Breast Cancer In High-risk Women Research Articles

MRI Insights in Breast Imaging.

In the world, breast cancer is the most commonly diagnosed cancer among women. Currently, MRI is the most sensitive breast imaging method for detecting breast cancer, although false positive rates are still an issue. To date, the accuracy of breast MRI is widely recognized across various clinical scenarios, in particular, staging of known cancer, screening for breast cancer in high-risk women, and evaluation of response to neoadjuvant chemotherapy. Since technical development and further clinical indications have expanded over recent years, dedicated breast radiologists need to constantly update their knowledge and expertise to remain confident and maintain high levels of diagnostic performance in breast MRI. This review aims to detail current and future applications of breast MRI, from technological requirements and advances to new multiparametric and abbreviated protocols, and ultrafast imaging, as well as current and future indications.

Surgical Decision Making in Genetically High-Risk Women: Quantifying Postoperative Complications and Long-Term Risks of Supplemental Surgery After Risk-Reducing Mastectomy.

Risk-reducing mastectomy (RRM) helps prevent breast cancer in high-risk women but also carries a risk of unanticipated supplemental surgeries. We sought to determine the likelihood of supplemental surgeries following RRM. We performed a retrospective cohort study of female patients with a confirmed germline pathogenic variant (GPV) in a breast cancer susceptibility gene (BRCA1/2, PALB2 and others) who underwent bilateral or contralateral RRM at our institution between 2006 and 2022. Supplemental surgeries were defined as any operation requiring general or local anesthesia performed outside of the initially planned procedure(s). The Kaplan-Meier method was used to estimate the 5-years cumulative incidence of supplemental surgery. Of 560 GPV carriers, RRMs were performed in 258 (46.1%) women. The median age of the cohort was 44 years (interquartile range 37-52 years), with 33 (12.8%) patients undergoing RRM without reconstruction and 225 (87.2%) undergoing RRM with reconstruction. Following surgery, 34 patients (13.2%) developed early (< 30 days) postoperative complications, including infection, hematoma, seroma, loss of the nipple areola complex, flap necrosis, implant exposure and/or prosthesis removal. At a median follow-up of 3.8 years, 94 (36.4%) GPV carriers underwent at least one reoperation. Participants who experienced an early postoperative complication had the highest rate of reoperation (85.3% vs. 29.0%; p < 0.001) and a significantly higher likelihood of multiple additional surgical interventions (41.2% vs. 10.7%; p < 0.001). The 5-years rate of supplemental surgery was 39.2% [95% confidence interval (CI) 32.7-46.5] in the overall cohort and 31.5% (95% CI 24.9-39.3) in patients without an early postoperative complication. Unanticipated supplemental surgeries occur in 40% of GPV carriers following RRM andin nearly one-third of patients without early postoperative complications.

Breast cancer prevention with liquiritigenin from licorice through the inhibition of aromatase and protein biosynthesis in high-risk women’s breast tissue

Breast cancer risk continues to increase post menopause. Anti-estrogen therapies are available to prevent postmenopausal breast cancer in high-risk women. However, their adverse effects have reduced acceptability and overall success in cancer prevention. Natural products such as hops (Humulus lupulus) and three pharmacopeial licorice (Glycyrrhiza) species have demonstrated estrogenic and chemopreventive properties, but little is known regarding their effects on aromatase expression and activity as well as pro-proliferation pathways in human breast tissue. We show that Gycyrrhiza inflata (GI) has the highest aromatase inhibition potency among these plant extracts. Moreover, phytoestrogens such as liquiritigenin which is common in all licorice species have potent aromatase inhibitory activity, which is further supported by computational docking of their structures in the binding pocket of aromatase. In addition, GI extract and liquiritigenin suppress aromatase expression in the breast tissue of high-risk postmenopausal women. Although liquiritigenin has estrogenic effects in vitro, with preferential activity through estrogen receptor (ER)-β, it reduces estradiol-induced uterine growth in vivo. It downregulates RNA translation, protein biosynthesis, and metabolism in high-risk women’s breast tissue. Finally, it reduces the rate of MCF-7 cell proliferation, with repeated dosing. Collectively, these data suggest that liquiritigenin has breast cancer prevention potential for high-risk postmenopausal women.

