Internal mammary lymph node inclusion in standard tangent breast fields: effects of body habitus.

The purpose of this study was to determine the variability of internal mammary node (IMN) coverage with standard breast tangent fields using surface anatomy as determined by computed tomography (CT) planning for patients treated with either breast-conserving treatment or postmastectomy, and to evaluate the influence of body habitus and shape on IMN coverage with standard tangent fields. This prospective study included consecutive women with breast cancer who underwent either local excision or mastectomy and had standard tangent fields intended to cover the breast plus a margin simulated using surface anatomy. CT planning determined the location of the IMN with respect to the tangent fields designed from surface anatomy. The internal mammary vessels were used as surrogates for the IMNs. CT measurements of the presternal fat thickness and anteroposterior (AP) and transverse skeletal diameters were made to determine their relationship to the inclusion of IMNs within the tangent fields. Only seven patients (14%) had their IMNs completely within the tangent fields. Twenty patients (40%) had partial coverage of their IMNs, and 23 (46%) had their IMNs completely outside the fields. IMN inclusion was inversely correlated with presternal fat thickness. Thoracic skeletal shape was not associated with IMN inclusion. Standard tangent fields generally do not cover the IMNs completely but may cover them at least partially in a majority of patients. The presternal fat thickness is inversely correlated with IMN inclusion in the tangent fields.

Stereotactic core biopsy breast and blood cell by-products: a source of material for molecular genetics research--initial experience.

Stereotactic core biopsy washings and blood drop samples, routinely discarded by-products, provide satisfactory fresh cellular material for flow cytometry and molecular genetics microsatellite polymerase chain reaction (PCR) analysis for detection of loss of DNA alleles (loss of heterozygosity). Cytokeratin-positive (epithelial) cells from the core biopsy washings were sorted by means of flow cytometry prior to PCR analysis. DNA allele loss was detected in benign breast epithelial cells in three (20%) of 15 patients.

Wires should not be used routinely on skin scars for mammograms after breast-conserving surgery.

The accuracy of skin wire markers on surgical incision scars during mammography to locate the primary tumor excision site was prospectively determined for 100 women. The shortest distance between the excision site and skin scar wire on either the craniocaudal or mediolateral oblique projection was 10 mm or greater in 48 per cent of patients and 20 mm or greater in 30 per cent of patients. Wire markers placed on skin incision scars during mammography after breast-conserving surgery are inadequate for the localization of the primary excision site and should not be used routinely.

Mammographic local staging of breast carcinoma: methods and limitations.

Mammographic local staging of invasive carcinoma and DCIS begins during diagnostic mammography before the first biopsy intervention and continues through the wire localization, excision, and pathologic evaluation of the entire extent of the lesion. Better understanding of the limitations of mammographic staging can direct future research and development. For the evaluation of pre-existing or novel local staging techniques for breast carcinoma, outcomes not only include breast cancer overall survival and disease-free survival, but local recurrence after breast conservation treatment as well as the need for re-excision after primary excision.

Postexcision mammography is indicated after resection of ductal carcinoma-in-situ of the breast.

BACKGROUND: The adequacy of excision of ductal carcinoma-in-situ (DCIS) usually is confirmed with specimen mammography and histopathological assessment of specimen margins. Postexcision mammography of the involved breast is used at some centers. The objective of this study was to evaluate the impact of postexcision mammography in DCIS. METHODS: We conducted a retrospective chart review of all patients treated for DCIS at our institution from 1995 to 1998. RESULTS: Sixty-seven patients had postexcision mammography performed. Residual microcalcifications were identified in 16 patients (24%). Further surgery was precluded by precise mammographic-pathological correlation by using sliced-specimen mammography in two patients. Twelve patients had repeat wide excision, and two patients underwent mastectomy. Residual DCIS was identified at re-excision in 9 of 14 patients (64%). The margin status of the initial resection was negative in three of nine patients (33%) and positive or unknown in six of nine patients (67%). CONCLUSIONS: Postexcision mammography is a valuable technique that complements specimen mammography and histopathological margin assessment in confirming that an adequate excision of DCIS has been performed. Postexcision mammography should be performed in all patients with DCIS associated with mammographic calcifications who are treated with breast-conserving therapy.

