Hormonal treatment of advanced breast cancer

Endocrine therapy for breast cancer has been used for almost a century, but because of the enormous success of tamoxifen there has been a resurgence of interest by the pharmaceutical industry to develop new and innovative endocrine therapies. Overall, the strategy is quite simple. Estrogen stimulates growth; therefore, the goal is to deny the breast tumor estrogens. Tamoxifen accomplishes this by blocking the estrogen receptor. The new antiestrogens, toremifene and droloxifene, however, appear to have no greater activity than tamoxifen in the treatment of advanced disease and therefore may ultimately offer no advantages over current therapy. In contrast, the pure antiestrogens hold additional promise as they may produce a more profound inhibitory effect on the tumor, and the response may be maintained longer. An orally active, pure antiestrogen, however, would be an important advance. The strategy of using GnRH agonists for premenopausal patients clearly has merit to produce a chemical oophorectomy. The strategy could be integrated into the general treatment plan for the young premenopausal patient taking tamoxifen who may not have had her menstrual cycles stopped by combination chemotherapy. The GnRH agonists would block the reflex rise in estradiol caused by tamoxifen therapy and ultimately produce a more efficient antihormonal therapy. Indeed, the different specific aromatase inhibitors can also be integrated into the treatment plan to produce a complete estrogen blockade. Whether the use will be found to be superior to pure antiestrogens, however, must await the completion of comparative clinical studies. If all the results of endocrine therapy are therapeutically similar, the final strategy may depend on the acceptability by the patient of an individual delivery method for each pharmaceutical approach.     

Hormonal therapy and genital tract cancer

Patient B.G. is a 29-yr-old female with a lifelong bleeding disorder characterized clinically by a highly increased bleeding time, menorrhagias, long-lasting bleeding after cuts and tooth extractions and large post-traumatic haematomas. Her coagulation tests were within normal range, platelet count was 140,000-160,000 per microliters, but platelet function was impaired as demonstrated by the absence of collagen-induced aggregation, although no abnormalities were detected in aggregation response to ADP and ristocetin. Morphologically her platelets were characterized by gigantic size-average profile area was about 2.5 times higher than that of control donors, and severe deficiency of alpha-granules-only 16% of their number in control donors. These features taken together indicated the diagnosis of grey platelet syndrome. As has been shown by quantitative immunoblotting, patient's platelets contained small amounts of alpha-granule membrane protein P-selectin-about 15% of that in control donors. The content of plasma membrane glycoproteins IIb-IIIa and Ib was not reduced, suggesting the specific deficiency of alpha-granule membrane protein. Thus, B.G. is the second patient described in the literature (see also Lages et al, J Clin Invest 1991: 87: 919-929) with combined deficiency of alpha-granules and P-selectin.     

Eczema of the nipple: cancer or not?

Paget disease of the nipple is a rare unique presentation of breast cancer. The main differential diagnosis is dermatitis. We describe two patients with mammary Paget: one, a women aged 41, with limited ductal carcinoma in situ and the other, a women of 56 years, with invasive carcinoma. A third patient, a woman of 46 years, had typical eczema of the areola. This disease usually leads to less well circumscribed lesions than Paget. The treatment of Paget disease is not essentially different from that of any other mammary carcinoma. Eczema of the areola is treated with corticosteroids, to which the disease should respond favourably within three weeks.     

