Göran Liljegren

10-Year Results After Sector Resection With or Without Postoperative Radiotherapy for Stage I Breast Cancer: A Randomized Trial

PURPOSE To study the long-term effectiveness of postoperative radiotherapy after sector resection for breast cancer in a randomized trial in which mammography is a major pathway to diagnosis. PATIENTS AND METHODS Three hundred eighty-one women with a unifocal breast cancer < or = 20 mm in diameter on the preoperative mammogram and without histopathologic signs of axillary metastases were treated by sector resection plus axillary dissection. Of these patients, 184 women were randomized to receive postoperative radiotherapy to the breast (XRT group), and 197 women received no further treatment (non-XRT group). RESULTS The local recurrence rate was 8.5% (95% confidence interval [CI], 3.9% to 13.1%) in the XRT group and 24.0% (95% CI, 17.6% to 30.4%) in the non-XRT group (P =.0001). Survival free from regional and distant recurrence was 83. 3% in the XRT group (95% CI, 77.5% to 89.1%) and 80.0% in the non-XRT group (95% CI, 73.9% to 86.1%) (P =.23). Overall survival was 77.5% in the XRT group (95% CI, 70.9% to 84.1%) and 78% in the non-XRT group (95% CI, 71.7% to 84.3%) (P =.99). A subgroup analysis suggested that women older than 55 years of age without comedo or lobular carcinomas had a low risk of local recurrence of 6.1% (95% CI, 0.1% to 9.1%) in the XRT-group and 11.0% (4.0% to 18.0%) in the non-XRT group (P =.16). CONCLUSION Sector resection plus radiotherapy resulted in an absolute reduction in local recurrence of 16% at 10 years compared with surgery alone. Women older than 55 years of age without comedo or lobular carcinomas may have a low risk of local recurrence. Postoperative radiotherapy was not shown to reduce distant recurrences or improve overall survival.

Case-Control Study on Concentrations of Organohalogen Compounds and Titers of Antibodies to Epstein-Barr Virus Antigens in the Etiology of Non-Hodgkin Lymphoma

A rapid increase in incidence of non-Hodgkin lymphoma (NHL) has been reported from many countries. Exposure to certain pesticides and organochlorines has been shown to be risk factors. Epstein-Barr virus (EBV) is a human herpesvirus that has been associated with some subgroups of NHL, such as Burkitt lymphoma and lymphomas related to severe immunosuppression. In this study, we measured lipid adjusted blood concentrations of 36 congeners of polychlorinated biphenyls (PCBs), p,p′-dichlorodiphenyl-dichloroethylene (p,p′-DDE), hexachlorobenzene (HCB), four different subgroups of chlordanes (trans-nonachlordane, cis-nonachlordane, MC6 and oxychlordane) and 2,2′,4,4′-tetrabrominated diphenyl ether (TBDE) in incident cases of NHL and controls from the general population. Titers of antibodies to the Epstein-Barr early antigen (EA) were correlated to concentrations of organochlorines. We found a significant difference in lipid adjusted blood concentrations of total PCBs and TBDE between cases and controls. Titers of antibodies to EA IgG > 80 were correlated to an increased risk for NHL with odds ratio (OR) = 1.9, 95% confidence interval (CI) =0.94–3.8. This risk was further increased in those with a level above the median value of “sum of PCBs” (OR=4.0, CI=1.2–14), HCB (OR=5.3, CI=1.6–19), sum of chlordanes (OR=4.0, CI=1.2–14) and TBDE (OR=21, CI=4.6–124), suggesting an interaction between EBV and a higher concentration of these chemicals. Also for the “sum of immunotoxic PCBs” increased risk was found in that group (OR=6.4, CI=1.9–24). Subdivision of NHL in histological types yielded highest risks for low-grade B-cell NHL.