Mammographic considerations for patients undergoing ancillary surgical procedures in the breast: a need for pre- and postoperative mammograms.

Mammographic evaluation of the pre- and postoperative breast has been primarily emphasized for patients undergoing diagnostic breast biopsies and breast-conserving surgery. There is limited literature addressing ancillary surgical procedures involving breast tissue that may complicate mammographic evaluation of the breasts during breast cancer screening. We present mammographic diagnostic dilemmas after ancillary surgical procedures in the breast. The placement and removal of devices, such as central venous access ports and pacemakers, may result in scarring that may appear suspicious for malignancy on mammography. In addition, the placement of devices can obscure lesions that are being followed mammographically. These cases illustrate the need for the application of a basic principle of breast surgery, that of pre- and postoperative mammography, to ancillary surgery of the breast to allow optimal mammographic evaluation of women who are breast screening candidates.

Use of specimen mammography-guided FNA (fine-needle aspirates) for flow cytometric multiple marker analysis and immunophenotyping in breast cancer.

A pilot study of a novel translational research method to simultaneously assay multiple molecular markers and DNA in fine-needle aspirates (FNA) of mammographically detected breast lesions is described. Specimen mammography-guided 20-gauge FNAs obtained from 86 lesions and 22 areas of normal tissue were analyzed by multiparameter flow cytometry for DNA content, her2/neu, transforming growth factor alpha (TGF alpha), and the epithelial marker cytokeratin (CK) simultaneously. Epithelial cell her2/neu positivity was detected in 12 of 44 (27%) of invasive ductal carcinomas and 3 of 9 (33%) ductal carcinoma in situ (DCIS), 10 of 30 (33%) benign lesions, and 4 of 22 (18%) normal tissue aspirates. All lesions and normal tissue showed a similar positive rate for TGFalpha ranging from 61 to 76%. The CK(+)TGF alpha(-)her2/neu(+) immunophenotype was more frequently positive in aneuploid tumors (22%) than all other lesions (7%) (P < 0.05). Specimen mammography-guided FNAs provide fresh cells for flow cytometric multiple marker analysis and immunophenotyping of clinically occult breast lesions and normal tissue.

Flow cytometric DNA analysis of specimen mammography-guided fine-needle aspirates of ductal carcinoma in situ.

Flow cytometric studies of screening mammography detected ductal carcinoma in situ (DCIS) are limited by the lack of fresh cell samples. We have performed flow cytometric DNA analyses of specimen mammography-guided fine-needle aspirates of 50 consecutive DCIS lesions detected by screening mammography. The comedo histologic subtype had an aneuploidy rate of 39% (9 of 23); noncomedo subtypes had an aneuploidy rate of 19% (5 of 27), p=ns. Noncomedo subtypes were more likely to have low (less than 2.2%) S-phase percentages, 59% (16 of 27) as compared to comedo, 9% (2 of 23), p<0.05. High and intermediate nuclear grade DCIS lesions had an insignificantly greater rate of aneuploidy, 35% (9 of 26) and 33% (4 of 12) respectively, as compared to low nuclear grade lesions, 8% (1 of 12), p=ns. Low and intermediate nuclear grade DCIS lesions had low S-phase percentage rates of 67% and 50% respectively, as compared to the high nuclear grade lesions low S-phase percentage rate, 15%, p=ns. Aneuploidy and lesser rates of low S-phase percentages were significantly associated with necrosis and apoptosis. Our data suggest that flow cytometric DNA analysis of mammographic lesion-specific, fresh cell samples obtained by fine-needle aspiration under specimen mammographic guidance can assess mammography-detected DCIS lesions when gross fresh tissue procurement is not possible.

