Risk factors for local and distant recurrence after breast-conserving therapy and mastectomy were compared to define guidelines for the decision making between both treatments.
The data of two ...randomized clinical trials for stage I and II breast cancer patients were pooled. The total number of patients in the study was 1,772, of whom 879 underwent breast conservation, and 893, modified radical mastectomy. Representative slides of the primary tumor were available for histopathologic review in 1,610 cases (91%).
There were 79 patients with local recurrence after breast-conservation and 80 after mastectomy, the 10-year rates being 10% (95% confidence interval CI, 8% to 13%) and 9% (95% CI, 7% to 12%), respectively. Age no more than 35 years (compared with age >60: hazard ratio HR, 9.24; 95% CI, 3.74 to 22.81) and an extensive intraductal component (HR, 2.52; 95% CI, 1.26 to 5.00) were significantly associated with an increased risk of local recurrence after breast-conserving therapy. Vascular invasion was predictive of the risk of local recurrence, irrespective of the type of primary treatment (P <.01). Tumor size, nodal status, high histologic grade, and vascular invasion were all highly significant predictors of distant disease after breast-conserving therapy and mastectomy (P <.01). Age no more than 35 years and microscopic involvement of the excision margin were additional independent predictors of distant disease after breast-conserving therapy (P <.01).
Age no more than 35 years and the presence of an extensive intraductal component are associated with an increased risk of local recurrence after breast-conserving therapy. Vascular invasion causes a higher risk of local recurrence after mastectomy as well as after breast-conserving therapy and should therefore not be used for deciding between the two treatments.
Abstract ONCOPOOL is a retrospectively compiled database of primary operable invasive breast cancers treated in the 1990s in 10 European breast cancer Units. Sixteen thousand and nine hundred and ...forty four cases were entered, with tumours less than 5 cm diameter in women aged 70 or less (mean age 55). Data Data were date of birth, mode of diagnosis, pathology (size, lymph node status, grade, type, lympho-vascular invasion and hormone receptor) and therapies and outcome measures: first local, regional or distant recurrences, contralateral primary, date and cause of death. Tumour characteristics Mean diameter 1.8 cm, 66% lymph node negative, 24% 1–3 lymph nodes involved and 10% had 4 or more involved. Grade 1, 29%; Grade 2, 41%; and Grade 3, 30%. Polynomial relationships were established between grade, stage and size. Seventy-five percent were oestrogen receptor (ER) positive. ER closely related to grade. Outcomes Overall Survival was 89% at 5 years from diagnosis, 80% 10 years and 73% 15 years; Breast Cancer-Specific survivals were 91%, 84% and 79%. Survival strongly related to the Nottingham Prognostic Index (NPI). Cases detected at screening had 84% 10-year survival, those presenting symptomatically 76%. ER positive cases treated with adjuvant hormone therapy had a reduction in risk of death of 13% over those not receiving adjuvant therapy ( p = 0.000). ER negative cases treated with chemotherapy showed a risk reduction of 23% over those not receiving chemotherapy ( p = 0.000).
The purpose of this study was to estimate the incidence and prognostic value of axillary lymph node micrometastases (Nmic) of 2 mm or less in breast carcinomas. Results are based on data from the ...Danish Breast Cancer Cooperative Group (DBCG). The study was carried out as a nationwide, population‐based trial with a study series consisting of 6,959 women under 75 years of age registered in the national DBCG data base from 1 January 1990 to 31 October 1994. All patients had contracted operable primary breast carcinoma, stage I–III, classified according to the TNM system as T1‐T3, N0‐N1, M0. Women with four or more metastatic axillary lymph nodes were excluded. All patients were treated systematically according to approved national guidelines and treatment protocols. Metastases were recognized microscopically on haematoxylin and eosin‐stained sections. In case of doubt immunohistochemical staining for cytokeratin was performed. There was no serial sectioning. Micrometastases were tumour deposits of 2 mm or smaller, and accordingly included deposits of 0.2 mm and smaller. With a median observation time of 10 years and 2 months, women with Nmic (N=427) experienced a significantly worse overall survival (OS) compared with node‐negative (Nneg) women (N=4,767) (relative risk (RR)=1.20, 95% CI: 1.01–1.43), irrespective of menopausal status. Women with macrometastases (Nmac) (N=1,765) had significantly worse final outcome than women with Nmic (RR=1.54, 95% CI: 1.29–1.85), irrespective of menopausal status. Multivariate analysis adjusted for patient‐, histopathologic‐, and loco‐regional therapeutic variables showed that cases with Nmic had a significantly higher risk of death relative to Nneg cases (adjusted RR=1.49, 95% CI: 1.18–1.90). Interaction analysis showed that the number of nodes examined had a significant impact on adjusted relative risk of death according to axillary status. Furthermore, the number of nodes involved significantly influenced adjusted risk of death in the Nmic compared to the Nmac series. In conclusion, the results of the present study revealed worse final outcome in women with Nmic compared with Nneg, where all Nmic cases received adjuvant systemic treatment. Interaction analysis showed that the number of retrieved axillary nodes and the number of affected nodes had a different influence on survival related to axillary status. The different risk pattern in Nmic vs Nmac patients indicates that Nmic cases do not show the traditional risk pattern as revealed by the Nmac cases, in which increasing number of positive nodes is associated with an orderly increasing adjusted RR.
