Breast Cancer Abstracts 13


Can rye intake decrease risk of human breast cancer
            (Adlercreutz, 2010)  Download
BACKGROUND:  Rye contains more fibre and bioactive compounds than other cereals used for bread production. The fibre and compounds of the fibre complex could provide protection against breast cancer (BC). OBJECTIVE:  To review the evidence and theoretical background for a role of rye and some of its components in the prevention of BC. DESIGN:  A short review based to a great extent on the work by scientists in the Nordic countries. RESULTS:  Some of the possible mechanisms by which the fibre complex could reduce BC risk are presented. The fibre through its effect on fermentation increases esterification of bile acids reducing toxicity of the free bile acids and is involved in the production of butyrate with potential anticancer effects including BC. The fibre reduces the enterohepatic circulation of the oestrogens leading to lower plasma oestrogen concentrations. The fibre complex contains bioactive compounds such as lignans and alkylresorcinols that are antioxidative and potentially anticarcinogenic. In addition, vitamins, minerals, and phytic acid in rye may provide protection against BC. CONCLUSION:  Rye products made from wholegrain rye flour are likely to contribute to reduced BC risk.

Inflammation and behavioral symptoms after breast cancer treatment: do fatigue, depression, and sleep disturbance share a common underlying mechanism
            (Bower et al., 2011)  Download
PURPOSE:  Fatigue, depression, and sleep disturbance are common adverse effects of cancer treatment and frequently co-occur. However, the possibility that inflammatory processes may underlie this constellation of symptoms has not been examined. PATIENTS AND METHODS:  Women (N = 103) who had recently finished primary treatment (ie, surgery, radiation, chemotherapy) for early-stage breast cancer completed self-report scales and provided blood samples for determination of plasma levels of inflammatory markers: soluble tumor necrosis factor (TNF) receptor II (sTNF-RII), interleukin-1 receptor antagonist, and C-reactive protein. RESULTS:  Symptoms were elevated at the end of treatment; greater than 60% of participants reported clinically significant problems with fatigue and sleep, and 25% reported elevated depressive symptoms. Women treated with chemotherapy endorsed higher levels of all symptoms and also had higher plasma levels of sTNF-RII than women who did not receive chemotherapy (all P < .05). Fatigue was positively associated with sTNF-RII, particularly in the chemotherapy-treated group (P < .05). Depressive symptoms and sleep problems were correlated with fatigue but not with inflammatory markers. CONCLUSION:  This study confirms high rates of behavioral symptoms in breast cancer survivors, particularly those treated with chemotherapy, and indicates a role for TNF-α signaling as a contributor to postchemotherapy fatigue. Results also suggest that fatigue, sleep disturbance, and depression may stem from distinct biologic processes in post-treatment survivors, with inflammatory signaling contributing relatively specifically to fatigue.

Reactivation of RASSF1A in breast cancer cells by curcumin.
            (Du et al., 2012)  Download
Reactivation of tumor suppressor genes (TSGs) involved in carcinogenesis by nontoxic bioactive food component represents a promising strategy for cancer chemoprevention. Recently, curcumin has been demonstrated to inhibit a bacterial DNA methyltransferase (M. Sss I) activity, induce global DNA hypomethylation in leukemia cells, and reactivate several hypermethylation silenced genes in lung and prostate cancer cells. Herein, we demonstrated that curcumin can enhance the mRNA and protein levels of ras-association domain family protein 1A (RASSF1A), 1 hypermethylation-silenced TSG, and decrease its promoter methylation in breast cancer cells. Mechanistic study demonstrated that curcumin can decrease DNA methylation activity of nuclear extract and downregulate the mRNA and protein levels of DNMT1 in MCF-7 cells, which may be associated with curcumin-induced disruption of NF-κB/Sp1 complex bound to the promoter region of DNMT1. Altogether, this study reveals a novel molecular mechanism of curcumin as a chemo-preventive agent for breast cancer through hypomethylation reactivation of RASSF1A.

