Breast cancer survival and stage at diagnosis in Australia, Canada, Denmark, Norway, Sweden and the UK, 2000-2007: a population-based study.

BACKGROUND: We investigate whether differences in breast cancer survival in six high-income countries can be explained by differences in stage at diagnosis using routine data from population-based cancer registries. METHODS: We analysed the data on 257,362 women diagnosed with breast cancer during 2000-7 and registered in 13 population-based cancer registries in Australia, Canada, Denmark, Norway, Sweden and the UK. Flexible parametric hazard models were used to estimate net survival and the excess hazard of dying from breast cancer up to 3 years after diagnosis. RESULTS: Age-standardised 3-year net survival was 87-89% in the UK and Denmark, and 91-94% in the other four countries. Stage at diagnosis was relatively advanced in Denmark: only 30% of women had Tumour, Nodes, Metastasis (TNM) stage I disease, compared with 42-45% elsewhere. Women in the UK had low survival for TNM stage III-IV disease compared with other countries. CONCLUSION: International differences in breast cancer survival are partly explained by differences in stage at diagnosis, and partly by differences in stage-specific survival. Low overall survival arises if the stage distribution is adverse (e.g. Denmark) but stage-specific survival is normal; or if the stage distribution is typical but stage-specific survival is low (e.g. UK). International differences in staging diagnostics and stage-specific cancer therapies should be investigated.

Oestrogen receptor co-activator AIB1 is a marker of tamoxifen benefit in postmenopausal breast cancer.

BACKGROUND: The oestrogen receptor (ER) co-activator amplified in breast cancer 1 (AIB1) has been suggested as a treatment predictive and prognostic marker in breast cancer. Studies have however not been unanimous. PATIENTS AND METHODS: AIB1 protein expression was analysed by immunohistochemistry on tissue micro-arrays with tumour samples from 910 postmenopausal women randomised to tamoxifen treatment or no adjuvant treatment. Associations between AIB1 expression, clinical outcome in the two arms and other clinicopathological variables were examined. RESULTS: In patients with ER-positive breast cancer expressing low tumour levels of AIB1 (<75%), we found no significant difference in recurrence-free survival (RFS) or breast cancer-specific survival (BCS) between tamoxifen treated and untreated patients. In patients with high AIB1 expression (>75%), there was a significant decrease in recurrence rate (HR 0.40, 95% CI 0.26-0.61, P < 0.001) and breast cancer mortality rate (HR 0.38, 95% CI 0.21-0.69, P = 0.0015) with tamoxifen treatment. In the untreated arm, we found high expression of AIB1 to be significantly associated with lower RFS (HR 1.74, 95% CI 1.20-2.53, P = 0.0038). CONCLUSION: Our results suggest that high AIB1 is a predictive marker of good response to tamoxifen treatment in postmenopausal women and a prognostic marker of decreased RFS in systemically untreated patients.

Time dependent effects of adjuvant tamoxifen therapy on cerebrovascular disease: results from a randomised trial.

BACKGROUND: Tamoxifen has been associated with an increased risk of stroke. There is, however, little information on the effect in the post-treatment period. Using data from the Swedish Breast Cancer Group adjuvant trial of 5 vs 2 years of tamoxifen treatment, we now report both short-term and long-term effects on morbidity as well as mortality because of cerebrovascular disease. METHODS: Data from the Swedish National Hospital Discharge Registry combined with information from the Swedish Cause of Death Registry was used to define events of disease. Hazard ratios (HRs) were estimated using Cox regression. RESULTS: Comparing patients randomised to 5 years of tamoxifen with patients randomised to 2 years of tamoxifen, the incidence of cerebrovascular diseases was increased (HR 1.70, 95% CI 1.05-2.75) during the active treatment phase and reduced after the active treatment period (HR 0.78, 95% CI 0.63-0.96), and the difference in HR between the two time-periods was significant (P=0.0033). The mortality from cerebrovascular diseases was increased during the treatment period (HR 3.18, 95% CI 1.03-9.87) and decreased during the post-treatment period (HR 0.60, 95% CI 0.40-0.90) with a significant difference in HR between the two periods of follow-up (P=0.0066). Similar results were seen for subgroups of cerebrovascular diseases, such as stroke and ischaemic stroke. CONCLUSION: In an adjuvant setting, tamoxifen was associated with an increased risk of cerebrovascular disease during treatment, but a decreased risk in the post-treatment period.

