Stage of breast cancer at diagnosis among women with cosmetic breast implants.

Concern has been raised about the potential delay in breast cancer diagnosis in the augmented breast. We linked a cohort of 2955 women, who received cosmetic breast implants in Denmark during the period 1973-1997 with the Danish Cancer Registry and the Danish Breast Cancer Cooperative Group register. We identified 23 incident cases of invasive breast cancer diagnosed subsequent to breast implantation. We randomly selected 11 controls for each case from the Danish Breast Cancer Cooperative Group's register, and obtained detailed information on all study subjects about surgery, histopathology and stage of breast cancer at diagnosis, intended adjuvant treatment according to trial protocols and overall survival. We found that women with breast implants on average were diagnosed with breast cancer at the same stage as controls. Significantly more women with breast implants had tumour cells in the surgical margins according to the Danish Breast Cancer Cooperative Group's data. There was no significant difference in overall survival between the two groups after an average of 6.4 years of follow-up. Based on this limited number of women with breast cancer subsequent to breast augmentation, breast implants do not appear to delay the diagnosis of breast cancer, and no evidence of impaired survival after breast cancer diagnosis in augmented women was found.

[Surgical treatment of sequelae after facial paralysis]. / Kirurgisk behandling af sequelae efter facialisparese.

This review describes some of the principal surgical possibilities in the treatment of established facial palsy of long duration in which the opportunity for nerve reconstruction is lost and no remission can be expected. In such cases, ipsilateral or cross-facial nerve grafting, followed by microneurovascular muscle transfer are the methods of choice for providing controlled and emotional movement of the paralyzed side. Regional muscle transfer is also applicable. For patients who are not candidates for these extensive surgical procedures, symmetry to the face can be restored by one of several static procedures. Lastly, the eye-related problems and their surgical solutions are also addressed. Modern plastic surgery has much to offer this group of patients, who should not be left to live with their ailment, but should be referred to a few national centres for specialised treatment.

Cancer occurrence after cosmetic breast implantation in Denmark.

Most studies on cancer incidence after breast implantation have focused on breast cancer, while the risk of cancers at other sites has been less well investigated. We examined cancer incidence among 1,653 women who underwent cosmetic breast implant surgery at private clinics of plastic surgery in Denmark and 1,736 women attending the same clinics for other reasons during the period 1973-1995. Furthermore, we updated previously reported results among 1,114 women who received implants for cosmetic indications at public hospitals. All women were followed for cancer through the Danish Cancer Registry. In comparison with the general female population, the overall standardized incidence ratio (SIR) for cancer among women who received implants in private clinics was 1.65 [95% confidence interval (CI) = 1.17-2.27]. This elevated SIR reflected increased incidence ratios for almost all major cancer sites; however, only for non-melanoma skin cancer was there an excess of more than 2 cases. No significant excess of cancer was observed among women who received implants in public hospitals (SIR = 1.10, 95% CI = 0.76-1.52) or among women attending the private clinics for other problems (SIR = 1.10, 95% CI = 0.78-1.52). The SIRs for breast cancer after breast implantation were 1.1 (95% CI = 0.5-2.2) among private clinic patients and 0.9 (95% CI = 0.4-1.7) among public hospital patients. The overall findings of these 2 implant cohorts and results from other investigations suggest that cancer risk is probably not increased among women receiving cosmetic breast implants. The inconsistent results for private clinics and public hospitals are likely related to selection bias and confounding among the private clinic patients, but our data did not permit exploration of these possibilities. Further research into the determinants of these inconsistencies is warranted.

[Silicone breast implants and breast cancer]. / Silikonebrystproteser og brystkraeft.

Sarcomas have been shown to develop next to foreign body implants, silicone included, in animal experiments. However, this carcinogenesis is not believed to have any human relevance. A review of the existing epidemiological studies suggests that women with silicone breast implants have a reduced risk for developing breast cancer. However, the presence of breast implants does obscure mammographic visualization as well as palpation of mammary tissue. This has led to the assumption that breast cancer detection could be compromised in women with breast implants. In the few studies that have dealt with this issue, women with breast implants were diagnosed with the same stage of disease as women without implants. However, the percentage of false negative mammographies was increased in one study. In conclusion, there is currently no evidence of an association between breast implants and cancer or postponed breast cancer detection.

Silicone mammary implants and connective tissue disease.

The American Food and Drug Administration recently restricted the use of silicone gel-filled mammary implants for breast augmentations and reconstructions because a number of case reports had suggested that there was an association between silicone and connective tissue disease. We have found 36 such case reports published since 1982. Systemic sclerosis is the most common reported diagnosis (n = 15). Implants were removed from 15 patients, in nine of whom symptoms improved. The mechanism behind the postulated relationship is obscure, and most authors focused on an auto-immune-like response to silicone, which acts directly as a hapten or as an adjuvant. We found no conclusive evidence to implicate silicone mammary implants in connective tissue diseases. We do, however, recommend removal of implants from patients with severe connective tissue diseases. Patients with symptoms or active connective tissue disease should not be considered for silicone implants.