1 Oral - Early detection of breast cancer in high-risk women based on longitudinal changes in serum-based proteins: the TESTBREAST study

Background: Women who have a high risk of developing breast cancer due to a familial predisposition or mutations in susceptibility genes undergo adapted screening programs. The earlier onset of screening and higher number of screening moments leaves quite a burden on these women, next to that interval cancers can still occur between scheduled screening moments. Therefore, the prospective, multicenter Dutch TESTBREAST study aims to identify a novel panel of blood-based protein biomarkers. Hereby, the aim is to enable early breast cancer detection for high-risk women using a relatively simple blood test to monitor biomarker levels.

Application of the ultrafast sequence in the dynamic contrastographic study in the magnetic resonance imaging of the breast: our experience

In the last decade, breast MRI has played a role of primary importance, as a “gold standard” method in the earlydiagnosis of breast cancer in high-risk women, in assessing the extent of the disease and the response to neoadjuvantchemotherapy. Currently, the 3D GRE Rapid-Acquisition sequence in dynamic acquisition without and with endovenous administration of contrast medium, is fundamental for the breast MRI protocol, as the current diagnosticapproaches in Magnetic Resonance are based precisely on this sequence, able to guarantee accurate diagnosticperformances detecting pathological mass and non-mass-enhancement. Ultrafast sequences are modern sequencesbased on the 4D Time-Resolved technique with k-space sampling modalities which allow the evaluation of post-contrast images with very high temporal resolution. The purpose of our work is to illustrate in particular the use of the4D-THRIVE sequence implemented in our breast MRI study protocol.

Application of the ultrafast sequence in the dynamic contrastographic study in the magnetic resonance imaging of the breast: our experience

In the last decade, breast MRI has played a role of primary importance, as a "gold standard" method in the early diagnosis of breast cancer in high-risk women, in assessing the extent of the disease and the response to neoadjuvant chemotherapy. Currently, the 3D GRE Rapid-Acquisition sequence in dynamic acquisition without and with endovenous administration of contrast medium, is fundamental for the breast MRI protocol, as the current diagnostic approaches in Magnetic Resonance are based precisely on this sequence, able to guarantee accurate diagnostic performances detecting pathological mass and non-mass-enhancement. Ultrafast sequences are modern sequences based on the 4D Time-Resolved technique with k-space sampling modalities which allow the evaluation of post-contrast images with very high temporal resolution. The purpose of our work is to illustrate in particular the use of the 4D-THRIVE sequence implemented in our breast MRI study protocol.

Abstract PS8-41: Low dose tamoxifen for breast cancer prevention and mammographic density reduction - a randomized controlled trial

