Inflammatory carcinoma of the breast

Eighty-six patients with the clinical features of inflammatory carcinoma of the breast (erythema, peau d'orange, wheals or ridges) were treated with irradiation for potential cure between July 1948 and December 1970. Long protracted irradiation alone with a strong skin reaction offers 50% local control, which is the best rate yet reported. Any surgical procedure beyond biopsy is probably damaging: all patients subjected to mastectomy developed distant metastases and died. Ninety per cent of the patients were dead by five years and only 3 patients remain alive without evidence of disease 7, 10 and 14 years after radiotherapy. Analysis of survival rates, incidence, sites and times of appearance of local recurrences, and distant metastases is presented.     

Radiotherapy in the treatment of breast carcinoma

In the treatment of breast cancer a radiation therapy is indicated under the following conditions: 1. Postoperative irradiation only of the regional lymph-nodes also in stage I (T1, N0). 2. Postoperative irradiation of the regional lymph-nodes and the thorax wall in cases with great primary tumours (T2), in cases with involved axillary lymph-nodes and, of course, in all cases with "grave signs". 3. Preoperative irradiation only in those cases when it seems possible that an inoperable tumour would become operable. 4. As the sole local treatment only in cases with very large inoperable tumours or in special cases (e.g. very high risc or refusal of the operation). 5. As local treatment of a local recidive or of isolated metastases. 6. As supporting local therapy (e.g. threatening fracturation of our fracturated bone metastases; brain metastases) in cases of generalized metastatic disease treated by hormonal or cytostatic therapy.     

Tubulolobular carcinoma of the breast

To assess the adequacy of antihypertensive treatment in the French population, a survey was conducted from October 1990 to April 1991 in five French cities during sales exhibitions. A total of 7107 individuals visited the stand of the French National Committee to have their blood pressure (BP) measured. Among them, 1289 were treated hypertensive subjects fully aware of their treatment. The efficacy of antihypertensive treatment was assessed in this population. Among those hypertensive treated subjects 35 to 65 years old, 60% had a BP < 160/95 mm Hg and 27% < 140/90 mm Hg. Among those > 64 years of age, 44% had a BP < 160/90 mm Hg. In 1992, these results were included in a publication by the World Hypertension League. Data obtained with this new and interesting approach were reviewed 4 years later. The approach is inexpensive (the equivalent of US $28,000) and made it possible to directly inform thousands of people, normotensive and hypertensive, about arterial hypertension and antihypertensive drug therapy, as well as risk factors for cardiovascular disease. This kind of approach may be worth a strict evaluation, to assess whether it is really useful in improving high blood pressure control in the population.     

Ductal carcinoma in situ of the breast

PURPOSE: The increasing incidence and biological heterogeneity of ductal carcinoma in situ (DCIS) of the breast have made the management of this entity challenging and controversial. This paper reviews data on the natural history of the disease and results obtained with various management approaches. DATA SOURCES: Computerized MEDLINE search of articles related to DCIS published since 1966. STUDY SELECTION: Randomized trials were given higher value; however, because these were relatively scarce, retrospective studies and data published in abstract form were also included. DATA EXTRACTION: The authors reviewed all sources critically. No formal statistical calculations were made. DATA SYNTHESIS: The incidence of DCIS is increasing, and a greater proportion of diagnoses are being made in asymptomatic patients. No data from randomized trials compare mastectomy and breast-conserving therapy for the treatment of DCIS. A large randomized trial comparing lumpectomy with lumpectomy plus radiotherapy showed lumpectomy plus radiotherapy to be effective for management of this disease. The presence of comedo necrosis and surgical margin status are frequently used as predictors of subsequent recurrence, although this practice is controversial. The risk for in-breast recurrence at 5 years after lumpectomy and radiotherapy is approximately 8%. With more refined molecular analysis, the relation of DCIS to invasive breast cancer will be better defined. CONCLUSIONS: Treatment strategies for DCIS have evolved, and lumpectomy followed by radiotherapy is an appropriate alternative for most patients. The use of lumpectomy alone in selected patients remains controversial.     

Paget's disease of the breast in a man without underlying breast carcinoma

A case of histologically confirmed Paget's disease of the breast in a 72 year old man, without underlying breast carcinoma, is reported. This report raises questions about the pathogenesis of this condition and suggests that Paget's disease is an independent, intraepidermal carcinoma rather than a direct extension of intraductal carcinoma of the breast to the nipple and areola.     