T-lymphocyte clones initiated from lesional psoriatic skin release growth factors that induce keratinocyte proliferation.

To investigate whether growth factors derived from T cells in psoriatic lesions are able to stimulate keratinocyte growth, T-cell lines were initiated from lesional psoriasis skin and cloned by limiting dilution. Eight clones with good proliferative capacity out of 40 clones from one patient were stimulated. After 24 h, the conditioned medium was harvested and the growth modulatory effect of the conditioned medium on keratinocytes was assessed. Seven of the eight T-cell clones stimulated keratinocyte growth to an extent ranging from 22% +/- 19 to 64% +/- 9 (mean +/- SD of three experiments) of maximal inducible keratinocyte growth, and one T-cell clone had no effect (-5% +/- 2) on keratinocyte growth. Keratinocyte growth was also induced by T-cell clones obtained from two other patients. Several cytokines were tested in this system to determine which T-cell growth factor may induce the keratinocyte growth. None of the cytokines interferon-g, transforming growth factor-beta, interleukin (IL)-2, IL-3, IL-4, IL-6, IL-8, or granulocyte-macrophage colony stimulating factor alone was found to possibly be responsible for the T-cell-induced keratinocyte growth. Thus the nature of the T-cell keratinocyte growth-promoting stimulus remains to be elucidated.

Wide local excision of recurrent breast cancer in the thoracic wall.

BACKGROUND: Local recurrence is one of the major problems in treatment of breast cancer. Approximately 20% of patients who have radical or modified radical mastectomy have a local recurrence. METHODS: The records of 98 women with locally recurrent breast cancer treated with wide local excision, in the years 1983-1987, were reviewed. The median age at excision was 62 years (range, 32-84 years). All patients were observed until death or December 31, 1989. The median follow-up period was 36 months (range, 2-79 months). RESULTS: At follow-up, 44 of 98 patients (45%) had had a new local relapse and 47 of 98 (48%) were dead. The median duration of local control for all patients was 21 months (range, 1-79 months). The diameter of the local recurrence seemed to influence the duration of local disease control but not total survival. Patients admitted directly for surgery had a longer period of local control compared with patients admitted after unsuccessful oncologic treatment of the local recurrence. The 5-year local control rates were 50% and 24%, respectively (P > 0.92). No statistically significant difference in local control could be shown whether or not the patient received additional oncologic therapy in continuity with the wide local excision. The 5-year local control rate in patients treated only by surgery was 33% compared with 42% in patients also receiving additional oncologic treatment (P > 0.63). CONCLUSIONS: Wide local excision of recurrent breast cancer seems to provide as good or even better local control than other treatment modalities. Surgery should not be postponed in cases of ineffective medical treatment or radiation therapy.

The role of the internal thoracic artery in the sternal blood supply.

The altered arterial supply to the sternum after use of the internal thoracic artery in coronary bypass surgery was studied by delineation of the sternal arterial system with plastic material and by injection of ink/barium contrast for radiography and microscopy. The study was performed on 17 anterior chest walls from human cadavers. The total arterial supply was charted before and after 'harvest' of the internal thoracic artery. The dominant blood supply to the sternum was found to be periosteal and derived almost exclusively from branches of the internal thoracic artery. Following harvest of that artery, the arterial supply to the upper part of the corpus sterni was compromised, and based only on sparse ramifications to the periosteal membrane from the thoracoacromial artery via branches from the pectoralis major muscle.

[Silicone breast implants and connective tissue disease]. / Silikone-brystimplantater og bindevaevssygdomme.

The American Food and Drug Administration (FDA) recently introduced a temporary stop for silicone breast prosthesis implants. The reason is a suspected connection between silicone implants and the development of autoimmune disease. The present authors have reviewed the 32 cases of connective tissue disease which have hitherto been reported in the literature, of these 13 were cases of systemic sclerodermia. On the basis of approximately 2 million silicone prosthesis implants which were introduced in USA alone during the past 20 years, approximately 200 cases of systemic sclerodermia would be anticipated. Nevertheless, the fact that several patients had spontaneous remission of their chronic disease after removal of the silicone implant speaks in favour of a possible connection. It is concluded that on account of the limited number of cases of connective tissue disease which have been reported in patients with silicone implants, insufficient evidence is present to stop implantation of these. Implantation of prostheses filled with saline are recommended for patients with connective tissue disease.

Melanoma and pregnancy. A review.