Abstract Introduction: Tamoxifen prevents breast cancer in high-risk women and reduces recurrence in the adjuvant setting but comes with side-effects. The optimal dose to increase uptake and retain therapeutic effect is unknown. We tested if the efficacy of low-dose tamoxifen is non-inferior to standard dose using mammographic density as a proxy for therapy response and if lower doses are associated with fewer symptoms.Methods: Healthy pre- and postmenopausal women attending a mammography screening program aged 40 to 74 years were invited to participate. N=2,314 screening women were investigated for eligibility. Exclusion criteria were women with a low mammographic density (BI-RADS A), high blood pressure, pregnancy, use of hormonal therapy, previous cardiovascular disorder, uncontrolled diabetes, any previous cancer. N=1,440 women entered a six-months double-blind placebo-controlled randomized dose-determination trial that was conducted in 2016-2019. Women were allocated into six months oral daily administration of 1, 2.5, 5, 10, and 20 mg of tamoxifen or placebo.Mammographic density was assessed as radiographic dense fibro-glandular tissue using a fully automated density tool. Symptoms were assessed using a self-reported questionnaire including vasomotor, gynecological, sexual, and joint pain symptoms. Non-inferior reduction of mammographic density and fewer severe symptoms in lower doses were compared with standard dose 20 mg. Post-hoc analyses were performed by menopause status. Both per protocol and intension to treat populations were analyzed.Results: Premenopausal (N=566) and postmenopausal (N=873) participants were recruited to the study. Premenopausal women showed non-inferior reduction in mammographic density following 2.5, 5 and 10 mg tamoxifen compared with the median 9.7% decrease observed in the 20 mg group (Table 1). No reduction in density was seen in postmenopausal participants. Severe vasomotor symptoms (hot flashes, cold and night seats) were reduced by approximately 50% in the 2.5 mg group compared with the 20 mg group (Table 2).Conclusion: Premenopausal women experienced fewer side effects with non-inferior decrease in breast density at lower dose of tamoxifen (2.5 mg) compared with standard dose (20 mg). A low dose of tamoxifen could be used for prevention and to increase sensitivity of a mammogram in premenopausal women. The table shows the proportions of women that had a larger decrease than median density decreases in the 20 mg arm (-9.7%) at six-months, stratified by menopausal status and tamoxifen dose. The table shows the prevalence ratios (PR) of severe vasomotor symptoms stratified by menopausal status and tamoxifen dose. Table 1. Non-inferior dense area reduction at six-months in the 2.5 mg arm compared with the standard dose 20mg arm.All womenPremenopausalPostmenopausalDoseProportion (97.5%CI)p-valueHolm p-valueProportion (95%CI)Proportion (95%CI)0 mg41.0 (29.2,100)0.1010.20333.9 (15.0,52.8)44.6 (33.3,55.9)1 mg40.8 (28.1,100)0.1250.20333.3 (17.9,48.8)46.1 (31.9,60.3)2.5 mg55.3 (44.2,100)&amp;lt;0.01&amp;lt;0.0171.9 (57.7,86.0)44.2 (31.2,57.2)5 mg54.8 (44.8,100)&amp;lt;0.01&amp;lt;0.0177.3 (64.4,90.1)38.5 (26.8,50.1)10 mg54.5 (42.9,100)&amp;lt;0.01&amp;lt;0.0172.7 (59.6,85.8)42.6 (28.9,56.3)20 mg50.0 (ref.)63.841.2 Table 2. Significantly lower prevalence ratios of severe vasomotor symptoms by 50% at six-months in the 2.5 mg arm compared with the standard dose 20 mg arm.All womenPremenopausalPostmenopausalDosePR (95%CI)PR (95%CI)PR (95%CI)0 mg0.41 (0.27,0.62)0.10 (0.02,0.39)0.56 (0.36,0.88)1 mg0.48 (0.33,0.71)0.37 (0.19,0.75)0.56 (0.35,0.89)2.5 mg0.47 (0.32,0.71)0.37 (0.18,0.78)0.54 (0.33,0.88)5 mg0.72 (0.51,1.01)0.36 (0.18,0.75)0.97 (0.65,1.42)10 mg0.76 (0.55,1.06)0.68 (0.39,1.19)0.81 (0.54,1.22)20 mg1 (ref.)1 (ref.)1 (ref.) Citation Format: Per Hall, Mikael Eriksson, Kamila Czene. Low dose tamoxifen for breast cancer prevention and mammographic density reduction - a randomized controlled trial [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS8-41.

Risk versus Benefit of Chemoprevention among Raloxifene and Tamoxifen Users with a Family History of Breast Cancer.

