Using mammographic density to improve breast cancer screening outcomes.

It is possible that the performance of mammographic screening would be improved if it is targeted at women at higher risk of breast cancer or who are more likely to have their cancer missed at screening, through more intensive screening or alternative screening modalities. We conducted a case-control study within a population-based Australian mammographic screening program (1,706 invasive breast cancers and 5,637 randomly selected controls). We used logistic regression to examine the effects of breast density, age, and hormone therapy use, all known to influence both breast cancer risk and the sensitivity of mammographic screening, on the risk of small (15 mm) screen-detected and interval breast cancers. The risk of small screen-detected cancers was not associated with density, but the risk of large screen-detected cancers was nearly 3-fold for the second quintile and approximately 4-fold for the four highest density categories (third and fourth quintiles and the two highest deciles) compared with the lowest quintile. The risk of interval cancers increased monotonically across the density categories [highest decile odds ratio (OR), 4.65; 95% confidence interval (95% CI), 2.96-7.31]. The risk of small and large screen-detected cancers, but not interval cancers, increased with age. After adjusting for age and density, hormone therapy use was associated with a moderately elevated risk of interval cancers (OR, 1.43; 95% CI, 1.12-1.81). The effectiveness of the screening program could be improved if density were to be used to identify women most likely to have poor screening outcomes. There would be little additional benefit in targeting screening based on age and hormone therapy use.

Can mammographic findings help discriminate between atypical ductal hyperplasia and ductal carcinoma in situ after needle core biopsy?

In a screening population of women, the mammographic characteristics for 68 cases of atypical ductal hyperplasia (ADH) diagnosed by needle core biopsy (NCB) were reviewed to seek mammographic findings which differentiate between ductal carcinoma in situ (DCIS) and ADH. A blinded analysis by two radiologists was performed for 48 cases with microcalcification. The mammographic findings were correlated with the surgical histological results of benign non-atypical, ADH and carcinoma (DCIS or invasive) to identify features which were associated with a higher or lower odds ratio (OR) for malignancy. Underestimates for malignancy occurred in 14 of 29 cases with granular calcification form (OR 7.9, 95% confidence interval (CI) 1.5-41) and 6 of 8 cases with segmental/linear branching distribution (OR 9.0, 95%CI 1.6-52). No malignancy was found at surgical excision in 16 cases with fine, rounded calcification. In conclusion, detailed assessment of calcification distribution and form gave helpful predictors for malignancy. Lesions with fine rounded calcification were always benign.

The heritability of mammographically dense and nondense breast tissue.

BACKGROUND: Percent mammographic density (PMD) is a risk factor for breast cancer. Our previous twin study showed that the heritability of PMD was 63%. This study determined the heritabilities of the components of PMD, the areas of dense and nondense tissue in the mammogram. METHODS: We combined two twin studies comprising 571 monozygous and 380 dizygous twin pairs recruited from Australia and North America. Dense and nondense areas were measured using a computer-assisted method, and information about potential determinants was obtained by questionnaire. Under the assumptions of the classic twin model, we estimated the heritability of the log dense area and log nondense area and the genetic and environmental contributions to the covariance between the two traits, using maximum likelihood theory and the statistical package FISHER. RESULTS: After adjusting for measured determinants, for each of the log dense area and the log nondense area, the monozygous correlations were greater than the dizygous correlations. Heritability was estimated to be 65% (95% confidence interval, 60-70%) for dense area and 66% (95% confidence interval, 61-71%) for nondense area. The correlations (SE) between the two adjusted traits were -0.35 (0.023) in the same individual, -0.26 (0.026) across monozygous pairs, and -0.14 (0.034) across dizygous pairs. CONCLUSION: Genetic factors may play a large role in explaining variation in the mammographic areas of both dense and nondense tissue. About two thirds of the negative correlation between dense and nondense area is explained by the same genetic factors influencing both traits, but in opposite directions.

