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Human epidermal growth factor receptor 2 (HER2) belongs to the ErbB family, a group of four transmembrane glycoproteins with tyrosine kinase activity, all structurally related to epidermal growth factor receptor (EGFR). These tyrosine kinases are involved in the transmission of cellular signals controlling normal cell growth and differentiation. If this transmission goes awry, it can lead to dysregulated growth of the cell. HER2 specifically can be implicated in the pathogenesis of at least eight malignancies. HER2 positivity quickly became a well-characterized indicator of aggressiveness and poor prognosis, with high rates of disease progression and mortality. After realizing the implication of HER2, it first became investigated as a target for treatment in breast cancer, and later expanded to areas of research in other cancer types. To this day, the most therapeutic advancements of anti-HER2 therapy have been in breast cancer; however, there have been strong advancements made in the incorporation of anti-HER2 therapy in other cancer types as well. This comprehensive review dissects HER2 to its core, incorporating the most up to date information. The topics touched upon are discussed in detail and up to 200 published sources from the most highly recognized journals have been integrated. The importance of knowing about HER2 is exemplified by the groundbreaking advancements that have been made, and the change in treatment plans it has brought to the oncological world in the last twenty years. Since its groundbreaking discovery there have been significant breakthroughs in knowledge regarding the actual receptor, the receptors biology, its mechanism of action, and advancements in tests to detect HER2 and significant strides on how to best incorporate targeted treatment. Due to the success of this field thus far, the review concludes by discussing the future of novel anti-HER2 therapy currently in development that everyone should be aware of.

Importance: Patients with breast cancer and comorbid HIV experience higher mortality than other patients with breast cancer., Objective: To compare time to cancer treatment initiation and relative dose intensity (RDI) of neoadjuvant and adjuvant chemotherapy among patients with breast cancer with vs without HIV., Design, Setting, and Participants: A retrospective, matched cohort study enrolled women who received a diagnosis of breast cancer from January 1, 2000, through December 31, 2018. The electronic medical records of 3 urban, academic cancer centers were searched for women with confirmed HIV infection prior to or simultaneous with diagnosis of stage I to III breast cancer. Tumor registry data were used to identify 2 control patients with breast cancer without HIV for each participant with HIV, matching for study site, stage, and year of cancer diagnosis. Statistical analysis was performed from December 2022 to October 2023., Exposure: HIV infection detected before or within 90 days of participants' breast cancer diagnosis., Main Outcomes and Measures: The primary outcome was time to breast cancer treatment initiation, defined as the number of days between cancer diagnosis and first treatment. The secondary outcome was overall RDI for patients who received chemotherapy. These outcomes were compared by HIV status using Cox proportional hazards regression and linear regression modeling, respectively, adjusting for confounding demographic and clinical factors. Exploratory outcomes included instances of anemia, neutropenia, thrombocytopenia, and liver function test result abnormalities during chemotherapy, which were compared using Fisher exact tests., Results: The study enrolled 66 women with comorbid breast cancer and HIV (median age, 51.1 years [IQR, 45.7-58.2 years]) and 132 with breast cancer alone (median age, 53.9 years [IQR, 47.0-62.5 years]). The median time to first cancer treatment was not significantly higher among patients with HIV than those without (48.5 days [IQR, 32.0-67.0 days] vs 42.5 days [IQR, 25.0-59.0 days]; adjusted hazard ratio, 0.78, 95% CI, 0.55-1.12). Among the 36 women with HIV and 62 women without HIV who received chemotherapy, the median overall RDI was lower for those with HIV vs without HIV (0.87 [IQR, 0.74-0.97] vs 0.96 [IQR, 0.88-1.00]; adjusted P = .01). Grade 3 or higher neutropenia during chemotherapy occurred among more women with HIV than those without HIV (13 of 36 [36.1%] vs 5 of 58 [8.6%])., Conclusions and Relevance: This matched cohort study suggests that patients with breast cancer and HIV may have experienced reduced adjuvant chemotherapy RDI, reflecting greater dose reductions, delays, or discontinuation. Strategies for supporting this vulnerable population during chemotherapy treatment are necessary.