Tamoxifen and raloxifene have been approved for the primary prevention of breast cancer in high-risk women, but are associated with an increased risk of serious side effects. Few studies have characterized risk-benefit profiles for chemoprevention among women who initiate tamoxifen or raloxifene outside of a clinical trial setting. Use of raloxifene and tamoxifen for chemoprevention was self-reported in 2014 to 2016 by participants in The Sister Study, a prospective cohort of women with a sister who had been diagnosed with breast cancer. After exclusions, 432 current raloxifene users and 96 current tamoxifen users were matched to 4,307 and 953 nonusers, respectively, on age and year of cohort enrollment. Conditional logistic regression was used to evaluate characteristics associated with chemoprevention use. Risk-benefit profiles were examined using published indices that assess the level of evidence (none, moderate, strong) that the benefits of chemoprevention outweigh the risk of serious side effects. Among current chemoprevention users, 44% of tamoxifen users and 5% of raloxifene users had no evidence of a net benefit. In analyses of factors associated with chemoprevention use, having strong evidence of benefit was a significant predictor of raloxifene use, but not of tamoxifen use. In our sample of women with a first-degree family history of breast cancer, raloxifene was more commonly used for breast cancer prevention than tamoxifen. Most raloxifene users, but <60% of tamoxifen users, were likely to benefit. Use of risk-benefit tables can help women and their healthcare providers make an informed decision about breast cancer chemoprevention.

Preventing Breast Cancer in High-Risk Women: Is There Still a Role for Oophorectomy?

Preventing Breast Cancer in High-Risk Women: Is There Still a Role for Oophorectomy?

Polygenic risk score for breast cancer in high-risk women.

1508Background: While assessment of genetic contribution to breast cancer (BC) risk was once limited to high-penetrance genes such as BRCA1/2, additional genes conferring two- to five-fold increase...

Abstract P4-02-10: Breast cancer surveillance in high-risk women with dynamic contrast-enhanced magnetic resonance imaging every 6 months: Results from a single institution study

Abstract Purpose: To develop a novel approach for early detection of breast cancer and examine molecular features of screen detected cancers in prospectively ascertained high-risk women undergoing semi-annual dynamic contrast-enhanced breast magnetic resonance imaging (DCE-MRI) for women at high genetic risk. Background: Women with a personal or family history of breast cancer and genetic mutation carriers of BRCA1 and BRCA2 have a higher than normal risk of breast cancer. An intensified screening surveillance regimen is an early detection strategy in high-risk women. The American Cancer Society recommends annual DCE-MRI in addition to annual mammogram based off several pivotal screening studies that demonstrated improved sensitivity and cancer detection rates and decreased interval cancer rates with the addition of annual DCE-MRI. Questions remain regarding the optimal screening modality and interval regimen in these high-risk women. Methods: Between 2004 and 2016, we assembled a prospective cohort of high-risk women undergoing semi-annual DCE-MRI and annual mammography. To be eligible, women had a lifetime breast cancer risk &amp;gt;20% and/or tested positive for a pathogenic mutation using a cancer gene panel including BRCA1, BRCA2, CDH1, PALB2, CHEK2 and other cancer susceptibility genes in the DNA repair pathway. Somatic mutation events in screen-detected tumors were investigated using UW-OncoPlex cancer gene panel using DNA extracted from FFPE shavings. Results: 295 women were recruited to the study; 44% of the study participants had pathogenic mutations in BRCA1 or BRCA2 genes. At a median follow-up of 3.3 years (range 0-12 years), 3 DCIS and 13 early stage invasive breast cancers were detected, of which 14 occurred in subjects with identifiable pathogenic mutations (11 BRCA1, 2 BRCA2, 1 CDH1). The incidence rate is 1.3% in all subjects, but 3.5 % per year in BRCA1 carriers. DCE-MRI identified all 13 invasive cancers at a mean size of 0.61 cm (range 0.1-1.0 cm); none had lymph node metastasis. No interval cancers occurred. In addition, 7 of the breast cancers were detected on DCE-MRI imaging obtained at the 6 months screening interval; they would be interval cancers if only annual screening were implemented. There was very little DNA for somatic mutation testing in the majority of cases. However, as expected, there was heterogeneity in the spectrum of mutations but the most commonly somatically mutated gene in the early cancers was TP53. Conclusions: DCE-MRI every 6 months performed well for early detection of invasive breast cancer in high-risk women, accomplishing the ultimate goal of breast cancer screening—detecting node-negative, invasive tumors less than 1 cm. Semi-annual DCE-MRI performed especially well in BRCA1 mutation carriers at risk for the most aggressive subtype of breast cancer. Further interventional studies evaluating this novel screening approach are warranted to personalize breast cancer risk assessment and prevention. Citation Format: Whitaker K, Guindalini R, Abe H, Sheeth D, Huo D, Hong S, Churpek J, Verp M, Obeid E, Zheng Y, Amico A, Yoshimatsu T, Olopade O. Breast cancer surveillance in high-risk women with dynamic contrast-enhanced magnetic resonance imaging every 6 months: Results from a single institution study [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-02-10.