Invasive micropapillary carcinoma of the breast

Nine examples of a rare variant of invasive breast carcinoma characterized by the formation of micropapillae within clear spaces separated by a fibrocollagenous or delicate fibrovascular stroma are presented. Designated as invasive micropapillary carcinoma, the unusual morphology of this tumor requires its distinction from metastatic ovarian serous papillary carcinoma and extensive vascular/lymphatic invasion by either a primary or metastatic breast carcinoma. The micropapillary pattern is retained in metastatic foci and areas of recurrence. This pattern also occurs admixed with regular infiltrating duct carcinoma either in the primary mammary tumor or when it recurs.     

Clinical problems of the breast carcinoma in situ

The results of diminution mammoplasties are reported. From 1972 to 1974, 70 diminution mammoplasties according to Str?mbeck were carried out. Indication for the operation was hypertrophy of the breasts with side effects of morbid value. In 47 patients side effects of the body posture were the leading indication. In 23 patients, psychosocial problems were the indication. Only patients with side effects of morbid value were considered to be sufficiently motivated to tolerate the total stress of the operation and the possible post-operative complications. The technical problems of the operation and the post-operative complications are described. 43 patients were followed up at least one year after the operation. In 36 patients the pre-operative complaints were alleviated by the operation. In 7 patients there was improvement. No patient had continuing pre-operative complaints. The mentally depressed and physically and psychologically in their relationship to their environment handicapped patients became usually more satisfied by the operation. Diminution mammoplasties are recommended for the operative treatment of hypertrophy of the breast with side effects of morbid value.     

A strong predictor in carcinoma of the breast

A case of sustained lung fistula after lung surgery is reported here. This case of a sustained pulmonary fistula was diagnosed by sustained air leak through the chest drain and a positive culture of the drainage fluid. The third re-operation was performed successfully by omentopexy via median sternotomy. Careful postoperative observation with chest radiography, bronchial fiberscopy, and determining whether infection is present in the drainage fluid are important for precise diagnosis and therapy for complications following pulmonary lobectomy.     

Modern dilemmas in the treatment of breast carcinoma

By means of a detailed analysis of literature data and our own results when available, the paper presents different therapeutic options in the treatment of breast cancer patients that are applied in our country today and the that might be applied in relation to modern knowledge and discoveries in experimental oncology, early detection and diagnostics of breast cancer. It is stressed that the use of this knowledge may result in slightly better rate of survival but the main emphasis is on the quality of life of treated patients and more rational delivery of available therapeutic options.     

Palliative irradiation in the treatment of breast carcinoma

It is considered that in 30% of female patients with breast cancer a certain form of evolutive disease occurs within 5 years from documented diagnosis. In these female patients, 58% develop distal metastases. Thus, a great number of these female patients enter the phase when hope for recovery is small. Then supportive therapy is used. It's main task is to alleviate the life of these patients. Palliative radiotherapy is one of the main elements of this therapy. It is directed to decrease the pain, and bleeding, to prevent fractures and decompression of the spinal cord, as well as many other evolution consequences of local or distal disease. The correct and timely definition of indications for radiotherapy, the optimal planning and conduction of the therapy should take into account the patient's characteristics as well as the main postulates on which radiotherapy is based. In this way the satisfying effects on patients with disseminated breast cancer, may be expected.     

Chemotherapy in metastasized breast carcinoma

Metastatic breast cancer is still an incurable disease. Standard hormonal and chemotherapeutic treatment modalities yield at the best a survival advantage of 1 to 2 years. However, palliation is still the second, very important goal of treatment for metastatic disease. First-line chemotherapeutic treatment with an anthracycline-containing regimen induces a response in about half the patients. In second-line treatment docetaxel is an effective agent even in patients failing first-line therapy with an anthracycline-containing regimen. There is no effective standard third-line chemotherapy scheme.     

Management of ductal carcinoma in situ of the breast

The natural course of primary osteoarthritis of the knee with or without treatment by intraarticular corticosteroid injections was investigated in 446 patients presenting from 1970 to 1973. Sixty-one of these patients were able to be followed up in 1982 and were divided into two groups. One group included 53 patients (82 knees) without corticosteroid injections. The other group had eight patients (14 knees) who received intraarticular steroids (mean number of injections: 25; range:4-78). The standing femorotibial angle at followup in the male patients receiving injections (p < 0.05) was four degrees of greater varus angulation. Radiographic degeneration was more advanced in 11 of the 24 steroid-treated knees (78.6%), and in 43 of the 82 knees without steroid injections (52.4%) (p < 0.01).     