Background: Compared to the many uses of DNA-level testing in clinical oncology, development of RNA-based diagnostics has been more limited. An exception to this trend is the growing use of mRNA-based methods in early-stage breast cancer. Although DNA and mRNA are used together in breast cancer research, the distinct contribution of mRNA beyond that of DNA in clinical challenges has not yet been directly assessed. We hypothesize that mRNA harbors prognostically useful information independently of genomic variation. To validate this, we use both genomic mutations and gene expression to predict five-year breast cancer recurrence in an integrated test model. This is accomplished first by comparing the feature importance of DNA and mRNA features in a model trained on both, and second, by evaluating the difference in performance of models trained on DNA and mRNA data separately., Results: We find that models trained on DNA and mRNA data give more weight to mRNA features than to DNA features, and models trained only on mRNA outperform models trained on DNA alone., Conclusions: The evaluation process presented here may serve as a framework for the interpretation of the relative contribution of individual molecular markers. It also suggests that mRNA has a distinct contribution in a diagnostic setting, beyond and independently of DNA mutation data.

Background: Numerous publications attempt to predict cancer survival outcome from gene expression data using machine-learning methods. A direct comparison of these works is challenging for the following reasons: (1) inconsistent measures used to evaluate the performance of different models, and (2) incomplete specification of critical stages in the process of knowledge discovery. There is a need for a platform that would allow researchers to replicate previous works and to test the impact of changes in the knowledge discovery process on the accuracy of the induced models., Results: We developed the PCM-SABRE platform, which supports the entire knowledge discovery process for cancer outcome analysis. PCM-SABRE was developed using KNIME. By using PCM-SABRE to reproduce the results of previously published works on breast cancer survival, we define a baseline for evaluating future attempts to predict cancer outcome with machine learning. We used PCM-SABRE to replicate previous work that describe predictive models of breast cancer recurrence, and tested the performance of all possible combinations of feature selection methods and data mining algorithms that was used in either of the works. We reconstructed the work of Chou et al. observing similar trends - superior performance of Probabilistic Neural Network (PNN) and logistic regression (LR) algorithms and inconclusive impact of feature pre-selection with the decision tree algorithm on subsequent analysis., Conclusions: PCM-SABRE is a software tool that provides an intuitive environment for rapid development of predictive models in cancer precision medicine.

Little is known about how alcohol consumption promotes the onset of human breast cancer(s). One hypothesis is that ethanol induces metabolic changes in the tumor microenvironment, which then enhances epithelial tumor growth. To experimentally test this hypothesis, we used a co-culture system consisting of human breast cancer cells (MCF7) and hTERT-immortalized fibroblasts. Here, we show that ethanol treatment (100 mM) promotes ROS production and oxidative stress in cancer-associated fibroblasts, which is sufficient to induce myofibroblastic differentiation. Oxidative stress in stromal fibroblasts also results in the onset of autophagy/mitophagy, driving the induction of ketone body production in the tumor microenvironment. Interestingly, ethanol has just the opposite effect in epithelial cancer cells, where it confers autophagy resistance, elevates mitochondrial biogenesis and induces key enzymes associated with ketone re-utilization (ACAT1/OXCT1). During co-culture, ethanol treatment also converts MCF7 cells from an ER(+) to an ER(-) status, which is thought to be associated with "stemness," more aggressive behavior and a worse prognosis. Thus, ethanol treatment induces ketone production in cancer-associated fibroblasts and ketone re-utilization in epithelial cancer cells, fueling tumor cell growth via oxidative mitochondrial metabolism (OXPHOS). This "two-compartment" metabolic model is consistent with previous historical observations that ethanol is first converted to acetaldehyde (which induces oxidative stress) and then ultimately to acetyl-CoA (a high-energy mitochondrial fuel), or can be used to synthesize ketone bodies. As such, our results provide a novel mechanism by which alcohol consumption could metabolically convert "low-risk" breast cancer patients to "high-risk" status, explaining tumor recurrence or disease progression. Hence, our findings have clear implications for both breast cancer prevention and therapy. Remarkably, our results also show that antioxidants [such as N-acetyl cysteine (NAC)] can effectively reverse or prevent ethanol-induced oxidative stress in cancer-associated fibroblasts, suggesting a novel strategy for cancer prevention. We also show that caveolin-1 and MCT4 protein expression can be effectively used as new biomarkers to monitor oxidative stress induced by ethanol.