Prognostic utility of HOXB13:IL17BR and molecular grade index in early-stage breast cancer patients from the Stockholm trial.

BACKGROUND: A dichotomous index combining two gene expression assays, HOXB13:IL17BR (H:I) and molecular grade index (MGI), was developed to assess risk of recurrence in breast cancer patients. The study objective was to demonstrate the prognostic utility of the combined index in early-stage breast cancer. METHODS: In a blinded retrospective analysis of 588 ER-positive tamoxifen-treated and untreated breast cancer patients from the randomised prospective Stockholm trial, H:I and MGI were measured using real-time RT-PCR. Association with patient outcome was evaluated by Kaplan-Meier analysis and Cox proportional hazard regression. A continuous risk index was developed using Cox modelling. RESULTS: The dichotomous H:I+MGI was significantly associated with distant recurrence and breast cancer death. The >50% of tamoxifen-treated patients categorised as low-risk had <3% 10-year distant recurrence risk. A continuous risk model (Breast Cancer Index (BCI)) was developed with the tamoxifen-treated group and the prognostic performance tested in the untreated group was 53% of patients categorised as low risk with an 8.3% 10-year distant recurrence risk. CONCLUSION: Retrospective analysis of this randomised, prospective trial cohort validated the prognostic utility of H:I+MGI and was used to develop and test a continuous risk model that enables prediction of distant recurrence risk at the patient level.

Factors influencing return to work: a narrative study of women treated for breast cancer.

The purpose of this qualitative study was to identify factors contributing to a successful return to the labour market after treatment for breast cancer from the women's own perspective. The study is based on 16 narratives - open-ended, in-depth interviews - about women's experiences and thoughts from the period after breast cancer surgery when they focused on their return to work. The women were recruited from participants of a multicentre trial, which allowed comparisons across a range of adjuvant therapies. The narratives of women who worked full time at a cut-off point of 1 year after surgery are analysed separately from the narratives of women still sick-listed at that point of time. The findings show that while all the women strove to belong to the labour market, the study also reveals changes in women's perceptions of the value of employment. The quality of social support received from employers and coworkers differed between women who returned to work and those still sick-listed 1 year after breast cancer treatment. A need to design interventions focusing on the work arena of women treated for breast cancer is pointed out.

Impact of tumour size on axillary involvement and distant dissemination in breast cancer.

BACKGROUND: Tumour size and nodal involvement are the two main prognostic factors in breast cancer (BC). Their impact on the natural history of BC is not fully captured by analyses that ignore their quantitative nature. METHOD: Data pertaining to 18 159 patients treated with primary surgery: 3661 at the Institut Gustave-Roussy (IGR, France) between 1954 and 1983, and 14 498 in the breast cancer registry in the Stockholm-Gotland Health Care region (SG, Sweden) between 1976 and 1999, were collected. The risks of distant metastases (DMs) and of nodal involvement were analysed according to tumour size with parametric models. RESULTS: Using SG 1976-1990 as the reference group, relative risks (RRs) for DM were equal to 1.42 (95% CI: 1.29-1.56; P<10(-10)) in IGR and 0.61 (95% CI: 0.55-0.67; P<10(-10)) in SG 1991-1999. Differences in tumour size explained the increased risk in IGR (RR adjusted for tumour size 1.09; 95% CI: 0.99-1.20; P=0.07), but not the decreased risk in SG 1991-1999 (adjusted RR: 0.63; 95% CI: 0.57-0.69; P<10(-10)). The relationship between tumour size and DM risk changed significantly during the 1990s. CONCLUSION: Early diagnosis is sufficient to explain differences in the prognosis before 1990. After 1990, the use of adjuvant systemic therapies is the main reason for the reduction in DM.

Adjuvant goserelin and ovarian preservation in chemotherapy treated patients with early breast cancer: results from a randomized trial.

