Edward Azavedo

Guideline Implementation for Breast Healthcare in Low-Income and Middle-Income Countries Overview of the Breast Health Global Initiative Global Summit 2007

Breast cancer outcomes in low‐ and middle‐income countries (LMCs) correlate with the degree to which 1) cancers are detected at early stages, 2) newly detected cancers can be diagnosed correctly, and 3) appropriately selected multimodality treatment can be provided properly in a timely fashion. The Breast Health Global Initiative (BHGI) invited international experts to review and revise previously developed BHGI resource‐stratified guideline tables for early detection, diagnosis, treatment, and healthcare systems. Focus groups addressed specific issues in breast pathology, radiation therapy, and management of locally advanced disease. Process metrics were developed based on the priorities established in the guideline stratification. The groups indicated that cancer prevention through health behavior modification could influence breast cancer incidence in LMCs. Diagnosing breast cancer at earlier stages will reduce breast cancer mortality. Programs to promote breast self‐awareness and clinical breast examination and resource‐adapted mammographic screening are important early detection steps. Breast imaging, initially with ultrasound and, at higher resource levels with diagnostic mammography, improves preoperative diagnostic assessment and permits image‐guided needle sampling. Multimodality therapy includes surgery, radiation, and systemic therapies. Government intervention is needed to address drug‐delivery problems relating to high cost and poor access. Guideline dissemination and implementation research plays a crucial role in improving care. Adaptation of technology is needed in LMCs, especially for breast imaging, pathology, radiation therapy, and systemic treatment. Curricula for education and training in LMCs should be developed, applied, and studied in LMC‐based learning laboratories to aid information transfer of evidence‐based BHGI guidelines. Cancer 2008;113(8 suppl):2221–43. Published 2008 by the American Cancer Society.

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.

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.

The General Mammography Screening Program in Stockholm: Organisation and first-round results

This presentation describes the organization and first-round results of the Stockholm mass mammography screening program, and discusses ways of checking the quality of an ongoing screening program. The Stockholm mammography screening program started in 1989 at five independent screening units, and comprises more than 150,000 women aged 50 to 69 years. The first round was completed in June 1991. Compliance during the studied period was 70.6%, and the recall rate was 3.0% of the attending women. Breast cancer was diagnosed in 676 women, of whom 90 (13.3%) had a cancer in situ. The cancer prevalence rate was thus 6.3 cancers per 1,000 screened women. Surgery was performed on 925 women, of whom 249 had benign lesions, giving a benign/malignant ratio of 0.37 to 1. Fifty-two per cent of the cancer patients were operated with breast conserving surgery. The median size of the invasive cancers was 12 mm; almost 80% were node-negative. Experience from the first two years of this mass mammography screening program shows that it meets the major quality requirements. One of the main future goals is to maintain the high quality of the program. Another important goal is a further increase in compliance.

Nuclear DNA content and behavior of oxyphil thyroid tumors

Microspectrophotometric measurement of nuclear DNA content was made on archival smears of fine‐needle aspirates from 23 oxyphil thyroid neoplasms. Fourteen tumors were considered benign as judged from the histologic picture as well as follow‐up for 7 to 18 years after the operation. Nine tumors were malignant; five of these showed capsular penetration and/or blood vessel invasion as the only signs of malignancy, whereas the remaining four in addition had histologically verified metastases and were the cause of death. The DNA patterns found—diploid, polyploid or aneuploid—appeared to have a limited diagnostic value, since malignancy could not be excluded on this basis. A practically useful finding was, however, that aneuploidy appeared to be associated with a high probability of invasive growth. As regards prognostic information, it was found that euploid patterns occurred in tumors from patients with long survival after surgical treatment, while tumors with aneuploid patterns showed a variable clinical course. Cancer 58:672‐675, 1986.

Guideline Implementation for Breast Healthcare in Low- and Middle-Income Countries Breast Healthcare Program Resource Allocation

Breast cancer is serious public health problem in countries of all resource levels. Although major advances in the detection and treatment of the disease have occurred in higher income settings, similar progress has been slow or scarce in most low‐ and middle‐income countries (LMCs). The poorer outcomes in LMCs may relate to the limited capability of their healthcare systems (HCS) to provide successful early detection, diagnosis, and treatment of breast cancer. Impediments to better outcomes include insufficient numbers of appropriately trained healthcare workers, limited access to screening/treatment facilities, inadequate supplies of necessary drugs, and timeliness of treatment after diagnosis. Clearly, these HCS deficiencies are broader than the scope of the Breast Health Global Initiative (BHGI) and are not unique to the issue of breast cancer. To address issues in HCS that hinder the delivery of breast health services, the BHGI Healthcare Systems and Public Policy Panel explored the HCS structures and function needed to operate a breast care program (BCP). Like with all BHGI guidelines, those proposed by this panel were expressed in terms of 4 strata of resource levels: basic, limited, enhanced, and maximal. The current report describes the issues and questions related to HCS that are important to consider when designing, implementing, and measuring the performance of a BCP. Health ministers, other policymakers, healthcare personnel, administrators, and anyone else involved in developing a BCP can use and adapt this framework to improve outcomes and ensure the more effective use of resources. Cancer 2008;113(8 suppl):2282–96.

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 2.5u2009mg, estradiol 2u2009mg/norethisterone acetate 1u2009mg (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 1.0–1.1u2009nmol/l, were increased to 44.7u2009nmol/l by E2/NETA and to only 1.7u2009nmol/l by tibolone (pu200a<u200a0.001). 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.

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

Objectiveu2003To analyze the expression of Syndecan-1 in dense and non-dense human breast tissue. Methodsu2003Specimens 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. Resultsu2003The 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. Conclusionu2003An increase of Syndecan-1 in all tissue compartments and a redistribution from epithelium to stroma may be a characteristic feature for dense breast tissue.

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 non- palpable 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.

Autologous Fat Transplantation to the Reconstructed Breast Does not Hinder Assessment of Mammography and Ultrasound: A Cohort Study

BackgroundAutologous fat transplantation (AFT) to the breast can correct defects and be a part of a breast reconstruction to achieve a better aesthetic result. The impact of AFT on the radiological evaluation and detection of cancer remains unclarified. The aim of this study is to investigate whether AFT induces lasting modifications.MethodsIn the present study, a valuation was performed of 44 breasts from 37 patients examined with mammography and ultrasound before and after autologous fat transplantation. Breast radiologists evaluated the images using a study specific protocol.ResultsAFT did not hinder post-operative assessment of mammograms or ultrasound. No detectable changes with serious clinical impact were found after injections of mean 177xa0ml (34–516) of fat in one to four sessions. The rate of oil cysts was significantly higher after AFT than pre-operatively (2.3 vs. 34.1xa0% pxa0=xa00.0013). Significantly more post-operative oil cysts were detected after injection of larger volumes of fat (144 vs. 243xa0ml, pxa0=xa00.013). No significant differences were found in the post-operative images regarding age at surgery, follow-up time, or time from previous breast surgery.ConclusionAFT does not impair assessment of mammograms and ultrasound in patients who have a history of breast cancer surgery or prophylactic mastectomy.