Based on the oncogenic role of phosphatidylinositol glycan (PIG) class U in human tumors, we explored the role of two additional subunits of the glycosylphosphatidylinositol (GPI) transamidase complex in human breast cancer. We found that PIG class T (PIG-T) and GPI anchor attachment 1 (GPAA1) were overexpressed in breast cancer cell lines and primary tumors. Forced expression of PIG-T and GPAA1 transformed NIH3T3 cells in vitro and increased tumorigenicity and invasion of these cells in vivo. Suppression of PIG-T expression in breast cancer cell lines led to inhibition of anchorage-independent growth. Moreover, we found that PIG-T and GPAA1 expression levels positively correlated with paxillin phosphorylation in invasive breast cancer cell lines. Furthermore, suppression of PIG-T and GPAA1 expression led to a decrease in paxillin phosphorylation with a concomitant decrease in invasion ability. These results suggest that the GPI transamidase complex is composed of a group of proto-oncogenes that individually or as a group contribute to breast cancer growth. This aberrant growth is mediated, at least partially, by phosphorylation of paxillin, contributing to invasion and progression of breast cancer.

Epithelial-mesenchymal transition (EMT) is increasingly recognized as a mechanism whereby cells in primary noninvasive tumors acquire properties essential for migration and invasion. Microarray analyses of microdissected epithelial cells from bone metastasis revealed a HOXB7 overexpression that was 3-fold higher than in primary breast carcinomas and 18-fold higher compared with normal breast. This led us to investigate the role of HOXB7 in neoplastic transformation of breast cells. Expression of HOXB7 in both MCF10A and Madin-Darby canine kidney (MDCK) epithelial cells resulted in the acquisition of both phenotypic and molecular attributes typical of EMT. Loss of epithelial proteins, claudin 1 and claudin 7, mislocalization of claudin 4 and E-cadherin, and the expression of mesenchymal proteins, vimentin and alpha-smooth muscle actin, were observed. MDCK cells expressing HOXB7 exhibited properties of migration and invasion. Unlike MDCK vector-transfected cells, MDCK-HOXB7 cells formed highly vascularized tumors in mice. MDCK-HOXB7 cells overexpressed basic fibroblast growth factor (bFGF), had more active forms of both Ras and RhoA proteins, and displayed higher levels of phosphorylation of p44 and p42 mitogen-activated protein kinase (MAPK; extracellular signal-regulated kinases 1 and 2). Effects initiated by HOXB7 were reversed by specific inhibitors of FGF receptor and the Ras-MAPK pathways. These data provide support for a function for HOXB7 in promoting tumor invasion through activation of Ras/Rho pathway by up-regulating bFGF, a known transcriptional target of HOXB7. Reversal of these effects by HOXB7-specific siRNA further suggested that these effects were mediated by HOXB7. Thus, HOXB7 overexpression caused EMT in epithelial cells, accompanied by acquisition of aggressive properties of tumorigenicity, migration, and invasion.

Background: Sentinel node biopsy (SNB) for breast cancer has a false-negative rate of approximately 5%. Initial reports of follow-up show lower axillary recurrence rates than expected. We performed axillary ultrasonography to determine whether occult recurrences could be detected., Methods: In a community hospital setting, 289 patients who had SNB for breast cancer in a single surgeon's practice underwent axillary examination by the surgeon followed by axillary ultrasonography by a dedicated breast radiologist. Ultrasonography was performed one time from 4 to 79 months (median, 25 months) after surgery. Five patients with suspicious nodes had ultrasound-guided fine-needle aspiration, and one had a core biopsy., Results: No patient had suspicious nodes on clinical examination. Only six patients had ultrasound findings that warranted intervention. Five patients had benign cytological characteristics, and one had a benign core biopsy result. No evidence of axillary recurrence was found in any patient., Conclusions: Axillary ultrasonography did not detect occult metastases in any patient and is not recommended for routine follow-up after SNB. The lack of ultrasound evidence of metastasis suggests that the recurrence rate is likely to remain low.

Intracellular polyamines are absolutely required for cell proliferation and many tumors have abnormal requirements for polyamines. Therefore, the polyamine metabolic pathway represents a rational target for antineoplastic intervention. A number of polyamine analogues act as potent modulators of cellular polyamine metabolism and exhibit encouraging effects against tumor growth in both cell culture and animal studies. In this study we demonstrate that specific polyamine analogues exhibit differential inhibitory action against growth of human breast cancer MCF-7 cells. Treatment of MCF-7 cells with oligoamine analogues and the symmetrically substituted bis(alkyl)-substituted analogue, BENSpm, produced a G1 cell cycle arrest, while the unsymmetrically substituted bis(alkyl)-substituted analogue, CHENSpm, induced a G2/M cell cycle arrest. All four compounds significantly upregulated p53 and p21 expression in MCF-7 cells. Stable transfection of small interfering RNA (siRNA) targeting p53 blocked the expression of p21 induced by the polyamine analogues and significantly reduced polyamine analogue-induced growth inhibition and apoptosis, suggesting that polyamine analogue-induced p21 expression occurs through p53-dependent mechanisms. The effects of analogue exposure on cyclins and cyclin dependent kinases varied with the specific agent used. Expression of p53 siRNA reversed only BENSpm-modulated the cell cycle arrest, suggesting that regulation of cell cycle arrest by p53/p21 induced by polyamine analogues occurs through agent-specific mechanisms. Understanding the mechanism of p53-mediated cellular responses to polyamine analogue may help to improve the therapeutic efficacy of polyamine analogues in human breast cancer.

