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Opportunities to study the natural history of ductal carcinoma in situ are rare. A few studies of incompletely excised lesions in the premammographic era, retrospectively recognized as ductal carcinoma in situ , have demonstrated a proclivity for local recurrence in the original site. The authors report a follow-up study of 45 women with low-grade ductal carcinoma in situ treated by biopsy only, recognized retrospectively during a larger review of surgical pathology diagnoses and original histological slides for 26 539 consecutive breast biopsies performed at Vanderbilt, Baptist and St Thomas Hospitals in Nashville, TN from 1950 to 1989. Long-term follow-up was previously reported on 28 of these women. Sixteen women (36%) developed invasive breast carcinoma, all in the same breast and quadrant as their incident ductal carcinoma in situ . Eleven invasive breast carcinomas were diagnosed within 10 years of the ductal carcinoma in situ biopsy. Subsequent cases were diagnosed at 12, 23, 25, 29 and 42 years. Seven women, including one who developed invasive breast cancer 29 years after her ductal carcinoma in situ biopsy, developed distant metastasis, resulting in death 1–7 years postdiagnosis of invasive breast carcinoma. The natural history of low-grade ductal carcinoma in situ may extend more than four decades, with invasive breast cancer developing at the same site as the index lesion. This protracted natural history differs markedly from that of patients with high-grade ductal carcinoma in situ or any completely delimited ductal carcinoma in situ excised to negative margins. This study reaffirms the importance of complete margin evaluation in women treated with breast conservation for ductal carcinoma in situ as well as balancing recurrence risk with possible treatment-related morbidity for older women.

The aim of this professional Doctor of Creative Industries (DCI) Research Project was to investigate music-making practice and self as a practitioner in the process of creating and producing a DIY music artefact, specifically to investigate why I as the practitioner felt an authentic connection with one form of music-making (acoustic instrument-based) and not a connection with another form of music-making (digital virtual-based). As a phenomenologist, I situated self into this auto-ethnographic study in the dual roles of researcher and practitioner, developing first-person narratives of my personal journey, critical reflection, and reflexive practice. The holistic and multidimensional nature of this research has provided rich and nuanced data, illuminating the co-constituted nature of self, interpreting meaning, and practice. In particular, the research study contextualizes contemporary DIY creative practice relative to three interdependent tenets: Music & Sound-making practice, meaning-making, and self-making, where these tenets are understood in terms of hybridity, agency, and subjectivity. The emergent cultural production artefact exemplifies a broader interpretation of Music & Sound-making practice: an authentic, subjective, auto-ethnographic Music & Soundscape.

Micropapillomas/papillomas and complex sclerosing lesions of the breast have been associated with a slightly increased risk for subsequent carcinoma, although benign squamous metaplasia and reactive hypercellular stroma are seen within these lesions. There are few reports of these fibrosclerotic lesions associated with metaplastic tumors. Here we describe a series of metaplastic tumors arising within fibrosclerotic breast lesions. Thirty-three metaplastic tumors associated with fibrosclerotic lesions were selected from a breast pathology consultative practice. Relevant clinical and pathological features were reviewed. Representative sections were evaluated immunohistochemically for expression of cytokeratins, vimentin, and smooth muscle and muscle-specific actins. Both the metaplastic component (spindled and squamous cells) and the glandular elements were graded. The metaplastic tumors arose within papillomas (20 cases), complex sclerosing lesions (7 cases), both papilloma and complex sclerosing lesions (3 cases), and nipple adenoma (3 cases). A majority of the metaplastic tumors showed a dominant spindle cell component with various degrees of atypia, ranging from fibromatosis-like (16 cases) to low-grade (13 cases), intermediate-grade (2 cases), and high-grade (2 cases) fibrosarcoma phenotype. Squamous metaplasia was present in 25 cases, and low-grade glandular elements, in 21 cases. Eleven tumors had a low-grade adenosquamous growth pattern. Ductal carcinoma in situ was present in 7 cases, and invasive mammary carcinoma, in 5 cases. The very low-grade tumors were histologically similar to limited areas of stromal reaction and myofibroblastic proliferation, seen in partially sclerotic micropapillomas/papillomas and complex sclerosing lesions, but usually more cellular. Cytokeratin positivity (13+/13 tested) supports the metaplastic nature of the more plump spindled cells. The spindle cells were also positive for vimentin (8+/8 tested) and smooth muscle (2+/5 tested) and muscle-specific actins (6+/6 tested). Spindle cell metaplastic tumors, from fibromatosis-like to fibrosarcoma, may arise within a variety of fibrosclerotic breast lesions.