Down-regulation of gelsolin expression in human breast ductal carcinoma in situ with and without invasion.

Expression of gelsolin, an actin filament regulatory protein, in human breast ductal carcinoma in situ (DCIS) was analyzed by immunohistochemistry using a monoclonal antibody. Formalin-fixed paraffin-embedded tissues from 59 pure DCIS specimens and 33 DCIS specimens with associated invasive components were evaluated for gelsolin reactivity and compared to eight normal breast cases and 76 invasive breast cancers. The proportion of cases exhibiting negative/low expression of gelsolin in the epithelium was as follows -- normal, 0%; pure DCIS, 56%; DCIS associated with invasion, 58% in the DCIS component and 66% in the invasive component; invasive carcinoma, 70%. These data demonstrate that down-regulation of gelsolin expression in breast epithelium frequently parallels progression to malignancy. Testing gelsolin expression (normal vs. negative/low levels) in the DCIS lesions for associations with patient age or any of the following histopathologic parameters revealed no significant (95% probability level) correlations -- tumor size; pathologic (Van Nuys system) grade; nuclear grade; necrosis; presence of histologic calcifications; presence or type of adjacent benign lesions; architectural histologic pattern; and mammographic extent. Gelsolin loss was more commonly associated with mammographic soft tissue lesions as compared to calcified lesions (P = 0.009). A positive trend of borderline significance (P = 0.06) found in the DCIS with invasion group was a correlation between down-regulated gelsolin expression in the DCIS component and size (< versus > or = 15 mm) of the invasive tumor. In conclusion, reduced gelsolin protein is detectable in at least half of breast lesions which have progressed to DCIS. The trend between increasing gelsolin loss and malignant progression from normal epithelium to DCIS to invasive breast cancer (P < 0.0001) suggests additional investigation is needed to determine the potential of altered gelsolin expression as a marker for prognosis and for therapeutic interventions in breast cancer.

Assessing suspected spinal cord compression: a multidisciplinary outcomes analysis of 342 episodes.

The object of this work was to evaluate the assessment and document the outcomes of cancer patients with suspected spinal cord compression (SCC). In a retrospective cohort study of 342 episodes of suspected SCC in cancer patients evaluated by computed tomography (CT) of the spine, a multidisciplinary team of neurologists, radiologists, and oncologists assessed the impact of varying the anatomical criterion for SCC and including new SCC diagnosed shortly after definitive radiographical imaging. We developed a logistic regression model to identify independent clinical predictors of SCC, including the natural history of the underlying cancer as well as neurological and radiological risk factors. Management of suspected SCC infrequently involved neurology consultation (21% of episodes). The frequency of SCC increased more than four-fold when the definition was expanded to include epidural cancer rather than spinal cord displacement only (36% vs. 8%), and 90-day clinical follow-up identified few new lesions not evident on definitive imaging studies. Clinical information about the course of cancer (documentation and duration of metastatic cancer) added independent predictive information to that yielded by neurological assessment and prior imaging studies in a multiple regression model. The a priori predicted risk of SCC, which ranged from 4% to 87% in this study, may vary enough to affect treatment strategies, although our population may have excluded very-low-risk patients. Consistent anatomical definitions of SCC, clinical follow-up of definitive imaging studies and the addition of information on the natural history of cancer to traditional neurological and radiographical evaluation may all improve clinical assessment of suspected SCC in cancer patients.

Flow cytometric DNA analysis of invasive carcinomas detected by screening mammography: use of specimen mammography-guided fine-needle aspirates.