The purpose of this randomized study was to examine if goserelin concomitant to CMF-chemotherapy as adjuvant treatment for premenopausal breast cancer, protects the ovaries from premature failure. A total of 285 premenopausal breast cancer patients, in a randomized adjuvant trial (Zoladex in premenopausal patients (ZIPP)), were assigned to a study on ovarian function. Node positive patients were assigned to CMF-(cyclophosphamide, methotrexate and 5-fluorouracil) chemotherapy in addition to endocrine therapy. All patients were randomly assigned to receive 2 years of goserelin, goserelin plus tamoxifen, tamoxifen alone or no endocrine treatment. We studied, if menses were affected in the treatment groups, up to 36 months after randomization. One year after completed CMF- and endocrine therapy, 36% of the women in the goserelin group reported menses, compared to 7% in the goserelin plus tamoxifen group, 13% in the tamoxifen group and 10% of the controls. Among women treated with goserelin, there was a statistically significant increase in the proportion of menstruating women, 1 year after completed treatment compared to at 24 months of treatment (P = 0.006), in contrast to all other treatment groups, who were unchanged or more often amenorrheic. In our study, there is some evidence of protective effect of goserelin on ovarian function in CMF treated women. This effect was not observed in the combined tamoxifen and goserelin treatment.

Amplification of CCND1 and PAK1 as predictors of recurrence and tamoxifen resistance in postmenopausal breast cancer.

The 11q13 region is amplified in approximately 15% of all breast tumors. Situated in this region are the cyclin D1 gene (CCND1) and the p-21-activated kinase 1 (PAK1) gene. Both genes encode proteins shown to activate the estrogen receptor (ER), leading to transcription of CCND1 and other ER-responsive genes. Here, we investigate the prognostic and treatment predictive role of CCND1 and PAK1 gene amplification in postmenopausal breast cancer patients randomized to tamoxifen treatment or no adjuvant treatment. Amplification of CCND1 and PAK1, assessed by real-time PCR, was observed in 12.5 and 9.3%, respectively. Amplification of PAK1 was seen in 37% of the CCND1-amplified tumors, indicating coamplification (P<0.001). In ER-positive patients, amplification of at least one of the genes indicated a reduced recurrence-free survival (P=0.025). When response to tamoxifen treatment was analysed, patients with PAK1 amplification showed decreased benefit from the drug (ER+; relative risk ratio (RR)=1.62; 95% confidence interval (CI), 0.47-5.55) compared to patients without amplification (ER+; RR=0.53; 95% CI, 0.32-0.88). This was not evident for CCND1 amplification. We show that PAK1 may be a predictor of tamoxifen resistance and furthermore, we do not discard PAK1 as a potential candidate oncogene in the 11q13 amplicon. In addition, we show that high pak1 protein levels may predict tamoxifen insensitivity.

Adjuvant goserelin in pre-menopausal patients with early breast cancer: Results from the ZIPP study.

The Zoladex In Pre-menopausal Patients (ZIPP) study was designed to determine whether addition of goserelin ('Zoladex') and/or tamoxifen to adjuvant therapy (radiotherapy and/or chemotherapy), provided benefit to pre- or peri-menopausal women with operable, early breast cancer. A combined analysis of four randomised trials using a core protocol was performed. Patients (n = 2710) were randomised into a 2 x 2 factorial trial based on goserelin and tamoxifen (n = 1800) or randomised to receive goserelin or not (n = 910; some received elective tamoxifen) for 2 years. The analysis presented here compares women who did (n = 1354) or did not (n = 1356) receive goserelin. After a median follow-up of 5.5 years, goserelin provided a significant benefit for event-free survival (hazard ratio [HR] 0.80; 95% confidence interval [CI] 0.69, 0.92; P = 0.002) and overall survival (HR 0.81; 95% CI 0.67, 0.99; P = 0.038). Goserelin was well tolerated. These data show that the addition of goserelin to standard adjuvant therapy is more effective than standard therapy alone in pre-menopausal women with early breast cancer.

Descriptive clinicopathologic study of 17 patients with endometrial cancer during or after adjuvant tamoxifen in early breast cancer.

