Standard Treatment For Breast Cancer Research Articles

Repurposing propofol for breast cancer therapy through promoting apoptosis and arresting cell cycle.

Breast cancer is the most prevalent cancer among women worldwide, characterized by a high mortality rate and propensity for metastasis. Although surgery is the standard treatment for breast cancer, there is still no effective method to inhibit tumor metastasis and improve the prognosis of patients with breast cancer after surgery. Propofol, one of the most widely used intravenous anesthetics in surgery, has exhibited a positive association with improved survival outcomes in patients with breast cancer post‑surgery. However, the underlying molecular mechanism remains to be elucidated. The present study revealed that triple negative breast cancer cells, MDA‑MB‑231 and 4T1, exposed to propofol exhibited a significant decrease in cell viability. Notably, propofol exhibited minimal cytotoxic effects on HUVECs under the same conditions. Furthermore, propofol significantly inhibited the migration and invasion ability of MDA‑MB‑231 and 4T1 cells. Propofol promoted apoptosis in 4T1 cells through upregulation of Bax and cleaved caspase 3, while downregulating B‑cell lymphoma‑extra large. Concomitantly, propofol induced cell cycle arrest of 4T1 cells by downregulating cyclin E2 and phosphorylated cell division cycle 6. Furthermore, propofol exhibited excellent anticancer efficacy in a 4T1 breast cancer allograft mouse model. The present study sheds light on the potential of propofol as an old medicine with a novel use for breast cancer treatment.

Non-metastatic primary neuroendocrine neoplasms of the breast: a reference cancer center's experience of a heterogenous entity.

Primary neuroendocrine neoplasms of the breast (Br-NENs) are rare. The classification has been updated in recent years making interpretation of the data published challenging. It is unclear whether neuroendocrine differentiation is associated with poorer prognosis and what treatment approaches should be applied. The database for breast cancer patients treated between 2009 and 2022 at the Maria Sklodowska-Curie National Research Institute of Oncology Branch Krakow was explored to search for Br-NENs. Patients' medical and pathological data were collected and analyzed. We included 22 females with Br-NEN without metastases at the time of diagnosis. The median age was 64 years (range: 28-88), Of the cases, 18 were hormone receptor positive, all were HER-2 negative, the median Ki67 was 27% (10-100%). The median tumor size at the time of diagnosis was 29.5mm (7-75mm), 9 patients were N-positive. DCIS was present in 5 cases. Only one case was negative for chromogranin and synaptophysin staining, but data were missing for 4 cases. Nine patients received adjuvant chemotherapy, mainly based on anthracyclines and taxanes, while 16 received adjuvant hormonal therapy and 15 received postoperative radiotherapy. Radical surgery was performed in all patients, but two underwent suboptimal tumorectomy. One patient had local recurrence, three experienced metastatic disease, all involving the lungs, but these patients are still alive. The median follow-up was 96 months (8-153). Two patients died, with a follow up time of no recurrence >4 years. Our results were compared to twelve case series collecting clinical data on Br-NENs, with median patient number of 10.5 (range: 3-142). Br-NENs represent a heterogenous group of diseases, lacking data from prospective studies or clinical trials. There are no established treatment standards tailored for Br-NENs. Our patients' cohort exhibited a favorable prognosis, potentially attributed to lower tumor stage and Ki67 index compared to other reported case series. We suggest that radical surgery and postoperative radiotherapy be administered akin to standard treatment for breast cancer of no special type. ESMO also advocates for this approach in systemic treatment, although we recommend considering platinum-based chemotherapy for patients with poorly differentiated Br-NENs exhibiting high Ki67.

The Japanese breast cancer society clinical practice guidelines for radiation treatment of breast cancer, 2022 edition.

The Breast Cancer Clinical Practice Guidelines, organized by the Japanese Breast Cancer Society (JBCS), were published in 2022. We present the English version of the Radiation Therapy (RT) section of the guidelines. The JBCS formed a task force to update the 2018 version of the JBCS Clinical Practice Guidelines. The Background Questions (BQs) contain the standard treatments for breast cancer in clinical practice, whereas the Clinical Questions (CQs) address daily clinical questions that remain controversial. Future Research Questions (FRQs) explore the subjects that are considered important issues, despite there being insufficient data for inclusion as CQs. The task force selected the 12 BQs, 8 CQs, and 6 FRQs for the RT section. For each CQ, systematic literature reviews and meta-analyses were conducted according to the Minds Manual for Guideline Development 2020, version 3.0. The recommendations, strength of recommendation, and strength of evidence for each CQ were determined based on systematic reviews and meta-analyses, and finalized by voting at the recommendation decision meeting.

