Mammography casting-type calcification and risk of local recurrence in DCIS: analyses from a randomised study.

BACKGROUND: We studied the association between mammographic calcifications and local recurrence in the ipsilateral breast. METHODS: Case-cohort study within a randomised trial of radiotherapy in breast conservation for ductal cancer in situ of the breast (SweDCIS). We studied mammograms from cases with an ipsilateral breast event (IBE) and from a subcohort randomly sampled at baseline. Lesions were classified as a density without calcifications, architectural distortion, powdery, crushed stone-like or casting-type calcifications. RESULTS: Calcifications representing necrosis were found predominantly in younger women. Women with crushed stone or casting-type microcalcifications had higher histopathological grade and more extensive disease. The relative risk (RR) of a new IBE comparing those with casting-type calcifications to those without calcifications was 2.10 (95% confidence interval (CI) 0.92-4.80). This risk was confined to in situ recurrences; the RR of an IBE associated with casting-type calcifications on the mammogram adjusted for age and disease extent was 16.4 (95% CI 2.20-140). CONCLUSION: Mammographic appearance of ductal carcinoma in situ of the breast is prognostic for the risk of an in situ IBE and may also be an indicator of responsiveness to RT in younger women.

The ongoing revolution in breast imaging calls for a similar revolution in breast pathology.

COMMUNICATION BETWEEN PATHOLOGISTS AND RADIOLOGISTS SUFFERS FROM A LACK OF COMMON GROUND: the pathologists examine cells in ultrathin tissue slices having the area of a postage stamp, while the radiologists examine images of an entire organ, but without seeing the cellular details. The current practice of examining breast cancer specimens is analogous to scrutinizing individual pieces of a jigsaw puzzle, without examining all of them and never putting all the pieces into place. The routine use of large section histopathology technique could help to alleviate much of this problem, especially with nonpalpable, screen-detected breast cancers. The study of three-dimensional (3D) images of subgross, thick section pathology specimens by both radiologists and pathologists could greatly assist in the communication of findings.

Differences in endpoints between the Swedish W-E (two county) trial of mammographic screening and the Swedish overview: methodological consequences.

OBJECTIVES: To characterize and quantify the differences in the number of cases and breast cancer deaths in the Swedish W-E Trial compared with the Swedish Overview Committee (OVC) summaries and to study methodological issues related to trials in secondary prevention. SETTING: The study population of the W-E Trial of mammography screening was included in the first (W and E county) and the second (E-county) OVC summary of all Swedish randomized mammography screening trials. The OVC and the W-E Trial used different criteria for case definition and causes of death determination. METHOD: A Review Committee compared the original data files from W and E county and the first and second OVC. The reason for a discrepancy was determined individually for all non-concordant cases or breast cancer deaths. RESULTS: Of the 2615 cases included by the W-E Trial or the OVC, there were 478 (18%) disagreements. Of the disagreements 82% were due to inclusion/exclusion criteria, and 18% to disagreement with respect to cause of death or vital status at ascertainment. For E-County, the OVC inclusion rules and register based determination of cause of death (second OVC) rather than individual case review (W-E Trial and 1st OVC) resulted in a reduction of the estimate of the effect of screening, but for W-County the difference between the original trial and the OVC was modest. CONCLUSIONS: The conclusion that invitation to mammography screening reduces breast cancer mortality remains robust. Disagreements were mainly due to study design issues, while disagreements about cause of death were a minority. When secondary research does not adhere to the protocols of the primary research projects, the consequences of such design differences should be investigated and reported. Register linkage of trials can add follow-up information. The precision of trials with modest size is enhanced by individual monitoring of case status and outcome status such as determination of cause of death.

[Posterior retinal hole secondary to a candida retinitis]. / Agujero retiniano en polo posterior secundario a un foco de retinitis por cándida.

CASE REPORT: We describe the case of a 36-year-old man with a history of intravenous heroin use, who was HIV negative. Left ocular examination disclosed a focal candida retinitis in the posterior pole associated with vitritis and moderate iritis. Treatment with fluconazole inactived the chorio-retinal lesion and resolved the vitritis, but developed an inner limiting membrane contraction over the macula. Two years later, vitreous traction produced a retinal hole that needed argon laser photocoagulation. DISCUSSION: Candida retinitis which penetrates into the vitreous cavity can produce retinal holes by vitreous traction over the lesion.

