Gunilla Svane

STEREOTACTIC FINE-NEEDLE BIOPSY IN 2594 MAMMOGRAPHICALLY DETECTED NON-PALPABLE LESIONS

To assess the accuracy of detection of breast cancers by mammography and stereotactic fine-needle biopsy (SFNB) 2594 mammographically detected non-palpable lesions were sampled. On the basis of combined evaluation by mammography and cytology of these samples, 2005 (77.3%) of the cases were judged as benign lesions without need of surgery and only 1 of these turned out to be a cancer 14 months later. In 567 (21.9%) patients diagnostic and/or therapeutic surgery was done. Breast cancer was confirmed by histopathology in 429 (75.7%) of the patients operated on and a further 60(10.6%) had non-malignant pathological changes (eg, sclerosing adenosis, epitheliosis, fibroadenoma, or papilloma). Thus, surgery was justified in 86.3% (489) of the patients. In addition to the histopathologically verified cancers, another 22 (0.8%) breast cancers were diagnosed by mammography and cytology but these patients were not subjected to surgery for various reasons. A combination of mammography and SFNB offers a procedure of high sensitivity for early diagnosis of breast cancer.

Early response of lung in breast cancer irradiation: radiologic density changes measured by CT and symptomatic radiation pneumonitis☆

PURPOSE To quantify radiologic changes in the lung with CT after radiotherapy (RT) for breast cancer (BC) and to study their association with treatment techniques and symptomatic radiation pneumonitis (RP). METHODS AND MATERIALS CT scans of the lungs were performed before and 4 months after RT in 121 BC patients treated with four different RT techniques. The changes in mean density (MDCs) were analyzed at two lung levels (i.e., the central and apical CT slice). The central CT slice was also analyzed with respect to the MDCs in the anterior third and anterior half of the ipsilateral lung area. In mastectomized patients who received chest wall RT with an en-face electron beam, the maximal depths for a range of isodose curves were measured. The occurrence of mild/moderate symptomatic RP was assessed prospectively 1, 4, and 7 months after RT. Data on covariates with potential confounding effect on RT-induced lung toxicity were also collected prospectively. RESULTS In the entire study population, an association between the MDCs in the anterior third of the central CT slice and treatment technique (p <0.001) and symptomatic RP (p <0.001) was found. Among patients with chest wall treatment consisting of an en-face electron beam, the MDCs of the anterior third of the central CT slice correlated with the 35% isodose curve (16-30 Gy) (p = 0.046) and age (p <0.001). No association between post-RT lung density changes and pre-RT chemotherapy, concurrent tamoxifen intake, or smoking habits was found. Among patients treated with locoregional RT, an association was found between the MDCs in the anterior third of the central CT slice and the incidence of RP. MDCs in the apical CT slice, however, were not associated with RP. CONCLUSION The results imply that short-term post-RT lung density changes and symptomatic RP were associated with RT techniques, total doses as low as 16-30 Gy, and increasing age. Structural changes in the central part of lung appeared to be more important for the development of RP than changes in the apex.

Influence of radiation therapy on the lung-tissue in breast cancer patients: CT-assessed density changes and associated symptoms

The relative electron density of lung tissue was measured from computer tomography (CT) slices in 33 breast cancer patients treated by various techniques of adjuvant radiotherapy. The measurements were made before radiotherapy, 3 months and 9 months after completion of radiation therapy. The changes in lung densities at 3 months and 9 months were compared to radiation induced radiological (CT) findings. In addition, subjective symptoms such as cough and dyspnoea were assessed before and after radiotherapy. It was observed that the mean of the relative electron density of lung tissue varied from 0.25 when the whole lung was considered to 0.17 when only the anterior lateral quarter of the lung was taken into account. In patients with positive radiological (CT) findings the mean lung density of the anterior lateral quarter increased 2.1 times 3 months after radiotherapy and was still increased 1.6 times 6 months later. For those patients without findings, in the CT pictures the corresponding values were 1.2 and 1.1, respectively. The standard deviation of the pixel values within the anterior lateral quarter of the lung increased 3.8 times and 3.2 times at 3 months and 9 months, respectively, in the former group, as opposed to 1.2 and 1.1 in the latter group. Thirteen patients had an increase in either cough or dyspnoea as observed 3 months after completion of radiotherapy. In eleven patients these symptoms persisted 6 months later. No significant correlation was found between radiological findings and subjective symptoms. However, when three different treatment techniques were compared among 29 patients the highest rate of radiological findings was observed in patients in which the largest lung volumes received the target dose. A tendency towards an increased rate of subjective symptoms was also found in this group.

Clinical experience of photon counting breast tomosynthesis: comparison with traditional mammography.