Plasma carotenoids and risk of breast cancer over 20 y of follow-up.
            (Eliassen et al., 2015)  Download
BACKGROUND: Increasing evidence suggests that carotenoids, which are micronutrients in fruit and vegetables, reduce breast cancer risk. Whether carotenoids are important early or late in carcinogenesis is unclear, and limited analyses have been conducted by breast tumor subtypes. OBJECTIVES: We sought to examine issues of the timing of carotenoid exposure as well as associations by breast tumor subtypes. DESIGN: We conducted a nested case-control study of plasma carotenoids measured by using reverse-phase high-performance liquid chromatography and breast cancer risk in the Nurses' Health Study. In 1989-1990, 32,826 women donated blood samples; in 2000-2002, 18,743 of these women contributed a second blood sample. Between the first blood collection and June 2010, 2188 breast cancer cases were diagnosed (579 cases were diagnosed after the second collection) and matched with control subjects. RRs and 95% CIs were calculated by using conditional logistic regression adjusted for several breast cancer risk factors. RESULTS: Higher concentrations of alpha-carotene, beta-carotene, lycopene, and total carotenoids were associated with 18-28% statistically significantly lower risks of breast cancer (e.g., beta-carotene top compared with bottom quintile RR: 0.72; 95% CI: 0.59, 0.88; P-trend < 0.001). Associations were apparent for total carotenoids measured >/=10 y before diagnosis (top compared with bottom quintile RR: 0.69; 95% CI: 0.50, 0.95; P-trend = 0.01) as well as those <10 y before diagnosis (RR: 0.79; 95% CI: 0.64, 0.98; P-trend = 0.04, P-interaction = 0.11). Carotenoid concentrations were strongly inversely associated with breast cancer recurrence and death (e.g., beta-carotene top compared with bottom quintile RR: 0.32; 95% CI: 0.21, 0.51; P-trend < 0.001) compared with not recurrent and not lethal disease (P-heterogeneity < 0.001). CONCLUSION: In this large prospective analysis with 20 y of follow-up, women with high plasma carotenoids were at reduced breast cancer risk particularly for more aggressive and ultimately fatal disease.

Premenopausal breast cancer: estrogen receptor status and insulin-like growth factor-I (IGF-I), insulin-like growth factor binding protein-3 (IGFBP-3), and leptin
            (Eng-Wong et al., 2009)  Download
To better determine the relationship of these factors we examined a group of premenopausal women with newly diagnosed breast cancer to further define the relationships between tumor ER status, the IGF pathway, and leptin. We hypothesized that high IGF-I, high leptin, and low IGFBP-3 levels would be associated with ER-positive disease status compared with ER-negative tumors and that BMI may modify this association, such that the associations would be stronger among larger premenopausal women. In summary our analysis of premenopausal breast cancer cases found no significant associations between serum IGF-I, IGFBP-3, and leptin levels and the ER status of tumors. Yet, we made two intriguing obser- vations: first, women with ER negative tumors had higher IGFBP-3 levels than their counterparts with ER positive disease. The findings support our a priori hypothesis that greater levels of IGFBP-3 would be inversely associated with ER positivity. Second, we also observed that nonoverweight premenopausal patients with ER-negative tumors had higher leptin levels than their counterparts with ER-positive disease. This observation supports findings for higher leptin levels among pre and postmenopausal breast cancer patients with ER-negative tumors reported by Goodwin et al. (6). One could imagine that leptin has a different role in carcinogenesis and determining ER status below a certain BMI threshold, just as obesity is associated with both increased and decreased risk of breast cancer depending upon menopausal status