Margins and outcome of screen-detected breast cancer with extensive in situ component.

BACKGROUND: In situ disease surrounding invasive tumours is an important consideration in the management of patients with early breast cancer. This study of screen-detected breast cancers assessed the influence of in situ disease including an extensive in situ component (defined as ductal carcinoma in situ involving more than 25% of the area within the invasive tumour) on surgical management, local recurrence and survival of a group of patients. METHODS: A total of 595 cases of invasive breast cancer detected at St Vincent's BreastScreen were retrospectively reviewed to determine presence and extent of in situ disease, the surgical procedure and adequacy of excision. Outcome was examined in a cohort of 126 cases. RESULTS: A total of 438 (74%) patients had in situ foci in or around the invasive tumour and 107 (18%) were defined as extensive in situ component (EIC)-positive. The initial procedure was mastectomy in 20% of the cases and breast-conserving surgery in 80% including 18% who underwent further surgery. Re-excision (P = 0.02) or mastectomy (P = 0.01) was more often required in patients with EIC. After definitive local excision, margins were close or involved with invasive disease in 3% but the patients with EIC were more likely to have margins close or involved with in situ disease (16 vs 2%; P = 0.001). There were seven deaths and one local invasive recurrence in the follow-up group and none of the deaths were in patients who were EIC-positive. CONCLUSIONS: EIC predicts for a higher rate of re-excision and/or mastectomy. For patients with EIC, there is an acceptably low risk of local recurrence if margins are clear.

Can sonography be used to help differentiate between radial scars and breast cancers?

The aim of this study was to determine whether sonography can help differentiate radial scars (RS) from breast cancers. Series of 75 consecutive mammographic screen-detected RS and carcinomas were reviewed: shape, orientation, echotexture, halo, acoustic attenuation and architectural distortion were compared for sonographic RS and cancers. RS were 43% sonopositive (25/58 examined) vs. 93% sonopositive carcinomas (68/73 examined); P<0.001. Of 22 RS and 66 cancers available for film review, findings were: echogenic halo in zero RS vs. 38 cancers (0% vs. 58%); tiny sonographic cysts in 3 RS vs. zero carcinomas (14% vs. 0%); assessment category malignant vs. indeterminate/suspicious (8% vs. 59%, P<0.001); breast architecture disruption (43% vs. 91%, P<0.001); sound attenuation (55% vs. 86%, P<0.005), taller-than-wide shape (36% vs. 56%, P=0.11). RS showed echogenic components more than cancers (32% vs. 9%, P=0.016). Jagged margins were equally seen (77% vs. 76%, P=0.89). The findings suggest that sonographic differences can help discriminate between RS and carcinomas.

Examining the sensitivity of ultrasound-guided large core biopsy for invasive breast carcinoma in a population screening programme.

INTRODUCTION: To evaluate the sensitivity of ultrasound-guided core-needle biopsy (UCB) in invasive breast carcinoma and to establish causes of false-negative biopsy in a population screening programme. METHOD: We identified 571 consecutive women diagnosed with surgically proven invasive breast cancer. Histology from 14-gauge UCB was compared with surgical histology to identify true-positive and false-negative ultrasound core biopsies. True-positive and false-negative groups were compared for tumour size and histology. On blinded review of UCB images and pathology reports from false negative (n = 20) and a random sample of true-positive cases (n = 80), we compared core sample number and needle visualisation in the lesion. RESULTS: Of 571 carcinomas sampled with UCB, 551 (96.5%) were true positive and 20 (3.5%) were false negative. The mean core number was 2.0 (range 1-3) for false negatives and 2.25 (range 1-4) for true positives (P = 0.27). Mean tumour sizes were 13.3 and 16.2 mm for the false-negative and true-positive groups, respectively (P = 0.25). Tubular carcinomas represented 30% (6/20) of false-negative cases compared with 5.1% (28/551) of the true-positive cases (P < 0.001). On blinded review, needle visualisation within the lesion was demonstrated in 47.4% (9/19) of false-negative cases and 76.3% (61/80) of true-positive cases (P = 0.02). CONCLUSION: We demonstrated a sensitivity of 96.5% with a mean of 2.21 cores. False-negative results were more likely in the absence of post-fire needle position verification and with tubular carcinomas. Neither tumour size nor core number predicted diagnostic accuracy.

