Screening Of High-risk Women Research Articles

Supplementary Imaging for Breast Cancer Screening in High-Risk Women

Supplementary Imaging for Breast Cancer Screening in High-Risk Women

Supplementary Imaging for Breast Cancer Screening in High-Risk Women—Reply

Supplementary Imaging for Breast Cancer Screening in High-Risk Women—Reply

Supplementary Imaging for Breast Cancer Screening in High-Risk Women

Supplementary Imaging for Breast Cancer Screening in High-Risk Women

Cost-Effectiveness of Universal and Risk-Based Screening for Autoimmune Thyroid Disease in Pregnant Women

Hypothyroidism in pregnancy can lead to adverse maternal and fetal outcomes. Although screening of high-risk women is advocated, universal screening remains controversial. The objective of the study was to compare the cost-effectiveness of universal screening of pregnant women for autoimmune thyroid disease (AITD) with screening only high-risk women and with no screening. A decision-analytic model compared the incremental cost per quality-adjusted life-year (QALY) gained among the following: 1) universal screening, 2) high-risk screening, and 3) no screening. Screening consisted of a first-trimester thyroid-stimulating hormone level and antithyroid peroxidase antibodies. Women with abnormal results underwent further testing and, when indicated, levothyroxine therapy. Randomized controlled trials provided probabilities for adverse obstetrical outcomes. The model accounted for the development of postpartum thyroiditis and overt hypothyroidism. Additional scenarios in which therapy prevented cases of decreased child intelligence quotient were explored. Medical consequences of AITD in pregnancy, QALY, and costs were measured. Risk-based screening and universal screening were both cost-effective relative to no screening, with incremental cost-effectiveness ratios (ICERs) of $6,753/QALY and $7,138/QALY, respectively. Universal screening was cost-effective compared with risk-based screening, with an ICER of $7,258/QALY. Screening remained cost-effective in various clinical scenarios, including when only overt hypothyroidism was assumed to have adverse obstetrical outcomes. Universal screening was cost-saving in the scenario of untreated maternal hypothyroidism resulting in decreased child intelligence, with levothyroxine therapy being preventive. Universal screening of pregnant women in the first trimester for AITD is cost-effective, not only compared with no screening but also compared with screening of high-risk women.

Large Prospective Study of Ovarian Cancer Screening in High-Risk Women: CA125 Cut-Point Defined by Menopausal Status

Previous screening trials for early detection of ovarian cancer in postmenopausal women have used the standard CA125 cut-point of 35 U/mL, the 98th percentile in this population yielding a 2% false positive rate, whereas the same cut-point in trials of premenopausal women results in substantially higher false positive rates. We investigated demographic and clinical factors predicting CA125 distributions, including 98th percentiles, in a large population of high-risk women participating in two ovarian cancer screening studies with common eligibility criteria and screening protocols. Baseline CA125 values and clinical and demographic data from 3,692 women participating in screening studies conducted by the National Cancer Institute-sponsored Cancer Genetics Network and Gynecologic Oncology Group were combined for this preplanned analysis. Because of the large effect of menopausal status on CA125 levels, statistical analyses were conducted separately in pre- and postmenopausal subjects to determine the impact of other baseline factors on predicted CA125 cut-points on the basis of 98th percentile. The primary clinical factor affecting CA125 cut-points was menopausal status, with premenopausal women having a significantly higher cut-point of 50 U/mL, while in postmenopausal subjects the standard cut-point of 35 U/mL was recapitulated. In premenopausal women, current oral contraceptive (OC) users had a cut-point of 40 U/mL. To achieve a 2% false positive rate in ovarian cancer screening trials and in high-risk women choosing to be screened, the cut-point for initial CA125 testing should be personalized primarily for menopausal status (50 for premenopausal women, 40 for premenopausal on OC, and 35 for postmenopausal women).