Treatment Patterns and Survival Outcomes in Patients With Breast Cancer on Medicaid, Pre- and Post-Expansion.

The objective of this study was to evaluate the impact of Medicaid expansion on breast cancer treatment and survival among Medicaid-insured women in Ohio, accounting for the timing of enrollment in Medicaid relative to their cancer diagnosis and post-expansion heterogeneous Medicaid eligibility criteria, thus addressing important limitations in previous studies. Using 2011-2017 Ohio Cancer Incidence Surveillance System data linked with Medicaid claims data, we identified women aged 18 to 64 years diagnosed with local-stage or regional-stage breast cancer (n=876 and n=1,957 pre-expansion and post-expansion, respectively). We accounted for women's timing of enrollment in Medicaid relative to their cancer diagnosis, and flagged women post-expansion as Affordable Care Act (ACA) versus non-ACA, based on their income eligibility threshold. Study outcomes included standard treatment based on cancer stage and receipt of lumpectomy, mastectomy, chemotherapy, radiation, hormonal treatment, and/or treatment for HER2-positive tumors; time to treatment initiation (TTI); and overall survival. We conducted multivariable robust Poisson and Cox proportional hazards regression analysis to evaluate the independent associations between Medicaid expansion and our outcomes of interest, adjusting for patient-level and area-level characteristics. Receipt of standard treatment increased from 52.6% pre-expansion to 61.0% post-expansion (63.0% and 59.9% post-expansion in the ACA and non-ACA groups, respectively). Adjusting for potential confounders, including timing of enrollment in Medicaid, being diagnosed in the post-expansion period was associated with a higher probability of receiving standard treatment (adjusted risk ratio, 1.14 [95% CI, 1.06-1.22]) and shorter TTI (adjusted hazard ratio, 1.14 [95% CI, 1.04-1.24]), but not with survival benefits (adjusted hazard ratio, 1.00 [0.80-1.26]). Medicaid expansion in Ohio was associated with improvements in receipt of standard treatment of breast cancer and shorter TTI but not with improved survival outcomes. Future studies should elucidate the mechanisms at play.

Stomatological complications and comprehensive oral care of post-menopausal patients undergoing breast cancer treatment

Breast cancer is one of the widespread diseases all over the world. Breast cancer is the leading variant of cancer among females. Oral diseases are potentially thought to be relevant to systemic disease. Surgical approaches lumpectomy, partial mastectomy along with post surgical radiotherapy (RT) or chemotherapy (CT) is the mainstream gold standard treatment of breast cancer. But unfortunately RT/CT comes with some unavoidable stomatological complications especially in post menopausal age. There are many studies found some definite oral complications during the treatment periods of breast cancer therapy like sore mouth, mucositis, salivary gland dysfunctions, dysguesia, dysesthesia, cervical caries, periodontitis, alveolar bone loss, opportunistic infections, and osteoradionecrosis etc. Obtained from present knowledge available, different oral complications are discussed like proper oral hygiene (both professional and domiciliary), pretreatment prophylaxis, appropria te diet, periodontal check up, fluoride varnish, salivary substitutes which minimize the chance to develop complications. Certain measures are to be taken at pretreatment and post treatment sessions in order to prevent possible complications. We will try to discuss the possible oral complications and way outs in the article.

Abstract A127: Comparing outcomes in breast cancer treatment between fee-for-service and Medicare Advantage patients