Abstract 3862: In vivo chemopreventive of pseudosemiglabrin via inhibition of tumor angiogenesis and manipulation of hormones in estrogen-responsive breast cancer

Abstract Breast cancer is the most frequently diagnosed form of malignancy and the second leading cause of death in Western women. Mortality and most of the complications associated with breast cancer are due to metastasis developing in regional lymph nodes and in distant organs, including bone, lung, liver and brain. Chemopreventive is administration of chemical agents to prevent the initiational and promotional events associated with carcinogenesis. Some chemopreventive agents can prevent reaction or attacking molecules by different ways, these agents can suppress growth factors or signaling pathway. On this study we examined (-)-Pseudosemiglabrin (SSG) a natural compound extracted from Tephrosia apollinea on breast cancer cells and tumor vascularization in vitro and in vivo. Hormone sensitive breast cancer cell MCF-7 was found subtitle susceptible to SSG, it showed profound antitumorgeneis via inhibiting breast cancer cell migration, invasion and colony formation in vitro settings. In silico investigation of potential PARP inhibitor, SSG showed high binding affinity comparable to Rucaparib (standard PARP inhibitor). The natural compound significantly inhibited the sprouting of new blood vessels in ex vivo rat aorta ring assay; the antiangiogenic efficacy is perturbed by targeting VEGF expression and VEGFR phosphorylation. SSG completely inhibited the onset of breast cancer in animals pretreated with the compound. Molecular docking study showed that SSG binds to active site of Aromatase (the enzyme responsible for a key step in the biosynthesis of estrogens) with binding affinity better than standard aromatase inhibitor (Arimidex), moreover the compound has inhibitory activity against estrogen receptor in the breast cancer cells comparable to Tamoxifen. Our findings reveal that (-)-Pseudosemiglabrin can potentially be beneficial in preventing breast cancer in high-risk women or it can be adjuvant therapy with standard chemotherapy or even can be used for the treatment of women who have been diagnosed with breast cancer. Note: This abstract was not presented at the meeting. Citation Format: Loiy E. Ahmed Hassan. In vivo chemopreventive of pseudosemiglabrin via inhibition of tumor angiogenesis and manipulation of hormones in estrogen-responsive breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3862. doi:10.1158/1538-7445.AM2017-3862

Evaluation of the Utility of Screening Mammography for High-Risk Women Undergoing Screening Breast MR Imaging.