Abstract B101: Cost comparison of high-risk targeted breast MRI vs. mammography in screening underserved women

Abstract Background: Our current recommendations for mammographic and MRI screening are based on studies in European, European-Canadian and European-American women. To our knowledge, there has been no large-scale analysis of the effectiveness of mammographic screening in African-American and Latino women. We have little information on the relative benefits of general mammography screening versus high-risk targeted breast Magnetic Resonance Imaging (MRI) screening in underserved women. Mammography has the advantage of being relatively inexpensive and well accepted. In contrast, MRI is expensive and has the potential to increase the number of benign biopsy. Methods: We compared the ability of mammography screening in a general risk underserved population (standard-of-care) with targeted breast MRI screening in high-risk underserved women to a) detect breast cancer, b) cost of screening/breast diagnosis, c) number of benign biopsies, and d) compliance. From 6/15/2004 to 5/7/2011, 1) 299 general risk women underserved women were underwent digital mammographic screening and 2) 299 high-risk women underwent combined mammogram and breast MRI screening. Women were recruited by our Breast Navigation team from sites throughout central North Carolina and underwent screening accompanied by a member of our Navigation team. Women found to have an abnormal mammogram were evaluated by ultrasound, ultrasound guided biopsy, and/or stereotactic biopsy. Women with an abnormal breast MRI were evaluated with ultrasound, ultrasound guided biopsy, and/or MRI guided biopsy. All follow-up services were provided for free. Results: The average age of women was 50 years for women undergoing mammographic screening and 47 years for women undergoing MRI. The racial composition of general-risk women undergoing mammographic screening was 40% African American, 25% Caucasian, 25% Hispanic, and 1% other vs. 33% African American, 62% Caucasian, 3% Hispanic, and 2% other for high-risk women undergoing breast MRI. Mammographic screening detected 1 breast cancer vs. 9 for MRI. The cost per diagnosis was $37,375.00 vs. $21,561.22. The number of benign breast biopsies/total biopsies was 7/8 (88%) for mammographic screening vs. 31/40 (78%) for MRI. Compliance with follow-up studies was 75% for mammographic screening vs. 90% for MRI. Conclusions: Breast MRI screening in high-risk underserved women is highly feasible and with Navigation, there is a high rate of compliance with follow up studies. The cost per breast cancer diagnosis is significantly lower for targeted breast MRI screening of high-risk women than for mammographic screening of general risk women. Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):B101.

Automated Whole-Breast Ultrasound: Advancing the Performance of Breast Cancer Screening

Screening has been successful in the early detection of some cancers, including cervical, colon, and breast. However, the success in mortality reduction by screening mammography has been limited in women with mammographically dense tissue. Magnetic resonance imaging has been used with success in the screening of high-risk women, but it is expensive. Also, its use in a screening program requires a contrast medium that has not been tested in humans or animals for long-term safety in humans or animals for repeated biannual or annual injections. Ultrasound also has the potential to be an ideal screening tool because it is relatively inexpensive and requires no injected contrast or ionizing radiation. However, the relatively poor conspicuity of some cancers by hand scanning and the considerable radiologist time necessary limit its use. Automated whole-breast ultrasound (AWBU) allows the radiologist to read the images quickly, at a convenient time, while being free from doing the scan. Two-dimensional AWBU uses a cine loop of axial images, with <1 mm image spacing, which are read on a high-resolution monitor to improve the conspicuity of small cancers. A blinded study of this system combined with screening mammography showed that adding AWBU both doubles overall cancer detection and triples the 1 cm-or-less invasive cancers found in dense-breasted women. As expected, mammography had a significantly greater detection rate of ductal carcinoma in situ than AWBU. As yet no clinical studies of other AWBU systems have been published.

