Lobular carcinoma in situ of the breast: clinical, pathologic, and mammographic features

Lobular carcinoma in situ (LCIS) was diagnosed in 165 surgical specimens (119 patients) at our institution between 1974 and 1987. LCIS was seen more often in younger women (mean age, 49 years) than other breast carcinomas were (mean age, 58 years). Sampling of a single breast revealed multifocal disease in 70% (96/138). When both breasts were sampled, bilateral foci were found in 50% (41/82). Of 165 breasts with foci of LCIS, 37% (61/165) had simultaneously occurring invasive cancers in the same breast. Direct mammographic-pathologic correlation of foci of LCIS was possible in 73 breasts (67 patients). Microcalcifications were an indication for biopsy in 49% (20/41) of breasts with a mammographic abnormality, but were a nonspecific finding often found in tissues adjacent to foci of LCIS. The mammogram was normal in 44% (32/73) of breasts with foci of LCIS. The mammograms of patients with LCIS and those from a group of age-matched control subjects were compared by using a modified form of Wolfe's criteria and the percentage of fibroglandular elements. LCIS was seldom found in an N1 breast (1% vs 29%) or in a breast with less than 25% of its parenchymal area occupied by fibroglandular density (3% vs 33%). Compared with the control group, breasts with LCIS had more than 50% fibroglandular density (85% vs 45%) and a much higher frequency of the DY pattern (56% vs 36%). More fibroglandular density was seen in the LCIS group at all ages. Postmenopausally, the frequencies of the DY pattern and fibroglandular density greater than 50% in LCIS patients were nearly double those in the control group. LCIS patients have disease of the entire breast parenchyma, characterized by multifocality and bilaterality of various forms of lobular disease. Their mammograms reveal a higher rate of the DY pattern and higher percentages of fibroglandular or parenchymal density than those of age-matched controls. In LCIS patients, persistence of the DY pattern, or large amounts of fibroglandular density postmenopausally supports the concept that mammographically dense breasts are a marker for increased cancer risk in women 50 years old and older.     

Mammographic follow-up after breast conserving surgery and postoperative radiotherapy without boost irradiation for mammary carcinoma

Pre- and postoperative mammograms were reviewed in 103 women undergoing conservation surgery and irradiation for breast cancer stage I. The main reactions to radiotherapy were increased breast parenchymal density and increased skin thickness. Changes reached a peak at 9 months. No new changes were seen at 2 years, and most had regressed at this time. Following surgery, 71 of the patients displayed noticeable scar tissue in the surgical area, sometimes causing diagnostic difficulties. Two of the patients had a local recurrence of carcinoma, while 3 developed cancer in the other breast.     

Can tamoxifen cause a significant mammographic density change in breast parenchyma?

To evaluate tamoxifen-induced glandular tissue density changes in women who are on an adjuvant tamoxifen therapy. We examined serial mammograms of 27 women (average age 67) who had surgery for unilateral breast carcinoma and were on tamoxifen for 5 years. Mammograms obtained at the beginning of treatment, within 2 or 3 years, at the end of 5 years and 1 year after cessation of tamoxifen treatment, were evaluated by two radiologists experienced in reading mammograms. Four 1-cm-diameter circular areas of the glandular tissue and retroglandular fat were sampled by a densitometer and a relative glandular density (glandular tissue/fat density) was used for comparison between serial mammograms. Most cases (79%) did not show tamoxifen-induced change in glandular density. Three patients (13%) showed an early and two (8%) a delayed mild reduction in glandular density as compared to baseline mammograms. No patient was found to have increased glandular density following the cessation of tamoxifen therapy (in subjective evaluation). Densitometer readings showed a mild reduction in glandular densities in 16 cases (60%) during treatment and a minimal increase in 13 cases (48%) following cessation of treatment. There was a slight decrease in breast density during treatment [relative density of 0.012+/-0.006 (standard error) per interval, P value:.06] and the difference between years 5 and 6 was nearly zero [relative density of 0.00042+/-0.01 (standard error), P value:.97]. Long-term use of tamoxifen may cause a mild reduction in breast glandular density, although this, in part, may be attributed to the age-related mammographic density change. Following cessation of tamoxifen, no significant increase in glandular density was observed. Therefore, any increase in mammographic density during or after tamoxifen treatment should be viewed with suspicion and further evaluated.     

