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Background: Invasive lobular carcinoma (ILC) is traditionally considered less responsive to chemotherapy. Although the Oncotype recurrence score (RS) has been validated to identify high-risk patients who benefit from chemotherapy, some studies have questioned its relevance in patients with ILC. The objective of this study was to better characterize potential use of the RS in these patients., Methods: The National Cancer Database was used to identify women with stage I through III, T1 through T3, N0 or N1, hormone receptor-positive, HER2-negative ILC or invasive ductal carcinoma (IDC) who had an available RS between 2010 and 2016. Multivariable Cox regression was used to model the effect of variables on 5-year overall survival (OS). The Kaplan-Meier method was used to estimate OS according to the RS, nodal status, and chemotherapy., Results: In total, 15,763 patients with ILC and 100,070 with IDC were identified. The mean age of patients with ILC and IDC was 59.2 ± 9.1 and 57.2 ± 9.8, respectively. A lower percentage of patients with ILC versus those with IDC had a high RS, defined as >25 (6.6% vs 16.0%; P < .0001). ILC patients with a high RS who had N0 or N1 disease received approximately 10% less chemotherapy compared with similar patients who had IDC. The results indicated that the RS had statistically significant prognostic value for patients with ILC. In addition, an absolute OS advantage was correlated with the receipt of chemotherapy by patients with ILC who had a high RS with N0 or N1 disease., Conclusions: Patients with ILC who have a high RS are treated less often with chemotherapy compared with similar patients who have IDC. Nevertheless, the RS has a prognostic as well as a predictive value in ILC, with an association between OS benefit and chemotherapy receipt in patients who have ILC with a high RS, especially if they have N1 disease., Lay Summary: Invasive lobular carcinoma (ILC) is a subtype of breast cancer comprising about 15% of cases. The Oncotype recurrence score (RS) is a genetic test of breast tumors that helps predict which patients might benefit from chemotherapy. Some have doubted the relevance of the RS for patients with ILC. In this study, the authors show that the RS is relevant for patients who have ILC. The RS has the potential of predicting the risk of recurrence and identifying patients with ILC who might benefit from chemotherapy., (© 2022 American Cancer Society.)

The U.S. Preventive Services Task Force (USPSTF) recommended screening mammography every 1-2 years for women 40 years and older in 2002, and changed its recommendations in 2009 to no routine screening for women between 40 and 49 years of age; and biennial screening for women between 50 and 74 years of age. This study evaluates the change in mammographic use after the issuance of the revised recommendations. Women who participated in a cross-sectional study of breast cancer risk factors from 2007 to 2013 were asked if they had received a mammogram in the preceding 2 years. All 3442 study participants who enrolled in the study after January 1, 2011 were matched by race, age, and educational level with women enrolled between 2007 and 2010. The proportions of women who stated they had received a mammogram in the past 2 years were compared between the two groups. One fourth of the participants were African American and 39% were 40-49 years of age. Among white women, significant decreases in recent mammogram use from 2007-2010 to 2011-2013 were detected for women 40-49 years of age (-10.3%, p < 0.001) and 50-74 years of age (-8.8%, p < 0.001). Among African-American women, the change in recent mammogram use was not statistically significant for women 40-49 years of age (-2.7%, p = 0.440) or 50-74 years of age (-2.2%, p = 0.398). Following the change in the USPSTF guidelines, mammography use among white women declined; however, no change was observed among African-American women., (© 2016 Wiley Periodicals, Inc.)

This study examined the effect of oral glutamine (Gln) on radiation injury in breast cancer patients undergoing radiation therapy. The radiation injury was evaluated using Radiation Therapy Oncology Group (RTOG) scales. Cosmesis was scored. Blood Gln and glutathione (GSH) levels were determined. Serum protein profiling was determined using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS). Patients receiving Gln scored significantly better in RTOG score than the patients receiving placebo. Cosmetic scores averaged excellent in the Gln group vs fair to good in the placebo group. Blood Gln and GSH levels were significantly higher in the Gln group vs the placebo group. Serum protein profiling with SELDI-TOF MS identified a novel Gln-responsive protein that showed amino acid similarity with myoglobin. These results suggest that Gln is an effective way to reduce radiation morbidity to breast cancer and is associated with the increased expression of a novel serum protein biomarker.

The origin of cancer health disparities and mortality in Arkansas is multifactorial. In response to a cooperative agreement with the National Cancer Institute's Center to Reduce Cancer Health Disparities, the Arkansas Special Populations Access Network (ASPAN) was developed to reduce these disparities. ASPAN's partnership with local primary care physicians of the Arkansas Medical, Dental, and Pharmaceutical Association through the Cancer Education Awareness Program is the focus of this article. A quasi-experimental intervention, the Community Cancer Education Awareness Program, was employed that included 1) physician education to increase awareness of risk factors and cancer screening; and 2) patient education to increase screening, and 3) patient-generated screening questionnaires to prompt discussion of cancer risk and screening recommendations between patients and physicians. Two urban and 2 rural clinics were targeted during a 12-month period with interval intervention assessments. Baseline review of records (n = 200) from patients >/=40 were utilized to assess the rate of breast, prostate, and colorectal screenings among clinics. For the patient education intervention, patients (n = 120) were interviewed via a 34-item assessment. Physician awareness of cancer risk factors and screening recommendations significantly increased. Statistically significant increases were seen for prostate (P = .028), breast (P = .036), and colorectal (P < .001) cancer screening across all 4 clinics. Patients' increased likelihood of cancer screenings was associated with knowledge about consumption of animal fat (P < .001), dietary fiber (P < .013), and mammograms (P < .001). Utilizing the physician as the central change agent, the ASPAN provider network successfully enhanced cancer screening awareness of minority physicians and their patients. Cancer 2006. (c) 2006 American Cancer Society.