Purpose To evaluate the value of mammography in detecting breast cancer in high-risk women undergoing screening breast magnetic resonance (MR) imaging. Materials and Methods An ethics-approved, retrospective review of prospective databases was performed to identify outcomes of 3934 screening studies (1977 screening MR imaging examinations and 1957 screening mammograms) performed between January 2012 and July 2014 in 1249 high-risk women. Performance measures including recall and cancer detection rates, sensitivity, specificity, and positive predictive values were calculated for both mammography and MR imaging. Results A total of 45 cancers (33 invasive and 12 ductal carcinomas in situ) were diagnosed, 43 were seen with MR imaging and 14 with both mammography and MR imaging. Additional tests (further imaging and/or biopsy) were recommended in 461 screening MR imaging studies (recall rate, 23.3%; 95% confidence interval [CI]: 21.5%, 25.2%), and mammography recalled 217 (recall rate, 11.1%; 95% CI: 9.7%, 12.6%). The cancer detection rate for MR imaging was 21.8 cancers per 1000 examinations (95% CI: 15.78, 29.19) and that for mammography was 7.2 cancers per 1000 examinations (95% CI: 3.92, 11.97; P < .001). Sensitivity and specificity of MR imaging were 96% and 78% respectively, and those of mammography were 31% and 89%, respectively (P < .001). Positive predictive value for MR imaging recalls was 9.3% (95% CI: 6.83%, 12.36%) and that for mammography recalls was 6.5% (95% CI: 3.57%, 10.59%). Conclusion Contemporaneous screening mammography did not have added value in detection of breast cancer for women who undergo screening MR imaging. Routine use of screening mammography in women undergoing screening breast MR imaging warrants reconsideration. © RSNA, 2017 Online supplemental material is available for this article.

Association of atypia in ductal lavage and breast cancer risk.

e13040 Background: Atypical hyperplasia is considered a nearly obligate precursor of breast cancer and is associated with a higher risk of developing breast cancer (BC). Attempts to improve early detection of breast cancer and to provide individualized breast cancer risk assessment will greatly benefit from sampling cellular material from the target tissue. Ductal lavage (DL) is a minimally invasive technique which provides adequate material to detect atypical cells in mammary ducts. However, long term data of the association between atypia from and BC risk are lacking .We studied the prevalence of atypia in DL and its ability to predict BC development in women at risk. Methods: From March 2000 to July 2012 we performed DL in a consecutive series of 348 women with median age of 45 (range 19-74) at increased BC risk based on the following characteristics: 5 yrs Gail model &gt; 1.66% or &gt; 10% probability of BRCA mutation (n = 155), history of contralateral BC (CBC, n = 161), presence of a BRCA pathogenic variant (n = 32). We analyzed the presence of atypical cells in the baseline specimens and observed their evolution during follow-up. Results: The procedure was safe and well tolerated in most women, with pain and disconfort preventing the procedure in 5.4% of subjects. Overall, 126 (36%) women had atypia, with a prevalence of 32%, 39%, and 41% in the Gail, CBC and BRCA groups, respectively (p = 0.38). The overall prevalence of atypia considering all visits was 44% (range 36-51). After a median follow up of 6 years, cumulative BC events were 8% in women without atypia versus 14% in those with atypia (log-rank p = 0.08). In the highest risk groups (CBC and BRCA pathogenic variants), the number of BC events was 16 vs 11 in women with or without atypia (21% vs 10%; log-rank p = 0.05, Cox model adjusted for age p = 0.02). Conclusions: Our findings suggest that cytologic atypia in the fluid obtained by DL may predict the onset of BC in high-risk women. The reversal of atypia in DL as a surrogate biomarker of BC risk reduction warrants investigation.

The Preventive Intervention of Hereditary Breast Cancer.

Approximately 5-10% of breast cancer is considered to be hereditary. Familial breast cancers exhibit a dominant hereditary pattern, which typically have an early age of onset and are accompanied by symptoms of ovarian cancer, bilateral breast cancer, or male breast cancer. BRCA gene mutation carriers should be regarded as high-risk groups for breast cancer, which necessitates early examination of breast cancer. Studies have built up kinds of predictive models and recommended that female BRCA mutation carriers should receive breast self-test training and take monthly breast self-examination. Familial or hereditary breast cancer family members are high-risk groups, and their risks of breast cancer can be reduced by chemoprevention, including dietary composition adjustment and application of endocrine drugs. In recent years, large-scale clinical trials have shown the important role of chemoprevention in reducing the occurrence of hereditary breast cancer. Prophylactic mastectomy is also suitable for healthy women with high breast cancer risk factors. It can reduce the incidence rate of breast cancer in high-risk women by 90% and decrease the breast cancer mortality rate in medium-risk and high-risk women by 100% and 81%, respectively.