The mammographic parenchymal patterns of nulliparous women and women with a family history of breast cancer

One-hundred-and-thirteen mammograms of nulliparous women and 44 mammograms of women with a family history of breast cancer were graded according to Wolfe's parenchymal pattern classification. These were compared to 437 mammograms of women without these risk factors. Mammograms were read by two independent observers in order to evaluate inter- and intra-observer variation. The interobserver variation was reduced from 17% to 5% by combining high risk patterns (P2 and DY) and low risk patterns (N1 and P1). A significantly higher proportion of high risk patterns was found in nulliparous women compared to parous women (P less than 0.01). The proportion of high risk patterns decreased significantly with the number of children (P less than 0.01). Women with a family history of breast cancer had almost the same parenchymal patterns as women without a family history. In conclusion, while nulliparity and family history are recognized risk factors for developing breast cancer, only nulliparity would appear to influence the mammographic parenchymal pattern. This probably reflects the different mechanism by which the two factors affect breast tissue.     

Skin thickness in the therapeutically irradiated breast.

Skin thickening of the breasts of 22 women undergoing excision biopsy of a breast cancer and subsequent radiation therapy to 5,000 rad is considered. The skin thickness of the treated breast returned to normal in 17 of 22 patients studied. Of the 17, nearly 60% returned to normal in 2 years, over 80% in 3 years, and the rest by 4 years. The period of follow-up was less than 4 years in the five patients with residual skin thickening. The alterations in skin thickness are consistent with the histopathologic changes seen in radiation dermatitis.     

Impact of breast density on computer-aided detection for breast cancer

OBJECTIVE: Our aim was to determine whether breast density affects the performance of a computer-aided detection (CAD) system for the detection of breast cancer. MATERIALS AND METHODS: Nine hundred six sequential mammographically detected breast cancers and 147 normal screening mammograms from 18 facilities were classified by mammographic density. BI-RADS 1 and 2 density cases were classified as nondense breasts; BI-RADS 3 and 4 density cases were classified as dense breasts. Cancers were classified as either masses or microcalcifications. All mammograms from the cancer and normal cases were evaluated by the CAD system. The sensitivity and false-positive rates from CAD in dense and nondense breasts were evaluated and compared. RESULTS: Overall, 809 (89%) of 906 cancer cases were detected by CAD; 455/505 (90%) cancers in nondense breasts and 354/401 (88%) cancers in dense breasts were detected. CAD sensitivity was not affected by breast density (p=0.38). Across both breast density categories, 280/296 (95%) microcalcification cases and 529/610 (87%) mass cases were detected. One hundred fourteen (93%) of the 122 microcalcifications in nondense breasts and 166 (95%) of 174 microcalcifications in dense breasts were detected, showing that CAD sensitivity to microcalcifications is not dependent on breast density (p=0.46). Three hundred forty-one (89%) of 383 masses in nondense breasts, and 188 (83%) of 227 masses in dense breasts were detected-that is, CAD sensitivity to masses is affected by breast density (p=0.03). There were more false-positive marks on dense versus nondense mammograms (p=0.04). CONCLUSION: Breast density does not impact overall CAD detection of breast cancer. There is no statistically significant difference in breast cancer detection in dense and nondense breasts. However, the detection of breast cancer manifesting as masses is impacted by breast density. The false-positive rate is lower in nondense versus dense breasts. CAD may be particularly advantageous in patients with dense breasts, in which mammography is most challenging.     

Correlation between breast parenchymal patterns and mammographers' certainty of diagnosis

The density of breast tissue on a mammogram may affect radiologists' diagnostic decisions. To evaluate possible correlations among breast parenchymal pattern and diagnostic confidence, six radiologists classified 655 mammograms as N1, P1, P2, and DY, according to Wolfe's criteria. Evaluation of radiologists' confidence interpreting the mammograms (1 = absolutely certain, 2 = fairly certain, 3 = uncertain), shows a significant correlation between decreasing diagnostic certainty and increasing complexity of the mammographic breast parenchymal pattern. That readers are less confident in their interpretation of P2 and DY breast parenchymal patterns has implications for the operation of breast cancer screening programs.     