Explaining variance in the cumulus mammographic measures that predict breast cancer risk: a twins and sisters study.

BACKGROUND: Mammographic density, the area of the mammographic image that appears white or bright, predicts breast cancer risk. We estimated the proportions of variance explained by questionnaire-measured breast cancer risk factors and by unmeasured residual familial factors. METHODS: For 544 MZ and 339 DZ twin pairs and 1,558 non-twin sisters from 1,564 families, mammographic density was measured using the computer-assisted method Cumulus. We estimated associations using multilevel mixed-effects linear regression and studied familial aspects using a multivariate normal model. RESULTS: The proportions of variance explained by age, body mass index (BMI), and other risk factors, respectively, were 4%, 1%, and 4% for dense area; 7%, 14%, and 4% for percent dense area; and 7%, 40%, and 1% for nondense area. Associations with dense area and percent dense area were in opposite directions than for nondense area. After adjusting for measured factors, the correlations of dense area with percent dense area and nondense area were 0.84 and -0.46, respectively. The MZ, DZ, and sister pair correlations were 0.59, 0.28, and 0.29 for dense area; 0.57, 0.30, and 0.28 for percent dense area; and 0.56, 0.27, and 0.28 for nondense area (SE = 0.02, 0.04, and 0.03, respectively). CONCLUSIONS: Under the classic twin model, 50% to 60% (SE = 5%) of the variance of mammographic density measures that predict breast cancer risk are due to undiscovered genetic factors, and the remainder to as yet unknown individual-specific, nongenetic factors. IMPACT: Much remains to be learnt about the genetic and environmental determinants of mammographic density.

Cancer on a mammogram is not memorable: readers remember their recalls and not cancers.

AIM: To determine if presence of cancer on a mammogram makes that mammogram more memorable. MATERIALS AND METHODS: A total of 100 mammograms (25 cancers) were grouped into 5 sets of 20 cases. Set pairs were presented in five reads to eight radiologist readers. Readers were asked to 'clear' or 'call back' cases, and at post-baseline reads to indicate whether each case was 'new' or 'old' (remembered from prior read). Two sets were presented only at baseline, to calculate each reader's false recollection rate. For cases presented more than once ('old' cases, 100 presentations) readers could have 'correct memory' or 'memory loss'. Memory performance was defined as odds ratio of correct memory to memory loss. Multivariate logistic data regression analysis identified predictors of memory performance from: reader, set, time since last read, presence of cancer, and whether the case was called back at the last read. RESULTS: Memory performance differed markedly between readers and reader identity was a highly significant predictor of memory performance. Presence of cancer was not a significant predictor of memory performance (odds ratio 0.77, 95% CI: 0.49-1.21). Whether the case was called back at the last read was a highly significant predictor (odds ratio 4.22, 95% CI: 2.70-6.61) for the model incorporating reader variability, and also the model without reader variability (odds ratio 2.67, 95% CI: 1.74-4.08). CONCLUSION: The only statistically significant predictor of radiologist memory for a mammogram was whether the radiologist 'called it back' at a prior reading round. Presence of cancer on a mammogram did not make it memorable.

Malignancy detection in digital mammograms: important reader characteristics and required case numbers.