Menstrual and reproductive history and postmenopausal hormone use are well-established risk factors for breast cancer. However, previous studies that have assessed these factors in association with risk of benign proliferative epithelial disorders (BPED) of the breast, putative precursors of breast cancer, have yielded inconsistent findings. To investigate these associations, we conducted a cohort study among 68,132 postmenopausal women enrolled in the Women's Health Initiative randomized clinical trials. Women were prospectively followed and those reporting an open surgical biopsy or a core needle biopsy had histological sections obtained for centralized pathology review. Over an average of 7.8 years of follow-up, we identified 1,792 women with BPED of the breast. We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence limits (CLs) for the associations of interest. Menstrual and reproductive histories were not associated with risk of BPED of the breast, overall or by histological subtype. Women who had used postmenopausal hormones for 15 years or more had a two-fold increase in risk of BPED of the breast compared to women who had never used postmenopausal hormones (HR = 2.03 95% CL = 1.73, 2.38) and the increase in risk was observed for both BPED of the breast without atypia and for atypical hyperplasia. Furthermore, the risk of BPED of the breast decreased with time since cessation of use so that there was essentially no increase in risk 5 or more years after ending use (HR for stopping >=5 years earlier = 0.96, 95%CL = 0.79, 1.16; HR for stopping <5 years earlier = 1.32, 95% CL = 1.08,1.61).

Atypical hyperplasia of the breast (AH) is associated with increased risk of subsequent invasive breast cancer, yet little is known about the etiology of AH. Insulin-like growth factor binding protein 2 (IGFBP-2) may contribute to the development of AH due to its proliferative effects on mammary tissue. We conducted a nested case-control study of postmenopausal women enrolled in Women’s Health Initiative-Clinical Trial. Cases were 275 women who developed incident AH during follow-up, individually (1 : 1) matched to controls. Levels of IGFBP-2 were determined from fasting serum collected at baseline. Multivariable conditional logistic regression models were used to estimate odds ratios for the association of IGFBP-2 with risk of AH. Serum IGFBP-2 was associated with a nonsignificant decrease in risk for AH, when comparing the highest quartile to lowest quartile (OR = 0.65; 95% CI = 0.32–1.31). This decrease in risk was most evident when analyses were restricted to nondiabetic, nonusers of hormone therapy (OR = 0.33, 95% CI = 0.13–0.86, ptrend = 0.06) and nondiabetic women who were overweight or obese (OR = 0.43, 95% CI = 0.18–1.03, ptrend = 0.05). Results from this study provide some support for an inverse association between serum IGFBP2 levels and risk of AH, particularly in nondiabetic women who are overweight or obese. Further studies are required to confirm these results.

Clinical decisions about atypical lobular hyperplasia are based on the belief that later invasive breast-cancer risk is equal in both breasts. We aimed to show laterality and subsequent risk implications of invasive breast cancer in women with atypical lobular hyperplasia. We did a retrospective cohort study of 252 women who had undergone 261 benign surgical biopsies that showed atypical lobular hyperplasia from 1950 to 1985, as part of the Nashville Breast Studies. Primary outcomes were development of invasive breast cancer and laterality of cancer compared with side of the biopsied breast. 50 (20%) of 252 women treated by biopsy only developed invasive breast cancer. Relative risk of breast cancer in women with atypical lobular hyperplasia was 3·1 (95% CI 2·3–4·3, p<0·0001). Of these 50 women, the breast with invasive cancer was the same breast diagnosed with atypical lobular hyperplasia (ipsilateral) in 34 (68%) and the contralateral breast in 12 (24%). The ratio of ipsilateral/ contralateral cancers for atypical lobular hyperplasia without other atypical lesions was 17/5. For six women with atypical lobular hyperplasia plus atypical ductal hyperplasia, the ratio was 1/1. Invasive carcinoma after atypical lobular hyperplasia is about three times more likely to arise in the breast diagnosed with atypical lobular hyperplasia than in the opposite breast without these initial findings. Our findings suggest a model of premalignancy for atypical lobular hyperplasia intermediate between a local precursor and a generalised risk for both breasts.

Background. —Under the auspices of the College of American Pathologists, a multidisciplinary group of clinicians, pathologists, and statisticians considered prognostic and predictive factors in breast cancer and stratified them into categories reflecting the strength of published evidence. Materials and Methods. —Factors were ranked according to previously established College of American Pathologists categorical rankings: category I, factors proven to be of prognostic import and useful in clinical patient management; category II, factors that had been extensively studied biologically and clinically, but whose import remains to be validated in statistically robust studies; and category III, all other factors not sufficiently studied to demonstrate their prognostic value. Factors in categories I and II were considered with respect to variations in methods of analysis, interpretation of findings, reporting of data, and statistical evaluation. For each factor, detailed recommendations for improvement were made. Recommendations were based on the following aims: (1) increasing uniformity and completeness of pathologic evaluation of tumor specimens, (2) enhancing the quality of data collected about existing prognostic factors, and (3) improving patient care. Results and Conclusions. —Factors ranked in category I included TNM staging information, histologic grade, histologic type, mitotic figure counts, and hormone receptor status. Category II factors included c- erb B-2 (Her2- neu ), proliferation markers, lymphatic and vascular channel invasion, and p53. Factors in category III included DNA ploidy analysis, microvessel density, epidermal growth factor receptor, transforming growth factor-α, bcl-2, pS2, and cathepsin D. This report constitutes a detailed outline of the findings and recommendations of the consensus conference group, organized according to structural guidelines as defined.

* Background.--Under the auspices of the College of American Pathologists, a multidisciplinary group of clinicians, pathologists, and statisticians considered prognostic and predictive factors in breast cancer and stratified them into categories reflecting the strength of published evidence. (Arch Pathol Lab Med. 2000;124:966-978)