In the last half-century the incidence of cutaneous malignant melanoma has increased all over the world according to available reports. No association between risk of melanoma and age at menarche, first birth, menopause or duration of reproductive period has been proven so far. Studies on the effect of parity on relative risk and survival have given divergent results with multiparous women possibly having a better prognosis than nullipara. Women with melanoma diagnosed during pregnancy tend to have thicker tumours, shorter disease-free interval and, maybe, lower 10-year survival rate than non-pregnant matched controls. There is no conclusive evidence that therapeutic abortion improves the cure rate. Multivariate analysis has failed to unveil impaired prognosis in women who become pregnant subsequent to diagnosis.

[Malignant melanoma of the skin in Denmark--epidemiology, diagnosis and treatment]. / Melanoma malignum cutis i Danmark--epidemiologi, diagnostik og behandling.

About 700 new cases of malignant melanoma of the skin are registered annually in Denmark. The incidence is increasing rapidly and the number of new cases increases by more than 5% per annum. The most important phenotypical risk factors are the number of acquired pigmented naevi and exposure to sunlight is the most important risk factor in the external environment so that severe sunburn in children and intermittent intense exposure to sunlight increase the risk of melanoma. The thickness of the tumour at the time of the diagnosis is the most important prognostic factor. The prognosis deteriorates with increasing thickness. Treatment is primarily surgical. In cases of inoperable local melanoma and regional recurrences, irradiation may be administered. Chemotherapy and/or immunotherapy are of experimental character. In the light of the rapidly increasing incidence, it is important that knowledge of risk factors for development of the disease and the clinical characteristics of early melanoma is spread to not only the medical profession but also to the general public.

Classical prognostic factors in node-negative breast cancer: the DBCG experience.

Classical prognostic factors were analyzed in patients with low-risk primary breast cancer, defined as absence of tumor-positive axillary lymph nodes, tumor size less than or equal to 5 cm in diameter, and no invasion into skin or deep fascia. The primary surgical treatment was total mastectomy and lower axillary dissection. None of the patients received adjuvant therapy. Between 1977 and 1990, 7315 patients entered the study, and at the time of this analysis (January 1, 1990), the median follow-up time is 5 years. In univariate analyses, the following variables were significantly related to recurrence-free survival: age in premenopausal patients; tumor size; number of negative nodes removed; histological grade; and in premenopausal patients, estrogen receptor and progesterone (PgR) status. In multivariate analyses, age in premenopausal patients was the most important factor, followed by tumor size and histological grade, whereas PgR status in premenopausal patients was just of borderline significance. These variables should be included in multivariate analyses testing the value of more recently introduced prognostic factors.

[Rationalization profits of radiographic diagnosis with systematic follow-up DBCG (Danish Breast Cancer Cooperative Group) programs. 1]. / Rationaliseringsgevinster inden for billeddiagnostik ved systematiske opfølgningsprogrammer i DBCG's regi. 1.

In the follow-up programme of the DBCG-77 control and treatment protocols for primary operable breast cancer, bone scintigraphy and chest X-ray were performed 6 months after surgery and thereafter yearly until the diagnosis of any recurrence or another cancer. In the present study, the value of the two examinations was examined to the 6th year control. As a result of a low incidence of primary recurrence to the bone (0.6-3.9%) and to the chest (0.0-3.0%) the value was found to be low. About two thirds of the patients with primary chest recurrence addressed themselves with or had at the time of control pulmonary symptoms. About one half of those patients, in whom (during a 12-month period after the scheduled bone scintigraphy) bone metastases were diagnosed by another method, had a normal scheduled bone scintigraphy. False positive changes were not infrequent, especially at the bone scintigraphies. The diagnosis of asymptomatic chest recurrence did not reduce the mortality among stage II patients, among whom the greatest value of the control examination was found. It is concluded, that systematic use of bone scintigraphy and chest X-ray is not justified in a follow-up programme for stage I and II breast cancer patients.

[Prognosis after surgical treatment of breast cancer. 3. The low-risk group of the DBCG (Danish Breast Cancer Cooperative Group)]. / Prognosen efter kirurgisk behandling af cancer mammae. 3. DBCG's lavrisikogruppe.