Tea polyphenol (-)-epigallocatechin-3-gallate inhibits DNA methyltransferase and reactivates methylation-silenced genes in cancer cell lines.
            (Fang et al., 2003)  Download
Hypermethylation of CpG islands in the promoter regions is an important mechanism to silence the expression of many important genes in cancer. The hypermethylation status is passed to the daughter cells through the methylation of the newly synthesized DNA strand by 5-cytosine DNA methyltransferase (DNMT). We report herein that (-)-epigallocatechin-3-gallate (EGCG), the major polyphenol from green tea, can inhibit DNMT activity and reactivate methylation-silenced genes in cancer cells. With nuclear extracts as the enzyme source and polydeoxyinosine-deoxycytosine as the substrate, EGCG dose-dependently inhibited DNMT activity, showing competitive inhibition with a K(i) of 6.89 microM. Studies with structural analogues of EGCG suggest the importance of D and B ring structures in the inhibitory activity. Molecular modeling studies also support this conclusion, and suggest that EGCG can form hydrogen bonds with Pro(1223), Glu(1265), Cys(1225), Ser(1229), and Arg(1309) in the catalytic pocket of DNMT. Treatment of human esophageal cancer KYSE 510 cells with 5-50 microM of EGCG for 12-144 h caused a concentration- and time-dependent reversal of hypermethylation of p16(INK4a), retinoic acid receptor beta (RARbeta), O(6)-methylguanine methyltransferase (MGMT), and human mutL homologue 1 (hMLH1) genes as determined by the appearance of the unmethylation-specific bands in PCR. This was accompanied by the expression of mRNA of these genes as determined by reverse transcription-PCR. The re-expression of RARbeta and hMLH1 proteins by EGCG was demonstrated by Western blot. Reactivation of some methylation-silenced genes by EGCG was also demonstrated in human colon cancer HT-29 cells, esophageal cancer KYSE 150 cells, and prostate cancer PC3 cells. The results demonstrate for the first time the inhibition of DNA methylation by a commonly consumed dietary constituent and suggest the potential use of EGCG for the prevention or reversal of related gene-silencing in the prevention of carcinogenesis.

Metabolic and hormonal profiles: HDL cholesterol as a plausible biomarker of breast cancer risk. The Norwegian EBBA Study.
            (Furberg et al., 2005)  Download
Low serum high-density lipoprotein cholesterol (HDL-C) is an important component of the metabolic syndrome and has recently been related to increased breast cancer risk in overweight and obese women. We therefore questioned whether serum HDL-C might be a biologically sound marker of breast cancer risk. We obtained cross-sectional data among 206 healthy women ages 25 to 35 years who participated in the Norwegian EBBA study. We included salivary ovarian steroid concentrations assessed by daily samples throughout one entire menstrual cycle, metabolic profile with measures of adiposity [body mass index (BMI) and truncal fat percentage], serum concentrations of lipids and hormones (insulin, leptin, testosterone, dehydroepiandrostendione sulfate, insulin-like growth factor-I, and its principal binding protein), and mammographic parenchymal pattern. We examined how components of the metabolic syndrome, including low serum HDL-C, were related to levels of hormones, and free estradiol concentration in particular, and studied predictors of mammographic parenchymal patterns in regression models. In women with BMI > or = 23.6 kg/m(2) (median), overall average salivary estradiol concentration dropped by 2.4 pmol/L (0.7 pg/mL; 13.2% change in mean for the total population) by each 0.33 mmol/L (12.8 mg/dl; 1SD) increase in serum HDL-C (P = 0.03; P(interaction) = 0.03). A subgroup of women characterized by both relatively high BMI (> or =23.6 kg/m(2)) and high serum LDL-C/HDL-C ratio (> or = 2.08; 75 percentile) had substantially higher levels of salivary estradiol by cycle day than other women (P = 0.001). BMI was the strongest predictor of overall average estradiol with a direct relationship (P< 0.001). Serum HDL-C was inversely related to serum leptin, insulin, and dehydroepiandrostendione sulfate (P < 0.001, P < 0.01, and P < 0.05, respectively). There was a direct relationship between breast density and healthy metabolic profiles (low BMI, high serum HDL-C; P < 0.001) and salivary progesterone concentrations (P < 0.05). Our findings support the hypothesis that low serum HDL-C might reflect an unfavorable hormonal profile with, in particular, increased levels of estrogens and gives further clues to biomarkers of breast cancer risk especially in overweight and obese women.