Abstract Introduction: Relative to Medicare beneficiaries receiving care through the traditional fee-for-service system (FFS), the percentage of Americans covered by Medicare Advantage (MA) plans has increased over the last decade. As more patients enroll in MA plans, the comparison of outcomes between FFS and MA groups has gained renewed importance. Ohio has a high penetration of MA plans, but differences in outcomes between FFS and MA plans in Ohio is under-studied. Breast cancer is the second most common type of cancer among women, therefore understanding nuances in breast cancer treatment outcomes has broad applicability. In this study, we compare receipt of standard care, time to treatment initiation (TTI), and overall survival (OS) between FFS and MA women diagnosed with incident breast cancer. Methods: We used the Ohio Cancer Incidence Surveillance System (OCISS) cancer registry data linked with Medicare enrollment files and identified patients diagnosed with local and regionally staged breast cancer between 2011-2016. All variables except for FFS and MA enrollment were derived from the OCISS. We developed logistic regression (for analysis of receipt of standard treatment) and Cox regression models (for analysis of TTI and OS) to evaluate the independent association between FFS/MA status and our outcomes of interest, adjusting for age, race, marital status, type of county of residence, neighborhood poverty level, stage at diagnosis, hormone receptor status, and Medicaid dual enrollment. Standard care was defined as receipt of breast-conserving surgery (BCS) or mastectomy, radiotherapy if BCS was received; chemotherapy if regionally staged; and hormone therapy if hormone receptor positive. Results: 12,349 patients were identified that met our inclusion criteria, with 6,801 and 5,548 patients in the FFS and MA groups at the time of diagnosis, respectively. A slightly higher percentage of MA patients were identified as Black (10.3 vs 8.0% on FFS plans). FFS Medicare patients were found to have similar odds of receiving standard care as patients on MA plans (adjusted odds ratio 0.95 [95% CI: 0.88, 1.03]). We detected no difference in TTI between FFS and MA patients, (adjusted hazard ratio (aHR) 0.98 [95% confidence interval (CI): 0.94, 1.01]), or in OS (aHR 1.06 [95% CI: 0.95, 1.18]). No difference was found in receipt of standard care between Black and White patients (aOR 0.88 [95% CI: 0.76, 1.03]). An interaction term with race found that FFS Black patients had significantly lower odds of receiving standard care than their MA counterparts (aOR 0.70 [95% CI: 0.54, 0.92]). We did not find any significant interaction between MA status and race for OS or TTI. Conclusions: MA plans were not associated with any difference in TTI, OS, nor odds of receiving standard treatment for breast cancer compared to FFS Medicare plans. These findings are reassuring given the growing market share of privately administered MA plans, but raise questions with the notable disparity in receipt of standard care between Black FFS enrollees versus Black MA enrollees. Citation Format: Galen Shearn-Nance, Rishi Sachdev, Long Vu, Weichuan Dong, Johnie Rose, Siran Koroukian. Comparing outcomes in breast cancer treatment between fee-for-service and Medicare Advantage patients [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr A127.

Neurocognitive impairment in females with breast cancer treated with endocrine therapy and CDK4/6 inhibitors: a pharmacovigilance study using the World Health Organization’s database

Importance: Endocrine therapies (ETs) and inhibitors of cyclin-dependent kinases-4/6 (iCDK4/6s) are a standard treatment in breast cancer. However, data on potential neurocognitive impacts remain inconsistent for ET and are scarce for iCDK4/6s.Objective: To evaluate whether ET and iCDK4/6s are associated with neurocognitive impairment (NCI).Methods: We used observational, real-world cases of NCI from the World Health Organization’s database VigiBase® to perform disproportionality analysis. Cases were defined as any symptom of NCI in females treated with ETs or iCDK4/6s. The study period was from the date of the first adverse event reported in VigiBase® with iCDK4/6s (1 January 2014) until the date of data extraction (16 March 2022). In our primary analysis, we calculated the reporting odds ratio (ROR) adjusted for age to identify a potential association between NCI and individual ETs in isolation or in combination with iCDK4/6s. We also performed subgroup analyses by the NCI class.Results: We identified 2.582 and 1.943 reports of NCI associated with ETs and iCDK4/6s, respectively. NCI was significantly associated with each ET [anastrozole: n = 405, aROR = 1.52 (95% CI: 1.37–1.67); letrozole: n = 741, aROR = 1.37 (95% CI: 1.27–1.47); exemestane: n = 316, aROR = 1.37 (95% CI: 1.22–1.53); tamoxifen: n = 311, aROR = 1.25 (95% CI: 1.12–1.40); and fulvestrant: n = 319, aROR = 1.19 (95% CI: 1.06–1.33)] and only with palbociclib for iCDK4/6s [n = 1,542, aROR = 1.41 (95% CI: 1.34–1.48)].Conclusion: These findings suggest that in females treated for breast cancer, all ETs may be associated with NCI. However, amongst iCDK4/6s, NCI may be specific to palbociclib. NCI most frequently involved learning and memory as well as language. Neurocognitive impact of treatments requires better consideration and management.

Self-Care Behaviour of Patients With Breast Cancer in the Management of Side Effects of Chemotherapy.