Background: 7,12-dimethylbenz [a] anthracene (DMBA) administration to pubertal rats causes breast tumors and inhibits glutathione (GSH) production. Our previous results have established that oral glutamine (GLN) supplementation significantly reduced tumor development, restored the depressed GSH production, and caused a significant decrease in the circulating levels of insulinlike growth factor-1 (IGF-1). The present study was designed to investigate the involvement of the IGF-1-activated phosphatidylinositol 3 kinase (PI-3K)/Akt apoptotic signaling pathway., Materials and Methods: Forty female Sprague-Dawley rats were randomly divided into 4 groups: DMBA+GLN (n = 16), DMBA+water (n = 8), Oil+GLN (n = 8) and Oil+water (n = 8). At the age of 50 days, rats received a single dose of 100 mg/kg DMBA (n = 24) or sesame oil (n = 16) and were gavaged with a GLN suspension formulation (AES-14) or water for the duration of the entire experiment. The animals were killed 11 weeks after the DMBA application, and the levels of IGF-1, IGF-1 receptor (IGF-IR), Akt, Bcl-2 and Bad in tumorous and nontumorous breast tissue samples were measured by Western blot analysis., Results: GLN supplementation resulted in a significant decrease in the levels of IGF-1, IGF-IR, Akt, and Bcl-2 in nontumorous samples. At the same time, the levels of pro-apoptotic protein Bad were significantly elevated. The samples collected from tumor tissues showed lower levels of IGF-1, Akt, Bcl-2, Bad, and IGF-IR in comparison with nontumorous tissues., Conclusions: GLN supplementation inhibited the PI-3K/Akt pathway that is thought to be important in increasing cell survival during tumorigenesis. These results are in agreement with our hypothesis that GLN counteracts the effects of DMBA and blocks carcinogenesis in vivo.

Background: Oral glutamine (GLN) has been shown to up-regulate tissue glutathione (GSH), augment natural killer (NK) cell activity, and prevent tumor growth in an implantable breast cancer model (MTF-7). We hypothesized that dietary GLN would likewise antagonize the induction or promotion of tumor formation by 7,12-dimethylbenz[a]anthracene (DMBA) via up-regulation of GSH or augmentation of NK activity., Methods: At age 55 days, 81 Sprague-Dawley rats were gavaged with a one-time dose of 80 mg/kg DMBA, time 0. Rats were randomized into 3 groups (GLN+DMBA, Freamine [FA]+DMBA, water (H2O)+DMBA), pair-fed chow, and gavaged with 1.0 g/kg/day GLN or isonitrogenous amount of FA or H2O for the indicated times: PreFed (-1 to + 16 weeks), Short-Fed (-1 to + 1 weeks) and PostFed (+ 1 to +16 weeks). After 16 weeks, rats were killed and examined for mammary tumors, blood was assayed for GLN and GSH content, and spleens were assayed for NK cytotoxicity., Results: Over the 4-month study period, there was no significant difference in tumorigenesis between FA and H2O groups, regardless of timing of feeding and amino acid diet, except GLN. In Pre- and PostFed GLN groups, there was no significant difference between groups, but there were significant decreases in tumorigenesis in GLN groups compared with either FA or H2O groups. However, in the Short-Fed group, there was no significant difference in tumorigenesis from the GLN, FA, or H2O groups., Conclusions: Continuously supplemented GLN significantly reduced DMBA-induced breast cancer growth when compared with the non-GLN-supplemented and Short-Fed supplemental GLN groups. Furthermore, GLN appears to have its primary effect on promotion and not initiation of tumor formation. This decreased tumor formation was associated with significantly higher arterial GLN and GSH levels and NK activity at killing in the GLN+DMBA group. Protein in the presentation of FA did not promote or prevent tumor growth. These data indicate that GLN may be useful in the chemoprevention of breast cancer.

Background: The gastrointestinal tract is recognized as having important metabolic functions. This study examined gut glutathione (GSH) extraction and the effect of supplemental oral glutamine (GLN) on gut GSH fractional release., Methods: Healthy female Fisher-344 rats weighing approximately 150 to 200 g were pair-fed chow and supplemented by gavage with 1 g/kg/d GLN or an isonitrogenous amount of Freamine (McGaw, St. Louis, MO). Rats were sacrificed at 6 weeks. Arterial and portal blood was assayed for GLN and GSH content. The gut GLN and GSH extractions were calculated., Results: The gut GLN fractional uptake was increased by approximately 50%, and there was a near threefold increase in gut GSH fractional release in the GLN-supplemented group., Conclusions: The discovery of gut's role as a major producer of GSH may give insight into why feeding via the gut rather than by the venous route is so important. Supplemental oral GLN further enhances GLN extraction as well as GSH fractional release in the gut.

