Carcinoma in situ of the female breast. 10 year follow-up results of a prospective nationwide study.

In a Danish nationwide prospective study of in situ carcinoma of the breast, a total of 275 women, treated with excision alone, were registered from 1982 to 1989. The series included 142 cases of ductal carcinoma in situ (DCIS), 100 cases of lobular carcinoma in situ (LCIS), 26 cases of DCIS+LCIS, and seven cases of atypical hyperplasia (AH). Within a median follow-up of 120 months, a crude recurrence rate of 28% (76 cases) was found, of which 53% (40 cases) recurred as invasive carcinomas (IC) and 47% (36 cases) as CIS. CIS recurrences appeared after median 18 months, compared to median 42 months for IC recurrences. No statistical difference was found with respect to development of IC between the three groups of DCIS, DCIS+LCIS, and LCIS. The majority of recurrences were ipsilateral, also for LCIS. Forty four of 49 recurrences following DCIS, and seven of nine recurrences following DCIS+LCIS occurred as local recurrences. Histopathologically, in DCIS a strong association was found between large nuclear size and comedonecrosis. Univariate analysis showed a significant association to recurrence for nuclear size, comedonecrosis, and size of the original lesion. Multivariate analysis showed that only comedonecrosis and size of lesion were independent predictors of recurrence, however, specimen margins were not included in the analysis, as this parameter could not be adequately evaluated in the present series. Nuclear size of original DCIS lesion was related to histologic grade of the IC recurrence. The recurrence rate for DCIS of small nuclear size increased from 6% at five years of follow-up to 16% at 10 years, possibly due to a slower growth rate and a continued but delayed risk. Similarities were found between LCIS and DCIS of small nuclear size, both showing a continued risk and comparable rate of recurrence. Further, progression to IC of similar, highly differentiated type was seen, indicating a linkage between biological behavior of the two histological types.

Immunohistochemical assessment of oestrogen and progesterone receptors: correlations with the DCC method and clinical outcome in primary breast cancer patients.

Two different methods to determine steroid receptors were analysed with respect to their ability to estimate prognosis in primary breast cancer patients. The immunohistochemical assay (IHA) was compared with the dextran-coated charcoal (DCC) method of receptor determination. A random sample of 281 patients with invasive ductal carcinoma was drawn from 841 consecutive patients with primary breast carcinoma treated at Odense University Hospital between 1 January 1980 and 31 December 1990. Receptor determination by the DCC method had been carried out previously in 164 patients for the oestrogen receptor and in 132 patients for the progesterone receptor. The former group was reassessed by IHA with the antibody ER1D5, and the latter with the antibody PgR-ICA. The median follow-up time was 8.3 years (range 2.9-12.9 years). A cutoff of zero was used for the DCC method. Immunohistochemical results were quantified by counting in systematically random sampled fields of vision and values above zero were considered to be positive. Overall agreement of positive and negative cases was 86% for the oestrogen receptor and 83% for the progesterone receptor. Although the study included a limited number of patients, receptor positive cases fared better than negative cases in all situations. Investigation of the prognostic power revealed that classification based on IHA allowed better discrimination of patients than classification based on the DCC method. The reason for this difference might be because distinction between benign and malignant tissue is possible using the IHAmethod. Thus, IHAresults appear to be more clinically relevant.

The importance of surgery and accurate axillary staging for survival in breast cancer.