Aim The breast is the leading site of cancer among females. Chemotherapy is the standard treatment of breast cancer and it results in multiple side effects. Apart from pharmacological management, self-care behaviors may significantly influence the management of these side effects. The study aimed to assess the self-care behavior of patients with breast cancer in the management of side effects of chemotherapy. Methods A longitudinal descriptive study was conducted at the Daycare chemotherapy unit of the Radio Therapy Department, Government Medical College Hospital Thiruvananthapuram, Kerala, India. In total, 170 female patients with breast cancer receiving their first cycle of chemotherapy participated in the study.Self-care behavior was the primary outcome variable of the study. Sociodemographic and clinical data were measured by using a structured questionnaire. The severity of side effects and self-care behaviors for their management were measured by a Self Care Diary (SCD). Result A total of 170 with breast cancer receiving chemotherapy participated in the study. The severity of side effects and self-care behaviors for their management were measured at two separate time intervals, T1 and T2. Severe fatigue was found in 80.0% of participants at T1 and 61.2% at T2. Vomiting (47.7%), mucositis (48.2%), and nausea (49.1%) were also found to be severe at T1, but these side effects were moderate (53.8%, 58.8%, and 51.8% respectively) at T2. Despite the high number of self-care behaviors used to prevent infection, nausea/vomiting, bleeding, decreased appetite, sleeping difficulty, and constipation, overall self-care behaviors were found to be poor. A negative correlation was found between self-care behavior and side effects of chemotherapy. Conclusion The study revealed a negative correlation between self-care behaviors and side effects. This indicates that supportive education and training should be given to patients and caregivers to enhance the self-care behaviors of patients to manage the side effects.

Radiotherapy refusal in breast cancer with breast-conserving surgery

BackgroundAlthough radiotherapy after breast-conserving surgery has been the standard treatment for breast cancer, some people still refuse to undergo radiotherapy. The aim of this study is to identify risk factors for refusal of radiotherapy after breast-conserving surgery.MethodsTo investigate the trend of refusing radiotherapy after breast-conserving surgery in patients with breast cancer using the Surveillance, Epidemiology, and End Results database. The patients were divided into radiotherapy group and radiotherapy refusal group. Survival results were compared using a multivariate Cox risk model adjusted for clinicopathological variables. Multivariate logistic regression was used to analyze the influencing factors of patients refusing radiotherapy after breast-conserving surgery and a nomogram model was established.ResultsThe study included 87,100 women who underwent breast-conserving surgery for breast cancer between 2010 and 2015. There were 84,948 patients (97.5%) in the radiotherapy group and 2152 patients (2.5%) in the radiotherapy refusal group. The proportion of patients who refused radiotherapy after breast-conserving surgery increased from 2.1% in 2010 to 3.1% in 2015. The Kaplan–Meier survival curve showed that radiotherapy can improve overall survival (p < 0.001) and breast cancer specific survival (p < 0.001) in the patients with breast-conserving surgery. The results of multivariate logistic regression showed that age, income, marital status, race, grade, stage, subtype and chemotherapy were independent factors associated with the refusal of radiotherapy.ConclusionsPostoperative radiotherapy can improve the benefits of breast-conserving surgery. Patients with old age, low income, divorce, white race, advanced stage, and no chemotherapy were more likely to refuse radiotherapy.

De-implementation of Axillary Dissection in Women Undergoing Mastectomy for Breast Cancer.

Completion axillary lymph node dissection (cALND) was standard treatment for breast cancer with positive sentinel lymph nodes (SLNs) until 2011, when data from the Z11 and AMAROS trials challenged its survival benefit in early stage breast cancer. We assessed the contribution of patient, tumor, and facility factors on cALND use in patients undergoing mastectomy and SLN biopsy. Using the National Cancer Database, patients diagnosed from 2012 to 2017 who underwent upfront mastectomy and SLN biopsy with at least one positive SLN were included. A multivariable mixed effects logistic regression model was used to determine the effect of patient, tumor, and facility variables on cALND use. Reference effect measures (REM) were used to compare the contribution of general contextual effects (GCE) to variation in cALND use. From 2012 to 2017, the overall use of cALND decreased from 81.3% to 68.0%. Overall, younger patients, larger tumors, higher grade tumors, and tumors with lymphovascular invasion were more likely to undergo cALND. Facility variables, including higher surgical volume and facility location in the Midwest, were associated with increased use of cALND. However, REM results showed thatthe contribution of GCE to the variation in cALND use exceeded that of the measured patient, tumor, facility, and time variables. There was a decrease in cALND use during the study period. However, cALND was frequently performed in women after mastectomy found to have a positive SLN. There is high variability in cALND use, mainly driven by interfacility practice variation rather than specific high-risk patient and/or tumor characteristics.