Multicenter Surveillance of Women at High Genetic Breast Cancer Risk Using Mammography, Ultrasonography, and Contrast-Enhanced Magnetic Resonance Imaging (the High Breast Cancer Risk Italian 1 Study)

: To prospectively compare clinical breast examination, mammography, ultrasonography, and contrast-enhanced magnetic resonance imaging (MRI) in a multicenter surveillance of high-risk women. : We enrolled asymptomatic women aged ≥ 25: BRCA mutation carriers; first-degree relatives of BRCA mutation carriers, and women with strong family history of breast/ovarian cancer, including those with previous personal breast cancer. : A total of 18 centers enrolled 501 women and performed 1592 rounds (3.2 rounds/woman). Forty-nine screen-detected and 3 interval cancers were diagnosed: 44 invasive, 8 ductal carcinoma in situ; only 4 pT2 stage; 32 G3 grade. Of 39 patients explored for nodal status, 28 (72%) were negative. Incidence per year-woman resulted 3.3% overall, 2.1% <50, and 5.4% ≥ 50 years (P < 0.001), 4.3% in women with previous personal breast cancer and 2.5% in those without (P = 0.045). MRI was more sensitive (91%) than clinical breast examination (18%), mammography (50%), ultrasonography (52%), or mammography plus ultrasonography (63%) (P < 0.001). Specificity ranged 96% to 99%, positive predictive value 53% to 71%, positive likelihood ratio 24 to 52 (P not significant). MRI showed significantly better negative predictive value (99.6) and negative likelihood ratio (0.09) than those of the other modalities. At receiver operating characteristic analysis, the area under the curve of MRI (0.97) was significantly higher than that of mammography (0.83) or ultrasonography (0.82) and not significantly increased when MRI was combined with mammography and/or ultrasonography. Of 52 cancers, 16 (31%) were diagnosed only by MRI, 8 of 21 (38%) in women <50, and 8 of 31 (26%) in women ≥ 50 years of age. : MRI largely outperformed mammography, ultrasonography, and their combination for screening high-risk women below and over 50.

Large Prospective Study of Ovarian Cancer Screening in High-Risk Women: CA125 Cut-Point Defined by Menopausal Status

Large Prospective Study of Ovarian Cancer Screening in High-Risk Women: CA125 Cut-Point Defined by Menopausal Status

Use of Breast MRI Surveillance in Women at High Risk for Breast Cancer: A Single-Institutional Experience

The study aim is to investigate indications for breast magnetic resonance imaging (MRI) screening for high-risk women and to determine outcomes, correlation with routine imaging, and adherence to current guidelines for use. We identified 200 patients undergoing 275 breast MRIs for high-risk surveillance from 2005 to 2008. Data collected included patient characteristics, need for additional imaging and/or biopsy, correlation with routine imaging, and outcomes. Gail scores were calculated for patients without hereditary breast cancer syndromes or previous chest radiation. Descriptive statistics were utilized for data summary. Two hundred patients underwent 275 breast MRIs for high-risk surveillance (mean age 45 years, range 18-76 years). Indications included BRCA mutation (n =21), history of chest radiation (n = 10), and perceived high risk (n =169). The mean Gail score for the latter group was 25% (range 10-46%); 32 (16%) patients had Gail score <20%. Of 275 MRIs, 49 (18%) required additional imaging and 21 (8%) prompted biopsy. Of 21 biopsies, 4 were malignant; 2 were also visible on routine imaging performed concurrently with breast MRI. The false-positive rate for breast MRI screening in our cohort of high-risk patients was 23%. The rate of cancer detection in high-risk patients undergoing breast MRI at our institution is similar to that of large, multicenter trials. Sixteen percent of patients undergoing breast MRI did not meet high-risk criteria. Because the need for additional imaging and biopsy remains high, further investigation is necessary to determine if this strategy is cost effective.

Use of Serum Progesterone Concentration for Timing Breast MRI Examinations and Avoiding False-Negative Findings

Use of Serum Progesterone Concentration for Timing Breast MRI Examinations and Avoiding False-Negative FindingsSergi Ganau, Melcior Sentís and Lidia TortajadaAudio Available | Share

The use of fetal fibronectin in primiparous women with cervical surgery

BackgroundFetal fibronectin (fFN) is an excellent predictor of preterm birth (PTB). However its use in primiparous women is limited, including those with previous cervical surgery, who are at increased risk...