BACKGROUND: Studies have shown that patients with early-stage endometrial cancer who have previously used endogenous estrogen (oral contraceptives or estrogen replacement therapy) have a favorable prognosis. This has not yet been demonstrated for patients with early-stage endometrial cancer who have received tamoxifen. In addition, studies have raised the question of whether women receiving tamoxifen are at increased risk of endometrial cancer. PURPOSE: Our aim was to determine whether the prognosis is favorable for patients with diagnosis of endometrial cancer after adjuvant treatment with tamoxifen for breast cancer. METHODS: We matched 931 patients from the Stockholm Adjuvant Tamoxifen Trial in early breast cancer against the Swedish Cancer Registry and identified 17 who subsequently had endometrial cancer. These patients had been randomly assigned to receive 40 mg/d tamoxifen orally for 2 years beginning 4 weeks after surgery for breast cancer. Histologic specimens, patient records, and death certificates were reviewed to verify treatment and causes of death. RESULTS: Thirteen of the 17 patients diagnosed with endometrial cancer were alive; for three of the four who had died, the cause of death was endometrial cancer. All 16 evaluable tumors except one were World Health Organization (WHO) histologic grades I-II. Only one patient had advanced disease (stage IV); the remaining tumor was a mixed mesodermal malignant tumor that could not be classified under the WHO grading system. Median time for adjuvant tamoxifen use was 24 months (range, 6-60 months) with a median cumulative tamoxifen dose of 29 g (range, 7-72 g). Median time from initiation of adjuvant tamoxifen to diagnosis of endometrial cancer was 32 months (range, 6-130 months). Ten-year actuarial survival after diagnosis of endometrial cancer for the 17 patients treated with tamoxifen was 73%. CONCLUSION: Because of the small number of patients, our results do not rule out the possibility of a favorable prognosis for patients with a diagnosis of endometrial cancer following tamoxifen treatment. IMPLICATIONS: The incidence of secondary endometrial cancer reported in this study following treatment of breast cancer patients with tamoxifen at doses of 40 mg/d in a large clinical trial is higher than that reported for previous large trials of tamoxifen at doses of 20 mg/d. Thus, tamoxifen dosage may be a critical factor in the subsequent occurrence of endometrial cancer. Our results also suggest two important considerations for improved follow-up in long-term tamoxifen trials: careful registration of second cancers and routine gynecologic examinations to ensure early detection of endometrial cancer.

Adjuvant tamoxifen therapy for early stage breast cancer and second primary malignancies. Stockholm Breast Cancer Study Group.

BACKGROUND: Tamoxifen is being increasingly used for the treatment of breast cancer and is undergoing study for the primary prevention of breast cancer. However, concerns have been raised that the drug may increase the incidence of new primary malignancies, such as endometrial, liver, and colorectal cancers. PURPOSE: Our goal was to assess the carcinogenic risks associated with long-term use of tamoxifen in women with early stage breast cancer. METHODS: The incidence of new primary cancers among 2729 women participants of the Stockholm Trial was determined at a median follow-up of 9 years. In this trial, after primary surgery, postmenopausal patients aged less than 71 years with unilateral invasive breast cancer were randomly allocated to receive either 2 years of adjuvant tamoxifen (40 mg daily) or no adjuvant endocrine therapy. Information on second cancers was obtained by retrospective linkage to the Swedish Cancer Registry. To increase statistical power, a joint analysis of the incidence of endometrial and gastrointestinal cancers was performed in the following three major studies in Scandinavia evaluating adjuvant tamoxifen therapy: the Stockholm Trial, the Danish Breast Cancer Group Trial, and the South-Swedish Trial. These studies included a total of 4914 patients with a median follow-up of 8-9 years. All P values were calculated from two-tailed tests of statistical significance. RESULTS: In the Stockholm Trial, there was a statistically significant (P = .008) reduction in the incidence of second primary cancers in the contralateral breast among the tamoxifen-treated patients. However, there was a nearly sixfold increase in endometrial cancers (P < .001) and a threefold increase in gastrointestinal cancers in the tamoxifen-treated patients. The results of the joint studies showed a statistically significant increase in endometrial cancers among the tamoxifen-treated patients (relative risk [RR] = 4.1; 95% confidence interval [CI] = 1.9-8.9). There was also an excess of gastrointestinal cancers associated with tamoxifen. Most of this excess involved colorectal cancers (RR = 1.9; 95% CI = 1.1-3.3) and stomach cancer (RR = 3.2; 95% CI = 0.9-11.7). There was no substantial increase in any other type of gastrointestinal cancer (e.g., liver cancer) among the tamoxifen-treated patients. CONCLUSION: The endometrium and gastrointestinal organs may be target sites for tamoxifen-induced carcinogenesis in humans. IMPLICATIONS: The increased incidence of colorectal and stomach cancers reported here should be regarded as tentative until supported by long-term data from a larger number of tamoxifen trials. Also, appropriate surveillance of cancer incidence is warranted for the protection of participants enrolled in current tamoxifen chemoprevention trials.