Correlation Among Tumor Size, Histopathological Grade and the Expression of RAC1 Protein with Breast Cancer Metastasis to Ipsilateral Axillary Lymph Nodes

Breast cancer (BC) is the most common cancer affecting women worldwide. Mastectomy is the standard treatment for breast cancer. The purpose of axillary lymph nodes (ALN) dissection in mastectomy is to examine the status and the presence of metastasis in ALN. This study is an analytic observational cross-sectional study coupled with a categorical comparative study in 60 BC patient’s with- and without-ALN metastasis. The data that used in this study were histopathological data from patients medical record and immunohistochemistry (IHC) of RAC1 expression data. The immunohistochemistry was performed with a cutoff point based on the result of a receiver operating characteristics (ROC). This study combined BC tumor size, histopathological grade, and expression of RAC1 protein in correlation with known risk factors on metastasis to ALN. From 60 subjects, there were 63.3 % (38) ALN (+) and 36.7 % (22), ALN (−). BC of T2 tumor size, grade 2 and RAC1(−), the ALN metastasis chance was 0.6 %. T2 tumor size, grade 2 and RAC1(+), the ALN metastasis chance was 4.5 %. T2 tumor size, grade 3 and RAC1(−), the ALN metastasis chance was 3.0 %. T2 tumor, grade 3 and RAC1(+), the ALN metastasis chance was 18.8 %; T3 tumor size, grade 3 and RAC1(−), the ALN metastasis chance was 12.7 %. T3 tumor size, grade 3 and RAC1(+), the ALN metastasis chance was 52.2 %; T4b tumor size, grade 3, RAC1(−) and RAC1(+), the ALN metastasis chance was 40.8 and 83.8 %, respectively. We conclude that smaller tumor size and lower histopathological grading with RAC1(−) has lesser possibility to ALN metastasize. HIGHLIGHTS Breast cancer (BC) is a malignant neoplasm originating from epithelial cells of the ducts and breast glands in the area of the lobules and terminal ducts known as the terminal duct lobular unit (TDLU) and the surgery performed is breast-conserving treatment or mastectomy that examine the status and the presence of metastasis in ALN RAC1 is a member of the RHO-GTPase family that plays an important role in the migration process, loss of adhesions between cells, and tumor metastasis also found in BC so it was used as parameter in this study Tumor size, histopathological grading, and the expression of RAC1 protein has correlation with with BC metastasis to the axillary lymph nodes that the smaller the tumor size, the lower the histopathological grading with RAC1(-) GRAPHICAL ABSTRACT

Abstract A061: Receipt of standard treatment by breast cancer patients on Medicaid, pre- and post-expansion

Abstract Background: Medicaid expansion in Ohio went into effect in 2014. While prior studies have shown earlier breast cancer stages at diagnosis post-expansion, its impact relative to receipt of standard treatment remains understudied. Here, we examined changes in stage-appropriate standard treatment by women with invasive incident breast cancer pre- and post-expansion, and by their timing of enrollment in Medicaid relative to cancer diagnosis – a key marker of inadequate access to care. Methods: We used 2011-2017 Ohio Cancer Incidence Surveillance System (OCISS) data linked with Medicaid enrollment and claims files. Our study population included women 18-65 years of age diagnosed with local- or regional-stage cancer (n=1,053 and n=2,264 women in the pre- and post-expansion periods, respectively). We identified women as Previously Enrolled if they enrolled in Medicaid at least 3 months prior to cancer diagnosis and remained continuously enrolled for 4 months post-diagnosis, and as Newly Enrolled if they enrolled in Medicaid in the 3 months before or after cancer diagnosis. We used the OCISS for sociodemographic and treatment data. We defined standard treatment as the receipt of mastectomy, or lumpectomy and radiation in all women. In those with regional-stage cancer, we required standard treatment to also include chemotherapy; and for those with positive hormonal status, we required hormonal therapy. From claims data, we identified comorbid conditions, grouped as none, physical conditions only, mental conditions only, and physical and mental conditions, with or without substance abuse. In addition to descriptive analysis, we conducted multivariable logistic regression analysis to evaluate the independent association between Medicaid expansion and receipt of standard treatment, after adjusting for patient demographics, tumor characteristics, and comorbid conditions. Results: The median age was 50.6 years and 51.8 years in the pre- and post-expansion periods. The percent of Newly Enrolled women relative to the total decreased from 24.8% to 18.9%. Women in this group were healthier than those in the Previously Enrolled group, as evidenced by the higher percent of women with no comorbid conditions (43.3% and 42.4% vs. 21.7% and 22.5%, Pre- and Post-expansion, respectively). From Pre- to Post-Expansion, receipt of standard treatment increased from 52.3% to 58.8% and from 58.6% to 61.6% among the Previously and Newly Enrolled, respectively. Results from the multivariable logistic regression analysis showed that compared to women diagnosed in the pre-expansion period, those diagnosed in the post-expansion period had 10% higher odds to receive standard treatment, after adjusting for patient covariates. Conversely, the timing of enrollment in Medicaid relative to cancer diagnosis was not associated with our outcome of interest. Conclusion: Medicaid expansion in Ohio was associated with improvements in receipt of stage-appropriate standard treatment for breast cancer. Future studies should elucidate the mechanisms at play. Citation Format: Siran M. Koroukian, Weichuan Dong, Kirsten Eom, Uriel M. Kim, Johnie Rose, Jeffrey Albert, Cynthia Owusu, Kristine Zanotti, Gregory S. Cooper, Jennifer Tsui. Receipt of standard treatment by breast cancer patients on Medicaid, pre- and post-expansion [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr A061.