AIMS: The purpose of this study was to investigate, within the context of the Danish Breast Cancer Cooperative Group (DBCG) programmes, whether a dedicated surgical approach had a significant bearing on the outcome of breast cancer treatment. METHODS: From 1 January 1980 to 31 December 1990, patients below 70 years of age with operable breast cancer from Odense University Hospital (n=743) were compared with those from the rest of Denmark (denoted rest-DK) (n=15,419). All patients were treated according to nationwide DBCG guidelines and reported to the DBCG Data Centre. The potential median observation time was 11.2 years (range 6.0-16.9). Patients underwent mastectomy or breast conserving therapy, and high risk lymph-node positive patients had adjuvant systemic therapy with or without radiotherapy. RESULTS: Comparing total patients series, overall survival (OS) was significantly superior in patients from Odense compared with rest-DK (P=0.02), with 10-year OSs of 62% (95% CI: 58-65%) and 56% (55-57%), respectively. In subgroups, the OS of low-risk node negative patients (protocol A) in Odense compared with rest-DK was significantly better (P=0.02); 10-year OS was 78% (73-84%) versus 72% (70-73%). Among the high-risk pre-menopausal patients (protocol B), the OS was significantly better in Odense (P=0.009); 10-year OS was 67% (60-75%) versus 53% (51-55%) in rest-DK. Post-menopausal high-risk patients (protocol C) did not differ significantly in OS between Odense and rest-DK (P=0.61). Locoregional control in the Odense series was superior compared with rest-DK. More lymph nodes were recovered and examined from the axilla in the Odense series than in rest-DK, a median of 10 vs. 6 nodes. In the Odense series, a significantly higher proportion of pre-menopausal patients had positive lymph nodes, predominantly one to three positive nodes, and subsequently a lower proportion of pre-menopausal patients had negative lymph nodes compared with rest-DK (P=0.02), indicating a more accurate staging in Odense vs. rest-DK. The survival benefit among the patients from Odense cannot be explained by stage migration alone, but seems to represent a true survival advantage. Overall mortality was significantly lower in the Odense series compared with rest-DK. Whether or not this difference could be explained by lower background mortality in the Odense series or was caused by superior treatment is discussed. CONCLUSIONS: The extent of surgery seems important for locoregional tumour control and accurate axillary lymph-node staging. In combination, these might lead to superior recurrence-free and overall survival, although differences in background mortality cannot be ignored. Surgery, therefore, might represent a risk factor by itself.

[Clinics for counseling on cancer genetics. Experiences with genetic studies and counseling on familial breast cancer and colorectal cancer]. / Cancergenetisk rådgivningsklinik. Erfaringer med genetisk udredning og rådgivning ved familiaer cancer mammae og familiaer cancer colorectalis.

Five to ten percent of cases of breast cancer and colorectal cancer are familial. These families can be divided into high-risk families and moderate-risk families. Cancer in high-risk families can often be explained by dominant inheritance of a gene causing increased susceptibility to cancer. There is a great demand for genetic counseling in these families, and the structure of and experiences from a familial cancer clinic at Odense University Hospital is described. The establishment of a familial cancer clinic involves three steps: 1) Identification of families with increased cancer susceptibility; 2) Molecular tests to identify gene carriers; 3) Clinical examinations for early detection of tumors. Achievement of these three steps requires the involvement of several medical specialties to ensure patient care. Experience with familial cancer clinics is still limited and the involvement of genetic testing and clinical examination programs at risk individuals are insufficiently examined. The rapidly improving techniques for genetic testing make it urgent that it is implemented as part of already established clinical programs.

[Effects of tobacco smoking on the incidence of flap necrosis after mastectomy]. / Konsekvens af tobaksrygning på incidens af randnekrose efter mastektomi.

One hundred and fifty-nine women undergoing mastectomy (simple or modified radical) were followed for the development of flap necrosis. The incidence of flap necrosis was found to 14%. The only significant risk factor for the development of flap necrosis was found to be smoking, which increased the risk by 4.9 times. The effects of nicotine and carbon monoxide, the two principal known detrimental factors in tobacco smoke, are described. Prophylactic efforts are advised.

A comparative study of post-operative psychosocial function in women with primary operable breast cancer randomized to breast conservation therapy or mastectomy.