Phytoestrogens and breast cancer: a complex story.
            (Helferich et al., 2008)  Download
Genistein is an isoflavone with oestrogenic activity that is present in a variety of soy products as a constituent of complex mixtures of bioactive compounds, whose matrix profiles play an important role in determining the overall oestrogenic bioactivity of genistein. We review data on how the profile of soy bioactive compounds can modulate genistein-stimulated oestrogen-dependent tumour growth. Our research has focused on the effects of dietary genistein on the growth of oestrogen (E)-dependent mammary tumours both in vitro and in vivo. Genistein enhances the proliferation of E-dependent human breast cancer tumour growth. In a similar manner, dietary genistein stimulates tumour growth in the chemically-induced (NMU) mammary cancer rodent model. Genistin, the glycoside of genistein, simulates growth similar to that of genistein and withdrawal of either genistein or genistin results in tumour regression. The extent of soy processing modulates the effects of dietary genistein in vivo as soy protein isolate, a highly purified and widely used source of protein that is processed to contain low, medium, and high amounts of isoflavones, stimulate the growth of the E-dependent mammary tumours in a dose dependent manner. In contrast to the more purified diets, studies with soy flour of equivalent genistein levels did not stimulate the growth of E-dependent breast cancer tumours in vivo. However, the size of these tumours also did not regress as is observed in control groups in which oestrogen and genistein have been withdrawn. The expression of the oestrogen-target genes of pS2, progesterone receptor, and cyclin D1 correlates with the growth of E-dependent tumours and has been consistently observed to be induced in response to treatment with dietary genistein. To evaluate whether dietary genistein interacts with current anti-oestrogen breast cancer therapies such as tamoxifen (TAM), we implanted E-dependent tumours into ovariectomized athymic mice and administered oestradiol, oestradiol plus TAM, or oestradiol, TAM, and dietary genistein. In these studies dietary genistein was able to negate the inhibitory effect of TAM on E-stimulated tumour growth. In summary, genistein can act as an oestrogen agonist resulting in proliferation of E-dependent human breast cancer tumours in vivo and its activity can be modulated by the presence of other bioactive components in complex soy foods. Additionally, dietary genistein can negate the inhibitory effects of TAM on E-stimulated growth of MCF-7 cell tumours implanted into ovariectomized athymic mice.


Vitamin D deficiency is correlated with poor outcomes in patients with luminal-type breast cancer.
            (Kim et al., 2011)  Download
PURPOSE:  Vitamin D deficiency may be an indicator of poor prognosis in patients with breast cancer before surgery. We investigated the association between serum vitamin D concentration and breast cancer prognosis according to intrinsic cancer subtypes. METHODS:  From June to December 2006, serum 25-OHD was measured in 310 Korean women with breast cancer who were treated at the Asan Medical Center, Korea. Clinicopathologic data were examined to determine the prognostic effects of serum 25-OHD. Expression of estrogen receptor (ER), progesterone receptor (PR), and epidermal growth factor receptor 2 (Her2) were measured using tissue microarrays. Patients were classified with luminal A, luminal B, Her2-enriched, or basal-like subtypes of breast cancer. RESULTS:  Mean patient age was 48.7 years, and mean serum 25-OHD concentration was 31.4 ± 16.1 ng/ml. The 25-OHD levels were deficient (< 20 ng/ml) in 75 patients (24.2%), insufficient (20-29 ng/ml) in 95 (30.6%), and sufficient (30-150 ng/ml) in 140 (45.2%). Women with deficient 25-OHD levels were at increased risk of recurrence compared with those with sufficient vitamin D levels (P = 0.002). The 25-OHD concentration was inversely associated with prognosis of patients with cancer of the luminal A (P = 0.012) and luminal B subtypes (P =0.023), but not with the prognosis of patients with Her2/neu-enriched (P = 0.245) or triple-negative (P = 0.879) cancer subtypes. This association remained valid after adjustment for age, tumor size, nodal status, and estrogen receptor status (hazards ratio = 3.97; 95% confidence interval = 1.77-9.61). CONCLUSIONS:  Vitamin D deficiency may be associated with poor outcomes in patients with luminal-type breast cancer.