Inhibition of Tumor Growth and Metastasis by Newcastle Disease Virus Strain P05 in a Breast Cancer Mouse Model.

Conventional therapies and surgery remain the standard treatment for breast cancer. However, combating the eventual development of metastasis is still a challenge. Newcastle disease virus (NDV) is one of the various species of viruses under clinical evaluation as a vector for oncolytic, gene-, and immune-stimulating therapies. The purpose of this study was to evaluate the antitumor activity of a recombinant NDV (rNDV-P05) in a breast cancer murine model. Tumors were induced by injecting the cellular suspension (4T1 cell line) subcutaneously. The virus strain P05 was applied three times at intervals of seven days, starting seven days after tumor induction, and was completed 21 days later. Determination of tumor weight, spleen index, and lung metastasis were done after sacrificing the mice. Serum levels of interferon (IFN)-α, IFN-γ, tumor necrosis factor (TNF)-α, and TNF-related apoptosis-inducing ligand (TRAIL) were quantified by enzyme-linked immunosorbent assay. CD8+ infiltrated cells were analyzed by immunofluorescence. rNDV-P05 showed a route-of-administration-dependent effect, demonstrating that the systemic administration of the virus significantly reduces the tumor mass and volume, spleen index, and abundance of metastatic clonogenic colonies in lung tissue, and increases the inhibition rate of the tumor. The intratumoral administration of rNDV-P05 was ineffective for all the parameters evaluated. Antitumor and antimetastatic capability of rNDV-P05 is mediated, at least partially, through its immune-stimulatory effect on the upregulation of TNF-α, TRAIL, IFN-α, and IFN-γ, and its ability to recruit CD8+ T cells into tumor tissue. Systemic treatment with rNDV-P05 decreases the tumoral parameters in the breast cancer murine model.

Gradient Boosting Machine Identified Predictive Variables for Breast Cancer Patients Pre- and Post-Radiotherapy: Preliminary Results of an 8-Year Follow-Up Study.

Radiotherapy (RT) is part of the standard treatment of breast cancer (BC) because of its effects on relapse reduction and survival. However, response to treatment is highly variable, and some patients may develop disease progression (DP), a second primary cancer, or may succumb to the disease. Antioxidant systems and inflammatory processes are associated with the onset and development of BC and play a role in resistance to treatment. Here, we report our investigation into the clinical evolution of BC patients, and the impact of RT on the circulating levels of the antioxidant enzyme paraoxonase-1 (PON1), cytokines, and other standard biochemical and hematological variables. Gradient Boosting Machine (GBM) algorithm was used to identify predictive variables. This was a retrospective study in 237 patients with BC. Blood samples were obtained pre- and post-RT, with samples of healthy women used as control subjects. Results showed that 24 patients had DP eight years post-RT, and eight patients developed a second primary tumor. The algorithm identified interleukin-4 and total lymphocyte counts as the most relevant indices discriminating between BC patients and control subjects, while neutrophils, total leukocytes, eosinophils, very low-density lipoprotein cholesterol, and PON1 activity were potential predictors of fatal outcome.