Background In two-dimensional mammography, a well-known problem is over- and underlying tissue which can either obstruct a lesion or create a false-positive result. Tomosynthesis, with an ability to layer the tissue in the image, has the potential to resolve these issues. Purpose To compare the diagnostic quality, sensitivity and specificity of a single tomosynthesis mammography image and a traditional two-view set of two-dimensional mammograms and to assess the comfort of the two techniques. Material and Methods One hundred and forty-four women, mainly chosen because of suspicious features on standard mammograms (76 malignant), had a single tomosynthesis image taken of one breast using a novel photon counting system. On average, the dose of the tomosynthesis images was 0.63 times that of the two-view images and the compression force during the procedure was halved. The resulting images were viewed by two radiologists and assessed both individually and comparing the two techniques. Results In 56% of the cases the radiologists rated the diagnostic quality of the lesion details higher in the tomosynthesis images than in the conventional images (and in 91% equal or higher), which means there is a statistically significant preference for the tomosynthesis technique. This included the calcifications which were rated as having better quality in 41% of the cases. While sensitivity was slightly higher for traditional mammography the specificity was higher for tomosynthesis. However, neither of these two differences was large enough to be statistically significant. Conclusion The overall accuracy of the two techniques was virtually equal despite the radiologists very limited experience with tomosynthesis images and vast experience with two-dimensional mammography. As the diagnostic quality of the lesion details in the tomosynthesis images was valued considerably higher this factor should improve with experience. The patients also favored the tomosynthesis examination, rating the comfort of the procedure as much higher than regular mammography which might affect screening attendance.

Two models for radiological reviewing of interval cancers.

Objectives To compare two different review methods of examining how many of our interval cancers could be regarded as missed cases (overlooked and misinterpreted owing to observers error). Setting A mass screening programme in Stockholm 1989–91, performed at five independent screening units. 107 846 women attended for screening (70.6% of those invited), and 207 women with interval breast cancers were identified. Interval cancers from two of the units, 104 cases, are reviewed in this study. Methods Screening examinations preceding the interval cancer diagnoses were reviewed both mixed with other screening images in a ratio 1:8 and non-mixed. Both internal reviewers (from the two units responsible for the screening mammograms) and external reviewers (from the other units) took part in the study. Results The proportion regarded as missed cases varied between 7% and 34%, depending on what review method was used, and on the number of reviewers included to identify a case as missed. Mixed reviewing reduced the number identified as missed cases by 50% compared with non-mixed reviewing. Whether the reviewer was internal or external made no difference to the results. Conclusions Comparing the rate of missed cases from different studies may be misleading unless the same review method is used. No difference in detection rate could be shown whether the radiologist reviewed images from his/her own screening unit or not. Most of our interval cancers were not regarded as missed cases by either of the two methods.

ABNORMALITIES BY PULMONARY REGIONS STUDIED WITH COMPUTER TOMOGRAPHY FOLLOWING LOCAL OR LOCAL-REGIONAL RADIOTHERAPY FOR BREAST CANCER

PURPOSE To study pulmonary radiological abnormalities with computer tomography (CT) following different radiotherapy (RT) techniques for breast cancer with respect to regions and density, and their correlation to pulmonary complications and reduction in vital capacity (VC). METHODS AND MATERIALS CT scans of the lungs were performed prior to and 4 months following RT in 105 breast cancer patients treated with local or local-regional RT. The radiological abnormalities were analyzed with a CT-adapted modification of a classification system originally proposed by Arriagada, and scored according to increasing density (0-3) and affected lung regions (apical-lateral, central-parahilar, basal-lateral). The highest density grade in each region were added together to form scores ranging from 0-9. The patients were monitored for RT-induced pulmonary complications. VC was measured prior to and 5 months following RT. RESULTS Increasing CT scores were correlated with both local-regional RT and pulmonary complications (p < 0.001). The mean reduction of VC for patients scoring 4-9 (-202 ml) was larger than for patients scoring 0-3 (-2 ml) (p = 0.035). The effect of confounding factors on the radiological scoring was tested in the local-regional RT group. Scores of 4-9 were less frequently seen in the patients who had received adjuvant chemotherapy prior to RT. The importance of the respective lung regions on the outcome of pulmonary complications was tested. Only radiological abnormalities in the central-parahilar and apical-lateral regions were significantly correlated to pulmonary complications. DISCUSSION Radiological abnormalities detected on CT images and scored with a modification of Arriagadas classification system can be used as an objective endpoint for pulmonary side effects in breast cancer. The described model should, however, be expanded with information about the volume of lung affected in each region before definite conclusions can be drawn concerning each regions relative importance for the development of pulmonary complications. The negative association between sequential chemotherapy and radiological abnormalities should be confirmed in future studies.

