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.

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 Arriagada's 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 region's relative importance for the development of pulmonary complications. The negative association between sequential chemotherapy and radiological abnormalities should be confirmed in future studies.

Mammographic features, predictors of early ipsilateral breast tumour recurrences?

Mammograms from 69 patients with Stage I/II breast cancer, operated on using breast-conserving surgery between 1987-1990 were blindly re-evaluated in order to predict retrospectively ipsilateral breast tumour recurrences. The study cohort was divided into two groups of 34 and 35 patients. Each group was matched according to age, the time at risk and to presence or absence of an ipsilateral breast tumour recurrence. The mammographic reinterpretation was performed by two radiologists that correctly predicted an ipsilateral breast tumour recurrence in 81%. Mammographic characteristics, such as diffuse microcalcifications, multifocality, solitary densities, especially of stellate type near the nipple and/or spicula in the vicinity of the retroareolar region were more often associated with an ipsilateral breast tumour recurrence. Data from this limited series suggest that certain mammographic features seem to correlate with the ability of the tumour to recur locally. Hence, mammography can play a prognostic role in deciding the treatment of choice in operable breast cancer.

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 observer's 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.

Radiological review of incidence breast cancers.

OBJECTIVES: To examine the rate of incidence cancers detectable on review of previous screening mammograms using two reviewing methods. To compare the results with a previous study of interval cancers using the same reviewing methods. SETTING: Almost 50000 women are regularly invited for service screening at Stockholm Söder Hospital. From 1989 to 1993, 119 women were identified with breast cancer detected at screening and the previous round attendance (incidence cancer). METHODS: Screening mammograms, obtained before detection of the incidence cancers, were reviewed first mixed with other screening images (ratio 1:8) and then non-mixed. Reviewers from the screening unit responsible for the mammograms as well as reviewers from other units interpreted all images by both single and double reading. RESULTS: The proportion detected on retrospective review varied between 5% and 50% depending on the review method used and the number of reviewers included to classify a case as truly identified. Generally more cancers were detected when non-mixed samples of mammograms were reviewed than when mixed samples were reviewed (mean increase 23%) and when interpreted by double reading compared with single reading (mean increase 14%). CONCLUSIONS: In an experimental retrospective set up, fewer incidence cancers were identified in mixed than in non-mixed review. Generally more incidence cancers were identified on review (22%) than previously reported for interval cancers (14%), probably reflecting differences in tumour biology and growth. How many women with potentially visible incidence cancers would have benefited from earlier tumour detection still needs to be evaluated.

Nuclear DNA content, histological grade, and clinical course in patients with nonpalpable mammographically detected breast adenocarcinomas.

Sixty-five consecutive female patients, age 35-83, with nonpalpable breast carcinomas detected by mammography were classified with both morphological and cytochemical malignancy grading. Cytochemically, the tumors were divided into euploid and aneuploid types indicating low and high malignancy potential, respectively. The mean follow-up time in the euploid group was 6.7 years and in the aneuploid group 8.0 years. No significant difference in mortality was observed in the two groups comprising 65% euploid and 35% aneuploid tumors. Our results here indicate that an early detection of breast cancer at a clinically occult and nonpalpable level leads to better prognosis even in patients with aneuploid tumors whose tumors otherwise are considered to be highly malignant.

Radiologic aspects of breast cancers detected through a breast cancer screening program.

Early detection of breast cancer and reduced mortality in women with this disease is today attributed to the widespread use of mammography. High-quality performance is essential in every step of breast cancer screening programs in order to avoid unnecessary anxiety and surgery in the women concerned. This report presents the radiologic aspects of screening cancers. A total of 8370 asymptomatic women aged between 50-69 years were screened with 2-view mammography, of which only 70 (0.84%) were selected for surgery after a thorough work-up. Cancers were verified histologically in 61 women and 9 showed non-malignant histology, giving a cancer detection rate of 7.3 cancers per thousand screened asymptomatic woman. The benign/malignant ratio in the operated cases is thus approximately 1:7. The cancers detected showed all existing types of mammographic features where 77% (47 cases) showed rather typical findings, such as spiculated densities both with and without microcalcifications and with microcalcifications only. The remaining 23% (14 cases) showed parenchymal distortions, asymmetric and well-defined densities, both with and without calcifications. Our results indicate that surgery can be minimized without impairing the breast cancer detection rate. Radiologists in screening programs should be aware that a large proportion of non-palpable breast cancers present in rather unconventional forms. This point is important in order to maintain a high cancer detection rate and thereby justify the widespread use of mammography as a screening tool for breast cancer in asymptomatic women.

Radial scars detected mammographically in a breast cancer screening programme.