Effect of Metformin vs Placebo on Invasive Disease–Free Survival in Patients With Breast Cancer

Metformin, a biguanide commonly used to treat type 2 diabetes, has been associated with potential beneficial effects across breast cancer subtypes in observational and preclinical studies. To determine whether the administration of adjuvant metformin (vs placebo) to patients with breast cancer without diabetes improves outcomes. MA.32, a phase 3 randomized, placebo-controlled, double-blind trial, conducted in Canada, Switzerland, US, and UK, enrolled 3649 patients with high-risk nonmetastatic breast cancer receiving standard therapy between August 2010 and March 2013, with follow-up to October 2020. Patients were randomized (stratified for hormone receptor [estrogen receptor and/or progesterone receptor {ER/PgR}] status, positive vs negative; body mass index, ≤30 vs >30; human epidermal growth factor receptor 2 [ERBB2, formerly HER2 or HER2/neu], positive vs negative; and any vs no chemotherapy) to 850 mg of oral metformin twice a day (n = 1824) or oral placebo twice a day (n = 1825) for 5 years. The primary outcome was invasive disease-free survival in hormone receptor-positive breast cancer. Of the 8 secondary outcomes, overall survival, distant relapse-free survival, and breast cancer-free interval were analyzed. Of the 3649 randomized patients (mean age, 52.4 years; 3643 women [99.8%]), all (100%) were included in analyses. After a second interim analysis, futility was declared for patients who were ER/PgR-, so the primary analysis was conducted for 2533 patients who were ER/PgR+. The median duration of follow-up in the ER/PgR+ group was 96.2 months (range, 0.2-121 months). Invasive disease-free survival events occurred in 465 patients who were ER/PgR+. The incidence rates for invasive disease-free survival events were 2.78 per 100 patient-years in the metformin group vs 2.74 per 100 patient-years in the placebo group (hazard ratio [HR], 1.01; 95% CI, 0.84-1.21; P = .93), and the incidence rates for death were 1.46 per 100 patient-years in the metformin group vs 1.32 per 100 patient-years in the placebo group (HR, 1.10; 95% CI, 0.86-1.41; P = .47). Among patients who were ER/PgR-, followed up for a median of 94.1 months, incidence of invasive disease-free survival events was 3.58 vs 3.60 per 100 patient-years, respectively (HR, 1.01; 95% CI, 0.79-1.30; P = .92). None of the 3 secondary outcomes analyzed in the ER/PgR+ group had statistically significant differences. Grade 3 nonhematological toxic events occurred more frequently in patients taking metformin than in patients taking placebo (21.5% vs 17.5%, respectively, P = .003). The most common grade 3 or higher adverse events in the metformin vs placebo groups were hypertension (2.4% vs 1.9%), irregular menses (1.5% vs 1.4%), and diarrhea (1.9% vs 7.0%). Among patients with high-risk operable breast cancer without diabetes, the addition of metformin vs placebo to standard breast cancer treatment did not significantly improve invasive disease-free survival. ClinicalTrials.gov Identifier: NCT01101438.

Evidence-based guidelines for hypofractionated radiation in breast cancer: conclusions of the Catalan expert working group

IntroductionDaily, moderate hypofractionation has become standard treatment for breast cancer following breast-conserving surgery, although substantial variation exists in its use. This paper describes the generation of consensus-based recommendations for the utilisation of this therapy at the healthcare system level and compares these to American Society for Radiation Oncology (ASTRO) guidelines.Materials and methodsConsensus-based guidelines were developed in three steps, including a systematic literature review and involvement of radiation oncologists specialising in breast cancer in Catalonia: (a) creation of a working group and evidence review; (b) consideration of the levels of evidence and agreement on the formulation of survey questions; and (c) performance of survey and development of consensus-based recommendations. Results were compared to the ASTRO recommendations.ResultsConsensus was above 80% for 10 of the 14 survey items. Experts supported hypofractionated radiotherapy for all breast cancer patients aged 40 years or more; with invasive carcinoma and breast-conserving surgery; without radiation of lymph nodes; and regardless of the tumour size, histological grade, molecular subtype, breast size, laterality, other treatment characteristics, or need for a boost. Over half favoured its use in all situations, even where available scientific evidence is insufficient. The resulting recommendations and the quality of the evidence are comparable to those from ASTRO, despite some differences in the degree of consensus.ConclusionSpecialists agree that hypofractionation is the standard treatment for breast cancer following breast-conserving surgery, but some specific areas require a higher level of evidence before unequivocally extending indications.

Anticancer action by natural ingredient NMN and its mechanism: Focusing on the molecular mechanism of NMN on breast cancer cells.