Evaluation of irradiated heart volumes in stage I breast cancer patients treated with postoperative adjuvant radiotherapy.

PURPOSE: To quantify the proportion of heart volumes that received at least 25 Gy with tangential photon fields in patients with left-sided stage I (T1 NOMO) breast cancer treated with breast-conserving surgery. METHODS AND MATERIALS: The dose planning of 100 consecutive patients was reviewed. All were irradiated with tangential photon fields that covered the left breast only. A three-dimensional computed tomographic (CT)-based dose planning was made for each patient. The prescribed dose to the tumor was 50 Gy. For each patient, the proportion of the heart included in the 50% isodose was determined from the cumulative dose-volume histogram (DVH). The same volume determination was made for the left-sided breast cancer patients treated with tangential fields during the first Stockholm Breast Cancer Trial. RESULTS: The mean irradiated heart volume that received at least 25 Gy was 5.7% (SD = 4.5%) for the whole group and 11.9% (SD = 3.7%) in those with the highest volumes. The mean irradiated heart volume included in the 50% isodose for patients in the Stockholm Trial was 25% (SD = 11.9%). CONCLUSION: In this study, the majority of patients with left-sided T1NOMO breast cancer did not receive irradiation to substantial heart volumes. However, in 6% of all studied patients, the proportion of irradiated heart volume was close to the irradiated heart volumes with one of the treatment techniques used in the Stockholm Trial for patients with left-sided tumors. That technique has been associated with significantly increased cardiac mortality during long-term follow-up evaluation in a previous study. The CT-based three-dimensional treatment-planning system (TMS) represents a valuable tool in identifying such patients; thus, treatment may be conformed to reduce the irradiated heart volume.

Bone mineral density among premenopausal women with early breast cancer in a randomized trial of adjuvant endocrine therapy.

PURPOSE: To examine the effects on bone mineral density of 2 years of treatment with a luteinizing hormone-releasing hormone (LHRH) agonist alone or in combination with tamoxifen or tamoxifen alone in premenopausal breast cancer. PATIENTS AND METHODS: We recruited 89 women from two centers in Stockholm participating in a randomized multicenter trial of three different endocrine approaches in the adjuvant setting (Zoladex in Premenopausal Patients Trial). The women were assigned to receive the LHRH agonist goserelin with or without tamoxifen, tamoxifen alone, or no endocrine therapy. The treatment was given for 2 years. We measured total-body bone density before start of treatment and at 12, 24, and 36 months. RESULTS: After 2 years of treatment, there was a significant loss of bone mineral density (mean change, -5%; P <.001) in the women receiving goserelin alone. The combined goserelin and tamoxifen treatment, as well as tamoxifen alone, resulted in a lesser but statistically significant decline in bone mineral density (mean change, -1.4%; P =.02; and -1.5%; P <.001). One year after cessation of treatment, the goserelin group alone showed a partial recovery from bone loss (mean change, 1.5%; P =.02). CONCLUSION: Two years of ovarian ablation from goserelin treatment caused a significant reduction in bone mineral density but there was a partial recovery from the bone loss 1 year after cessation of treatment. The addition of tamoxifen seems to partially counteract the demineralizing effects of goserelin.

Long-term adjuvant tamoxifen in early breast cancer: effect on bone mineral density in postmenopausal women.