Radial scars are getting more and more common since the implementation of mammography as a diagnostic tool in screening women for breast cancer. At the Karolinska Hospital, 18,987 asymptomatic women, between the ages of 50 and 69, were screened for breast cancer by means of mammography during the period August 1989 to May 1991. A total of 735 (3.87%) women were recalled for additional views after initial mammograms and 463 (2.44%) were assessed with the help of cytology. In all 175 (0.92%) women were selected for surgery and 146 (0.77%) had histologically verified cancers. The remaining 29 (0.15%) had non-malignant lesions of which 11 (0.06%) were radial scars. All radial scars were diagnosed on mammograms and later confirmed with histology. The radiologic characteristics were found to be (a) rather thick and long radiating structures accompanied by radiolucent linear structures parallel to some of the spicules, (b) absence of calcifications, (c) radiolucent areas in the central body of the lesion, (d) an average mean size of 6 mm and (e) changing image in different views. Most of the lesions, 73% (8/11), were in moderately dense breasts and there was no specific relation to the right or left breast. A majority of radial scars, 64% (7/11), were found in the upper outer quadrants, 27% (3/11) in the lower outer quadrants and 9% (1/11) in the lower inner quadrant. Literature shows that histology uses many synonyms for radial scars and therefore team work between the radiologists and pathologists is suggested for better conformity of the diagnosis.

Testosterone addition during menopausal hormone therapy: effects on mammographic breast density.

OBJECTIVE: To study the effect on mammographic breast density of testosterone addition during combined estrogen/progestogen therapy in postmenopausal women. METHODS: A prospective, randomized, double-blind, placebo-controlled trial. A total of 99 women were given 2 mg 17beta-estradiol and 1 mg norethisterone acetate in combination with either a testosterone patch (300 mug/24 h) or a placebo patch. Mammographic breast density at baseline and after 6 months was assessed by visual classification scales and by digitized quantification. A standardized questionnaire was used to quantify subjective breast symptoms. RESULTS: Visual classifications showed an increase in mammographic density in 18-30% of the women, with no significant differences between the treatment groups. The mean increase of the area of dense breast during treatment according to digitized assessment was 7.4% in the placebo group and 5.4% in the testosterone group. Breast symptoms showed a positive association with the increase in density (r(s) = 0.34; p < 0.01). Symptoms were most pronounced at 2 months of treatment. Density, both at baseline (r(s) = -0.35; p < 0.01) and change during treatment (r(s) = -0.28; p < 0.01) showed a negative association with free testosterone levels. CONCLUSION: The addition of testosterone does not appear to influence mammographic breast density in women concurrently treated with a common oral estrogen/progestogen regimen for a period of 6 months.

Neutral effect of ultra-low-dose continuous combined estradiol and norethisterone acetate on mammographic breast density.

OBJECTIVE: To compare the effects of two different ultra-low doses of continuous combined hormone therapy and placebo on mammographic breast density in postmenopausal women. METHODS: A subpopulation of 255 postmenopausal women from the CHOICE trial were randomly assigned to 0.5 mg 17beta-estradiol (E2) + 0.25 mg norethisterone acetate (NETA), 0.5 mg E2 + 0.1 mg NETA, or placebo. Women using hormone replacement therapy (HRT) up to 2 months prior to the study were excluded; 154 women fulfilled the inclusion criteria. Mammograms were performed at baseline and after 6 months. Breast density was evaluated by visual classification scales and a computer-assisted digitized technique. RESULTS: No significant differences were detected between the active treatment groups and the placebo group in the digitized quantification. The mean baseline values for density around 20% were unchanged after 6 months. Also, visual classifications showed no increase in breast density in any study group. CONCLUSION: In contrast to currently available bleed-free regimens, the new ultra-low-dose combination of 0.5 mg E2 and 0.1 mg NETA seems to have very little or even a neutral effect on the breast. Both digitized quantification and visual assessment of breast density were unchanged after 6 months. Larger prospective studies should be performed to confirm this new finding.

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 alpha 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.

A stereotaxic technique for preoperative marking of non-palpable breast lesions.

A new method for preoperative marking has been evaluated in 56 non-palpable lesions of the breast. With the aid of a stereotaxic biopsy instrument the lesion is located and an aqueous suspension of carbon particles is injected so as to leave a distinct trail from the lesion out to the skin. This trail gives precise guidance to the site of the lesion, facilitating the removal of a minimum volume of tissue. According to current experience, the carbon does not diffuse into surrounding tissues and therefore the marking can be done well in advance of surgery.

Stereotaxic needle biopsy of non-palpable breast lesions. A clinical and radiologic follow-up.

A stereotaxic instrument has been evolved and is now routinely used for screw needle biopsy of non-palpable lesions of the breast detected at mammary radiography. A follow-up is presented of 323 such lesions which were not excised within 3 months of the initial radiography and biopsy. With a combination of results from radiographic and cytologic examinations of cellular material from stereotaxic biopsy, the incidence of 'false' negative results was less than one per cent. The biopsy method can therefore be recommended for the investigation of non-palpable lesions of the breast revealed at mammary radiography.