Angiogenesis and inflammation in invasive carcinoma of the breast

Transforming growth factor-beta (TGF-beta) plays an important role in the regulation of extracellular matrix (ECM) deposition by stimulating the synthesis of individual matrix proteins like tenascin and fibronectin. Cholesteatoma shows significant changes in the ECM, supporting the view of a disturbed cell-matrix interaction. The purpose of our present study was to evaluate the distribution of TGF-beta in comparison to the deposition of tenascin, fibronectin, and collagen as major components of the ECM in cholesteatoma (n = 12) by means of histochemistry and immunohistochemistry. We found TGF-beta in lymphocytes and fibrohistiocytes in the stroma of 7 cholesteatomas. In corresponding sections, a marked expression of tenascin and fibronectin was seen manifesting as a continuous band along the epidermal-stromal junction, extending to the deeper stroma. In addition, in those cases of TGF-beta expression, beginning collagen fibril formation was seen in adjacent deeper stroma layers, indicating beginning stromal fibrosis. These results suggest that TGF-beta may be involved in the stimulation of the synthesis of tenascin, fibronectin, and collagen. Furthermore, the enhanced expression of tenascin and fibronectin provides evidence for a deregulated cell-matrix interaction in cholesteatoma associated with the enhanced proliferative process of cholesteatoma formation.     

High dose chemotherapy in metastatic carcinoma of the breast

PURPOSE: To verify tolerance and clinical efficacy of high-dose chemotherapy (HDCT) in metastatic breast cancer (MBC). PATIENTS AND METHODS: We submitted to HDCT with autologous peripheral blood cells transplant 66 patients, with MBC responding to induction chemotherapy. The condizioning regimen was ICE: iphosphamide 3.3 g/m2 dd. -8/-6, carboplatin 450 mg/m2 plus etoposide 400 mg/m2 dd. -5/-3 (21 patients = 78%); CTM: cyclophosphamide 100 mg/kg dd. -4/-3, tyothepa 500 mg:m2 d.-5, mytoxantrone 40 mg/m2 d. -6 (6 patients, 22%). RESULTS: Median number of aphereses was 2 (range 1-5), median amount of CD34+ cells/kg bw of 10 x 10E6 (range 3.5-38.2). Median recovery time was 10th day for PMN (range 8-37) while for platelets it was 9th day (range 8-37): total hospital stay was of 24 days (range 22-48). After induction therapy we had PR in 13/27 metastatic patients (48%) and CR in 14/27 (52%). After conditioning treatment we had PR in 12/27 (44%) and CR in 15/27 (56%). Median time to progression was 19 months (range 7-38) and median survival 52 months (range 7-59+), with 30% surviving beyond 4 years. CONCLUSIONS: Feasibility of HDCT in advanced breast cancer seems verified. The promising results need to be confirmed.     

Second cancers following in situ carcinoma of the breast

Most reports of midbrain infarction have described clinicoanatomical correlations rather than associations and aetiologies. Thirty nine patients with midbrain infarction (9.4%) are described out of a series of 415 patients with vertebrobasilar ischaemic lesions in the New England Medical Center Posterior Circulation Registry. Patients were categorised according to the rostral-caudal extent of infarction. The "proximal" vertebrobasilar territory includes the medulla and posterior inferior cerebellar artery territory. The "middle" territory includes the pons and anterior inferior cerebellar artery territory. The "distal" territory includes the rostral midbrain, thalami, superior cerebellum, and medial temporal and occipital lobes. Midbrain infarction was accompanied by "proximal" territory infarcts in four patients, and by "middle" territory infarction in 19 patients. Thirteen patients had associated "distal" territory infarcts, three of whom had occipital or temporal lobe infarcts. Only three patients had isolated midbrain infarcts. Cardioembolism (n=11), in situ thrombosis (n=9), large artery to artery embolism (n=7), and intrinsic branch penetrator disease (n=5) were the most common aetiologies. Bilateral infarction and accompanying pontine infarction were associated with the most extensive vertebrobasilar occlusive disease. Midbrain infarction was 10-fold more likely to be accompanied by ischaemia of neighbouring structures than it was to occur in isolation. Recognition of the different patterns of infarction may act as a guide to the underlying aetiology and vascular lesions.     