Clinical studies of flow cytometric DNA analysis of breast carcinoma are often limited by the lack of fresh tissue samples from smaller, nonpalpable carcinomas. In addition, most studies measuring DNA in the current literature focus on larger palpable masses that may have less relevance to the smaller, nonpalpable lesions. A prospective study of flow cytometric DNA analysis of in vitro specimen mammography-guided fine-needle aspirates (FNAs) of 103 consecutive nonpalpable invasive carcinomas detected by screening mammography was performed to determine efficacy and explore associations with mammographic and pathological features. For 62 (60%) lesions for which DNA analysis on both FNA and standard tissue incision samples was performed, there was excellent (89%) agreement for ploidy determinations (kappa=0.77) and poor agreement for S-phase percentage determinations (kappa=0.23). Specimen mammography-guided FNA analysis detected aneuploidy in 36% of lesions overall, including 34% of 41 lesions for which standard tissue procurement was not possible. Mammographic microcalcifications had a higher aneuploid rate (14 of 28 lesions, 50%) as compared with soft tissue masses (22 of 75 lesions, 29%), P < 0.01. Lobulated masses with indistinct margins had a higher aneuploid rate (5 of 6 lesions, 83%) as compared with more irregular, spiculated masses (7 of 27 lesions, 26%), P < 0.01. The aneuploidy rate was independent of specific histological diagnosis, lesion size, nuclear grade, or nodal or estrogen receptor status. Flow cytometric DNA analysis of mammographic lesion-specific, fresh, cellular FNA samples obtained under specimen mammographic guidance can assess early invasive carcinomas when gross fresh tissue procurement is not possible. This technique could be incorporated into larger clinical follow-up studies to determine the prognostic significance of flow cytometric DNA analysis for these very early breast carcinomas.

Flow cytometric DNA analyses of benign breast lesions detected by screening mammography.

There is little information regarding flow cytometric DNA analyses of benign breast lesions. This prospective study consists of mammographic and pathological correlation of DNA flow cytometric analyses of specimen mammography-guided fine-needle aspirates (FNAs) of 189 consecutive benign breast lesions and 114 FNAs of adjacent normal tissue as a control. Clinical follow-up was also performed. Aneuploidy was detected in 14 of 189 (7%) benign lesion specimen mammography-guided FNAs and in only 1 of 114 (0.9%) FNAs of adjacent normal tissue (P = 0.01). Aneuploidy was detected in two (33%) benign intramammary lymph nodes compared with four (12%) benign lesions with atypia, one benign lesion (3%) with hyperplasia, four benign lesions (10%) with adenosis, and three (4%) other benign lesions (P = 0.01). There were no significant associations between DNA content and S-phase percentage and patient age, mammographic appearance, or extent. During a median follow-up of 40 months (range, 6-84 months), 2 of 13 (15%) patients with aneuploid benign lesions developed ipsilateral breast carcinoma compared with 5 of 175 (3%) patients with diploid benign lesions (odds ratio, 6.18; 95% confidence interval, 1.08-35.56). Our data suggest that aneuploidy, which is detected in a variety of benign breast lesions, may be associated with a higher risk of development of breast carcinoma. The combined techniques of specimen mammography-guided fine-needle aspiration and flow cytometry provide a practical translational research method for the study of benign breast disease.

Breast stereotactic core biopsy washings: abundant cell samples from clinically occult lesions for flow cytometric DNA analysis.

RATIONALE AND OBJECTIVES: The object of this study was to determine by flow cytometry the cellular and DNA content of the washings of core biopsy samples and needles obtained during stereotactic core biopsies of clinically occult suspicious lesions. METHODS: Fourteen-gauge core multipass biopsy inner-needle saline washings obtained after dislodgment of the tissue core samples (n = 30) and 14-ga mammotomy core biopsy specimen washings (n = 30) were analyzed by flow cytometry. RESULTS: Multipass core biopsy needle washings of 7 malignant and 23 benign lesions yielded a median of 10,584 cells per lesion (range 562-29,019 cells). Mammotomy core biopsy specimen washings of 10 malignant and 20 benign lesions yielded a median of 12,164 cells per lesion (range 1,295-115,150). Forty-four (73%) washings in each technique had more than 5000 cells. Flow cytometric DNA ploidy analysis was possible in 60 (100%) and the S phase percentage determination was possible in 59 (98%) of the washings. Aneuploidy was detected in 53% of malignant lesions and 2% of benign lesions. CONCLUSIONS: Core biopsy specimen or needle washings provide abundant fresh cellular material from clinically occult lesions for DNA analysis by flow cytometry.