Toluidine blue dye as a breast localization marker

We compared the efficacy of toluidine blue dye vs methylene blue as a visual marker for breast localizations in vitro and in vivo. In phase 1, the dyes were injected into 10 mastectomy specimens and allowed to diffuse for 24-48 hr. In phase 2, the breasts of four premastectomy patients were injected with the dyes and the dyes were allowed to diffuse for 3 3/4, 12, 24, and 47 hr before mastectomy. In phase 3, the breasts of 18 women in whom 20 breast localizations were performed before excisional biopsy were injected with methylene blue or toluidine blue up to 2 hr 10 min before the biopsy. All excised stained breast tissue was evaluated blindly. The amount of pain associated with injections of the dye was recorded. The 22 women in phases 2 and 3 had had mammograms before, and the parenchymal patterns had been classified according to Wolfe. In the patients injected 3 3/4, 12, 24, and 47 hr before mastectomy, more intense staining with less diffusibility was seen with toluidine blue than with methylene blue. In the 20 localization procedures before excisional biopsy, no difference in intensity of staining or radius of diffusion was seen between methylene blue and toluidine blue with maximal diffusion times of 2 hr 10 min. Breast parenchymal pattern did not correlate with stain intensity or diffusibility. The six patients in whom both methylene blue and toluidine blue were injected and the 18 patients in whom either dye was injected felt less discomfort at the time of injection of toluidine blue than of methylene blue. Our results suggest that toluidine blue causes less discomfort and produces a more intense stain with a smaller diffusion radius than methylene blue regardless of breast parenchymal pattern.     

The significance of circumscribed malignant mammographic masses in the surveillance of BRCA 1/2 gene mutation carriers

Breast cancers in gene mutation carriers may escape mammographic detection because of rapid growth and tumor expansion. Therefore, they may mimic benign lesions on the mammogram. Twenty-nine BRCA 1/2 mutation carriers under surveillance developed 31 breast cancers between 1994 and 2001 at a mean age of 44.2 years. Controls were 63 women with 67 breast cancers in the same period at a mean age of 53.8 years, also under surveillance because of a life time risk of at least 15%. In 26% of the carriers vs. 48% of the controls, mammography was the method that first suspected a malignancy. Seven radiologists performed a retrospective review of the original mammograms to establish technical assessment, with special attention for circumscribed lesions and estimated probability of malignancy. In the mutation carriers seven (23%) circumscribed non-calcified mammographic masses were found and three in the controls (4.5%) P=0.01. These masses were proven to be malignant. In both groups around 70% of these fast-growing circumscribed lesions were detected by the patients. The masses were situated in breasts with a good interpretable breast pattern. BRCA 1/2 mutation carriers had a significantly higher percentage of circumscribed non-calcified mammographic masses that proved to be malignant. These mammographic lesions in women at high risk should be described as at least Birads 0 and worked-up with ultrasound and needle biopsy.     

Breast MR imaging during or soon after radiation therapy

PURPOSE: To investigate the degree and prevalence of radiation-induced changes on breast magnetic resonance (MR) images in patients who were undergoing radiation therapy at that time or soon after, to assess prospectively whether possible radiation-induced effects impair diagnostic accuracy of imaging, and to investigate the prevalence of residual ipsilateral and synchronous contralateral breast cancer in patients undergoing radiation therapy after resection of a supposedly solitary breast cancer. MATERIALS AND METHODS: A total of 116 dynamic bilateral breast MR studies were performed during and up to 12 months after radiation therapy in 72 patients who had undergone breast-conservation surgery without preoperative MR imaging. Patients were assigned to four groups according to the time span between imaging and radiation therapy. Structural changes, parenchymal enhancement pattern, and prevalence and imaging features of incidental lesions were analyzed and compared with those of the nonirradiated breast. RESULTS: Radiation therapy led to parenchymal edema and a significant (two-tailed paired Student t test) increase in enhancement rates in the irradiated compared with those in the contralateral breasts during and up to 3 months after radiation therapy. Neither during nor at any time after radiation therapy did the mean enhancement rates reach diagnostically relevant rates. Unsuspected residual or recurrent breast cancers were identified in irradiated breasts of five patients and in contralateral breasts of two patients. False-positive MR findings resulted in a biopsy in three patients with irradiated and in one patient with nonirradiated breasts. There was no difference in enhancement kinetics or morphology of benign or malignant lesions in irradiated versus nonirradiated breasts. CONCLUSION: Radiation-induced changes occur at MR imaging during or up to 3 months after radiation therapy but are much less severe than reported. Detection and characterization of lesions were feasible with comparable diagnostic accuracies in irradiated and nonirradiated breasts.     