Magnetic resonance imaging of the breast: Recommendations from the EUSOMA working group

The use of breast magnetic resonance imaging (MRI) is rapidly increasing. EUSOMA organised a workshop in Milan on 20–21st October 2008 to evaluate the evidence currently available on clinical value and indications for breast MRI. Twenty-three experts from the disciplines involved in breast disease management – including epidemiologists, geneticists, oncologists, radiologists, radiation oncologists, and surgeons – discussed the evidence for the use of this technology in plenary and focused sessions. This paper presents the consensus reached by this working group. General recommendations, technical requirements, methodology, and interpretation were firstly considered. For the following ten indications, an overview of the evidence, a list of recommendations, and a number of research issues were defined: staging before treatment planning; screening of high-risk women; evaluation of response to neoadjuvant chemotherapy; patients with breast augmentation or reconstruction; occult primary breast cancer; breast cancer recurrence; nipple discharge; characterisation of equivocal findings at conventional imaging; inflammatory breast cancer; and male breast. The working group strongly suggests that all breast cancer specialists cooperate for an optimal clinical use of this emerging technology and for future research, focusing on patient outcome as primary end-point.

Kontrastmittel-MRT der Brust bei Staging und Früherkennung: Wo benötigen wir sie?

PURPOSE: When imaging is used for screening or preoperative staging, a considerable number of diagnoses show normal breasts or breast tissue. Thus, in contrast to other indications, a high specificity of the methods employed is required in addition to a good sensitivity. Ample data is available for both indications and is analyzed here. MATERIAL AND METHODS: A search of the Pubmed und Cochrane libraries was performed. Original work, systematic reviews, meta-analyses, national and international recommendations and guidelines were considered. RESULTS: Contrast-enhanced breast MRI proved to be the most sensitive method for high risk patients. However, false positive findings leading to “short-term” (4-6 months) follow-up recommendations or to histopathological assessment may occur in 15-20 % of cases, and MR-guided histopathological assessment and, in particular, MR-guided percutaneous biopsy, constitute a bottleneck. The most important advantage of intensified screening programs using MRI is the earlier detection of malignancy, even though evidence from randomized studies is lacking. For preoperative staging no evidence exists to date for an improved outcome, as measured by a decreased number of re-excisions, a decreased rate of recurrences, or improved survival. However, more aggressive treatment has been documented after preoperative MRI. Therefore updated guidelines have not recommended using MRI for preoperative staging in general, but only recommend it for certain subgroups. CONCLUSION: MRI can be recommended as an additional imaging method for the screening of high risk women. However, good quality control and appropriate patient information is necessary. Preoperative MRI is only recommended for selected subgroups. More research is needed before further recommendations can be given.

Classification of Dynamic Contrast-Enhanced Magnetic Resonance Breast Lesions by Support Vector Machines

Early detection of breast cancer is one of the most important factors in determining prognosis for women with malignant tumors. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has been shown to be the most sensitive modality for screening high-risk women. Computer-aided diagnosis (CAD) systems have the potential to assist radiologists in the early detection of cancer. A key component of the development of such a CAD system will be the selection of an appropriate classification function responsible for separating malignant and benign lesions. The purpose of this study is to evaluate the effects of variations in temporal feature vectors and kernel functions on the separation of malignant and benign DCE-MRI breast lesions by support vector machines (SVMs). We also propose and demonstrate a classifier visualization and evaluation technique. We show that SVMs provide an effective and flexible framework from which to base CAD techniques for breast MRI, and that the proposed classifier visualization technique has potential as a mechanism for the evaluation of classification solutions.

The utility of MRI for the screening and staging of breast cancer

Contrast-enhanced magnetic resonance imaging (MRI) of the breast has been recently introduced as a potential clinical tool for the detection, diagnosis, staging and management of breast cancer. In this article, we consider the established and evolving roles of MRI with particular reference to screening in high risk women and staging of the primary tumour. Controversies are discussed in the context of the tumour biology and natural history of breast cancer. Articles were identified by searches of PubMed and MEDLINE up to October 2007. Contrast-enhanced MRI is an effective tool for screening women at high risk of breast cancer. However, randomized trials have yet to demonstrate a reduction in mortality. MRI can also facilitate local staging, in particular, the evaluation of ipsilateral multicentric or multifocal lesions and synchronous contralateral disease which may be 'missed' by conventional imaging. However, efficacy with respect to clinically relevant and patient oriented end-points has yet to be addressed in the context of clinical trials. In women at high risk of breast cancer, screening MRI should be used in conjunction with published guidelines. In women with newly diagnosed breast cancer, the utility of MRI is less clearly defined and should be restricted to selected cases within the multidisciplinary setting.