Number needed to screen: lives saved over 20 years of follow-up in mammographic screening.

OBJECTIVE: To estimate the number needed to screen with mammography to save one life, based on a stated amount of screening activity and long-term follow-up for breast cancer death. SETTING: A randomised controlled trial of mammographic screening for breast cancer, with 77,080 women invited to screening and 55,985 not invited. The invited group was offered screening for seven years. Follow-up continued for a total of just over 20 years. METHODS: Number needed to screen for seven years to save one life over 20 years was calculated by dividing the number screened (not the number invited) by the total number of lives saved. Similarly, we calculated the number of mammographic examinations required to save one life. RESULTS: We estimate that the number of women needed to screen for seven years to save one life over 20 years is 465 (95% CI 324-819). The number of mammographic examinations needed to save one life was 1499 (95% CI 1046-2642). CONCLUSIONS: The number needed to screen to save one life is smaller than has been reported in the past. Mammographic screening is effective in absolute terms as well as relative. Long-term follow-up allowed us to estimate the absolute benefit with greater accuracy.

Clinical assessment of a radiolucent cushion for mammography.

PURPOSE: To determine whether use of a radiolucent cushion could significantly decrease pain during screening mammography without compromising image quality or other technical factors. MATERIAL AND METHODS: 838 patients presenting for routine screening mammography were evaluated. The radiolucent cushions were placed on the compression surfaces of the mammographic equipment and were used while imaging the right breast. No pads were used while imaging the left breast. Patient age, hormonal status, compression force, and radiation dose values were collected on all patients. Each subject completed a visual analog pain scale (VAS) rating the degree of pain experienced with and without the cushions. All mammographic images obtained (CC and MLO views) were compared, side by side (cushioned versus non-cushioned) by the readers. RESULTS: Use of radiolucent cushions reduced pain by 10% or more in 66% (555/838) of women. Patients in this "benefited group" experienced an average pain reduction of 53%. No compromise of image quality was observed. Compression force and radiation dose values were highly correlated between the cushioned and non-cushioned sides. CONCLUSION: Two-thirds of women experienced a significant reduction of pain when the radiolucent cushions were used during mammography. Pain reduction was accomplished without any clinically significant change in compression force, radiation dose values, or image quality.

Mammography and breast cancer: the new era.

OBJECTIVES: To review the evidence demonstrating that early detection of breast cancer substantially decreases death from the disease, and to demonstrate that the significant change in the outcome of breast cancer patients results from a combination of early detection and surgical removal of breast cancer, as treatment of the late stage disease provides little impact on ultimate outcome. METHOD: Review results of the randomized controlled trials of mammographic screening and the published results of service screening. RESULTS: Both randomized controlled trials and service screening, when performed properly, provide unequivocal evidence demonstrating that arresting the disease in its preclinically detectable phase has significant impact on outcome. Primary emphasis should be upon preventing breast cancer from developing to metastatic disease. CONCLUSIONS: Numerous scientific trials have repeatedly and convincingly confirmed that breast cancer is progressive rather than a systemic disease from its inception. Progression of breast cancer can be arrested through detection and treatment at an early phase. The time at which disease progression is arrested has significant impact on clinical outcome, making mammographic screening a key factor in the control of breast cancer.

The Swedish Two-County Trial of mammographic screening: cluster randomisation and end point evaluation.