Decreasing rate of fatty involution at screening mammography

RATIONALE AND OBJECTIVES: This study was performed to document the perceived decrease in fatty involution at screening mammography during the past decade and evaluate the influence of hormone replacement therapy (HRT). MATERIALS AND METHODS: In December 1996, the mammograms of 261 consecutive screening patients with a comparison study obtained 5 years earlier were evaluated, and their breasts were categorized according to Breast Imaging Reporting and Data System categories for breast density. The women, aged 50-59 years, included 119 who had been receiving HRT for 0.25-15 years (mean, 3 years). From the files, 261 age-matched screening mammograms from 1986 were obtained; these patients also had comparison mammograms from 1981. Analysis of variance was used to determine differences between the 1980s group, the 1990s group receiving HRT, and the 1990s group not receiving HRT. Scheffé tests were used for post hoc comparisons. Stepwise regression analysis was used to evaluate the relative influence of age, decade, score of the first mammogram, and HRT. RESULTS: Breast density for the 1991 mammograms did not differ significantly from that in 1981 (P < .05). Initial breast density was the best predictor of final breast density in both decades (P < .001), regardless of HRT status. The change in breast density (toward fatty) over the 5-year interval in the 1980s (mean, 0.48) was significantly greater than that in both 1990s groups (mean for HRT group, 0.11; no HRT, 0.30; P < .05). CONCLUSION: These results confirm that breast density at screening mammography in the 1990s did not decrease with age at the same rate as in the 1980s, even in patients not receiving HRT.     

Mammographic detection of breast cancer in women under the age of 35

There have been few studies of the radiographic findings of breast cancer in young women. We report our series of 42 cancers in 39 women under the age of 35 who had a mammogram prior to biopsy. Abnormal findings were present on 86% of the mammograms with 94% of the abnormalities classified as high or intermediate suspicion. Mammographic findings were: mass in 50%, calcifications in 31%, diffuse inflammatory changes in 11%, and an asymmetric density in 8%. Six of the mammograms were normal. While young women are usually expected to have dense breasts, 23 mammograms showed either entirely fatty or mixed fatty/glandular tissue. Dense parenchyma infrequently obscured a palpable malignancy. We conclude that mammography can provide important diagnostic information in young women with breast cancer.     

Assessing breast tissue density by transillumination breast spectroscopy (TIBS): an intermediate indicator of cancer risk

Risk assessment by parenchymal density pattern, a strong physical indicator of future breast cancer risk, is available with the onset of mammographic screening programmes. However, due to the use of ionizing radiation, mammography is not recommended for use in younger women, thereby rendering risk assessment unattainable at an earlier age. Visible and near infrared light was used on 292 women with radiologically normal mammograms to determine whether transillumination breast spectroscopy (TIBS) can identify women with a high parenchymal density pattern as an intermediate indicator of breast cancer risk. Principal component analysis (PCA) was used to reduce the spectral data and generate density scores for each woman. To assess the accuracy of TIBS, logistic regression was used to calculate crude and adjusted odds ratios (OR) and 95% confidence intervals (CI) for each score. Receiver operator characteristic (ROC) curves and area under the curve (AUC) were also calculated for the crude and adjusted logistic models. Optical information relating to tissue chromophores, such as water, lipid and haemoglobin content, was sufficient to identify women with high parenchymal density. The resulting AUC for the final and most parsimonious multivariate logistic model was 0.922 (95% CI 0.878-0.967). TIBS provides information correlating to high parenchymal density and is a promising tool for risk assessment, particularly for younger women.     