Regulation of cancer stem cells by cytokine networks: attacking cancer's inflammatory roots
            (Korkaya et al., 2011)  Download
There is substantial evidence that many human cancers are driven by a subpopulation of cells that display stem cell properties. These cancer stem cells (CSC) may also contribute to metastasis and treatment resistance. Furthermore, just as normal stem cells are regulated by their microenvironment, or niche, CSCs interact with and in turn are regulated by cells in the tumor microenvironment. These interactions involve inflammatory cytokines, such as interleukin (IL)-1, IL-6, and IL-8, which in turn activate Stat3/NF-kappaB pathways in both tumor and stromal cells. Activation of these pathways stimulates further cytokine production, generating positive feedback loops that in turn drive CSC self-renewal. These cytokine loops and the pathways they regulate resemble those activated during chronic inflammation and wound healing, and may contribute to the known link between inflammation and cancer. Inhibitors of these cytokines and their receptors have been developed as anti-inflammatory agents. By blocking signals from the tumor microenvironment, these agents have the potential to target CSCs. Future clinical trials using these compounds will be needed to determine whether targeting the CSC population has clinical benefit.

Mixed tocopherols prevent mammary tumorigenesis by inhibiting estrogen action and activating PPAR-gamma.
            (Lee et al., 2009)  Download
PURPOSE:  Tocopherols are lipophilic antioxidants present in vegetable oils. Although the antioxidant and anticancer activities of alpha-tocopherol (vitamin E) have been studied for decades, recent intervention studies with alpha-tocopherol have been negative for protection from cancer in humans. The tocopherols consist of four isoforms, which are the alpha, beta, gamma, and delta variants, and recent attention is being given to other isoforms. In the present study, we investigated the inhibitory effect of a tocopherol mixture rich in gamma- and delta-tocopherols against mammary tumorigenesis. EXPERIMENTAL DESIGN:  Female Sprague Dawley rats were treated with N-methyl-N-nitrosourea (NMU), and then fed diets containing 0.1%, 0.3%, or 0.5% mixed tocopherols rich in gamma- and delta-tocopherols for 9 weeks. Tumor burden and multiplicity were determined, and the levels of markers of inflammation, proliferation, and apoptosis were evaluated in the serum and in mammary tumors. The regulation of nuclear receptor signaling by tocopherols was studied in mammary tumors and in breast cancer cells. RESULTS:  Dietary administration of 0.1%, 0.3%, or 0.5% mixed tocopherols suppressed mammary tumor growth by 38%, 50%, or 80%, respectively. Tumor multiplicity was also significantly reduced in all three mixed tocopherol groups. Mixed tocopherols increased the expression of p21, p27, caspase-3, and peroxisome proliferator activated receptor-gamma, and inhibited AKT and estrogen signaling in mammary tumors. Our mechanistic study found that gamma- and delta-tocopherols, but not alpha-tocopherol, activated peroxisome proliferator activated receptor-gamma and antagonized estrogen action in breast cancer. CONCLUSION:  The results suggest that gamma- and delta-tocopherols may be effective agents for the prevention of breast cancer.

Flaxseed sprouts induce apoptosis and inhibit growth in MCF-7 and MDA-MB-231 human breast cancer cells.
            (Lee and Cho, 2012)  Download
Flaxseeds have been shown to play a role in the prevention of cancer and heart disease, and it is believed that their more favorable fatty acid composition is responsible. Sprouting is a natural method to modify nutritional components and to decrease cyanide poisoning of raw flaxseeds. Here, we investigated the in vitro effects of flaxseed sprouts on cell growth and apoptosis of human breast cancer cells. In a series of in vitro experiments, estrogen-receptor-positive (MCF-7) and estrogen-receptor-negative (MDA-MB-231) cells were cultured and treated with flaxseed sprouts, and then cell proliferation, apoptosis, and gene expression were measured. Flaxseed sprouts significantly reduced the growth of both of MCF-7 and MDA-MB-231 cells and also increased apoptosis. However, flaxseed sprouts did not affect the growth of MCF-10A mammary epithelial cells. In gene transcription analysis using quantitative real-time polymerase chain reaction, flaxseed sprout treatment significantly upregulated p53 mRNA in both cell cancer lines. These results suggest that flaxseed sprouts induce apoptosis and inhibit cancer cell growth, thereby demonstrating their anti-proliferative effects in breast cancer cells. This study may provide important information for devising dietary strategies to reduce breast cancer risk.