BACKGROUND: The Swedish Two-County Trial has been criticised on the grounds of the cluster randomisation and alleged bias in classification of cause of death. PATIENTS AND METHODS: In the Two-County Trial, 77 080 women were randomised to regular invitation to screening (active study population, ASP) and 55 985 to no invitation (passive study population, PSP), in 45 geographical clusters. After approximately 7 years, the PSP was invited to screening and the trial closed. We analysed data using hierarchical statistical models to take account of cluster randomisation, and performed a conservative analysis assuming a systematic difference between ASP and PSP in baseline breast cancer mortality in one of the counties. We also analysed deaths from causes other than breast cancer and from all causes among breast cancer cases diagnosed in the ASP and PSP. RESULTS: Taking account of the cluster randomisation there was a significant 30% reduction in breast cancer mortality in the ASP. Conservatively, assuming a systematic difference between ASP and PSP clusters in baseline breast cancer mortality, there was a significant 27% reduction in mortality in the ASP. Ignoring classification of cause of death, there was a significant 13% reduction in all-cause mortality in breast cancer cases in the ASP. CONCLUSIONS: Breast cancer mortality is a valid end point and mammographic screening does indeed reduce mortality from breast cancer. The criticisms of the Swedish Two-County Trial are unfounded.

Quantifying the potential problem of overdiagnosis of ductal carcinoma in situ in breast cancer screening.

The relevance of detection of ductal carcinoma in situ (DCIS) in a breast cancer screening programme, and the extent of overdiagnosis of non-progressive lesions, remains controversial. It was the purpose of this paper to estimate the incidence of non-progressive, 'overdiagnosed' DCIS. We defined non-progressive DCIS (DCIS(0)) as DCIS which could not have progressed to invasive disease if left untreated. Progressive DCIS (DCIS(1)) was defined as DCIS which has the propensity to progress to invasive disease. We fitted a Markov process model of the incidence of progressive and non-progressive DCIS, the transition of the former to preclinical invasive disease and the subsequent progression to clinical symptomatic cancer. We used data from the Swedish Two-County Trial and from service screening programmes in the UK, Netherlands, Australia and the USA to estimate the incidence of progressive and non-progressive DCIS, and the detection rates of each at the first and subsequent screening. Average incidence of non-progressive DCIS was 1.11 per 100000 per year. Average incidence of progressive DCIS was 2.1 per 1000 per year. At prevalence screen, 37% of DCIS cases were estimated to be non-progressive. A woman attending prevalence screen has a 19 times greater chance of having a progressive DCIS or an invasive tumour diagnosed than of having a non-progressive DCIS diagnosed. At incidence screen, only 4% of DCIS cases were estimated to be non-progressive. A woman attending an incidence screen has a 166 times higher probability of having a progressive DCIS or invasive lesion diagnosed than of having a non-progressive DCIS diagnosed. There is an element of overdiagnosis of DCIS in breast cancer screening, but the phenomenon is small in both relative and absolute terms.

The relative contributions of screen-detected in situ and invasive breast carcinomas in reducing mortality from the disease.

We aimed to quantify the benefits of detecting ductal carcinoma in situ (DCIS) and of downwards stage-shifting within invasive tumours in mammographic screening. Using data from the Swedish Two-County Trial of breast cancer screening, we examined the 20-year death rates from invasive tumours of stage II or worse, invasive tumours of stage I and DCIS. We then used these rates and their respective incidences in invited (active study population, ASP) and control (passive study population, PSP) arms of the trial, to estimate the numbers of deaths avoided by downward stage-shifting the larger stage II or worse tumours to stage I and the stage I cancers to DCIS. We also studied the association between the mortality reduction achieved and the proportion of DCIS cases detected in the randomised trials of breast cancer screening. In the Swedish Two County Trial, 141 breast cancer deaths were avoided in the ASP compared with the PSP at approximately 20 years of follow-up. Of these, 65% (91/141) were avoided as a result of stage-shifting from invasive stage II or worse to invasive stage I, and 5% (7/141) as a result of stage-shifting from invasive stage I to DCIS. If we assumed that 10% of stage II or worse tumours avoided were shifted not to stage I, but to DCIS, the estimated number of deaths prevented by shifting from invasive disease to in situ was 17, which is 12% of all deaths prevented. When the results of all the randomised trials of breast cancer screening were reviewed, there was no clear association between the percentage of DCIS cases diagnosed and the observed mortality reduction. We conclude that compared with downward stage-shifting of invasive tumours, detection of DCIS plays a small part in saving lives from breast cancer. Treatment decisions in DCIS, as in invasive carcinoma, should take full account of histopathological, clinical and radiological attributes of the tumour.