The visibility of cancer on previous mammograms in retrospective review

AIM: To study how many tumours were visible in restrospect on mammograms originally reported as normal or benign in patients coming to surgery with proven breast cancer. The effect of making the pre--operative mammogram available was also assessed. MATERIALS AND METHODS: Three hundred and twenty initial mammograms of consecutive new breast cancer cases were analysed by a group of radiologists in the knowledge that all patients were later diagnosed with breast cancer. The films were read twice, first without and then with the later (pre-operative) mammograms available. The parenchymal density in the location of the tumour was classified as fatty, mixed or dense, and the tumours were classified as visible or not visible. The reasons for the invisibility of the tumour in the earlier examination were analysed. RESULTS: Fourteen per cent (45) of cancers were retrospectively visible in earlier mammograms without the pre-operative mammograms having been shown, and 29% (95) when pre-operative mammograms were shown. Breast parenchymal density decreased with age and the visibility of tumours increased with age. When considered simultaneously, the effect of age (over 55 vs under 55) was greater (OR = 2.9) than the effect of density (fatty vs others) (OR = 1.5). The most common reasons for non-detection were that the lesion was overlooked (55%), diagnosed as benign (33%) or was visible only in one projection (26%). Growing density was the most common (37%) feature of those lesions originally overlooked or regarded as benign. CONCLUSIONS: Tumours are commonly visible in retrospect, but few of them exhibit specific signs of cancer, and are recognized only if they grow or otherwise change. It is not possible to differentiate most of them from normal parenchymal densities. Saarenmaa, I. (2001). Clinical Radiology56, 40-43.     

Mammographic parenchymal patterns as risk indicators for incident cancer in a screening program: an extended analysis.

In a screening program of self-referred women, different mammographic parenchymal patterns were related to significantly different rates for developing breast cancer. The risk of cancer detection subsequent to a negative mammographic examination was 7.6 times greater for women in the highest parenchymal risk class compared with the lowest, an increase in risk comparable to that of a personal history of breast cancer and greater than that reported for any other combination of historical risk factors. These differences are qualitatively similar to, but of a lesser magnitude than, those in previous reports which were based on symptomatic women with previous negative mammograms. Data suggest this difference in risk is inherent between parenchymal patterns, rather than indicating difficulty in identifying small cancers in dense breasts. Findings of differential parenchymal risk, coupled with other risk factors, may lead to concentrating mammographic screening on a smaller segment of the population, thus improving the benefit-to-cost ratio.     

Analysis of optical density and contrast in mammograms

The objective of this project is the development of tools for the UK NHSBSP to assess image quality quantitatively in clinical films, for the purposes of optimizing imaging procedures and audit. As an initial step, 120 mammograms of 46 women on a single day of screening were digitized and analysed to produce indices of optical density (OD) and contrast. Analysis was performed on three regions of interest (ROI): pectoral muscle, main breast and skin edge. Two radiologists independently graded the quality of information in the different parts of each mammogram, and categorized breast type as either "dense", "mixed density" or "fatty". Measurements of contrast and OD generally correlated well with the opinions of the radiologists. For the oblique mammograms, the mean OD in the main breast ranged between films from 1.25 to 2.24 with a mean of 1.69 +/- 0.02. In the craniocaudal mammograms, the mean OD in the main breast ROI ranged from 1.14 to 1.94 with a mean of 1.61 +/- 0.05. The OD for a quality control film of a 40 mm block of PMMA exposed on the same day with this system was 1.53. A contrast index (CI) was calculated for each mammogram as the difference between the points of maximum and minimum OD in the main breast. Mean CI was 1.02 +/- 0.09 for fatty breasts, 1.50 +/- 0.10 for mixed density breasts and 2.05 +/- 0.23 for dense breasts. A review of the radiologist assessments indicated that the main breast was satisfactorily displayed when glandular and fatty tissues were displayed within the OD range 0.8-2.9. An analysis of the dynamic range requirements showed that 17% of films had a dynamic range that lay above that calculated using the suggested OD limits.     