Curcumin is a potent DNA hypomethylation agent.
            (Liu et al., 2009)  Download
Molecular docking of the interaction of curcumin and DNMT1 suggested that curcumin covalently blocks the catalytic thiolate of C1226 of DNMT1 to exert its inhibitory effect. This was validated by showing that curcumin inhibits the activity of M. SssI with an IC(50) of 30 nM, but no inhibitory activity of hexahydrocurcumin up to 100 microM. In addition, curcumin can induce global DNA hypomethylation in a leukemia cell line.

Estrogenic botanical supplements, health-related quality of life, fatigue, and hormone-related symptoms in breast cancer survivors: a HEAL study report.
            (Ma et al., 2011)  Download
BACKGROUND:  It remains unclear whether estrogenic botanical supplement (EBS) use influences breast cancer survivors' health-related outcomes. METHODS:  We examined the associations of EBS use with health-related quality of life (HRQOL), with fatigue, and with 15 hormone-related symptoms such as hot flashes and night sweats among 767 breast cancer survivors participating in the Health, Eating, Activity, and Lifestyle (HEAL) Study. HRQOL was measured by the Medical Outcomes Study short form-36 physical and mental component scale summary score. Fatigue was measured by the Revised-Piper Fatigue Scale score. RESULTS:  Neither overall EBS use nor the number of EBS types used was associated with HRQOL, fatigue, or hormone-related symptoms. However, comparisons of those using each specific type of EBS with non-EBS users revealed the following associations. Soy supplements users were more likely to have a better physical health summary score (odds ratio [OR] = 1.66, 95% confidence interval [CI] = 1.02-2.70). Flaxseed oil users were more likely to have a better mental health summary score (OR = 1.76, 95% CI = 1.05-2.94). Ginseng users were more likely to report severe fatigue and several hormone-related symptoms (all ORs ≥ 1.7 and all 95% CIs exclude 1). Red clover users were less likely to report weight gain, night sweats, and difficulty concentrating (all OR approximately 0.4 and all 95% CIs exclude 1). Alfalfa users were less likely to experience sleep interruption (OR = 0.28, 95% CI = 0.12-0.68). Dehydroepiandrosterone users were less likely to have hot flashes (OR = 0.33, 95% CI = 0.14-0.82). CONCLUSIONS:  Our findings indicate that several specific types of EBS might have important influences on a woman's various aspects of quality of life, but further verification is necessary.

Glycemic index, glycemic load and mammographic breast density: the EPIC Florence longitudinal study.
            (Masala et al., 2013)  Download
A few studies have evaluated the association between diet and mammographic breast density (MBD) and results are inconsistent. MBD, a well-recognized risk factor for breast cancer, has been proposed as a marker of cumulative exposure to hormones and growth factors. Diets with a high glycemic index (GI) or glycemic load (GL) may increase breast cancer risk, via an effect on the insulin-like growth factor axis. We have investigated the association between carbohydrate intake, GI, GL and MBD in a prospective study. We identified a large series of women, in the frame of the EPIC-Florence cohort, with a mammogram taken five years after enrolment, when detailed information on dietary and lifestyle habits and anthropometric measurements had been collected. Mammograms have been retrieved (1,668, 83%) and MBD assessed according to Wolfe's classification. We compared women with high MBD (P2+DY Wolfe's categories) with those with low MBD (N1+P1) through logistic models adjusted for age, education, body mass index, menopause, number of children, breast feeding, physical activity, non-alcohol energy, fibers, saturated fat and alcohol. A direct association between GL and high MBD emerged in the highest quintile of intake in comparison with the lowest quintile (OR = 1.73, 95%CI 1.13-2.67, p for trend = 0.048) while no association with glycemic index was evident. These results were confirmed after exclusion of women reporting to be on a diet or affected with diabetes, and when Hormone Replacement Therapy at the date of mammographic examination used to assess MBD was considered. The effect was particularly evident among leaner women, although no interaction was found. A positive association was suggested for increasing simple sugar and total carbohydrates intakes limited to the highest quintiles. In this Italian population we observed an association between glycemic load, total and rapidly absorbed carbohydrates and high MBD. These novel results warrant further investigations.

