies of pure DCIS breast cancer with treatment of mastectomy and studies that reported surgical RM and LR were included. Results:A total of 12 retrospective studies were included, encompassing 2902 patients with a mean follow-up of 86.4 months. Overall LR rates were 5.3% (27/508) for positive or close margins and 1.6% (37/2367) for negative margin, and most of the recurrences (93.7%) are invasive cancers. Patients with positive or close margins showed a 3.72-fold (95% confidence interval [CI] = 2.30–6.01,P < 0.01, I[2] = 11%) higher risk of LR than patients with negative margin. Patients with positive margin showed a 2.91-fold (95% CI = 1.14–7.41,P = 0.03, I[2] = 0%) higher risk of LR than patients with close margin. Postmastectomy radiation therapy (RT) was not associated with a decreased risk of LR (Risk ratio 0.50; 95% CI = 0.06–4.08,P= 0.52, I[2] = 0%) in patients with positive or close margins. Conclusions: The RM status after mastectomy has a great impact on LR. However, the recurrence rate was insufficient to warrant a recommendation for postmastectomy RT in patients with close or positive margins.

Efficacy and toxicity of FLASH radiotherapy: A systematic review Gilnaz Omyan, Ahmed Eleojo Musa, Dheyauldeen Shabeeb, Niloofar Akbardoost, Somayeh Gholami Journal of Cancer Research and Therapeutics 2020 16(6):1203-1209 In recent times, research on the use of ultrahigh-dose rates delivered in super-fast times in cancer treatment has been garnering interest. This has brought about the term “FLASH” radiotherapy (RT). Thus, in the present study, we systematically review these recent studies on FLASH RT with regard to its efficacy and safety. The reporting of this systematic review was done in line with the statement of Preferred Reporting Items for Systematic reviews and Meta-Analyses. Electronic search of the databases such as PubMed, Scopus, and Embase was conducted to retrieve relevant studies investigating the FLASH effect. From an initial search of 216 potential articles, 16 articles (in vivo, in vitro , and clinical studies) were finally included in this systematic review. Results showed that FLASH RT dose rates had protective effects on normal tissues in addition to antitumor effect. Although still in its early research stages, FLASH RT has the potential to rival present RT regimens in terms of safety and antitumor effect. However, further studies are needed to address the aspects such as optimal dose rate, effect on deep tumors, tumor recurrence, longer follow-up time, and mechanism of action.

Addressing and targeting earnest condition of advance breast cancer-related anorexia and cachexia through Rasayana therapy Avinash Kadam, Yogesh Bendale, Poonam Birari-Gawande Journal of Cancer Research and Therapeutics 2020 16(6):1210-1214 Anorexia and cachexia are major clinical problems seen in a large proportion of patients with advanced cancer. Weight loss has also been identified as an indicator of poor prognosis in cancer patients. Around 20% of patients with advanced cancer present mortality from the effects of malnutrition rather than from cancer itself. Early nutrition intervention has seen to improve outcomes in cancer patients such as weight gain, treatment tolerance, and improved quality of life (QoL). Effective therapies for addressing these threatening conditions are lacking. Pharmacotherapeutic agents such as corticosteroids, megestrol acetate, and cyproheptadine have several adverse reactions and also lack satisfactory results. Rasayana therapy is known to prevent loss of body mass and at the same time help to improve appetite and increase patient's QoL. The Rasayana compound used by us to prevent cachexia mainly includes swarna sindoor, Hirak bhasma, and suvarna bhasma. To evaluate benefits of Rasayana therapy on these variables, we maintain complete documentation of different clinical variables in all cancer patients. Here, in this observational study, we analyzed the data collected from a group of stage IV breast cancer patients (n = 30) receiving Rasayana therapy. Patients were followed at an interval of every 15 days from baseline for 3 months. Furthermore, at each visit, there weight was recorded on calibrated digital weight balance. QoL in these patients was recorded at quarterly interval using functional assessment of cancer therapies questionnaire. It was seen that in the duration of 3 months patients appetite increased significantly (P = 0.03). Significant weight gain was seen in patients (P = 0.04). Significant improvement was also seen in QoL especially related to QoL subdomains of physical wellbeing (P = 0.01), emotional wellbeing (P < 0.04), and functional wellbeing (P < 0.001). Rasayana therapy was seen to be well tolerated by all patients.