RATIONALE AND OBJECTIVES: To determine the relationship between heightened levels of reader performance and reader practice in terms of number of cases read and previous experience. MATERIALS AND METHODS: A test set of mammograms was developed comprising 50 cases. These cases consisted of 15 abnormals (biopsy proven) and 35 normals (confirmed at subsequent rescreen). Sixty-nine breast image readers reviewed these cases independently and their performance was measured by recording their individual receiver operating characteristic score (area under the curve), sensitivity, and specificity. These measures of performance were then compared to a range of factors relating to the reader such as years of certification and reporting, number of cases read per year, previous experiences, and satisfaction levels. Correlation analyses using Spearman methods were performed along with the Mann-Whitney test to detect differences in performance between specific reader groups. RESULTS: Improved reader performance was found for years certified (P = .004), years of experience (P = .0001), and hours reading per week (P = .003) shown by positive statistical significant relationships with Az values (area under receiver operating characteristic curve). Statistical comparisons of Az values scored for individuals who read varying number of cases per year showed that those individuals whose annual mammographic case load was 5000 or more (P = .03) or between 2000 and 4999 (P = .05), had statistically significantly higher scores than those who read less than 1000 cases per year. CONCLUSION: The results of this study have shown variations in reader performance relating to parameters of reader practice and experience. Levels of variance are shown and potential acceptance levels for diagnostic efficacy are proposed which may inform policy makers, judicial systems and public debate.

Variation in mammographic appearance between projections of small breast cancers compared with radial scars.

AIMS: The study aims to assess variation in appearance between mammographic projections (conspicuity variation) for invasive breast cancers (IBCs) compared with radial scars (RS). Conspicuity variation has been previously described as characteristic of RS. The lesions were also compared with respect to breast density and the proportion of cases detected by one of two readers and required a third (consensus) read. MATERIALS AND METHODS: The study was approved by the BreastScreen Victoria research committee. Mammograms of 75 randomly selected invasive breast cancers, with histological diameter ≤10 mm (IBC), were mixed with 67 consecutively detected RS, all from a double-reading population-based breast cancer screening programme. On blinded review, these 142 lesions were classified for mammographic findings and assessed for marked or minor conspicuity variation between views. We assessed the associations between lesion type, lesion spicules and centres, breast density, conspicuity variation and proportion detected by one reader only. RESULTS: Marked conspicuity variation was common, but not statistically different for IBC and RS (64% vs. 66%, χ(2) = 0.8, P = 0.04). Conspicuity variation did not correlate with spiculation type (long, fine or short, broad based) or lesion centres (lucent or dense) (ρ < 0.05, P = 0.5), and showed no significant change with increasing Breast Imaging Reporting and Data System breast density (IBC, χ(2) = 2.3, P = 0.5; RS, χ(2) = 0.95, P = 0.6). Density did not vary by lesion type. In the screening programme, 29% of IBC (125 of 431) versus 43% of RS (32 of 75) had been detected by one of two readers (χ(2) = 2.7, P = 0.098). CONCLUSIONS: Two-thirds of small IBCs displayed marked conspicuity variation, similar to RS. Therefore, conspicuity variation does not discriminate between IBC and RS.

Common genetic variants associated with breast cancer and mammographic density measures that predict disease.

Mammographic density for age and body mass index (BMI) is a heritable risk factor for breast cancer. We aimed to determine if recently identified common variants associated with small gradients in breast cancer risk are associated with mammographic density. We genotyped 497 monozygotic and 330 dizygotic twin pairs and 634 of their sisters from 903 families for 12 independent variants. Mammographic dense area, percent dense area, and nondense area were measured by three observers using a computer-thresholding technique. Associations with mammographic density measures adjusted for age, BMI, and other determinants were estimated (a) cross-sectionally using a multivariate normal model for pedigree analysis (P(x)), (b) between sibships, and (c) within sibships using orthogonal transformations of outcomes and exposures. A combined test of association (P(c)) was derived using the independent estimates from b and c. We tested if the distributions of P values across variants differed from the uniform distribution (P(u)). For dense area and percent dense area, the distributions of P(c) values were not uniform (both P(u) <0.007). Consistent with their breast cancer associations, rs3817198 (LSP1) and rs13281615 (8q) were associated with dense area and percent dense area (all P(x) and P(c) <0.05), and rs889312 (MAP3K1), rs2107425 (H19), and rs17468277 (CASP8) were marginally associated with dense area (some P(x) or P(c) <0.05). All associations were independent of menopausal status. At least two common breast cancer susceptibility variants are associated with mammographic density measures that predict breast cancer. These findings could help elucidate how those variants and mammographic density measures are associated with breast cancer susceptibility.