Impact of a Panel of 88 Single Nucleotide Polymorphisms on the Risk of Breast Cancer in High-Risk Women: Results From Two Randomized Tamoxifen Prevention Trials.

PurposeAt least 94 common single nucleotide polymorphisms (SNPs) are associated with breast cancer. The extent to which an SNP panel can refine risk in women who receive preventive therapy has not been directly assessed previously.Materials and MethodsA risk score on the basis of 88 SNPs (SNP88) was investigated in a nested case-control study of women enrolled in the International Breast Intervention Study (IBIS-I) or the Royal Marsden study. A total of 359 women who developed cancer were matched to 636 controls by age, trial, follow-up time, and treatment arm. Genotyping was done using the OncoArray. Conditional logistic regression and matched concordance indices (mC) were used to measure the performance of SNP88 alone and with other breast cancer risk factors assessed using the Tyrer-Cuzick (TC) model.ResultsSNP88 was predictive of breast cancer risk overall (interquartile range odds ratio [IQ-OR], 1.37; 95% CI, 1.14 to 1.66; mC, 0.55), but mainly for estrogen receptor–positive disease (IQ-OR, 1.44; 95% CI, 1.16 to 1.79; P for heterogeneity = .10) versus estrogen receptor–negative disease. However, the observed risk of SNP88 was only 46% (95% CI, 19% to 74%) of expected. No significant interaction was observed with treatment arm (placebo IQ-OR, 1.46; 95% CI, 1.13 to 1.87; tamoxifen IQ-OR, 1.25; 95% CI, 0.96 to 1.64; P for heterogeneity = .5). The predictive power was similar to the TC model (IQ-OR, 1.45; 95% CI, 1.21 to 1.73; mC, 0.55), but SNP88 was independent of TC (Spearman rank-order correlation, 0.012; P = .7), and when combined multiplicatively, a substantial improvement was seen (IQ-OR, 1.64; 95% CI, 1.36 to 1.97; mC, 0.60).ConclusionA polygenic risk score may be used to refine risk from the TC or similar models in women who are at an elevated risk of breast cancer and considering preventive therapy. Recalibration may be necessary for accurate risk assessment.

FAST MRI breast screening revisited.

Screening for breast cancer in high-risk women takes about 40minutes to acquire an MRI scan and is time-intensive to report. There is recent interest in the performance of an abbreviated MRI protocol (FAST) in the screening setting. FAST scans have a reported negative predictive value of 99.8%. This study evaluates the false positive rates (FPR) and recall rates for FAST scans as compared to full diagnostic studies (FD). A database of all screening breast MRI scans performed at our institution between 30 June 2013 and 1 July 2014 (n=591) was created by one of the researchers, who did not subsequently analyse the MRI scans. The T1W and first post-contrast and subtracted images from each of these scans (FAST protocol) were assessed by experienced breast MRI radiologists, blinded to the final diagnosis. The findings were then compared with the FD result. The recall rates were 6.6% for FAST scans and 5.8% for FD scans. FPR rates were 4.7% and 3.9% respectively. There is no statistically significant difference in the recall rates or FPR of FAST scans in comparison with full diagnostic studies. Given the absence of statistically significant difference in the FPR and recall rates in comparison with FD, FAST scans can replace FD for screening of breast cancer.

An international survey of surveillance schemes for unaffected BRCA1 and BRCA2 mutation carriers.