Hippocampal-sparing radiotherapy and neurocognitive impairment: A systematic literature review Zanirato Rambaldi Giuseppe, Cammelli Silvia, Farina Eleonora, Macchia Gabriella, Ferro Marica, Chiesa Silvia, Balducci Mario, Deodato Francesco, Cilla Savino, Buwenge Milly, Giovanni P Frezza, Zompatori Maurizio, Alessio G Morganti Journal of Cancer Research and Therapeutics 2020 16(6):1215-1222 Introduction: Whole-brain radiation therapy (WBRT) is an effective therapeutic modality in patients with brain metastases. However, nearly 90% of patients undergoing WBRT suffer from a neurocognitive function (NCF) impairment at diagnosis, and up to two-thirds will experience a further decline within 2–6 months after WBRT. Focal-dose reduction on bilateral hippocampus is thought to improve NCF preservation. The aim was to present a systematic review of clinical results on NCF after hippocampal-sparing (HS) WBRT. Materials and Methods: A systematic review of published literature was performed on PubMed and the Cochrane Library. Only prospective clinical trials reporting NCF outcome in patients treated with HS-WBRT have been analyzed. Results: A total of 165 patients from three studies were included. These studies are characterized by small sample size and different methods in terms of WBRT technique but with similar planning analysis and NCF assessment tests. No significant changes in NCF (i.e., verbal and nonverbal learning memory, executive functions, and psychomotor speed) between baseline and 4-month follow-up after RT and only a mean relative decline in delayed recall at 4 months (7% compared to 30% of historical control) were observed. Conclusions: Considering preliminary results on NCF preservation, further studies seem justified in patients undergoing brain irradiation for brain metastases or referred for prophylactic cranial irradiation to evaluate long-term effects on NCF and quality of life.

Underexpression of circulating miR-145-5p and miR-133a-3p are associated with breast cancer and immunohistochemical markers Noemí García-Magallanes, Saúl Armando Beltran-Ontiveros, Emir Adolfo Leal-León, Fred Luque-Ortega, José Geovanni Romero-Quintana, Ignacio Osuna-Ramirez, María Barbosa-Jasso, Eliakym Arámbula-Meraz Journal of Cancer Research and Therapeutics 2020 16(6):1223-1228 Background: MicroRNAs (miRNAs) are involved in the regulation of genes with important roles in cancer. Therefore, they represent interesting targets as biomarkers for early detection, follow-up, and prognosis of the disease. Context: In early stages of breast cancer, differences in the expression of miR-148b-3p, miR-145-5p and miR-133a-3p have been reported. Aims: To compare the expression of miR-148b-3p, miR-145-5p and miR-133a-3p in serum samples from female patients with and without breast cancer. Setting and Design: Case control study. Materials and Methods: We quantified the expression by real-time polymerase chain reaction of miR-148b-3p, miR-145-5p, and miR-133a-3p in serum samples from 27 breast cancer (BC) and 17 benign breast tumor patients. Statistical Analysis Used: Comparison between groups with categorical variables was made using the Pearson's Chi-square test. Comparative analysis for continuous variables between two groups was performed using the Student's t-test. One-way analysis of variance (ANOVA) was used for multigroup comparison, followed by Tukey HSD analysis. Results: The use of contraceptives and a high number of births were identified as risk factors for BC. We observed that miR-145-5p expresses in low levels in BC and positively diagnosed Her2 patients. In addition, BC patients with either ductal carcinoma or positive molecular diagnosis for estrogen receptor, progesterone receptor, luminal A, or Her2 negative, presented a decreased expression of miR-133a-3p. Conclusions: We observed an existing association between the molecular characteristics of BC and levels of circulating miR-133a-3p and miR-145-5p, proving the potential role of miRNAs as biomarkers for BC.