This study was designed to determine if complementary ultrasound (US) imaging and Doppler could decrease the number of biopsies for benign masses. A total of 761 breast masses were sequentially scored on a level of suspicion (LOS) of 1-5, where 1 represented low, and 5 was a high suspicion of malignancy, for mammography, US, and color flow with pulse Doppler (DUS). After biopsy, the results were analyzed using 2 x 2 contingency tables and ROC analysis, for mammography alone and in combination with US and DUS. The addition of US increased the specificity from 51.4% to 66.4% at a prevalence of 31.3% malignancy. ROC analysis showed that the addition of US significantly improved the performance over mammography alone in women < 55 years old (p = 0.049); > 55 years old (p = 0.029); masses < 1 cm (p = 0.016) and masses > 1 cm (p = 0.016). These results show that the addition of US to mammography alone could substantially reduce the number of breast biopsies for benign disease.

Background: The objective of this study was to determine whether the use of ultrasound and percutaneous breast biopsies in patients with screen-detected nonpalpable abnormalities can reduce benign open surgical biopsies of the breast without increasing cost or sacrificing detection of potentially curable breast carcinomas., Method: Using a computerized mammography database and consecutive logs of needle localization procedures and fine- and large core needle biopsies of a single university-based breast imaging practice, the authors determined the breast carcinoma yield and cost of diagnosis over a 14-year period and the changes that occurred over time with the sequential introduction of ultrasound, ultrasound-guided biopsies, and stereotactic biopsies., Results: The overall breast carcinoma yield for needle localization biopsies of nonpalpable lesions increased from 21% in 1984 to 68% in 1998 (P < 0.0001). The yield for nonpalpable masses increased from 21% to 87% (P < 0.0001) over the same period. The selective use of ultrasound alone and percutaneous fine- and large core needle biopsy resulted in a substantial reduction in benign open surgical biopsies. A cost analysis showed a 50% reduction in the average expense of discovering breast carcinoma. The breast carcinomas detected after introduction of these methods were prognostically favorable with 88% measuring 1.5 cm or less in size and 66% measuring less than 1 cm., Conclusions: Selective use of ultrasound and imaging-guided percutaneous biopsies can significantly reduce the number of benign open surgical biopsies generated by mammographic screening. This can result in substantial cost savings without decreasing the sensitivity for detecting small potentially curable lesions.

Purpose: Because of the increasing use of sonography to rule out cancer in women with palpable breast abnormalities, this study was performed to determine the rate of sonographically occult malignancy in this clinical setting., Methods: Women who were recommended for biopsy based on mammographic and/or clinical findings underwent breast sonography. This study retrospectively analyzed the subset of patients with palpable malignant lesions. Lesions were classified as visible or occult on mammography and sonography. Patients without a tissue diagnosis of tumor were excluded., Results: Of 1,346 masses that underwent biopsy or aspiration, 616 lesions were palpable, and of these, 293 were malignant. Sonography detected all 293 palpable malignant lesions (95% confidence interval for sensitivity, 99-100%). Eighteen lesions were mammographically occult. The median lesion size as determined by sonography was 1.8 cm; for the lesions that were mammographically occult, the median size was 1.6 cm. The most common histopathologic diagnosis for both groups of lesions was infiltrating ductal carcinoma., Conclusions: All palpable malignant breast lesions were visible by sonography in patients in whom a biopsy was recommended. However, we caution that until the false-negative rate of sonography for equivocal palpable abnormalities is determined prospectively, sonography cannot be accurately applied to rule out malignancy in this setting., (Copyright 2000 John Wiley & Sons, Inc.)