Oral contraceptive use and mammographic patterns.

High-risk mammographic patterns represent an increased risk of contracting breast cancer and may be used as a surrogate endpoint for the disease. We examined the relationship between oral contraceptive (OC) use and mammographic patterns among 3218 Norwegian women, aged 40-56 years. Information on ever OC use, duration, and age of first OC use and other epidemiological data were obtained through questionnaires. The mammograms were categorized into five groups. Patterns I-III were combined into a low-risk group and patterns IV and V into a high-risk group. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression and adjusted for age, menopausal status, parity, age at first birth, and body mass index. Women who reported ever having used OCs were 20% more likely (OR 1.27, 95% CI 1.0-1.6) to have high-risk mammographic patterns compared with those reporting never having used OCs. There was no dose response between different measures of OC use and high-risk patterns. Among nulliparous women, ever OC users were four times more likely (OR 4.65, 95% CI 2.1-10.3) to have high-risk patterns compared with never users. Our findings suggest that, especially among nulliparous women, ever OC use may exert its effect on breast cancer risk through changes in breast tissue, which can be observed on a mammogram.

All-cause mortality among breast cancer patients in a screening trial: support for breast cancer mortality as an end point.

BACKGROUND: It has recently been suggested that all-cause mortality is a more appropriate end point than disease specific mortality in cancer screening trials, and that disease specific mortality is biased in favour of screening. This suggestion is based partly on supposed inconsistencies between all-cause mortality results and disease specific results in cancer screening trials, and alleged increases in deaths from causes other than breast cancer among breast cancer cases diagnosed among women invited to screening. METHODS: We used data from the Swedish Two-County Trial of mammographic screening for breast cancer, in which 77 080 women were randomised to an invitation to screening and 55 985 to no invitation. We estimated relative risks (RRs) (invited v control) of death from breast cancer, death from other causes within the breast cancer cases, and death from all causes within the breast cancer cases. RRs were adjusted for age and took account of the longer follow up of breast cancer cases in the invited group due to lead time. RESULTS: There was a significant 31% reduction in breast cancer mortality in the invited group (RR 0.69, 95% confidence interval (CI) 0.58-0.80; p<0.001). There was no significant increase in deaths from other causes among breast cancer cases in the invited group (RR 1.12, 95% CI 0.96-1.31; p=0.14). A significant 19% reduction in deaths from all causes was observed among breast cancer cases in the group invited to screening (RR 0.81, 95% CI 0.72-0.90; p<0.001). A more conservative estimation gave a significant 13% reduction (RR 0.87, 95% CI 0.78-0.97; p=0.01). These findings are consistent with the magnitude of the reduction in breast cancer mortality. CONCLUSIONS: Invitation to screening was associated with a reduction in deaths from all causes among breast cancer cases, consistent with high participation rates in screening. There is no significant evidence of bias in cause of death classification in the Two-County Trial, and as breast cancer mortality is the targeted clinical outcome in breast cancer screening, it is the appropriate end point in a breast cancer screening trial. All-cause mortality is a poor and inefficient surrogate for breast cancer mortality.

A treatment scale for axillary management in breast cancer.