Breast cancer screening in high risk women

Women who are at a significantly raised risk of developing breast cancer should be assessed by a medical geneticist to confirm their history, counselled as to appropriate management and offered breast screening. Currently mammography with magnetic resonance imaging is considered the optimal method of early detection of breast cancer in these women. While there is no evidence of mortality benefit there is evidence from surrogate markers that this intervention is worthwhile and cost effective. National recommendations have been produced by the National Institute of Clinical Excellence in the UK and also by the American Cancer Society.

WE-B-M100J-01: Effective Breast Cancer Detection and Treatment: The Big Picture for Physicists

Mammography: The benefit of early detection of breast cancer by mammography has been proven by several randomized controlled trials. Mass public screening of asymptomatic women detects a prevalence rate of approximately 2–5/ 1000. Note that the prevalence of breast cancer in autopsy series may be as high as 20/1000. In spite of multiple studies, controversy still exists regarding the benefit of mammography. Magnetic Resonance Imaging: Screening of High Risk women with MR has recently been supported by the American Cancer Society due to a few observational studies. Note that there are no randomized control trials of MR screening. Additionally, some advocate pre-operative MR ‘screening’ for those with newly diagnosed breast cancer from core biopsy. MR may show additional foci of cancers, at the expense of increased false positives, that could alter surgical treatment from breast conservation to mastectomy. Those opposed to this idea cite the recurrence rate of 2–5% at ten years after breast conservation surgery (lumpectomy) and whole breast radiation to question the efficacy of MR, as well as the additional cost and time. Ultrasound: Ultrasound screening is also being studied as part of a large multi-institutional study (American College Imaging Network (ACRIN) 6666) in women at High Risk. Unique to this study is that the US results are independent to the mammographic results. Published detection rates for US are approx. 3/1000. Limitations are, again, no randomized control trials of mortality benefit and marked operator dependence making this procedure very time consuming, subject to many pitfalls, and challenging for follow-up. Tumor Histologies: The common types of breast cancer are the ductal, invasive ductal carcinoma, arising from the glands in the ducts, and lobular, invasive lobular, arising from the cells in the lobules. There are some unique differences to the imaging appearance of these types. Treatment: Treatment is tailored per patient. Factors that are taken into consideration are tumor type, tumor size per breast size for cosmetic results, tumor grade, tissue markers, lymph node involvement, distal organ involvement, age of the patient, family history, risk factors, and patient wishes. Complete surgical excision is mandatory with clean margins. The addition of radiation- whole breast vs. partial- and chemotherapy vs. hormonal therapy are dependent on the above factors. New Devices under Investigation: Examples of the following will be illustrated. 1. Tomosynthesis; 2. Optical imaging of hemoglobin concentrations (indirectly); 3. Electrical impedence. Educational Objectives: 1. Understand the value and limitations of mammographic screening to early detection of breast cancer. 2. Understand the value and limitations of other techniques, MR and US, to early detection of breast cancer. 3. Understand treatment options of radiation and chemotherapy. 4. Develop awareness of the common breast cancer histologies. 5. Develop awareness of new modalities being studied.