Overexpression of the RON gene in human breast carcinoma

Constitutive activation of the RON gene, known to code for the tyrosine-kinase receptor for Macrophage Stimulating Protein (also known as Scatter Factor 2), has been shown to induce invasive-metastatic phenotype in vitro. As yet, nothing is known about the expression of this novel member of the MET-oncogene family in spontaneously occurring human cancers. Here we report that Ron is expressed at abnormally high levels in about 50% primary breast carcinomas (35/74 patients). Among these, the expression is increased more than 20-fold in 12 cases and the overexpressed protein is constitutively phosphorylated on tyrosine residues. Notably, Ron is only barely detectable in epithelial cells of the mammary gland, and its expression remains unchanged in benign breast lesions (including adenomas and papillomas). Overexpression was observed in different histotypic variants of carcinomas; it is associated with the disease at any stage and correlates with the post-menopausal status. In breast carcinoma cells grown in vitro, activation of the Ron receptor resulted in proliferation, migration and invasion through reconstituted basement membranes. Altogether, these data suggest a role for the RON gene in progression of human breast carcinomas to the invasive-metastatic phenotype.     

Adhesion systems in normal breast and in invasive breast carcinoma

To analyze the role of various elements of the adhesion system in the organization of the normal mammary gland and in breast carcinoma, we have studied simultaneously the expression of integrins, E- and P-cadherins, and cytoplasmic constituents of adherens junctions. In the normal gland, E-cadherin and alpha-catenin are present in luminal epithelial and myoepithelial cells, whereas integrins are more abundant in acinar epithelial and in myoepithelial cells. We demonstrate here that, in addition, myoepithelial cells express much more vinculin and alpha-actinin than luminal epithelial cells, whereas talin and focal adhesion kinase (pp125FAK) are restricted to the basal cell layer. In invasive carcinoma, E-cadherin is usually present although often in reduced amount; different integrin subunits are expressed either by a fraction or by all of the cells or are absent. However, the cytoplasmic components of adherens junctions, such as alpha-catenin, vinculin, alpha-actinin, talin, and pp125FAK, are expressed at low levels or cannot be detected in the carcinoma cells. Our data suggest that 1), in the normal mammary gland, the myoepithelial cells, being particularly rich in integrins and cytoplasmic components of the adherens junctions, play an important role in the maintenance of tissue integrity; 2), in invasive carcinoma, cell aggregates may be maintained due to varying levels of expression of E-cadherin and/or integrins; and 3), interaction of the transmembrane adhesion molecules with the cytoskeleton in carcinoma may be impaired as revealed by reduced levels of expression of alpha-catenin, vinculin, alpha-actinin, talin, and pp125FAK. Importantly, carcinoma cells, when exposed to stroma during invasion, do not acquire the adhesion apparatus characteristic of normal cells in contact with the extracellular matrix.     

Surgical therapy strategies in carcinoma in situ of the breast

The surgical treatment of carcinoma in situ of the breast depends on the histological type. After detecting a lobular carcinoma in situ (CLIS) either an intensive (aftercare) follow-up is recommended or a bilateral mastectomy. The choice for one of these two very different forms of therapy can be done only after intensive psychological dialog with patient. The reason for the different forms of further treatment is the multicentric and often bilateral occurrence of CLIS and the potential risk of developing an invasive cancer. The therapy of the ductal carcinoma in situ (DCIS), which often spread out in a segment of one breast, is the total excision of the lesion with clear margins. The Van Nuys Prognostic Index depending on the histological results (tumor-diameter, thickness of clear margins, pathocytologic classification) indicates further treatment such as radiotherapy or mastectomy to lower the chance of local recurrence.     

Sentinel node detection in breast carcinoma

The aim of sentinel node biopsy (SN) in breast cancer patients is to detect the tumor-draining lymph node by means of isosulfan blue or 99mTc-labelled colloids. SN can be detected in 80 to 85% of the patients, depending on the size of the tumor. Preoperative lymphoscintigraphy permits the draining nodes along the internal mammary artery also to be visualized. The predictive value of the histological findings of SN for lymph nodes obtained from axillary dissection is about 95%. Because of different diagnostic procedures using various radiotracers each center has to follow its own learning curve. To be sure that the nodal status derived from a SN procedure is of identical value to axillary dissection about 100 patients have to undergo sentinel node detection, followed by axillary dissection, and concordant results should be obtained in 95% of them at least. The SN, however, offers a chance of assessing the lymph node at risk for metastasis by more detailed histological procedures. Morbidity as a result of treatment for primary breast cancer can be decreased if only patients suffering from metastatic disease are subjected to axillary dissection. Currently, the indication criteria for a SN procedure should be restricted to small tumors (T1) with clinically uninvolved axillary status and patients with ductal carcinoma in situ (DCIS).