Pulsed dose rate brachytherapy as the sole adjuvant radiotherapy after breast-conserving surgery of T1-T2 breast cancer : first long time results from a clinical study

BACKGROUND AND PURPOSE To evaluate the long time outcome with regard to local tumour control, cosmetic outcome and side effects of a short (5 days) accelerated interstitial brachytherapy treatment delivered to the surroundings of the operated sector. PATIENTS AND METHODS Between 1993 and 2003 we treated 50 women with early T1 and T2 breast cancer. Radical sector resection was performed and followed later with an interstitial pulsed dose rate (PDR) brachytherapy of 50Gy in 5 days. The treatment was centred on the tumour with a margin of 30mm. One patient was treated bilaterally. The patients were followed for a median of 86 (32-126) months. RESULTS Ipsilateral breast cancer recurrence was seen in 3 patients (6%). Two of them occurred outside the treated volume. The 5- and 7-year rates of actuarial local control were 96% and 96%, respectively, overall survival 88% and 85%, disease free survival 88% and 88%, respectively. A dosimetrical analysis showed that the partial breast irradiation covered a median of 31% of the total breast volume. Fat necrosis was seen in 12% and local (moderate-strong) fibrosis in 26% of the patients. Independent cosmetic scoring showed good or excellent result in 56% of the patients. CONCLUSIONS Local outcome is favourable and very similar to other published studies of accelerated partial breast irradiation. Our long time cosmetic results are lower than other published results.

Risk factors for local recurrence after conservative treatment in stage I breast cancer. Definition of a subgroup not requiring radiotherapy

BACKGROUND Risk factors for local recurrence after breast-conserving treatment of early breast cancer have not previously been evaluated in settings where mammography has been a major pathway to diagnosis of both primary tumour and recurrences or in patients treated surgically by a formal sector resection. PATIENTS AND METHODS Three hundred eighty-one women with stage 1 primary breast cancer were randomised after a standardised sector resection to either a course of postoperative radiotherapy to 54 Gy to the breast (XRT group) or to surgery alone (non XRT group). At five years, 43 local recurrences, six of them in the XRT group, appeared. Patient characteristics collected from the medical records, histopathological characteristics determined by re-examination of slides, and mammographic characteristics from the pre-operative mammograms were evaluated as risk factors for recurrence by univariate and multivariate Cox proportional hazards models. Results are reported as relative hazards (RH) with 95% confidence intervals (95% CI). RESULTS In the univariate analysis comedo cancer, RH 3.5 (95%, CI 18 6.7), lobular cancers RH 2.8 (95% CI 1.1 7.1), mammographic appearance as circular/oval shaped density, RH 2.3 (95% CI 1.1 4.51, and mammographic appearance as a stellate lesion with microcalcifications inside the lesion, RH 3.8 (95% CI 1.1-13.0) were identified as risk factors for local recurrence. Age, with a RH of 0.97 (95% CI 0.94 0.99) for each increasing year was inversely associated with risk. A multivariate analysis, which also took postoperative radiotherapy into account, only showed comedo cancers with a RH 2.6 (95% CI 1.3-5.0) and mammographic appearance of a stellate lesion with microcalcification inside the lesion RH 4.5 (95% CI 1.1-17.6) to be statistically significant. The estimates for age RH 0.98 (95% CI 0.95 1.01 and lobular cancers RH 2.5 (95%, CI 0.98 6.6) were marginally changed, with widened CIs. Patients > 60 years of age, without comedo or lobular carcinomas were found to be at low risk 15.9% at five years in Kaplan Meyer estimate) of local recurrence, even without postoperative radiotherapy. CONCLUSION Low age, comedo and lobular cancers and mammographic appearance of the tumour as a stellate lesion with microcalcifications inside the lesion indicate an increased risk for local recurrence after sector resection in stage 1 tumours at five years. Patients > 60 years of age without comedo or lobular cancers are at low risk for local recurrence at five years even without postoperative radiotherapy.