In a randomized patient series of 184 women suffering from primary operable breast carcinoma, psychosocial adjustment to breast-conserving therapy (BCT) vs mastectomy (M) was analysed retrospectively, including: (i) a comparison of intergroup characteristics; (ii) patient experience of the quality of professional pre-operative information; and (iii) the extent to which influence on choice of treatment was required. Using LASA (Linear Analogue Self-Assessment Scale), STAI (State-Trait Anxiety Inventory), and a semi-structured interview, no psychosocial benefits were found in BCT compared with M. Mean observation time was 31 months (range: 15-65). Body image was less impaired in BCT than in M. Both groups scored highly on professional information, but reported reduced ability to take in such information in the peri-operative period. Both groups tended to depend on the surgeon when choosing between surgical options. Irrespective of primary therapy, women must still confront the fact that they have had cancer, a life-threatening disease which may recur. A need for further research into peri-operative information procedures was demonstrated, and some suggestions were derived concerning the surgeon's role in deciding on surgical options.

[Surgical treatment of primary hyperparathyroidism]. / Kirurgisk behandling af primaer hyperparatyreoidisme.

Neck exploration due to suspicion of primary hyperparathyroidism (pHPT) was performed in 309 instances (298 patients) during a 17 year period, in 44 instances (14%) as a second operation after former goitre surgery or surgery for pHPT. Adenomas were found in 247 patients (83%), 12 patients had double adenomas and one triple adenoma. Hyperplasia was registered in 34 patients (11%) and three had parathyroid cancer. Median weight of adenomas was 1200 mg and hyperplasia 1500 mg. In 14 patients only normal glands were identified. In six of these 14 patients the diagnosis was later withdrawn. In 276 out of 292 patients with pHPT normocalcaemia was established, 16 patients remained hypercalcaemic. Success-rate concerning verification of pHPT was therefore 97% (284 out of 292) and concerning attainment of normocalcaemia 95% (276 out of 292). There was one perioperative death due to myocardial infarction. Four patients had transient unilateral recurrent nerve injury. In one patient with parathyroid cancer vocal cord paralysis was permanent. Follow-up after at least one year revealed normocalcaemia in 91% of the patients, hypercalcaemia in 7% and hypocalcaemia in 2%. Twenty percent of the patients had died 0-12 years, median 2.8 years postoperatively. Death was related to the degree of hyperparathyroidism evaluated by weight of abnormal parathyroid tissue.

Experience in a specialist thyroid surgery unit: a demographic study, surgical complications, and outcome.

OBJECTIVE: To present a demographic study of thyroid diseases and thyroid surgical activity, to analyse the results of one department that has specialised in thyroid surgery during an 11-year period, and to try to define those groups of patients at increased risk of complications and untoward sequelae. DESIGN: Retrospective study. SETTING: Danish regional university hospital. SUBJECTS: The total series comprised 1099 consecutive patients who were operated on for benign goitre during an 11-year period. The demographic series comprised a subgroup of 933 patients with goitres from the defined catchment area composed of five municipalities. MAIN OUTCOME MEASURES: Annual number of operations for goitre, waiting time to operation, incidence of complications, and sequelae. RESULTS: In the demographic study the number of patients operated on for benign thyroid diseases declined from about 50 cases to about 25 cases/100000 inhabitants during the study period. At the same time the average waiting time between consultation and operation increased from 5-33 weeks. In the total series (n = 1099) 18 patients developed temporary unilateral vocal cord paralysis (2%), and 8 developed permanent paralysis (0.7%). There were no bilateral vocal cord paralyses, 7 patients developed temporary postoperative hypocalcaemia (0.6%), and an additional 8 patients (0.7%) developed permanent hypocalcaemia. 5 patients developed wound haematomas (0.5%), and 3 had wound infections (0.3%). A total of 16 patients (1.5%) had a permanent complication in the form of nerve injury or damage to the parathyroid glands. The rates of postoperative complications were significantly higher among patients who had two or more operations on the neck (p = 0.0004), intrathoracic goitres (p = 0.0002), large goitres (p = 0.0002), and those having emergency operations (p = 0.0091). CONCLUSION: The decline in the number of operations for benign goitre at Odense University Hospital parallels the increase it waiting time before operation. This can be explained by loss of operating room capacity rather than introduction of some alternative cure for goitre or change of criteria for operation. Certain groups of patients are at higher risk of complications than others.

Comparison of the surgical procedures for breast conserving treatment of early breast cancer in seven EORTC centres.