Suspected spinal cord compression in breast cancer patients: a multidisciplinary risk assessment.

Breast cancer is the most common cause of metastatic epidural spinal cord compression (SCC) in women, and this condition results in significant neurologic dysfunction and morbidity. Prior studies of patients with suspected SCC did not employ multivariate analysis techniques, often included persons with a wide variety of malignancies, and generally focused on identifying associated neurologic and radiologic features. We therefore conducted a study examining a more comprehensive set of potential clinical risk factors in breast cancer patients with suspected SCC. We retrospectively analysed 123 episodes of suspected SCC among 93 breast cancer patients evaluated by spine computed tomography (CT) scanning. Multiple logistic regression analysis was employed to identify independent predictors of SCC. Clinically significant metastatic epidural cancer was defined as thecal sac compression (TSC), which occurred in 33 episodes (27%). Four independent predictors of TSC were identified and included oncologic features (known bone metastases > or = 2 years, metastatic disease at initial diagnosis) in addition to neurologic and radiologic features (objective weakness, vertebral compression fracture on spine radiograph). These four predictors stratified episodes into subgroups with widely varying risks of TSC, ranging from 12% (0 risk factors) to 85% (> or = 3 risk factors). These results suggest that the evaluation of breast cancer patients with suspected SCC should include clinical information about their disease course in addition to neurologic examination and prior imaging studies. If confirmed, these predictors may help clinicians assess risk in this patient population.

Specimen mammography-guided fine-needle aspirates of mammographically normal fatty and dense benign tissue: analysis of cell number and type.

Specimen mammography-guided 20-gauge fine-needle aspirates (FNA) were obtained from normal dense or fatty tissue. Single aspirates of dense tissue yielded greater cell counts; 74% (32 of 43) had greater than 5,000 cells as compared to 20% (19 of 93) of fatty tissue FNA, p < 0.05. Dense tissue FNA also yielded greater percentages of epithelial cells; 95% (21 of 22) had greater than 50% epithelial cells as compared to 43% (17 of 40) of fatty tissue FNA, p < 0.05. Mammographic guidance toward dense tissue is suggested for clinical studies of risk assessment using FNA of normal breast tissue.

Angiogenesis and dynamic MR imaging gadolinium enhancement of malignant and benign breast lesions.

PURPOSE: To determine whether dynamic magnetic resonance (MR) imaging enhancement parameters are associated with vessel density of malignant and benign breast lesions. MATERIALS AND METHODS: Forty-five patients with 48 breast lesions underwent gadolinium-enhanced spoiled gradient-recalled echo (SPGR) MR imaging followed by excisional biopsy and Factor VIII staining and vessel density measurement in the lesions. RESULTS: The vessel densities were not significantly different in 25 malignant breast lesions as compared to 23 benign breast lesions. Among all 48 lesions, greater MR enhancement showed an association with increased vessel density. Seventy-four percent of all lesions with MRI enhancement amplitude greater or equal to three times post-precontrast ratio had vessel densities greater than the median of 172 as compared to 34% of lesions with enhancement amplitude less than three times, p = 0.02. The rate and washout of MR enhancement showed no significant association with vessel density. CONCLUSION: Although there is an overall significant association between greater MRI enhancement amplitude and vessel density, MRI gadolinium enhancement of breast lesions is not an accurate predictor of vessel density.

Prognostic factors and evaluation of mycosis fungoides and Sézary syndrome.