High percentage of abnormal findings on TVU needs further discussion

Sir, With great interest, we read the publication ‘Surveillance of women at high risk for hereditary ovarian cancer is inefficient' published by Oei et al (2006) in your journal. The authors evaluated the efficacy of 10-year gynaecological surveillance in 512 women at risk for hereditary ovarian cancer in a tertiary referral centre. This gynaecological surveillance included annual pelvic examination, transvaginal ultrasound (TVU) and serum CA125 measurements. In case of abnormal findings in at least one of the surveillance tests, revision of the abnormal test after 3–6 months was advised. A total of 1621 surveillance tests were performed. In 317 contacts (21%), TVU showed abnormal findings. Of these, 295 (93%) were not present during repeat TVU after 3–6 months. Because only two cases of ovarian cancer were diagnosed during this annual surveillance, it can be calculated that the highest estimate for a positive predictive value of an abnormal TVU is 0.6%. This figure of 21% abnormal findings on TVU needs further discussion than the authors give in this paper. The criteria in the method section of this study, according to which TVU was considered as abnormal were: multiple cysts, cysts with thick septa, papillary projection, irregular patterns or a variety in sonolucency. In the discussion section, the authors explain their high percentage of false-positive findings on TVU with the observation that the majority of their patients were premenopausal and that a variety of benign conditions (e.g. follicle cysts) have contributed to the high incidence of normalising abnormalities. It is remarkable that the list of criteria used in this study according to which TVU was considered abnormal, does not include the presence and/or size of monolocular cysts. According to the Sassone criteria, only cysts of more than 6 cm need further investigation in premenopausal women (Sassone et al, 1991). A second point of attention is that it is not mentioned whether the authors found any adverse effects in this group of patients who had to wait for 3–6 months before they could be reassured by a repeat TVU. It is known from literature that ovarian cancer screening in high-risk women can have a great impact on the anxiety score, especially of premenopausal women (Hensley et al, 2003). We agree with the authors that surveillance is highly ineffective to detect early ovarian (tubal) cancer in high-risk women. It can be questioned whether their suggestion to conduct a study with a larger group of BRCA mutation carriers with a longer follow-up is in line with this conclusion. However, if they need more definitive conclusions, as they suggested, they should define their TVU criteria more precisely in order to avoid this high percentage of false-positive TVU findings and the high loss of quality of life in women with a false-positive TVU finding.

Cost-effectiveness of MRI compared to mammography for breast cancer screening in a high risk population

6060 Background: Breast magnetic resonance imaging (MRI) is a sensitive method of breast imaging virtually uninfluenced by breast density. Because of the improved sensitivity, breast MRI is increasingly being used for detection of breast cancer among high risk young women. However, the specificity of breast MRI is variable and costs are high. The purpose of this study was to determine if breast MRI is a cost-effective approach for the detection of breast cancer among young women at high risk. Methods: A Markov model was created to compare annual breast cancer screening over 25 years with either breast MRI or mammography among young women at high risk. Data from published studies provided probabilities for the model including sensitivity and specificity of each screening strategy. Costs were based on Medicare reimbursement rates for hospital and physician services while medication costs were obtained from the Federal Supply Scale. Utilities from the literature were applied to each health outcome in the model including a disutility for the temporary health state following breast biopsy for a false positive test result. The analysis was performed from the payer perspective with results reported in 2005 U.S. dollars. Univariate and probabilistic sensitivity analyses addressed uncertainty in all model parameters. Results: Breast MRI provided 23.287 quality-adjusted life-years (QALYs) at a cost of $30,317 while mammography provided 23.141 QALYs at a cost of $7,895 over 25 years of screening. The cost-effectiveness ratios for the two strategies were $1302 and $341, respectively. The incremental cost-effectiveness ratio of breast MRI compared to mammography was $131,376/QALY. In univariate analysis, breast MRI screening became &lt;$50,000/QALY when the cost of the MRI was &lt;$405. In the probabilistic sensitivity analysis, MRI screening produced a net benefit of +0.146 QALYs (95% central range: -0.825 QALYs to +1.378 QALYs). However, breast MRI screening was superior in &lt;1%, &lt;$50,000/QALY in 27%, &gt;$50,000/QALY in 32%, and inferior in 41% of 10,000 probabilistic Monte Carlo simulations. Conclusions: Breast MRI provides a net benefit when compared to mammographic screening for high risk women, however, this approach does not appear to be cost-effective at this time. No significant financial relationships to disclose.