Objective To use data from two longstanding, population based screening programmes to study overdiagnosis in screening mammography.Design Population based cohort study.Setting Copenhagen municipality ...(from 1991) and Funen County (from 1993), Denmark.Participants 57 763 women targeted by organised screening, aged 56-69 when the screening programmes started, and followed up to 2009.Main outcome measures Overdiagnosis of breast cancer in women targeted by screening, assessed by relative risks compared with historical control groups from screening regions, national control groups from non-screening regions, and historical national control groups.Results In total, 3279 invasive breast carcinomas and ductal carcinomas in situ occurred. The start of screening led to prevalence peaks in breast cancer incidence: relative risk 2.06 (95% confidence interval 1.64 to 2.59) for Copenhagen and 1.84 (1.46 to 2.32) for Funen. During subsequent screening rounds, relative risks were slightly above unity: 1.04 (0.85 to 1.27) for Copenhagen and 1.14 (0.98 to 1.32) for Funen. A compensatory dip was seen after the end of invitation to screening: relative risk 0.80 (0.65 to 0.98) for Copenhagen and 0.67 (0.55 to 0.81) for Funen during the first four years. The relative risk of breast cancer accumulated over the entire follow-up period was 1.06 (0.90 to 1.25) for Copenhagen and 1.01 (0.93 to 1.10) for Funen. Relative risks for participants corrected for selection bias were estimated to be 1.08 for Copenhagen and 1.02 for Funen; for participants followed for at least eight years after the end of screening, they were 1.05 and 1.01. A pooled estimate gave 1.040 (0.99 to 1.09) for all targeted women and 1.023 (0.97 to 1.08) for targeted women followed for at least eight years after the end of screening.Conclusions On the basis of combined data from the two screening programmes, this study indicated that overdiagnosis most likely amounted to 2.3% (95% confidence interval −3% to 8%) in targeted women. Among participants, it was most likely 1-5%. At least eight years after the end of screening were needed to compensate for the excess incidence during screening.
Abstract According to EUSOMA position paper ‘The requirements of a specialist breast unit’, each breast unit should have a core team made up of health professionals who have undergone specialist ...training in breast cancer. In this paper, on behalf of EUSOMA, authors have identified the standards of training in breast cancer, to harmonise and foster breast care training in Europe. The aim of this paper is to contribute to the increase in the level of care in a breast unit, as the input of qualified health professionals increases the quality of breast cancer patient care.
The purpose of this study was to determine the impact of surgery and radiotherapy on late morbidity associated with the management of the axilla in breast cancer patients. Two hundred and sixty-six ...patients from a randomized breast conservation trial (DBCG-82TM protocol) were called in for a single follow-up interview and clinical examination of several functional outcome measures after a median of 6.6 years (3.5-10.5). All the patients were treated with lumpectomy and axillary dissection, followed by external beam radiotherapy to the residual breast. High-risk patients were given additional radiation to the regional lymph nodes plus adjuvant systemic treatment. Twenty-eight patients (11%) had arm edema (> or = 2 cm), which was associated with the extent of axillary node dissection as well as with age and radiotherapy (relative risk, RR = 4.5 (1.8-11.2, p = 0.001)). Impaired shoulder movement of any degree (7%) was associated with radiotherapy (RR = 4.0 (1.5-13.8, p = 0.007)) and advanced age (p = 0.002), while the extent of axillary dissection as described by the number of nodes retrieved was the only factor that predicted pain on logistic regression analysis (p = 0.02). A moderate to severe change in arm/shoulder strength and working ability was observed in 7% and 5% of patients, respectively, but no independent predisposing factor was discerned for these endpoints. It is concluded that the level of late functional morbidity several years after breast-conserving treatment is relatively low and clearly relates to age, extension of surgery, irradiation of the axilla or a combination of these factors, depending on the specific clinical outcome measure.