Background: It is known that tumor progression is associated with a depletion in host glutamine (Gln) stores and a depression of natural killer (NK) cell activity. After demonstrating an in vitro dependence of NK cell activity on Gln and glutathione concentration, this study evaluated the effects of oral Gln on Gln and glutathione metabolism, NK cell activity, and tumor growth in the tumor-bearing rat., Methods: Two days before tumor implantation, rats (n = 32) were randomized to receive Gln (1 g/kg/d) or an isonitrogenous amount of glycine by gavage and pair-fed food. On day 21 after tumor implantation, rats were killed, and tumors were measured and processed for glutaminase activity, glutathione content, and tumor morphometrics. Splenic lymphocytes were assayed for NK cell activity via a chromium (51Cr) release assay using YAC (NK-cell-sensitive mouse tumor cell line) target cells. Blood Gln and glutathione were measured. A second set of rats (n = 16) were treated similarly except that ketamine was given twice weekly to suppress NK cell activity., Results: During the 3-week study period, tumor growth was decreased by 40% in the Gln group. This decrease in growth was associated with a 30% increase in NK cell activity. Administration of ketamine to rats completely reversed the higher NK cell activity and decreased the tumor growth seen in the Gln-treated group., Conclusions: These data indicate that oral Gln supplementation, through support of host Gln stores and glutathione production, may decrease tumor growth by enhancing NK cell activity.

Dose intensification of chemotherapy is thought to increase survival. With recent advances in hemopoietic cell modulators such as granulocyte colony stimulating factor, the limiting toxicity of intensifying chemotherapeutic regimens has become the severity of the associated enterocolitis. In animal models, glutamine protects the host from methotrexate-induced enterocolitis. This study evaluates the effects of a glutamine-supplemented diet on the tumoricidal effectiveness of methotrexate. Sarcoma-bearing Fisher 344 rats (n = 30) were pair-fed an isocaloric elemental diet containing 1% glutamine or an isonitrogenous amount of glycine beginning on day 25 of the study. Rats from each group received two intraperitoneal injections of methotrexate (5 mg/kg) or saline on days 26 and 33 of the study. On day 40, rats were killed, tumor volume and weight were recorded, and tumor glutaminase activity and tumor morphometrics were measured. Blood was taken for arterial glutamine content, complete blood count, and blood culture. The gut was processed for glutaminase activity and synthesis phase of the deoxyribonucleic acid. In rats receiving methotrexate, the tumor volume loss was nearly doubled when glutamine was added to the diet. Significant differences in tumor glutaminase activity and morphometrics were not detected. The toxicity to the host was ameliorated. Significantly increased synthesis phase of deoxyribonucleic acid of the whole jejunum, decreased bacteremia, "sepsis," and mortality were demonstrated. Glutamine supplementation enhances the tumoricidal effectiveness of methotrexate while reducing its morbidity and mortality in this sarcoma rat model.

Glutamine may be an essential dietary component, especially for the support of intestinal mucosal growth and function. This study evaluated the effects of a glutamine-enriched elemental diet, administered before whole-abdominal radiation on gut glutamine metabolism, mucosal morphometrics, and bacterial translocation. Rats were randomized to receive a nutritionally complete elemental diet that was glutamine-enriched or glutamine-free for 4 days. The animals were then subjected to a single dose of 1000 cGy x-radiation to the abdomen. After irradiation, all animals received the glutamine-free diet. Four days later the animals underwent laparotomy for sampling of arterial and portal venous blood, culture of mesenteric lymph nodes, and removal of the small intestine for microscopic examination. There was no difference in arterial glutamine or gut glutamine extraction between the two groups, but body weight loss was significantly diminished in the glutamine-fed rats. Rats receiving the glutamine-enriched elemental diet before radiation had a significant increase in jejunal villous number, villous height, and number of metaphase mitoses per crypt. Scanning electron microscopy confirmed the presence of an intact gut epithelium in eight of eight rats receiving prophylactic glutamine compared to one of eight animals in the glutamine-free group. Three of eight rats fed glutamine had culture positive mesenteric lymph nodes compared with five of seven rats receiving the glutamine-free diet. Glutamine exerts a protective effect on the small bowel mucosa by supporting crypt cell proliferation effect on accelerate healing of the acutely radiated bowel.

Although glutamine-supplemented diets appear to be beneficial in the model described here, carefully designed clinical trials must be done before such therapy is recommended in patients receiving XRT. Such studies should examine the efficacy of glutamine-enriched parenteral nutrition as well as enteral feedings. They must address the issue of potential stimulation of tumor growth by glutamine supplementation. In addition, the question has been raised as to whether glutamine will result in the tumor being more refractory to radiation therapy.