Hormonal replacement therapy and breast cancer]

Hormonal replacement therapy is prescribed more and more frequently to increase quality of life and decrease the symptomatic and organic consequences of the menopausal status. The different studies which analyzed the risk of breast cancer for women under hormonal replacement therapy show opposed conclusion. We reviewed articles published between 1980 and 1997 to try to conclude about the consequences of the action of this treatment in the risk of breast cancer from the characteristic of the hormonal replacement therapy and from known risk of breast cancer. Hormonal replacement therapy increases the incidence of breast cancer. Risk increase with the treatment duration and a low estrogen dose would be sufficient to palliate to the hormonal lack (< 0.625 mg/j). The risk of breast cancer becomes the same that this of women without hormonal replacement treatment when treatment interrupted. The association of estrogen and progestin should not be protective of breast cancer. But the hormonal treatment seems to be synergistic for the risk of breast cancer with late menopause, late age at the birth of first child. Hormonal treatment could increase the estrogenic period and should increased the risk of breast cancer in women with late age at menarche, late age at menopause and late age at first child. It should not increase the risk of breast cancer in women with benign breast disease, with family history of breast cancer and in nulliparous women. For women who undergone a bilateral oophorectomy before hormonal replacement treatment the risk would be the same than for women with natural menopause and without hormonal replacement treatment. However breast cancer should be diagnosed earlier in women with hormonal treatment because mammographies were made more frequently. Overall survival should not different between the women who were under hormonal therapy and theses were not.     

Breast cancer diagnosis by lactate dehydrogenase isozymes in nipple discharge

BACKGROUND: The diagnosis of breast cancer based on nipple discharge, often the only clinical manifestation of early breast cancer, is currently unsatisfactory. Because M subunits of lactate dehydrogenase (LDH) have been noted to increase in cancer tissue, the author assessed the value of using LDH isozyme patterns in nipple discharge for the diagnosis of breast cancer. METHODS: LDH isozyme levels in (1) nipple discharge of patients diagnosed as having breast cancer, intraductal papilloma, mastopathy, drug-induced nipple discharge, mastitis, or benign nipple discharge; (2) control samples of normal nipple discharge (milk) 6 days, 1-5 months, and 6 months to 2 years postpartum; (3) the serum of patients presenting with nipple discharge; and (4) normal and cancerous breast tissue extracts were measured using a Ciba-Corning LDH isozyme system (Ciba Corning Diagnostic Corp., Tokyo, Japan). RESULTS: LDH isozyme levels in the nipple discharge of patients with benign breast diseases displayed various patterns. Levels in the nipple discharge of patients with breast cancer, including noninvasive carcinoma, tended to increase in ascending order from LDH1 to LDH5. This pattern was similar to that in breast cancer tissue and was unrelated to the pattern in serum. CONCLUSION: LDH isozyme assay of nipple discharge may be a useful technique for providing a supporting diagnosis of breast cancer.     

Tissue-engineered nipple reconstruction

We describe a simple, effective approach to the creation of autologous tissue-engineered cartilage in the shape of a human nipple by injecting a reverse thermosensitive polymer seeded with autologous chondrocytes in an immunocompetent porcine animal model. A biodegradable, biocompatible copolymer of polyethylene oxide and polypropylene oxide (Pluronic F-127), which exists as a liquid below 4 degrees C and polymerizes to a thick gel when it is exposed to physiologic temperatures (body temperatures), was used as a vehicle for chondrocyte delivery and as a scaffold to guide growth. Autologous chondrocytes isolated from porcine auricular elastic cartilage and suspended in 30% (weight/volume) Pluronic F-127 were injected on the ventral surface of the pigs from which the cells had been isolated. A circumferential subdermal suture was used to support the contour of the implant and assist in its projection in the form of a human nipple. After 3 weeks, the skin over and surrounding the implant was tattooed to create the appearance of a human nipple-areolar complex. As controls, an equal number of injections were made using either cells alone (not suspended in hydrogel), or hydrogel alone. After 10 weeks, all specimens were excised and examined both grossly and histologically. Before harvesting, visual inspection of the tattooed chondrocyte-Pluronic F-127 hydrogel implant sites revealed that they closely resembled a human female nipple-areolar complex. Nodules were similar in size, shape, and texture to a human nipple at each injection site. Glistening opalescent tissue was surgically isolated from each implant site. Hematoxylin and eosin, safranine o, trichrome blue, and Verhoeff's stains of the experimental implants showed nodules with the characteristic histologic signs of elastic cartilage. Control injections of copolymer hydrogel alone exhibited no evidence of cartilage formation. Control injections of chondrocytes alone showed evidence of dissociated microscopic nodules of elastic cartilage.     