Clinical features of metaplastic breast carcinoma: A single-center experience Gülçin Ertas, Fatma Buğdayci Başal, Ali Riza Üçer, Emine Benzer, Muzaffer Bedri Altundağ, Umut Demirci, Bahadir Çetin, Fatih Karatas Journal of Cancer Research and Therapeutics 2020 16(6):1229-1234 Aim: Metaplastic breast cancer (MBC) is a rare subtype with unusual clinical features. We aimed to analyze treatment results and define patients' characteristic features in our large MBC patient series. Materials and Methods: Fifty-six patients with early MBC who received adjuvant radiotherapy (RT) in our center were included in the study. The age, sex, subtypes of MBC, histopathology, hormone and nodal status, tumor size, and types of treatment were retrospectively provided from hospital records. Results: The median tumor size was 4 (1.3–16.5) cm, and triple-negative MBC cases were 38 (67.8%) of all patients. Axillary nodal involvements were present in 25 (44.6%) patients. The median follow-up time was 45.8 (4.9–130) months; the overall survival (OS) and disease-free survival (DFS) for 5 years were 67% and 64%, respectively. While distant metastases were seen in 15 (26.7%) patients, local recurrences were seen in only 4 patients. The median OS and DFS were higher in patients with ≤5.2 cm tumor than >5.2 cm ([130 vs. 49 months, P = 0.01] and [130 vs. 30 months, P = 0.009], respectively). Nodal involvement, hormone receptor status, surgical treatment, and type of RT had no effect on survival. In multivariate analysis, tumor size was not an independent prognostic factor for OS (P = 0.068; hazard ratio [HR]: 3.4, 95% confidence interval [CI] = 0.91–12.8), whereas age >65 years was found an independent poor prognostic factor for OS ([HR: 4.25, 95% CI: 0.23–0.78, P = 0.021] and DFS [HR: 3.1, 95% CI: 0.02–0. 87; P = 0.04], respectively). Conclusions: Distant metastasis is at the forefront rather than local recurrence in MBC patients. More studies are needed to determine the factors that affect survival independently in MBC.

Phytochemical fractions from Annona muricata seeds and fruit pulp inhibited the growth of breast cancer cells through cell cycle arrest at G0/G1 phase Shashanka K Prasad, Prashanth M Veeresh, Pushkal S Ramesh, Suma M Natraj, SubbaRao V Madhunapantula, Devananda Devegowda Journal of Cancer Research and Therapeutics 2020 16(6):1235-1249 Introduction: Annona muricata (L.) (AM), commonly known as Soursop and Lakshmanaphala/Hanumaphala in India, has been extensively used in ethnomedicine for treating tuberculosis, urinary tract infections (UTIs) and cancers. The fruit is a rich source of antioxidants and antitumor agents. Methods: In this study, we have extracted phytochemicals that exhibited anti-cancer property from the (a) fruit pulp using methanol (AMPM) and water (AMPW); and (b) seeds using methanol (AMSM). Qualitative phytochemical analysis showed the presence of phenolics, tannins, alkaloids, flavonoids, sterols, terpenoids, carbohydrates and proteins in AMPM and AMPW. All three extracts were first checked for in vitro antioxidant and anti-inflammatory properties and then tested for efficacy against MCF-7 and MDA-MB-231. Results: Among these three extracts, AMSM showed the highest antioxidant power as well as ~80% inhibition at 320μg/ml concentration in both cell lines upon treatment for 24h. However, only about 40% inhibition was observed with 320μg/ml AMPM treatment, despite its highest anti-inflammatory potential. Water extract AMPW exhibited about 80% growth inhibition at 50% dilution. Since fruit pulp is the one consumed, the extracts AMPM and AMPW were further tested for apoptosis induction and cell cycle arrest. Analysis of the data showed increased apoptosis and G0/G1 cell cycle arrest upon exposure to AMPM and AMPW.