A prospective evaluation of the durability of palliative interventions for patients with metastatic breast cancer.
            (Morrogh et al., 2010)  Download
BACKGROUND:  Although systemic therapy for metastatic breast cancer (MBC) continues to evolve, there are scant data to guide physicians and patients when symptoms develop. In this article, the authors report the frequency and durability of palliative procedures performed in the setting of MBC. METHODS:  From July 2002 to June 2003, 91 patients with MBC underwent 109 palliative procedures (operative, n=76; IR n=39, endoscopic n=3). At study entry, patients had received a mean of 6 prior systemic therapies for metastatic disease. System-specific symptoms included neurologic (33%), thoracic (23%), musculoskeletal (22%) and GI (14%). The most common procedures were thoracostomy with or without pleurodesis (27%), craniotomy with resection (19%) and orthopedic open reduction/internal fixation (19%). RESULTS:  Symptom improvement at 30 days and 100 days was reported by 91% and 81% of patients, respectively, and 70% reported continued benefit for duration of life. At a median interval of 75 days from intervention (range, 8-918 days), 23 patients (25%) underwent 61 additional procedures for recurrent symptoms. The durability of palliation varied with system-specific symptoms. Patients with neurologic or musculoskeletal symptoms were least likely to require additional maintenance procedures (P<.0002). The 30-day complication rate was 18% and there were no procedure-related deaths. At a median survival of 37.4 mos from MBC diagnosis (range, 1.6-164 months) and 8.4 months after intervention (range, 0.2-73 months), 7 of 91 patients remained alive. CONCLUSIONS:  Palliative interventions for symptoms of MBC are safe and provide symptom control for the duration of life in 70% of patients. Definitive surgical treatment of neurologic or musculoskeletal symptoms provided the most durable palliation; interventions for other symptoms frequently require subsequent procedures. The longer median survival for patients with MBC highlights the need to optimize symptom control to maintain quality of life.

A systematic assessment of benefits and risks to guide breast cancer screening decisions.
            (Pace and Keating, 2014)  Download
IMPORTANCE:  Breast cancer is the second leading cause of cancer deaths among US women. Mammography screening may be associated with reduced breast cancer mortality but can also cause harm. Guidelines recommend individualizing screening decisions, particularly for younger women. OBJECTIVES:  We reviewed the evidence on the mortality benefit and chief harms of mammography screening and what is known about how to individualize mammography screening decisions, including communicating risks and benefits to patients. EVIDENCE ACQUISITION:  We searched MEDLINE from 1960-2014 to describe (1) benefits of mammography, (2) harms of mammography, and (3) individualizing screening decisions and promoting informed decision making. We also manually searched reference lists of key articles retrieved, selected reviews, meta-analyses, and practice recommendations. We rated the level of evidence using the American Heart Association guidelines. RESULTS:  Mammography screening is associated with a 19% overall reduction of breast cancer mortality (approximately 15% for women in their 40s and 32% for women in their 60s). For a 40- or 50-year-old woman undergoing 10 years of annual mammograms, the cumulative risk of a false-positive result is about 61%. About 19% of the cancers diagnosed during that 10-year period would not have become clinically apparent without screening (overdiagnosis), although there is uncertainty about this estimate. The net benefit of screening depends greatly on baseline breast cancer risk, which should be incorporated into screening decisions. Decision aids have the potential to help patients integrate information about risks and benefits with their own values and priorities, although they are not yet widely available for use in clinical practice. CONCLUSIONS AND RELEVANCE:  To maximize the benefit of mammography screening, decisions should be individualized based on patients' risk profiles and preferences. Risk models and decision aids are useful tools, but more research is needed to optimize these and to further quantify overdiagnosis. Research should also explore other breast cancer screening strategies.