Objective: Infiltrating lobular carcinoma (ILC), which accounts for 7-10% of all breast malignancies, often poses diagnostic difficulties. The purpose of our study was to correlate the clinical, mammographic, and sonographic findings in each histologic subtype of ILC and to evaluate the sensitivity of sonography in its diagnosis., Materials and Methods: We reviewed 208 cases of invasive lobular carcinoma. In 81 of these tumors, sonography was performed to further examine a mammographically invisible palpable abnormality or a mammographically subtle lesion. A dedicated breast pathologist classified each of these tumors as pure invasive lobular carcinoma or mixed invasive lobular and ductal carcinoma. Pure ILC tumors were further subclassified as one of five histologic subtypes. We retrospectively studied the clinical, mammographic, and sonographic findings in each histologic tumor subtype., Results: The most common sonographic appearance of ILC was a heterogeneous, hypoechoic mass with angular or ill-defined margins and posterior acoustic shadowing, which was seen in 60.5% (49/81) of tumors. Of the remaining 32 tumors, 15% (12/81) showed focal shadowing without a discrete mass, 12% (10/81) appeared as a lobulated, well-circumscribed mass, and 12% (10/81) were sonographically invisible. Although considerable overlap occurred among histologic subtypes, classic ILC tended to present as focal shadowing without a discrete mass; pleomorphic ILC typically was seen as a shadowing mass; and, of all the tumor subtypes, signet, alveolar, and solid ILC were most likely to be revealed on sonography as a lobulated, well-circumscribed mass. In the 81 mammographically subtle or invisible lesions, sonography detected the tumor in 87.7% (71/81). The sensitivity of sonography in tumors smaller than 1 cm was 85.7% (12/14)., Conclusion: High-resolution sonography of the breast is a useful adjunct in the evaluation of ILC, a neoplasm that frequently presents a clinical and mammographic diagnostic challenge.

9-Amino-20(S)-camptothecin (9-AC) is an analog of camptothecin with limited water solubility which has shown significant preclinical activity in a variety of human solid tumor xenografts. A Phase I trial using a soluble formulation of 9-AC, given as a 72-hour continuous infusion, has been completed. Thirty-one patients with resistant cancers received 5-60 micrograms/M2/h at three week intervals. The Maximum Tolerated Dose (MTD) was 45 micrograms/M2/hour. Neutropenia was the dose limiting toxicity, with few significant non-myelosuppressive toxicities. Minor responses were seen in 3/31 patients. Pharmacokinetic studies of 9-AC lactone (closed ring) showed substantial interpatient variability with a predicted half-life of 36 hours. A phase I/II trial of the same formulation of 9-AC is ongoing in refractory leukemia. Stomatitis and diarrhea are the non-myelosuppressive dose limiting toxicities. Evidence of antineoplastic activity has been seen in 3/15 patients. A Phase II trial in previously untreated metastatic breast cancer is also underway. A Phase I trial of a colloidal dispersion formulation, not yet completed, is better tolerated with a MTD > 45 micrograms/M2/h as a 72-hour continuous infusion. Evidence of antineoplastic activity has also been demonstrated.

Purpose: To determine the effect of a selective core biopsy program on the yield at needle-localization biopsy (NLB) of nonpalpable lesions., Materials and Methods: Two hundred consecutive core biopsy samples of the breast were evaluated in an ongoing consecutive series of 1,172 NLB samples., Results: Before implementation of the core biopsy program, the yield at NLB improved from 21% at 100 cases to 35% just before the introduction of core biopsy. After implementation, the yield increased gradually to 55% at 200 cases. The yield in masses increased from 21% at 100 cases to 43% just before the initiation of the core biopsy program and then increased dramatically to 72% at 200 cases. The percentage of small lesions detected did not change with implementation: 88% of invasive cancers measured less than 1.5 cm and 60% measured less than 1 cm in the last 100 cases., Conclusion: Appropriate selection of cases for core biopsy can more than double the yield of cancer in NLB samples without a decrease in the percentage of small cancers detected.

We assessed the association between Wolfe mammographic patterns and breast cancer risk factors among 239 women who attended the Breast Evaluation Unit screening program of the Comprehensive Cancer Center of Alabama, University of Alabama at Birmingham, from November 1984 through April 1986. Evaluation consisted of a breast cancer risk assessment based on a questionnaire concerning commonly accepted breast cancer risk factors, along with a physical breast examination and mammogram. Increased age, weight, and parity were associated with a low-risk pattern; late age at first birth, alcohol consumption, and oral contraceptive use were associated with a high-risk pattern. Our findings support those of previous studies, except for those concerning use of oral contraceptives. Further exploration is needed to ascertain whether the association of oral contraceptive use with high-risk patterns indicates a pathway through which estrogens may increase the risk of breast cancer.