The aim of this study was to develop a standardised surgical report for breast-conserving procedures, supporting the systematic documentation of the different aspects of the surgery. The surgical procedure for tumourectomy and axillary clearance was translated into a series of steps that could be quantitatively documented. This description was submitted twice to a group of surgeons from different departments to ensure that all steps that are considered to have relevance for outcome were included and that no superfluous data were collected. After two corrective phases, a first test format was developed. Between February 1993 and May 1994, seven surgical departments, participating in EORTC trials, completed this questionnaire for a number of their patients. The data collected related to general information on the department, the tumour excision itself, the axillary dissection and, in a later phase, on pathology. 269 questionnaires (264 tumour excisions, 259 axillary dissections and 189 pathology reports) were collected and analysed. Even though the participating departments were involved in a single trial on breast-conserving surgery and had previously developed regular contacts about the practical aspects of treatment, many differences were detected. In general, variations were found in the waiting time between treatment prescription and execution, experience of the surgeon, duration of the procedure, and the use of prophylactic antibiotics. Also, in the practical execution of the procedure, major variations in the type of incision, width of tumour excision, closure of the breast tissue and skin, the use of frozen sections and the extent of the axillary dissection were found. The most relevant differences and their possible consequences are discussed. It has been proven possible and feasible to document quantitatively a surgical procedure. The fact that within a group of surgeons participating in the same clinical trials, many differences in the surgical techniques are observed, stresses the need to reach a consensus on a stricter set of guidelines for breast-conserving procedures and their documentation, especially when conducting clinical trials.

Long-term observation of serum thyroglobulin after resection of nontoxic goiter and relation to ultrasonographically demonstrated relapse.

The object was to carry out a prospective study of the changes in serum thyroid hormones and thyroglobulin (Tg) following resection of nontoxic goiter and to investigate if there was a correlation to the pattern of relapse. A group of 39 consecutive patients, mainly with nodular, nontoxic goiter, were studied for 13 years following thyroidectomy. No thyroid hormone replacement therapy was given after surgery. The preoperative serum Tg level was elevated. After operation the mean serum Tg declined to a nadir of 43 micrograms/L at 1 year and subsequently increased to 90 micrograms/L at 10 years, with large individual differences. In 19 patients the serum Tg increased, in 1 it decreased, and in 19 no significant alteration was observed. Serum free thyroxine and triiodothyronine indices decreased following resection but achieved normal levels within 6 to 12 months. Serum thyroid-stimulating hormone increased after resection, with a peak level 1 month after surgery, but it returned to normal levels at 1 year and remained stable for the rest of the period. At 13 years after resection the thyroid volume was determined by ultrasonography in 30 of the patients. In 10 patients the thyroid volume was enlarged (>/= 28 ml). In this group a rise of average serum Tg after resection [DeltaTg(10-1 year)] of 133 micrograms/L was observed, compared to 26 micrograms/L in the 20 patients without sonographic relapse (volume < 28 ml). A positive correlation was demonstrated between serum DeltaTg(10-1 year) postsurgically and thyroid volume 13 years after surgery. However, an overlap was observed between the groups with and without ultrasonographic relapse, probably in part due to large differences in the Tg synthesis activity of different follicle cell clones. It is concluded that repeated serum Tg determinations may provide biochemical evidence of increased growth activity of thyroid remnants monitored after goiter resection.

Cytogenetic abnormalities in an in situ ductal carcinoma and five prophylactically removed breasts from members of a family with hereditary breast cancer.

Short-term cultures of tissue samples from three bilateral prophylactic mastectomies and one in situ ductal carcinoma from four women belonging to a family with hereditary breast cancer were cytogenetically analyzed. Clonal chromosome abnormalities were detected in five of the six prophylactically removed breasts, all of which had the histologic diagnosis epithelial hyperplasia without atypia, and in the in situ carcinoma. The same karyotypic imbalance, a loss of 3p12-14, was detected in the in situ carcinoma as well as in one of the hyperplasias, indicating that these bands may harbor a pathogenetically relevant gene in this breast cancer family. The finding of chromosome aberrations in clonal proportions in the prophylactically removed breasts indicates that a neoplastic process was already present, lending support to the view that prophylactic bilateral mastectomy in these high-risk individuals prevented the development of breast carcinoma.