Hormonal replacement therapy in menopause and the risk of breast cancer

We report three patients with severe pontocerebellar atrophy (PCA) associated with a variable degree of cerebral atrophy. The clinical features consisted of progressive microcephaly, central hypotonia, visual impairment, abnormal eye movements and delayed psychomotor development. These are similar but not identical to the features of pontocerebellar hypoplasia type 2 described by Barth. The picture also differs from the classical form of autosomal dominant olivopontocerebellar atrophy. While in two patients the disease seemed to be genetic with highly suspicious autosomal recessive inheritance, the etiology in the third patient was probably nongenetic. We suggest that PCA is a morphologic entity with distinct radiologic features but variable clinical, pathophysiologic and etiologic backgrounds.     

Hormonal events during female puberty in relation to breast cancer risk

Cigarette smoking among adolescents continues to be a major public health problem in the United States. Smoking trends from 1976-1977 to 1992-1994 were examined in the Bogalusa Heart Study, an investigation of cardiovascular disease risk factors among black and white, male and female adolescents in a semirural town in the southern United States. Age-race-sex specific chi 2 tests for trends over five survey periods were conducted. In almost every age group, black boys and girls were less likely to be current smokers or to have ever smoked or tried cigarettes, as compared with white boys and girls, respectively (P < 0.01). Within age groups, few significant trends in smoking status from 1976-1977 through 1992-1994 were observed among white boys and girls. Among black males and females, however, sharp decreases were observed among all age groups in the prevalence of having ever smoked or tried cigarettes (P = 0.0001) and among the older age groups in the prevalence of being a current smoker (P = 0.0001). Thus, substantial declines in the prevalence of smoking were observed among black children but not among white children. Further research is required to understand why these ethnic differences in smoking occurred so that public health programs may target further the smoking behaviors in children.     

Erosive adenomatosis of the nipple

Erosive adenomatosis of the nipple is a rare, usually benign neoplasm of the major nipple ducts. Although morphologic features may distinguish it from Paget disease, histopathological differentiation is simple. Recognition of this tumor may spare needless mastectomy.     

Molecular aspects of breast and ovarian cancer

Side lobes and grating lobes are both unwanted parts of the ultrasound beam emitted off axis that produce image artifacts due to error in positioning the returning echo. The purpose of this study was to reproduce artifacts associated with side lobes and grating lobes in vitro using different transducer types and recognize these artifacts in vivo. A phantom, composed of a water bath, a metallic wire, and a wooden tongue depressor, was imaged using a linear array, a curved linear a vector array, and a sector mechanical transducer. When imaging the metallic wire in a transverse plane, an echogenic artifact was constantly seen on each side of the wire, with a shape and intensity variable with the transducer type. The artifact was curvilinear and concave (linear and curved linear arrays), or curvilinear and convex (vector array and the mechanical transducer). When the tongue depressor was imaged in a longitudinal plane, the artifact was a straight line (linear array), a curved convex line (curved array), a series of convex curvilinear echo (vector array) or a small convex curvilinear echo (mechanical transducer). In vivo situations similar to the phantom experiment were investigated using clinical patients. Artifacts produced in vitro were recognized in vivo when a highly reflective object (urinary bladder wall) was imaged adjacent to an anechoic region (urine). These artifacts corresponded to the principle of secondary ultrasound lobes, and were therefore interpreted as such.     

Treatment of colorectal cancer. Pharmaco-economic aspects

By using caring behaviors and recognizing the grief process, the nurse can help the dying patient and family gain emotional control, complete unfinished business, work through anticipatory grief, and learn how to let go.