Comparison of the effects of ultrasound in a repetitive mode and acoustically active lipospheres in the presence of doxorubicin on breast adenocarcinoma Homa Soleimani, Parviz Abdolmaleki, Manijhe Mokhtari-Dizaji, Tayebeh Toliat, Abbas Tavasoly Journal of Cancer Research and Therapeutics 2020 16(6):1250-1257 Purpose: We want to compare the synergistic effect of low-intensity, dual-frequency (dual) ultrasound (US), applied in a repetitive sonication mode, and acoustically active lipospheres (AALs) containing doxorubicin (DOX) in a murine model (Balb/C). Subjects and Methods: The tumor-bearing mice were divided into nine groups, namely two untreated groups (control and sham), and seven experimental groups, including treated with dual-frequency US (150 kHzcontinuous + 1MHzpulse), triple exposure (3×30min) dual-frequency US, DOX (2 mg/kg intravenous), DOX in combination with single exposure (30 min) to dual-frequency US (drug + dual), DOX in combination with triple (3 × 30 min) exposure to dual-frequency US (drug + dual [REP]), AALs containing the drug-loaded (AAL), and a group receiving AAL in combination with single exposure (30 min) dual-frequency US (AAL + dual), respectively. Results: The effectiveness of DOX on tumor growth was enhanced by a factor of three when combined with the triple exposures of dual US (drug + dual [REP]). This combination protocol further increased the times needed for each tumor to 2 and 7 times its initial volume, respectively by 94% and 36% compared to the drug group. During the 30 days, following the treatment of tumors, the relative volume of tumors in AAL group was 118% less than that of the drug group. The survival rate of the groups treated with drug and AAL + dual was increased by 78.7% and 167% compared with sham, respectively. Conclusion: Although as a short treatment, a major improvement in treatment was observed by (drug + dual [REP]) compared with other treatments, the AAL + dual treatment compared with (drug + dual [REP]) showed an increase in the survival rates, hence more preferable over long periods.

Mammographic breast density and breast cancer risk: Evaluation using volumetric breast density software Suzanne Koshi, Veenu Singla, Tulika Singh, Nidhi Prabhakar, Amanjit Bal, Gurpreet Singh Journal of Cancer Research and Therapeutics 2020 16(6):1258-1264 Purpose: The study aimed to assess breast density as a risk factor for breast malignancy using automated volumetric breast density software and to study the relationship of breast density with tumor histopathological characteristics. Materials and Methods: One hundred and thirty-four women with unilateral core biopsy-proven breast cancer were taken in the “case group.” Two hundred and one women with normal bilateral screening mammograms were enrolled in the “control group.” The cases and controls were further divided into pre- and post-menopausal subgroups. The mammograms of the contralateral breast of the cases and bilateral breasts of the controls were evaluated by automated volumetric breast density software and classified into four density grades. The tumor histopathological characteristics in the various density grades were also evaluated. Results: In premenopausal women, the odds of having breast cancer was significantly higher for Grade 3 breasts (odds ratio [OR] 3.03; 95% confidence interval [CI]: [1.19–7.71]) versus Grade 1 and 2 breasts. Grade 4 premenopausal breasts also had greater odds (OR 3.09; 95% CI [0.89–10.78]) of developing breast cancer. No such relationship was established for postmenopausal women. No significant difference was seen in the histopathology of breast cancer among various breast density groups. Conclusion: Increased breast density can be considered as an inherent, independent risk factor for breast cancer in premenopausal women.

Diagnostic accuracy of sentinel lymph node biopsy in determining the axillary lymph node metastasis Ozlem Okur, Julide Sagiroglu, Gozde Kir, Nurgul Bulut, Orhan Alimoglu Journal of Cancer Research and Therapeutics 2020 16(6):1265-1268 Background: Sentinel lymph node biopsy (SLNB) is accepted as the standard procedure to determine the axillary lymph node metastasis in breast cancer at early stage. However, in many cases with sentinel lymph node positivity, the axilla does not contain any tumor cells. As a result, the accuracy of SLNB to predict axillary lymph node metastasis must be evaluated. Patients and Methods: Thousand hundred and fourteen women operated for breast cancer were retrospectively examined. Breast cancer patients without axillary metastasis on clinical examination who had undergone SLNB were included in the study. Sentinel lymph node positivity and axillary lymph node positivity were compared. Results: Among 1114 women operated for breast cancer, 230 were clinically node negative preoperatively and undergone SLNB. Eighty-three (36%) of the patients were SLNB positive and undergone axillary dissection. Forty-three (51.8%) of them had tumor positive axillary lymph nodes and 40 (48.2%) of them had tumor negative axillary lymph nodes. Interpretation: In 48.2% of the patients, positive sentinel lymph node does not demonstrate a positive axilla. This finding supports sparing axillary dissection in patients with favorable prognostic factors even if the sentinel lymph node is found to be positive. Conclusion: Axillary lymph node dissection(ALND) may be spared even if there are macrometastatic sentinel lymph nodes in patients with favorable tumor types who will undergo breast-conserving surgery.

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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