BACKGROUND: Staging evaluations of patients with mycosis fungoides (MF) and Sézary syndrome (SS) are performed to individualize therapy and to predict survival. OBJECTIVE: Our purpose was to determine the prognostic factors in patients with MF and SS. METHODS: A retrospective study of 101 patients was performed. For inclusion in the study, patients had to have been evaluated for MF or SS within 6 months of the initial definitive histologic diagnosis. The evaluation included physical examination, chest radiograph, peripheral blood smear, lymph node biopsy, bone marrow biopsy, gallium 67 scan, liver-spleen scan and computed tomography (CT) of the chest, abdomen, and pelvis. RESULTS: The type of skin disease present at initial diagnosis was a good prognostic indicator of survival and clinical outcome. Univariate adverse prognostic features included hepatosplenomegaly or adenopathy by CT scan, abnormal liver-spleen scan, abnormal gallium scan, adenopathy, and peripheral blood, bone marrow, and lymph node involvement. Independent prognostic factors in multivariate analysis were the type of skin involvement as well as peripheral blood and visceral involvement. CONCLUSION: Our study confirms previous reports that type of skin and peripheral blood and visceral involvement are important prognostic factors in patients with MF or SS. Our results support the finding that patients with T1 stage disease have an excellent survival outlook and clinical outcome.

Specimen mammography-guided fine-needle aspirates of clinically occult benign and malignant lesions. Analysis of cell number and type.

RATIONALE AND OBJECTIVES: The authors determine the cell counts and percentages of epithelial cells in fine-needle aspirates (FNA) of mammographically detected breast lesions. METHODS: Specimen mammography-guided 20-gauge fine-needle aspirations were performed on 151 consecutive lesions. Cell counts were determined by flow cytometry of 106 consecutive aspirates. Semiquantitative determination of the percentage of epithelial cells was done by cytologic analysis of 151 aspirates. RESULTS: Single FNA cell counts were greater than 1000 for all lesions and greater than 7000 in 57% (31 of 54) of malignant and 35% (18 of 52) of benign lesions, P = 0.02. Fine-needle aspirates of soft tissue abnormalities had more than 7000 cells in 59% (27 of 46) of specimens, compared with 36% (22 of 61) in calcifications, P < 0.05. With the exception of fibroadenomas, the mammographic appearance of benign lesions, lesion size, and patient age had no association with cell counts. Ninety-three percent (76 of 82) of malignant lesion FNA and 80% (55 of 69) of benign lesion FNA had 50% or greater epithelial cells, P < 0.05. CONCLUSIONS: Fine-needle aspiration yields abundant cell counts of predominantly epithelial cells from most types of mammographically detected lesions and should be considered as a source of fresh cell samples for the study of benign and early malignant breast disease.

Cathepsin D and dynamic magnetic resonance imaging gadolinium enhancement in malignant and benign breast lesions.

Our purpose was to determine whether the expression of cathepsin D, a proteolytic enzyme implicated in basement membrane degradation, is associated with dynamic magnetic resonance imaging (MRI) enhancement of breast lesions. Forty-five patients with 48 breast lesions underwent gadolinium-enhanced spoiled gradient recalled echo MRI followed by excisional biopsy and cathepsin D staining and semiquantitative measurement in the lesions. There was no significant difference in cathepsin D staining of 25 malignant and 23 benign breast lesions. A significant association was seen between high cathepsin D staining and positive axillary lymph nodes in invasive carcinomas. Nine of nine (100%) node-positive carcinomas had high cathepsin D, as compared to three of seven (43%) node-negative carcinomas (P = 0.02). No significant associations were observed between cathepsin D staining and MRI enhancement amplitude, rate, or washout. Cathepsin D has no effect upon MRI gadolinium enhancement of malignant and benign breast lesions but is associated with positive axillary lymph nodes in invasive carcinomas.