The cost-effectiveness of routine postoperative radiotherapy after sector resection and axillary dissection for breast cancer stage I. Results from a randomized trial

BACKGROUND Cost-effectiveness of routine postoperative radiotherapy after breast-conserving surgery has not been prospectively evaluated earlier. In times of rationing of medical resources, valid assessments of cost-effectiveness are important for rational allocation of resources. PURPOSE Cost and cost-effectiveness of routine postoperative radiotherapy was calculated in a prospective randomized trial comparing sector resection plus axillary dissection with (XRT group) or without (non-XRT group) postoperative radiotherapy in breast cancer stage I. Three hundred eighty-one patients were included. After a median follow-up of five years 43 local recurrences, six of them in the XRT-group occurred (P < 0.0001). No difference in regional and distant recurrence (P = 0.23) or survival (P = 0.44) was observed. PATIENTS AND METHODS Direct medical costs as well as indirect costs in terms of production lost during the treatment period and travel expenses were estimated from data in the medical records and the national insurance registry of each patient. Average costs of different treatment activities and measures were estimated for the XRT-group and the non-XRT group respectively. From these estimates differences in costs and effectiveness between the groups were calculated and marginal cost-effectiveness ratios were estimated. For the construction of QALYs each life-year was quality-adjusted by a utility value depending on which health state the patient was considered to perceive. RESULTS Taking into account the cost of primary treatment, the cost of follow-up, the cost of treatment of a local recurrence, travel expenses and indirect costs (production lost) excluding costs for treatment of regional and distant recurrence the cost per avoided local recurrence at five years was SEK 337,727 (

Tumor Stage Affects Risk and Prognosis of Contralateral Breast Cancer: Results From a Large Swedish-Population–Based Study

44,438, Pounds 27,018). Adjustment for quality of life showed a cost for every gained QALY to be SEK approximately 1.6 million, (

Arm lymphoedema after axillary surgery in women with invasive breast cancer

210,526, Pounds 128,000), range SEK 0.2-3.9 million (

Topoisomerase II-|[alpha]| Expression in Different Cell Cycle Phases in Fresh Human Breast Carcinomas

26,315-513,158, Pounds 16,000-312,000). CONCLUSION The cost of routine postoperative radiotherapy after sector resection and axillary dissection in breast cancer stage I per avoided local recurrence and gained QALY is high. The cost per gained QALY show great variation depending on utility value, which in this study was derived from external observers and not from the patients themselves. These results stress the importance of identifying risk factors for local recurrence, better understanding of impact on quality of life of a local recurrence and adding cost evaluations to clinical trials in early breast cancer.

Sector Resection With or Without Postoperative Radiotherapy for Stage I Breast Cancer: 20-Year Results of a Randomized Trial

PURPOSE The number of breast cancer survivors at risk of developing contralateral breast cancer (CBC) is increasing. However, ambiguity remains regarding risk factors and prognosis for women with CBC. PATIENTS AND METHODS In a cohort of 42,670 women with breast cancer in the Uppsala/Örebro and Stockholm regions in Sweden in 1992 to 2008, we assessed risk factors for and prognosis of metachronous CBC by using survival analysis. Breast cancer-specific survival for women with CBC was evaluated and compared with results for women with unilateral breast cancer (UBC) by using time-dependent Cox-regression modeling. RESULTS An increased risk for CBC was observed among women who had primary breast cancer with ≥ 10 involved lymph nodes compared with node-negative women (adjusted hazard ratio [HR], 1.8; 95% CI, 1.2 to 2.7). The prognosis was poorer in women with CBC than with UBC. The hazard of dying from breast cancer was especially high for women with a short interval time to CBC (adjusted HR, 2.3; 95% CI, 1.8 to 2.8 for CBC diagnosed ≤ 5 years v UBC) and gradually decreased with longer follow-up time but remained higher than the hazard originating from the primary tumor for ≥ 10 years. CONCLUSION Women with advanced-stage primary breast cancer had an increased risk of developing CBC. CBC is associated with an increased risk of dying from breast cancer throughout a long period of follow-up after the primary tumor. Our findings suggest that the event of CBC marks a new clinical situation in terms of investigations for metastases, treatment considerations, and follow-up strategy.

Self-perceived, but not objective lymphoedema is associated with decreased long-term health-related quality of life after breast cancer surgery

The primary aim was to compare arm lymphoedema after sentinel lymph node biopsy (SLNB) alone versus axillary lymph node dissection (ALND) in women with node‐negative and node‐positive breast cancer. The secondary aim was to examine the potential association between self‐reported and objectively measured arm lymphoedema.