BACKGROUND: We have investigated a method, the Kaufman axillary treatment scale (KATS), to help assign patients with a clinically negative axilla to one of three current options of axillary management: standard axillary dissection, sentinel node sampling followed by axillary dissection if the sentinel node is positive, or no axillary surgery at all. The KATS score uses preoperative data to guide the choice of axillary treatment. METHODS: The KATS score is calculated by adding the preoperative values of tumor size, patient age, and pathologic grade. Values range from 1 to 4 for size (1 to 9 mm, 10 to 14 mm, 15 to 19 mm, and 20 to 30 mm), 1 to 3 for age (70 years and over, 50 to 69 years, less than 50 years), and 1 to 2 for grade (low or not low) to calculate the score. The KATS score ranges from 3 to 9. We have applied this score against the SEER (Surveillance, Epidemiology, and End Results) tumor registry of 529 patients with invasive breast cancer with known pathologic data. We then validated it by applying it to our own set of 190 patients using preoperative data. The chi-square test and logistic regression analysis were used for P values (all two sided), univariate and multivariate analysis, odds ratio and confidence intervals utilizing SPSS statistics software. RESULTS: In the SEER database using American Joint Committee on Cancer pathologic size alone, no sizable group was identified with a positive node rate neither below 8% (T1a) nor above 48% (T2). KATS scores of 3 and 4 (68 patients, group 1) identify patients with an average node positive rate of 4.4% (P <0.02, group 1 versus 2). Those patients with KATS scores of 5, 6, and 7 (341 patients, group 2) carry an average node positive rate of 22% (P <0.001, group 2 versus 3). KATS scores of 8 and 9 (120 patients, group 3) identify patients with an average node positive rate of 50% (P <0.001, group 3 versus 1). Similar results were found on our own group of 190 patients using preoperative available data. KATS scores of 3 or 4 (11 patients, group 1) had no positive nodes. Group 2 (100 patients, KATS score 5, 6, and 7) had an average 30% node positive rate. Group 3 (79 patients, KATS score 8 and 9) had 61% node positive rate. The KATS score allows the clinician to separate patients into three axillary management groups. Group 1 are those patients who may need no axillary surgery at all. Group 2 are patients who would benefit from sentinel node mapping. Group 3 has a node positive rate (61%) similar to that of clinically palpable nodes (since not all clinically palpable nodes are positive). Group 3 patients may be considered for standard axillary dissection, similar to the palpable node patient. If group 3 patients have sentinel node mapping, more than half of these patients require axillary dissection and the impact of false negative sentinel node procedures may become clinically significant. CONCLUSIONS: An axillary treatment score has been developed to aid in the triage of patients toward reasonable axillary treatment choices for the benefit of the patient. The KATS score is a guideline and not a mandate. The KATS score attempts to use breakpoints that are both clinically practical and validated by scientific data. Like many other attempts to categorize patients, there is a continuum of data points along any variable. The treating physician utilizing the full array of available data on each patient makes the final clinical decision of axillary management.

Estimating the benefits of adjuvant systemic therapy for women with early breast cancer.

BACKGROUND: Prognostic factors are commonly used to help identify women with node-negative breast cancer at high risk of recurrence. Although many are available, knowing which risk factor or combination of factors to use to estimate prognosis for an individual woman is often difficult. This study documented the baseline prognoses for a group of women with node-negative breast cancers, and estimated the potential benefits of adjuvant systemic therapy. METHODS: Ten-year, actuarial, cause-specific survival based on tumour size and histological grade using data from the Swedish Two-County Trial of mammographic screening was calculated for 1200 women with node-negative cancers of less than 30 mm diameter. The benefits of adjuvant systemic therapy for these women were then estimated using the published odds reductions in death from adjuvant systemic therapy from the Early Breast Cancer Trialists' Collaborative Group overview. RESULTS: The absolute 10-year survival benefits for subgroups of women based on tumour size and histological grade were estimated for women aged under 50 years by the addition of chemotherapy, and over 50 years by the addition of tamoxifen and/or chemotherapy. CONCLUSION: Decisions about adjuvant systemic therapy in women with node-negative breast cancer need to be individualized, taking into account treatment efficacy and toxicity. The quantitative methods presented in this paper facilitate such decisions.

Mammographic screening: international perspective.

The twentieth century saw the introduction of mammography as a diagnostic tool and its refinement as a screening method. It appears guaranteed that women who are well informed will seek mammography screening with high expectations of technical quality and accurate interpretation. More refined knowledge of breast anatomy and pathology will assist radiologists to interpret with high specificity. We will learn how to recognized more accurately normal structures and doubtful findings. We will gain experience in interpretation through faithful review of interval cancers and subtle screen-detected cancers, and will use educational tools that have the potential to improve the efficiency of education by directing attention to specific deficiencies. Mammographic screening has been advanced through the efforts of dedicated teams of physicians, scientists, and other professionals throughout the world. The international communication of ideas and discoveries will continue to challenge the boundaries of what can be accomplished in early detection as well as noninvasive therapy, and this body of knowledge will continue to be enriched by these diverse contributions.