Painful diabetic mastopathy as a reason for mastectomy.

A 34 year old woman with longstanding insulin-dependent diabetes mellitus experienced disabling bilateral breast pain and tenderness associated with the benign breast lesions of diabetic mastopathy. Diabetic mastopathy is typically associated with nontender lesions, however we present a case where disabling pain and tenderness lead to bilateral mastectomy, as requested by the patient. This relieved the patient of her symptoms.

Variants of sternal insertion of the pectoral muscle on mammography: a pictorial review.

The aim of this pictorial review is to demonstrate the diverse presentations of the medial insertion of pectoralis major on mammography. A collection of cases demonstrating the variations in appearance of this muscle insertion are presented. The factors contributing to the appearances of this artifact, the differential diagnoses and useful further investigations are discussed. Familiarity with the different presentations of this muscle insertion will facilitate recognition and prevent unnecessary investigations.

False-positive breast screening due to fat necrosis following mammography.

Traumatic fat necrosis can result in a spectrum of imaging appearances that range from characteristically benign to those indistinguishable from malignancy. In such cases, biopsy might be required for diagnosis. The present case demonstrates a suspicious mammographic mass lesion appearing following a haematoma caused by a previous screening mammogram.

Fourteen-gauge needle core biopsy of mammographically evident radial scars: is excision necessary?

BACKGROUND: Radial scars are benign lesions that may mimic breast carcinoma on mammography and usually are managed by excision biopsy. The authors report their experience with stereotactic needle core biopsy (SNCB) in sampling these lesions. METHODS: A prospective study examined a consecutive series of 75 mammographically detected radial scars from a population-based screening program. In patients who were sampled by SNCB followed by surgical biopsy, the histologic findings of core biopsy and the gold standard of excision biopsy were compared. RESULTS: Sixty-three patients were sampled by core biopsy: SNCB was used in 55 patients (87.0%), and ultrasound-guided needle core biopsy (UNCB) was used in 8 patients (13%). One patient who underwent SNCB did not undergo a follow-up excision biopsy. Radial scars were diagnosed preoperatively by core biopsy in 51 of 62 patients who underwent excision (82%; 95% confidence interval [95%CI], 70-91%). The sensitivity for SNCB was 85% (95%CI, 73-94%), and the sensitivity for UNCB was 63% (95%CI, 24-91%). Of 54 patients who underwent SNCB and excision, 4 patients had coexistent ductal carcinoma in situ (DCIS) at the time they underwent surgical excision: SNCB identified DCIS in 1 patient and identified atypical ductal hyperplasia (ADH) in 3 patients. In the entire group of 75 radial scars, 5 scars were associated with DCIS (7%), and there were no invasive carcinomas. ADH was present in association with 42 of 74 radial scars that were excised surgically (57%). Twenty-nine of those radial scars were sampled preoperatively by SNCB. ADH was found in 21 patients (72%; 95CI, 53-87%). CONCLUSIONS: The sensitivity of SNCB in the identification of radial scars was 85%. In four patients with associated DCIS, SNCB revealed either ADH or DCIS, both of which required excision. These findings suggest that patients with SNCB-proven radial scars among a screened population can be managed safely by mammographic follow-up, provided there is no associated DCIS, ADH, or lobular carcinoma in situ. Spiculated abnormalities with discordant SNCB results require surgical biopsy.