The two therapeutic protocols of The Danish Breast Cancer Cooperative Group (DBCG) DBCG 77a (1977-1982) and 82a (1982-1990) comprise patients who were classified as low risk patients after operation for cancer of the breast, a total of 7,315 women. Treatment consisted of mastectomy and dissection of the lower and middle axillary levels. The median period of observation for DBCG 77a was 9 1/2 years and for DBCG 82a 3 1/3 years. The curves for recurrence-free survival and survival were found to be congruent in the two protocols. The recurrence-free survival after five years was 70% and 55% after ten years. Survival was 87% after five years and 70% after ten years. Local recurrence developed in 12.7% and 1.1% had distant recurrences simultaneously. Local recurrence was distributed with 60% in the scar or thoracic wall, 33% in the axilla and 7% in the clavicular lymph nodes. Distant recurrence alone developed in 11.4%. The time curves for development of local or distant recurrences were practically congruent. Local recurrence developed in 3.8% of the patients per annum during the first four years and after that in 1.5% per annum. Distant recurrence was found in 3.5% per annum in the first four years and after that in 1.8% per annum. The survival was significantly different after local and distant recurrence. Patients with tumours of grade 1 anaplasia had better prognoses than patient with grade 2 og 3 tumours as regards recurrence-free survival and survival. Multivariate analysis revealed that age under 40 years and anaplasia grad were significant prognostic variables for the parameters: distant recurrence and local recurrence. In addition, the number of lymph nodes in the operation specimen was a prognostic variable for local recurrence.

[Adjuvant endocrine treatment of postmenopausal patients with breast cancer with high risk of recurrence. 5. Results from the DBCG (Danish Breast Cancer Cooperative Group) 77C randomized trial]. / Adjuverende endokrin behandling af postmenopausale brystkraeftpatienter med høj risiko for recidiv. 5. Resultater fra DBCG 77C, en randomiseret undersøgelse.

The role of antiestrogen treatment of postmenopausal breast cancer patients with high risk of recurrent disease is evaluated in a nationwide, prospective trial conducted by the Danish Breast Cancer Cooperative Group (DBCG). After total mastectomy and postoperative radiotherapy (RT), 840 patients were randomized to treatment with tamoxifen (RT + TAM) for one year, and 824 were randomized to no further therapy (RT). The recurrenceree survival (RFS) after ten years of lifeable analysis is 31% in the RT + TAM treated group, and 28% in the RT group (p = 0.01). Survival is 38% and 34% in the two treatment groups, respectively (p = 0.04). The data were further analyzed with respect to prognostic factors such as age, number of positive nodes, tumour size, and degree of anaplasia. Survival is prolonged in nearly all subgroups of patients treated with RT + TAM. However, the prolongation is only significant in patients with four or more positive nodes, with tumours of less than 5 centimeters or with tumours of anaplasia grade II. Estrogen (ER) and progesterone receptor (PgR) concentrations were measured in tumours from 309 and 219 patients, respectively. Only patients with ER and PgR values above 100 fmol/mg cytosol protein seemed to have a prolongation of survival. In conclusion, a modest survival benefit is achieved with one year of adjuvant tamoxifen treatment. Nevertheless, this is the first example of a systemic treatment approach being able to change the fatal course of breast cancer in postmenopausal patients. By means of endocrine therapy, and in the context of a new randomized trial, the DBCG will try to improve the survival in these patients even further.

[Adjuvant chemotherapy in premenopausal and menopausal high-risk patients with breast cancer. 4. Results of the DBCG (Danish Breast Cancer Cooperative Group) 77B study]. / Adjuverende kemoterapi af praemenopausale og menopausale højrisikopatienter med cancer mammae. 4. Resultater fra DBCG 77B undersøgelsen.

From October 1977 to November 1982 premenopausal and menopausal high-risk breast cancer patients were included in a randomized trial (DBCG 77B). The primary surgical treatment was total mastectomy with axillary dissection. In the trial, a total of 1,034 patients were enrolled and received postoperative radiotherapy (RT) and were further randomized to 1) no systemic treatment, 2) cyclophosphamide, or 3) cyclophosphamide + methotrexate + 5-fluorouracil. The chemotherapy was given for one year. With a median observation time of ten years, the survival was 45, 60 and 62%, respectively. Retrospectively, the survival benefit was observed to be most pronounced in the age group less than 40 years, in patients with tumour size less than or equal to 5 cm or with less than or equal to 3 positive lymph nodes. In high-risk premenopausal and menopausal patients adjuvant chemotherapy combined with RT thus resulted in a more than 25% relative reduction in mortality at ten years of observation compared with RT alone.

[Epitheloid sarcoma--an overlooked diagnosis?]. / Epiteloidt sarkom--en upåagtet diagnose?

Epitheloid sarcoma (ES) is a malignant soft-tissue tumour which occurs particularly on the hand and forearm in young adults. The tumour grows slowly and metastasizes relatively late but has, nevertheless, a considerable mortality and morbidity because it is frequently erroneously diagnosed, both clinically and pathologically, either as a benign tumour or as a reactive inflammatory process. Two typical cases with diagnostic delays of 12 and 15 years, respectively, which required amputations through the upper arm or forearm are described. Even although ES is a rare tumour form, clinicians and pathologists should be aware of this possibility as, in the early stages, the tumour can frequently be treated effectively and radically by wide local excision without amputation.