[Menstrual cycle and surgery of breast cancer. Point of time for the surgery of primary breast cancer in connection with menstrual cycle is without prognostic significance]. / Menstruationscyklus og operation for mammacancer. Tidspunktet for operation for primoer mammacancer i forhold til menstruationscyklus er uden prognostisk betydning.

From 1977 to 1989 6488 patients under fifty years with primary breast cancer were registered in the nationwide Danish Breast Cancer Cooperative Group (DBCG). Among these information on last menstrual period prior to surgery was available in 1635 cases which constitute the study group of the present analysis. The group was representative of the total group with regard to prognostic factors and survival. In the study group time of surgery in relation to last menstrual period was found to have no influence on five- and ten year survival.

Timing of surgery in relation to menstrual cycle does not predict the prognosis in primary breast cancer. Danish Breast Cancer Cooperative Group.

From 1977 to 1989 6488 patients under 50 years with primary breast cancer were registered in the nationwide Danish Breast Cancer Cooperative Group (DBCG). Among these, information on last menstrual period prior to surgery was available in 1635 cases which constitute the study group of the present analysis. The group was representative of all women operated upon during the period with regard to prognostic factors and survival. In the study group time of surgery in relation to last menstrual period was found to have no influence on 5 and 10 years survival.

[Intrathoracic goiter. Diagnostic aspects, surgical complications and permanent sequelae]. / Intratorakal struma. Diagnostiske aspekter, kirurgiske komplikationer og varige følgetilstande.

During the course of 1151 thyroidectomies performed during an 11-year period, 195 patients were found to have intrathoracic goitre. Centre experience of operating this disease and the usefulness of applied diagnostic methods are analysed. The sensitivity of physical examination (palpation), technetium scintigraphy and chest roentgenogram is respectively 52%, 33% and 65%, while specificity is respectively 99%, 98% and 95%. These three methods together ensure the diagnosis in 82% of the patients. Positive predictive values are respectively 95%, 78%, and 72%, while negative predictive values are found to be 91%, 89%, and 93%. Frequency of permanent unilateral vocal cord paresis is 2.5%, no cases of bilateral recurrent nerve damage occurred. The frequency of unilateral vocal cord paresis is found to be 1.4%, if nerves of risk are considered. The incidence of hypocalcemia requiring permanent treatment reaches 2%. Intrathoracic goitre can be treated surgically with an only slightly elevated risk for surgical complications and permanent sequelae, especially when performed in the elective phase and within the frame of centre facilities. Intrathoracic components can nearly always (97%) be reached through cervical incision.

[Surgical treatment of benign recurrent goiter. Technique, complications and permanent sequelae]. / Kirurgisk behandling af benign recidivstruma. Teknik, komplikationer og varige følgetilstande.

Centre experience of reoperation for recurrent goitre in 82 patients during an 11-year period is analysed. The lateralposterior approach is used as a standard surgical technique. Postoperative complications are prevalent only among patients previously operated on the thyroid gland twice or more, among patients with recurrent intrathoracic goitre, and among patients with large goitre relapse. Frequency of permanent unilateral vocal cord paresis amounts to 3.6%. There were no cases of bilateral recurrent nerve damage. The incidence of hypocalcemia requiring permanent treatment reaches 1.2%. Centre experience tends to reduce surgical complications rates with increasing specialized training. The surgical treatment for recurrent goitre ought to be radical to avoid further relapses. We recommend lobectomy in cases of unilateral recurrence and lobectomy of the dominant lobe with contralateral resection in case of bilateral relapse.

[The duct ectasia syndrome--an overlooked disease entity]. / Duktektasisyndromet--en overset sygdomsenhed.