Breast cancer in women 35 years old or younger: clinical and mammographic features

The purpose of our work was to describe the clinical and mammographic patterns of breast cancer in women aged 35 years old or less. From 1980 to 1985, 92 women 35 years old or younger were treated in our institution for breast cancer. Their mammograms were reviewed to determine the breast density and to describe the mammographic lesion. The clinical examination found a palpable breast mass (n = 84), nipple discharge (n = 2), axillary lymph node involvement (n = 3), metastasis (n = 1) or was normal (n = 2). The mammograms exhibited dense (n = 59), mixed dense/fatty (n = 29) or fatty (n = 4) parenchymal breast. The mammograms showed opacity with well-defined (n = 13) or ill-defined borders (n = 34), spiculated opacity (n = 11), architectural distortion (n = 9), isolated clusters of microcalcifications (n = 13) or were normal (n = 18). The diagnosis of breast cancer in young womensis difficult, because mammographic accuracy is less reliable and benign disease is far more prevalent.     

Significance of follow-up mammography in estimating the effect of tamoxifen in breast cancer patients who have undergone surgery.

OBJECTIVE: We evaluated mammographic changes to assess the effect of tamoxifen in breast cancer patients who had undergone surgery. MATERIALS AND METHODS: We reviewed the mammograms of 102 breast cancer patients treated with tamoxifen (20 mg per day); these patients were subgrouped into tamoxifen-only patients and patients treated with tamoxifen in combination with another therapy (chemotherapy, radiotherapy, or both). The control group was made up of 50 breast cancer patients who did not undergo tamoxifen therapy and 20 healthy women who had an age distribution and menstruation status similar to those of the breast cancer patients. Two radiologists evaluated parenchymal patterns on mammograms of the contralateral breast in the breast cancer patients and of the left breast in the healthy women. Parenchymal changes before and after surgery were also analyzed. RESULTS: Follow-up mammography showed decreased breast parenchyma in 59.8% of the tamoxifen group, 87.0% of the premenopausal tamoxifen-treated women, 36.0% of the nontamoxifen patients, and 10.0% of the healthy women. CONCLUSION: On follow-up mammography of breast cancer patients, breast parenchyma was shown to be decreased after tamoxifen therapy. Mammography can be a useful method for evaluating breast parenchymal changes after tamoxifen treatment.     

Breast Density Knowledge in a Screening Mammography Population Exposed to Density Notification

ObjectiveWomen are increasingly informed about their breast density due to state density reporting laws. However, accuracy of personal breast density knowledge remains unclear. We compared self-reported with clinically assessed breast density and assessed knowledge of density implications and feelings about future screening.MethodsFrom December 2017 to January 2020, we surveyed women aged 40 to 74 years without prior breast cancer, with a normal screening mammogram in the prior year, and ≥1 recorded breast density measures in four Breast Cancer Surveillance Consortium registries with density reporting laws. We measured agreement between self-reported and BI-RADS breast density categorized as “ever-dense” if heterogeneously or extremely dense within the past 5 years or “never-dense” otherwise, knowledge of dense breast implications, and feelings about future screening.ResultsSurvey participation was 28% (1,528 of 5,408), and 59% (896 of 1,528) of participants had ever-dense breasts. Concordance between self-report versus clinical density was 76% (677 of 896) among women with ever-dense breasts and 14% (89 of 632) among women with never-dense breasts, and 34% (217 of 632) with never-dense breasts reported being told they had dense breasts. Desire for supplemental screening was more frequent among those who reported having dense breasts 29% (256 of 893) or asked to imagine having dense breasts 30% (152 of 513) versus those reporting nondense breasts 15% (15 of 102) (P = .003, P = .002, respectively). Women with never-dense breasts had 6.3-fold higher odds (95% confidence interval:3.39-11.80) of accurate knowledge in states reporting density to all compared to states reporting only to women with dense breasts.DiscussionStandardized communications of breast density results to all women may increase density knowledge and are needed to support informed screening decisions.