Different effects of tibolone and continuous combined estrogen plus progestogen hormone therapy on sex hormone binding globulin and free testosterone levels – an association with mammographic density

Objective To compare the effects of tibolone and continuous combined hormone therapy on circulating sex steroids and their binding proteins and their relationship to mammographic density. Study design A prospective, double-blind placebo-controlled study. A total of 166 postmenopausal women were equally randomized to receive tibolone 2.5 mg, estradiol 2 mg/norethisterone acetate 1 mg (E2/NETA) or placebo. Serum analyses of sex steroids, insulin-like growth factor (IGF-I) and binding proteins and assessment of mammographic breast density were performed at baseline and after 6 months of treatment. Results Estrogens were markedly increased and androgens decreased by E2/NETA. In contrast, tibolone had only a minor influence on circulating estrogens. Sex hormone binding globulin (SHBG) levels were reduced by 50%, while levels of androgens increased. Baseline values of estrone sulfate (E1S), around 1.0–1.1 nmol/l, were increased to 44.7 nmol/l by E2/NETA and to only 1.7 nmol/l by tibolone (p < 0.001). Mammographic breast density displayed a negative correlation with age and body mass index and a positive association with SHBG. After 6 months there was also a negative correlation with levels of free testosterone. Conclusion We found that tibolone and E2/NETA caused distinct differences in estrogen/androgen status and blood levels of possible breast mitogens. The negative association between free testosterone and mammographic density could be a possible explanation for tibolone having less influence on the breast.

Reduction of radiation pneumonitis by V20-constraints in breast cancer

IntroductionAdjuvant local-regional radiotherapy (LRRT) is routinely recommended for breast cancer patients. It is well known being related to pulmonary side-effects. We studied post-RT radiological changes on X-ray and CT, and correlated the findings with Quality of Life (QoL), common dosimetric factors and co-variates. The results were compared with a previously reported cohort of 137 irradiated women.Methods88 women underwent chest X-ray and CT pre-and 4-5 months after 3-D planned LRRT, minimizing the dose to the ipsilateral lung to V20 < 30%. The lung field was divided into 3 regions and the development of post-RT density changes were graded (0-3). Patients with radiological changes were compared with non-responders. Clinical symptoms were registered and data on patient and treatment related co-variates were gathered prospectively. The ipsilateral lung dosimetric factors V13, V20, V30 and mean dose were calculated and QoL was assessed before and 4 months after RT.ResultsThe use of dose-volume constraints significally reduced moderate-severe radiological changes on chest X-ray compared with our earlier study (Chi square trend test: p < 0.001). Symptomatic pneumonitis was also rare in the present study. No agreement was found between CT and chest X-ray as diagnostic tools for post-RT pneumonitis. V13 correlated independently with radiological changes on CT (logistic regression: p = 0.04; ROC area: 0.7). The Co-variates smoking habits, age, chemotherapy, endocrine or trastuzumab therapy did not influence the outcome on multivariate analysis. QoL changes in physical function, i.e. fatigue, dyspnoea were not detected but there was a trend for a worse recovery after chemotherapy in patients with high V13 (Spearman Rank Correlation: p < 0.05).ConclusionsThe use of dose-volume constraints significantly reduced post-RT radiological changes on chest X-ray in LRRT for BC. The lung changes on CT were also generally limited when we used this strategy and was not always picked up on chest X-ray. Variation in V13 alone was correlated with occurrence of lung changes on CT.

Radiologic appearance of nonpalpable intramammary lymph nodes

Sixty-four well circumscribed nonpalpable lesions, mammographically evaluated as benign and cytomorphologically verified as lymph nodes, were studied concerning mammographic appearance, size and location within the breast. The great majority, 72%, were situated within the upper-outer quadrant, but lymph nodes were also diagnosed in other areas of the breast. Of the verified lymph nodes 50 (78%) had a lower density at the center than at the periphery. These were the only well circumscribed nodules with a low density center observed in a total of 3 623 nonpalpable lesions stereotaxically needled during the same period. Three of the lymph nodes were verified histopathologically. Till now, none of the other 61 lesions has turned out to be a malignant tumor during a follow-up time from 9 to 15 years. Thus a lesion presenting roentgenologically as a well circumscribed nodule with a central area of decreased density compared to the peripheral part can be confidentially diagnosed as a lymph node by the mammograms alone and no further investigation is indicated.

Expression of syndecan-1 in histologically normal breast tissue from postmenopausal women with breast cancer according to mammographic density

Objective To analyze the expression of Syndecan-1 in dense and non-dense human breast tissue. Methods Specimens of histologically normal tissue were obtained from postmenopausal women undergoing surgery for breast cancer. Each tissue block was subject to radiological examination and pair-wise samples of dense and non-dense tissue were collected. Semi-quantitative assessment of immunohistochemical staining intensity for Syndecan-1 and estrogen receptor subtypes was performed. Results The expression of Syndecan-1 in all tissue compartments was significantly higher in dense than in non-dense specimens. The strongest staining was recorded in stromal tissue. There was a strong correlation between epithelial estrogen receptor α and stromal cell Syndecan-1 expression in dense tissue (rs = 0.7; p = 0.02). This association was absent in non-dense tissue. Conclusion An increase of Syndecan-1 in all tissue compartments and a redistribution from epithelium to stroma may be a characteristic feature for dense breast tissue.