Mammary duct ectasia is a benign disease of the mammary gland, characterized by a frequently long history of tumour formation, nipple discharge, nipple retraction and mastalgia. Non-puerperal mammary abscess, which may be the presenting symptom, is also part of the syndrome. Diagnosis can often be made on the basis of the history and the clinical findings of nipple discharge, nipple retraction, tenderness on palpation, fistula formation and subareolar tumour/abscess formation. Mammography may guide diagnosis. Breast cancer is the most important differential diagnosis. If the clinical picture resembles cancer, it is necessary to perform diagnostic biopsy. Causal therapy of mammary duct ectasia is not available. Until now excision of the central mammary tissue and larger ducts has been used as treatment for the clinical manifestations of abscess, fistula and nipple discharge, apparently with good results.

[The duct ectasia syndrome. A prospective clinical study of patients with breast diseases]. / Duktektasisyndromet. En prospektiv klinisk undersøgelse of patienter med mammalidelser.

Mammary duct ectasia is a benign condition of the mammary gland histopathologically characterized by inflammatory changes in the collecting ducts. A prospective clinical and histopathological study was done of 316 consecutive patients with surgical mammary diseases. The syndrome of mammary duct ectasia (DES) was found in 42 patients (13%). The mean age was 44 years and 81% of the patients were pre- or menopausal. Forty-eight percent of the patients had a history of previous benign breast lesions and abnormality associated with lactation was also frequently represented in the history. Major symptoms were tumour formation, localised in the subareolar region in more than half of the cases, subareolar abscess and nipple discharge. Minor symptoms were mastalgia, mammary fistula, nipple retraction, general symptoms and enlarged axillary lymph nodes. Treatment for an abscess in DES seems to fail more often if only incision and drainage are performed. Excision of the entire focus and corresponding duct may prove to be better.

Needle biopsy of breast cancer. Appearance of tumour cells along the needle track.

Appearance of tumour cells along the needle track in patients with breast cancer diagnosed by SURECUT needle biopsy is found in two out of 47 consecutive cases. It is not known whether these cells are early implantation metastases or are harmless. To avoid any unnecessary risk to the patients, we recommend that needle biopsy is so performed, that it is possible to remove the track during the definite surgical procedure, and that penetration into the muscles of the thoracic wall during the biopsy procedure is avoided.

Lobular carcinoma in situ of the female breast. Short-term results of a prospective nationwide study. The Danish Breast Cancer Cooperative Group.

In a Danish nationwide prospective study of in situ carcinomas and atypical lesions of the breast, 88 women, comprising 69 patients with lobular carcinoma in situ (LCIS) and 19 patients with combined lobular and ductal carcinoma in situ (LCIS + DCIS), were accrued from 1982 through 1987. All cases were treated with excision only. Within a median follow-up time of 61 months, a recurrence rate of 17% (15 cases) was found, excluding nine cases of refinding of LCIS. No contralateral recurrences occurred. The recurrences were in eight cases invasive carcinomas (IC), in six cases LCIS + DCIS, and in one case DCIS alone. The recurrence rates among cases of LCIS and of LCIS + DCIS were not significantly different. The histopathological review included an estimate of the number of lobules with LCIS and nuclear size, both of which were significantly related to recurrence. The risk of developing IC was calculated to be increased by a factor 11 as compared with the reference population.

Ductal carcinoma in situ of the female breast. Short-term results of a prospective nationwide study. The Danish Breast Cancer Cooperative Group.

In a Danish nationwide prospective study of in situ carcinoma of the breast, 112 women with ductal carcinoma in situ, treated with excision only, were registered from 1982 to 1987. Within a median follow-up of 53 months, a crude recurrence rate of 22% (25 cases) was found, of which five cases recurred as invasive carcinomas and 20 cases as in situ carcinomas. The histopathologic review included a single-parameter analysis of histological growth pattern, size of lesion, nuclear size, presence of comedonecrosis, and subhistologic type. A strong interrelationship was found for histological growth pattern, nuclear size, and comedonecrosis. These parameters were also significantly related to recurrence. Cases that had clinical symptoms had a high recurrence rate as compared with cases that were discovered by mammography only or incidentally.