Adlercreutz, H (2010), ‘Can rye intake decrease risk of human breast cancer’, Food Nutr Res, 54 PubMed: 21311613
Bower, JE, et al. (2011), ‘Inflammation and behavioral symptoms after breast cancer treatment: do fatigue, depression, and sleep disturbance share a common underlying mechanism’, J Clin Oncol, 29 (26), 3517-22. PubMed: 21825266
Du, L, et al. (2012), ‘Reactivation of RASSF1A in breast cancer cells by curcumin.’, Nutr Cancer, 64 (8), 1228-35. PubMed: 23145775
Eliassen, AH, et al. (2015), ‘Plasma carotenoids and risk of breast cancer over 20 y of follow-up.’, Am J Clin Nutr, 101 (6), 1197-205. PubMed: 25877493
Eng-Wong, J., et al. (2009), ‘Premenopausal breast cancer: estrogen receptor status and insulin-like growth factor-I (IGF-I), insulin-like growth factor binding protein-3 (IGFBP-3), and leptin’, Breast J, 15 (4), 426-28. PubMed: 19601950
Fang, MZ, et al. (2003), ‘Tea polyphenol (-)-epigallocatechin-3-gallate inhibits DNA methyltransferase and reactivates methylation-silenced genes in cancer cell lines.’, Cancer Res, 63 (22), 7563-70. PubMed: 14633667
Furberg, AS, et al. (2005), ‘Metabolic and hormonal profiles: HDL cholesterol as a plausible biomarker of breast cancer risk. The Norwegian EBBA Study.’, Cancer Epidemiol Biomarkers Prev, 14 (1), 33-40. PubMed: 15668473
Helferich, WG, JE Andrade, and MS Hoagland (2008), ‘Phytoestrogens and breast cancer: a complex story.’, Inflammopharmacology, 16 (5), 219-26. PubMed: 18815740
Kim, HJ, et al. (2011), ‘Vitamin D deficiency is correlated with poor outcomes in patients with luminal-type breast cancer.’, Ann Surg Oncol, 18 (7), 1830-36. PubMed: 21573699
Korkaya, H., S. Liu, and M. S. Wicha (2011), ‘Regulation of cancer stem cells by cytokine networks: attacking cancer’s inflammatory roots’, Clin Cancer Res, 17 (19), 6125-29. PubMed: 21685479
Lee, HJ, et al. (2009), ‘Mixed tocopherols prevent mammary tumorigenesis by inhibiting estrogen action and activating PPAR-gamma.’, Clin Cancer Res, 15 (12), 4242-49. PubMed: 19509159
Lee, J and K Cho (2012), ‘Flaxseed sprouts induce apoptosis and inhibit growth in MCF-7 and MDA-MB-231 human breast cancer cells.’, In Vitro Cell Dev Biol Anim, 48 (4), 244-50. PubMed: 22438134
Liu, Z, et al. (2009), ‘Curcumin is a potent DNA hypomethylation agent.’, Bioorg Med Chem Lett, 19 (3), 706-9. PubMed: 19112019
Ma, H, et al. (2011), ‘Estrogenic botanical supplements, health-related quality of life, fatigue, and hormone-related symptoms in breast cancer survivors: a HEAL study report.’, BMC Complement Altern Med, 11 109. PubMed: 22067368
Masala, G, et al. (2013), ‘Glycemic index, glycemic load and mammographic breast density: the EPIC Florence longitudinal study.’, PLoS One, 8 e70943. PubMed: 23951047
Morrogh, M, et al. (2010), ‘A prospective evaluation of the durability of palliative interventions for patients with metastatic breast cancer.’, Cancer, 116 (14), 3338-47. PubMed: 20564060
Pace, LE and NL Keating (2014), ‘A systematic assessment of benefits and risks to guide breast cancer screening decisions.’, JAMA, 311 (13), 1327-35. PubMed: 24691608