Beyond randomized controlled trials: organized mammographic screening substantially reduces breast carcinoma mortality.

BACKGROUND: The efficacy of mammographic screening in the reduction of breast carcinoma mortality has been demonstrated in randomized controlled trials. However, the evaluation of organized screening outside of research settings (so-called "service screening") faces unique methodologic and conceptual challenges. The current study describes the evaluation of organized mammography screening in a clinical setting and demonstrates the benefit obtained from service screening in two Swedish counties. METHODS: In the group of subjects ages 20--69 years, there were 6807 women diagnosed with breast carcinoma over a 29-year period in 2 counties in Sweden and 1863 breast carcinoma deaths. All patients were classified from patient charts based on their screening status (i.e., whether they had been invited to undergo screening and whether they actually had undergone screening). The number of women who lived in the 2 counties during the 29-year study period was provided by the Central Bureau of Statistics. Breast carcinoma-specific mortality was compared across three time periods: 1) 1968--1977, when no screening was taking place because mammography had not been introduced; 2) 1978--1987, the approximate period of the Two-County randomized controlled trial of screening in women ages 40--74 years; and 3) 1988--1996, when all women in the 2 counties ages 40--69 years were invited to undergo screening (service screening). When comparing breast carcinoma mortality in screened women with that in women diagnosed before screening was introduced, a correction for self-selection bias was incorporated to prevent overestimation of the benefit of screening. RESULTS: The mortality from incident breast carcinoma diagnosed in women ages 40-69 years who actually were screened during the service screening period (1988--1996) declined significantly by 63% (relative risk [RR] = 0.37; 95% CI, 0.30--0.46) compared with breast carcinoma mortality during the time period when no screening was available (1968--1977). The mortality decline was 50% (RR = 0.50; 95% CI, 0.41--0.60) when breast carcinoma mortality among all women who were invited to undergo screening (nonattendees included) was compared with breast cancer mortality during the time period when no screening was available (1968--1977). The reduction in mortality observed during the service screening period, adjusted for selection bias, was 48% (RR = 0.52; 95% CI, 0.43--0.63). No significant change in breast carcinoma mortality was observed over the three time periods in women who did not undergo screening. This group included women ages 20--39 years because these individuals were never invited to undergo screening, and women ages 40--69 years who did not undergo screening (not invited during the randomized trial or invited during the second and third time periods but declined). CONCLUSIONS: Regular mammographic screening resulted in a 63% reduction in breast carcinoma death among women who actually underwent screening. The policy of invitation to organized screening with mammography appears to have reduced breast carcinoma mortality by 50% in these 2 counties.

International investigation of breast MRI: results of a multicentre study (11 sites) concerning diagnostic parameters for contrast-enhanced MRI based on 519 histopathologically correlated lesions.

A multicentre study was undertaken to provide fundamentals for improved standardization and optimized interpretation guidelines of dynamic contrast-enhanced MRI. Only patients scheduled for biopsy of a clinical or imaging abnormality were included. They underwent standardized dynamic MRI on Siemens 1.0 (163 valid lesions > or = 5 mm) or 1.5 T (395 valid lesions > or = 5 mm) using 3D fast low-angle shot (FLASH; 87 s) before and five times after standardized bolus of 0.2 mmol Gd-DTPA/kg. One-Tesla and 1.5 T data were analysed separately using a discriminant analysis. Only histologically correlated lesions entered the statistical evaluation. Histopathology and imaging were correlated in retrospect and in open. The best results were achieved by combining up to five wash-in or wash-out parameters. Different weighting of false-negative vs false-positive calls allowed formulation of a statistically based interpretation scheme yielding optimized rules for the highest possible sensitivity (specificity 30%), for moderate (50%) or high (64-71%) specificity. The sensitivities obtained at the above specificity levels were better at 1.0 T (98, 97, or 96%) than at 1.5 T (96, 93, 86%). Using a widely available standardized MR technique definition of statistically founded interpretation rules is possible. Choice of an optimum interpretation rule may vary with the clinical question. Prospective testing remains necessary. Differences of 1.0 and 1.5 T are not statistically significant but may be due to pulse sequences.