Female BRCA1/BRCA2 mutation carriers are at substantially increased risk for developing breast and/or ovarian cancer, and are offered enhanced surveillance including screening from a young age and risk-reducing surgery (RRS)-mastectomy (RRM) and/or salpingo-oophorectomy (RRSO). While there are established guidelines for early detection of breast cancer in high-risk women who have not undergone RRM, there are less developed guidelines after RRM. We evaluated the schemes offered before and after RRS in internationally diverse high-risk clinics. An e-mailed survey was distributed to high-risk clinics affiliated with CIMBA. Overall, 22 centers from 16 countries responded. Pre RRS surveillance schemes overwhelmingly included breast imaging (primarily MRI) from 18 to 30years and clinical breast exam (CBE) at 6-12month intervals. For ovarian cancer, all but 6 centers offered semiannual/annual gynecological exam, transvaginal ultrasound, and CA 125 measurements. Post RRM, most centers offered only annual CBE while 4 centers offered annual MRI, primarily for substantial residual breast tissue. After RRSO only 4 centers offered specific gynecological surveillance. Existing guidelines for breast/ovarian cancer detection in BRCA carriers are being applied pre RRS but are not globally harmonized, and most centers offer no specific surveillance post RRS. From this comprehensive multinational study it is clear that evidence-based, long-term prospective data on the most effective scheme for BRCA carriers post RRS is needed.

Natural Products for Chemoprevention of Breast Cancer.

Breast cancer is the primary cause of cancer death in women. Although current therapies have shown some promise against breast cancer, there is still no effective cure for the majority of patients in the advanced stages of breast cancer. Development of effective agents to slow, reduce, or reverse the incidence of breast cancer in high-risk women is necessary. Chemoprevention of breast cancer by natural products is advantageous, as these compounds have few side effects and low toxicity compared to synthetic compounds. In the present review, we summarize natural products which exert chemopreventive activities against breast cancer, such as curcumin, sauchinone, lycopene, denbinobin, genipin, capsaicin, and ursolic acid. This review examines the current knowledge about natural compounds and their mechanisms that underlie breast cancer chemopreventive activity both in vitro and in vivo. The present review may provide information on the use of these compounds for the prevention of breast cancer.

Selective estrogen receptor modulators and the combination therapy conjugated estrogens/bazedoxifene: A review of effects on the breast.

Traditional menopausal hormone therapy containing estrogens/progestin has been associated with an increased risk of breast cancer, and estrogen exposure is known to promote growth and proliferation of a majority of breast cancers. Therefore, it is important for clinicians to consider the breast safety profile of any hormone-based therapy used in postmenopausal women. This review provides an overview of the breast safety and tolerability profiles of currently marketed selective estrogen receptor modulators, antiestrogens, and the first tissue selective estrogen complex combining conjugated estrogens with the selective estrogen receptor modulator bazedoxifene in postmenopausal women. Selective estrogen receptor modulators and antiestrogens act as estrogen receptor antagonists in the breast. Tamoxifen, toremifene, and the selective estrogen receptor degrader fulvestrant are used to treat breast cancer, and tamoxifen and raloxifene protect against breast cancer in high-risk women. Postmenopausal women using selective estrogen receptor modulators for prevention or treatment of osteoporosis (raloxifene, bazedoxifene) can be reassured that these hormonal treatments do not adversely affect their risk of breast cancer and may, in the case of raloxifene, even be protective. There are limited data on breast cancer in women who use ospemifene for dyspareunia. Conjugated estrogens/bazedoxifene use for up to two years did not increase mammographic breast density or breast pain/tenderness, and there was no evidence of an increased risk of breast cancer, suggesting that conjugated estrogens/bazedoxifene has an improved breast safety profile compared with traditional menopausal hormone therapies. Future research will continue to focus on development of selective estrogen receptor modulators and selective estrogen receptor modulator combinations capable of achieving the ideal balance of estrogen receptor agonist and antagonist effects.