It was confirmed that NMN causes a decrease in breast cancer cells. Breast cancer is now a major problem for women because it is sensitive to estrogen. The standard treatments for breast cancer are generally surgery, anticancer drugs, and radiation therapy. In addition, as a complementary / alternative therapy, it is said that stress management, relaxation for stress re-duction, vitamins, and dietary fiber, which are said to have antioxidant effects as nutritional components, are used. However, although there is potential from an antioxidant perspective at this stage, no evidence is available at this time. Therefore, this time, this research group investi-gated the effect on breast cancer cells at the in vitro level using the component “NMN”, which is currently attracting attention. When NMN was added to breast cancer cells, a significant reduc-tion in breast cancer cells was observed in a concentration-dependent manner. Therefore, this time, we investigated α-ketoglutaric acid, NAD +, and AMPK, which are thought to be related to the anticancer effect. It was found that NMN has the effect of activating these, suggesting that NMN may be used as a complementary / alternative therapy for breast cancer patients in the fu-ture

FR-101 Dressing May Alleviate Radiation-Irritated Skin After Radiotherapy in Breast Cancer Patients ― A Pilot Clinical Trial

Whole breast radiotherapy after breast-conserving surgery reduces the risk of recurrence and death and is widely used as standard treatment for breast cancer. Radiation-irritated skin, defined as "post-radiotherapy pruritic dry skin easily irritated by external stimulation, such as seasonal change or topical products", affects quality of life of breast cancer survivors undergoing whole breast radiotherapy. FR-101 dressing is a novel dressing combined with biocellulose membrane and repair peptides to repair the damaged skin after radiotherapy. This study is aimed to test the safety and efficacy to alleviate radiation-irritated skin symptoms.The study was a single-arm, open label, single center pilot clinical study to evaluate the safety and clinical outcome of the FR-Mask intervention in breast cancer patients after WBRT. Patients who complete the post-operative radiotherapy and meet the inclusion and exclusion criteria had been enrolled into the study after the study team obtains their informed consent. Each subject had received 12 packages of FR-Mask (1 mask in each individual package) and be instructed to put the patch on the irritated-skin area caused by radiation for 20 minutes every 3 days. Subjects came back to clinics for evaluation every 4 weeks for 4 months, and received physical examination and investigations including questionnaires, skin observer measurement, and taking pictures. The total study duration for each subject took 4.5 months. This study had been conducted in China Medical University Hospital.A total of 10 subjects were enrolled, and all subjects applied FR-101 dressing. No one experienced adverse events during the study period. Efficacy evaluation revealed that 40% patients showed visible differences between the affected breast skin and the healthy breast skin. FR-101 dressing application may increase moisture and oil level of the affected breast skin, P = 0.08 and P = 0.01, respectively. Results of comparisons between the affected breast skin and the healthy breast skin showed a trend to improve breast sensitivity. (P = 0.08) CONCLUSION: Our findings demonstrate FR-101 dressing is a novel, safe, and feasible dressing for breast cancer patients undergoing whole breast radiotherapy. This pilot study also suggests that FR-101 dressing may promote the repair of the damaged skin appendages after radiotherapy and alleviate their radiation-irritated skin symptoms.

Updates on treating ductal carcinoma in situ: what's to know in 2021.

Ductal carcinoma in situ (DCIS) is a noninvasive stage of disease but understood to be a nonobligate precursor to invasive breast cancer. As such, women with DCIS are routinely recommended for standard breast cancer treatment to prevent progression to invasive disease. DCIS, however, represents a heterogeneous group of lesions that differs in its biologic behavior and risk of progression. Thus, optimal treatment is unclear. This review presents the clinical trials evaluating the de-escalation of therapy, attempts at risk stratification, and future directions in the management of this disease. The de-escalation of therapy for patients with DCIS is being actively explored. Although no group of patients based on clinicopathologic features has yet been identified as suitable for omission of therapy, molecular tests appear better able to stratify patients at low risk for whom omission of radiation may be considered. Trials considering omission of surgery are ongoing, and the use of Herceptin and vaccine therapy are also being explored. The current review provides a centralized summary enabling the clinician to better understand the complexity of DCIS and the controversies over the optimal management of this disease. It highlights the need for better risk stratification to individualize patient care. http://links.lww.com/COOG/A77.

MO11-1 Efficacy and safety of perioperative dose-dense chemotherapy for breast cancer patients, including elderly population

Perioperative dose-dense chemotherapy with primary pegfilgrastim prophylaxis has been as a standard treatment for breast cancer. We evaluated the efficacy and safety of perioperative dose-dense doxorubicin and cyclophosphamide (ddAC) followed by conventional weekly paclitaxel or tri-weekly docetaxel and/or trastuzumab for Japanese patients with resectable breast cancer in single-center.