The decrease in sex steroid hormone levels after the onset of menopause is associated with bone loss and subsequent osteoporosis. Tamoxifen has antiestrogenic properties and may thus theoretically decrease bone mineral density, particularly after long-term treatment. Bone mineral density (BMD) was assessed in 75 recurrence-free postmenopausal breast cancer patients included in a randomized trial of adjuvant tamoxifen (40 mg daily) for 2 or 5 years versus no adjuvant endocrine therapy. The measurements were done about 7 years after the initial randomization. BMD was measured with single-photon absorptiometry (SPA) at two levels of the distal forearm representing cortical and trabecular bone. The BMD was found to be similar among tamoxifen patients compared with the controls. For cortical bone, the BMD was 1.03 g/cm2 (95% confidence interval [Cl], 0.97 to 1.09) among tamoxifen patients and 1.03 g/cm2 (95% Cl, 0.96 to 1.11) in controls. For trabecular bone, the values were 0.74 g/cm2 (95% Cl, 0.70 to 0.79) and 0.73 g/cm2 (95% Cl, 0.68 to 0.79), respectively. The results thus did not indicate an accelerated postmenopausal bone loss with long-term adjuvant tamoxifen.

Adjuvant tamoxifen in early-stage breast cancer: effects on intercurrent morbidity and mortality.

Intercurrent mortality and the pattern of inpatient hospital care was studied among 1,846 postmenopausal patients included in the Stockholm randomized trial of adjuvant tamoxifen (40 mg daily for 2 years) versus no adjuvant endocrine therapy. The median follow-up time was 54 months (range, 2 to 123 months). The patients were matched to the Swedish National Registry of Causes of Death and a computerized register covering about 95% of all hospital admissions in Stockholm County. There was no significant difference in the pattern of intercurrent mortality among the tamoxifen and control patients. The total number of hospital admissions was similar in both groups, but the tamoxifen patients were admitted significantly less frequently because of immunologic diseases (relative risk [RR] = 0.4; 95% confidence interval [CI], 0.2 to 0.9). Admissions because of thrombotic diseases were slightly, but not significantly, more frequent among the tamoxifen patients (RR = 1.2; 95% [CI], 0.6 to 2.3). The risk of hospital stay for benign gynecologic diseases other than prolapse or uterine bleeding was increased in the tamoxifen group (RR = 3.2; 95% CI, 1.2 to 8.6). No significant differences were found for diseases related to arteriosclerosis or osteoporosis. The study confirms and extends previous reports, which have shown that tamoxifen has few and usually mild side effects. However, the current results should be judged cautiously because of the relatively short median follow-up time (4.5 years) and the limitation of data in detecting morbidity that does not necessarily result in hospitalization.

The relationship between hormone receptor content and the effect of adjuvant tamoxifen in operable breast cancer.

The relationship between hormone receptor status and the effect of adjuvant tamoxifen in early breast cancer remains controversial. This article presents the results of a randomized trial of adjuvant tamoxifen (40 mg daily for 2 years) versus no adjuvant endocrine therapy in postmenopausal patients. During 1976 to 1984, 1,407 patients were included in the study. Of these, 427 (30%) had high-risk tumors (pN + or pT greater than 30 mm) and were included in a concurrent randomized comparison of postoperative radiotherapy versus adjuvant polychemotherapy. The mean follow-up time was 61/2 years. Tamoxifen improved the recurrence-free survival (RFS) (P less than .01), but the overall survival difference in favor of the tamoxifen-allocated patients was not significant. Data on estrogen (ER) and progesterone receptor (PgR) content were available in 750 patients. Their mean follow-up time was 41/2 years. The effect of tamoxifen was significantly related to ER level (P less than .01). No benefit with tamoxifen was observed among ER-negative patients. The relation to PgR level was of borderline significance (P = .06). Multivariate analysis indicated that most of the interaction between treatment and receptor content was explained by the interaction with ER (P less than .01). The PgR status appeared to modify the effect of tamoxifen among the ER-positive patients and the greatest effect was observed among patients who were positive for both receptors. However, the additional predictive information provided by the PgR assay did not help to identify an unresponsive subgroup of patients.