Patient initiation of mammographic screening is one method of increasing compliance with screening mammography guidelines. A low-cost screening project using a mobile van was developed at the University of Alabama at Birmingham. Analysis of the first 2,099 patients revealed that the participants were generally white (92%), more likely to have had a previous mammogram than the norm (33% in this study vs 19% in a 1986 Gallup survey), and relatively high-risk (30% having a breast cancer risk factor). The cancer detection rate was 6.2 per 1,000 women screened, with a biopsy rate of 1.3% and a positive predictive value of 48%. More than half the cancers detected were in situ lesions or invasive carcinomas smaller than 1 cm. Our results suggest that low-cost mobile mammographic screening can operate at appropriate levels of sensitivity and specificity and is well accepted by participants. Such projects require considerable preliminary planning, significant financial and time commitment by the physicians involved, and meticulous follow-up. A mammography management software system was developed to facilitate tracking of patients for routine and diagnostic follow-up studies and rapid communication of results. Although most follow-up studies and biopsies were done in the community, resistance in the medical community was significant and is perhaps the greatest impediment to such screening endeavors.

A case of angiosarcoma of the skin of the breast is described in a woman 7 years after a primary breast carcinoma was treated by means of lumpectomy and irradiation. On mammograms, the angiosarcoma showed redevelopment of skin thickening and increase in breast density. Clinically, the skin showed patchy discoloration. Although there is an established association of angiosarcoma with lymphedema and therapeutic irradiation, there have been few other reports of this rare complication of local therapy for breast carcinoma. Recognition of the mammographic and clinical manifestations may help in the earlier diagnosis of additional cases.

A recent study of risk factors for breast cancer indicated elevated risks of 5.3 and 1.9 times, respectively, for women with biopsy specimens showing atypical hyperplasia (AH) and proliferative disease without atypia. These risks increase to 11 and 3.2 times, respectively, in women who also have a family history of breast cancer. This study reviews lesions detected mammographically in a series of patients with documented risk factors. The pathologic specimens of 100 consecutive localization breast biopsies performed for nonpalpable abnormalities detected mammographically were reviewed and classified according to the criteria of Dupont and Page in order to determine the incidence of AH and proliferative breast disease. The mammographic characteristics and historical risk factors of these women also were correlated. Twenty percent of the biopsy specimens showed carcinomas, 55% of which were noninvasive. AH was found in an additional 10% of the biopsy specimens, whereas proliferative disease without atypia occurred in 21% of the biopsy specimens. Forty-nine percent of the biopsy specimens showed nonproliferative changes. This study demonstrated that mammography, in addition to its ability to detect small nonpalpable cancers, identifies a high percentage (31% in this series) of women with pathologic lesions known to have an elevated risk for subsequent breast cancer. The current impetus for large-scale mammographic screening of asymptomatic women mandates the development of rational therapeutic protocols to accommodate the widening spectrum of high-risk pathologic lesions found in these selected populations.

The sera of patients who suffer from melanoma and mammary carcinoma show higher tyrosinase activity than normal sera. The enzyme tyrosinase oxidizes tyrosine to DOPA and also catalizes the oxidation of DOPA to Melanin. The catalytic oxidation might also occur in tyrosine while it is conjugated to other amino acids in a polypeptide or a protein molecule. It is theorized here that gamma globulins and interferons are vulnerable to this catalytic oxidation which eventually denaturates them and diminishes their immunological properties.

The results of real-time hand-held sonographic breast examinations on 86 patients are presented. The technique is described in detail. Sonography was found to be a useful adjunct to the x-ray mammogram in three groups of patients: (1) patients with dense breasts and localized symptomatology or a suspicious area on x-ray mammogram; (2) patients with nonpalpable abnormalities discovered on x-ray mammogram; and (3) patients with palpable masses considered indeterminate on x-ray mammogram. The examination was also found useful for guiding needle aspiration biopsies, in patients with persistent nipple discharge, and in those with breast prostheses. Advantages of the hand-held real-time technique include supine positioning, the ability to flexibly orient the probe, improved resolution due to higher frequency transducers and the lack of compounding, and the ability to vary the amount of compression to assess tissue compliance and fixation. The disadvantage of decreased resolution in the near field can be overcome by attaching a detachable water-path step-off device to the transducer. Geometric distortion from the pressure of the transducer was not believed to be a problem. Hand-held sonographic technique is useful when attention can be directed to a specific area of the breast. The additional information provided results in fewer equivocal interpretations of the x-ray mammogram; however, it should not be used as a substitute for routine mammography.