Objectives To evaluate the effect on breast cancer mortality during the first 10 years of the mammography service screening programme that was introduced in Copenhagen in 1991. Design Cohort study. ...Setting The mammography service screening programme in Copenhagen, Denmark. Participants All women ever invited to mammography screening in the first 10 years of the programme. Historical, national, and historical national control groups were used. Main outcome measures The main outcome measure was breast cancer mortality. We compared breast cancer mortality in the study group with rates in the control groups, adjusting for age, time period, and region. Results Breast cancer mortality in the screening period was reduced by 25% (relative risk 0.75, 95% confidence interval 0.63 to 0.89) compared with what we would expect in the absence of screening. For women actually participating in screening, breast cancer mortality was reduced by 37%. Conclusions In the Copenhagen programme, breast cancer mortality was reduced without severe negative side effects for the participants.
The aim of this study was to investigate and compare the prognosis after treatment for loco-regional recurrences (LR) after (modified) radical mastectomy (MRM) or breast conserving therapy (BCT), in ...terms of overall survival and time to subsequent LR, in patients originally treated in two European randomised trials. In EORTC trial 10801 and DBCG trial 82-TM, 1,807 patients with stage I and II breast cancer were randomised to receive MRM or BCT from 1980 to 1989. All patients with a LR in these trials were analysed for survival and time to subsequent LR after salvage treatment. Of these, 133 patients had their LR as a first event, the majority within 5 years after initial treatment. The prognostic significance for survival and time to subsequent LR after salvage treatment was analysed in uni-, and multivariate analyses for a number of original tumour- and recurrence-related variables. After salvage treatment of LR after MRM or BCT, actuarial survival curves and the actuarial loco-regional control curves were similar. The 5-year survival rates were 58% and 59% and the 5-year subsequent loco-regional control rates 62% and 63%, respectively. In a multivariate analysis, pN category (
P=0.03), pT category (
P=0.01) and vascular invasion (
P=0.02) of the primary tumour were the only independent prognostic factors for survival, whereas extensive LR (
P<0.001), interval ≤2 years (
P<0.002) and pN+ at primary treatment (
P=0.004) were significant predictive factors for time to subsequent LR. The type of original treatment (MRM or BCT) did not have any prognostic impact. It is concluded that the survival and time to subsequent LR after treatment for an early loco-regional recurrence after MRM or BCT was similar in these two European randomised trials. This suggests that both after MRM and BCT an early LR is an indicator of a biologically aggressive tumour; early loco-regional relapse carries a poor prognosis and salvage treatment only cures a limited number of patients, whether treated by MRM or BCT originally.
Cardiovascular disease atherosclerosis and subsequent myocardial infarction (MI) has been associated with primary hyperparathyroidism. We aimed at studying cardiovascular events before and after ...surgery and mortality after surgery for primary hyperparathyroidism using a historical follow‐up design. A total of 674 patients who underwent surgery at three Danish centers between January 1, 1979 and December 31, 1997 were compared with 2021 age‐ and gender‐matched controls. There was an increased incidence of acute MI up to 10 years prior to surgery relative risk (RR) 2.5, 95% confidence interval (95% CI) 1.5–4.2 and within the first year following surgery (RR 3.6, 95% CI 1.7–7.6). The risk of MI subsequently declined to a normal level more than 1 year after surgery. Patients with MI prior to diagnosis also had a higher postoperative risk of new infarction than did patients without odds ratio (OR) 6.0, 95% CI 1.2–30.0. The risk of hypertension, stroke, congestive heart failure, and diabetes was increased before surgery. More than 1 year after surgery only hypertension and congestive heart failure were more frequent in patients than controls. Preoperative cardiovascular disease was associated with an increased risk of death (RR 1.8, 95% CI 1.1–2.8). Mortality following surgery was higher than in the general population between 1979 and 1990 but not between 1991 and 1997. We concluded that there was an increase in acute MI up to 10 years prior to surgery. The risk of MI decreased to a normal level after surgery, which may be important for preventing cardiovascular disease in patients with primary hyperparathyroidism.
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