The RAD51 135G>C polymorphism is related to the effect of adjuvant therapy in early breast cancer.

PURPOSE: RAD51, a central player in the response to DNA damage, has been suspected to contribute to tumour resistance to therapy. A single-nucleotide polymorphism, RAD51 135G>C, in the untranslated region of the RAD51 gene elevates breast cancer risk among BRCA2 carriers. In this study, it was investigated whether this polymorphism is related to prognosis of breast cancer and RAD51 protein expression and whether it is indicative of resistance to radiotherapy or cyclophosphamide/methotrexate/5-fluorouracil (CMF) chemotherapy. PATIENTS AND METHODS: We genotyped 306 patients with early breast cancer, who were randomised to receive post-operative radiotherapy or CMF chemotherapy, for the RAD51 135G>C polymorphism. RAD51 protein expression was evaluated with immunohistochemistry. RESULTS: 15.4 % of the patients had at least one C-allele (three were C homozygotes). There was no correlation between genotype and protein expression. Patients who were G homozygotes benefitted from radiotherapy with decreased risk of local recurrences (RR = 0.32, 95 % C.I. 0.16-0.64, p = 0.001). CMF chemotherapy reduced the risk of distant recurrence for patients carrying at least one C-allele (RR = 0.29, 95 % C.I. 0.10-0.88, p = 0.03), whereas G homozygotes had no benefit from chemotherapy. There was a significant interaction between chemotherapy and genotype (p = 0.02). CONCLUSION: The results suggest that the RAD51 135G>C polymorphism predicts CMF chemotherapy effect in early breast cancer.

Late effects of adjuvant chemotherapy and postoperative radiotherapy on quality of life among breast cancer patients.

Late effects of adjuvant treatment on perceived health and quality of life were assessed through a questionnaire mailed to 448 premenopausal and postmenopausal breast cancer patients, free from recurrence 2-10 years after primary therapy. The patients had been randomised to postoperative radiotherapy or adjuvant chemotherapy as adjuncts to primary surgery. The differences between the two treatments were generally small. However, the radiotherapy patients had significantly greater problems with decreased stamina, symptoms related to the operation scar and anxiety. The chemotherapy patients had significantly more problems with smell aversion. Activity level inside and outside the home, anxiousness and depressive symptoms were similar in both groups. The chemotherapy patients scored their overall quality of life higher than the radiotherapy patients.

Lack of correlation between anxiety parameters and oestrogen receptor status in early breast cancer.

Correlation between anxiety parameters and oestrogen receptor levels (ER) were investigated in 89 patients with primary breast cancer. Patients were divided into two groups, ER poor (< 0.05 fmol/microgram DNA) and ER rich (> 0.05 fmol/microgram DNA). No differences were found between anxiety levels, determined by a modified Hospital Anxiety and Depression (HAD) scale, in the two groups. This report does not support the findings from other studies, claiming an association between psychological parameters and oestrogen receptor status, which is believed to be a prognostic predictor.

Oestrogenic effects of adjuvant tamoxifen in postmenopausal breast cancer.

Oestrogenic influence of the non-steroidal anti-oestrogen tamoxifen may have consequences for the morbidity pattern among women on long-term adjuvant treatment. Subclinical oestrogenic effects of adjuvant tamoxifen on the tissue level was studied among 16 postmenopausal women in three different organ systems: the pituitary, the liver and bone. After 3 months of adjuvant tamoxifen prolactin levels decreased 66% (P < 0.001) in comparison with pretreatment levels. There was an 80% increase in basal growth hormone after 3 months of treatment in comparison with pretreatment levels, which did not reach statistical significance (P = 0.07). Sex hormone binding globulin levels increased 39% (P < 0.01) and IGF-1 (somatomedin C) levels decreased 20% (P < 0.05). The levels of bone GLA protein (BGP; osteocalcin), a marker of bone osteoblastic activity, decreased 28% (P < 0.01). In 13 of the patients bone mineral density (BMD) was measured before treatment and after 1 year. No significant change in BMD was observed. The results thus suggest a clear oestrogenic effect of tamoxifen on the pituitary, liver and bone in postmenopausal women.