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.

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.

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.

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.

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.

Thymidine kinase 1 is a potential marker for prognosis and monitoring the response to treatment of patients with breast, lung, and esophageal cancer and non-Hodgkin's lymphoma.

Thymidine kinase 1 (TK1) is converting thymidine to thymidine monophosphate, and is related to DNA replication and cell proliferation. The use of the TK1 protein levels as a proliferation marker in malignancies is here summarized. TK1 protein in serum (STK1p) and TK1 expression in tissues were determined by a chemoluminescent dot blot assay and by immunohistochemistry staining, respectively. The expression of TK1 in tumor tissues correlated to pathological stages and clinical grades of carcinomas (ca) of esophagus, lung and in premalignancy of breast ductal ca. STK1p could monitor the out-come of tumor therapy by being correlated to remission [breast ca, non-Hodgkin's lymphoma], relapse [breast ca] and to survival [non-Hodgkin's lymphoma] of patients. In a health screening study of 12,641 persons, STK1p seemed to predict the risk of development of neoplasia related diseases at early stage.

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.

PTK (protein tyrosine kinase)-6 and HER2 and 4, but not HER1 and 3 predict long-term survival in breast carcinomas.

The HER receptors are of therapeutic and prognostic significance in breast cancer, and their function is modulated by cytoplasmic tyrosine kinases like PTK6 (brk). We performed a retrospective study on archival breast cancer samples from patients with long follow-up and compared the protein expression between individual HERs and between HERs and the PTK6. Univariate and multivariate analyses were used to study the prognostic value of parameters. Metastases-free survival of patients for longer than 240 months was inversely associated (P< or =0.05) with nodal status, tumour size, and oestrogen receptor status, but was also directly associated with high protein expression levels of HER4 and PTK6 in Kaplan-Meier analysis. In multivariate analysis for metastases-free survival of >240 months, the stepwise selected parameters were tumour size (relative risk 3.1), PTK6 expression (0.4), and number of positive lymph nodes (1.2). Furthermore, we demonstrated a timedependence of the prognostic value attributed to the parameters. The HER receptors (HER2,4), but not PTK6, were independent prognostic markers for metastases-free survival at 60 months, whereas at 240 months PTK6 is the strongest prognostic marker. We demonstrate that PTK6 is a prognostic marker of metastases-free survival in breast cancer, and is independent of the classical morphological and molecular markers of lymph node involvement, tumour size, and HER2 status.

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.

Tamoxifen and megestrol acetate for postmenopausal breast cancer: diverging effects on liver proteins, androgens, and glucocorticoids.

AIM: To compare the effects of tamoxifen and megestrol acetate on liver proteins, androgens, and glucocorticoids during adjuvant treatment for postmenopausal breast cancer. METHODS: A subgroup of women within a large prospective multicenter trial were followed with blood sampling every 3 mo during 2 yr. Women were randomized to receive either continuous tamoxifen 40 mg/d or repeated sequential treatment with tamoxifen and megestrol acetate (MA) 160 mg/d. RESULTS: We found profound and distinct differences between the two regimens. Tamoxifen increased steroid-binding proteins (SHBG and CBG) and suppressed circulating androgens and IGF-I. In contrast, the metabolic effects of tamoxifen were clearly antagonized by MA. There was a rise in IGF-I and marked suppression of steroid-binding proteins. Levels of free testosterone were reduced by 70%. MA also caused apparent adrenal suppression. CONCLUSION: The different effects on anabolic/catabolic balance and adrenal function may relate to certain clinical effects during treatment.

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.

Risk factors for local recurrence after breast-conserving surgery.

BACKGROUND: It is not clear whether risk factors for local recurrence after breast-conserving surgery differ in women having surgery for in situ or invasive cancer. Furthermore, the Nottingham Prognostic Index (NPI) and Nottingham Histological Grade (NHG) have been little studied as determinants of local recurrence risk. METHOD: In a case-control study (491 cases and 1098 controls) nested within a cohort of 7502 women who had surgery for in situ or invasive cancer of the breast, patient characteristics, tumour characteristics and treatment-related variables were evaluated as risk factors for local recurrence. RESULTS: Multivariate conditional logistic regression analyses showed that age below 40 years, tumour multicentricity and an unclear or unknown surgical margin were significant risk factors for local recurrence. Radiotherapy to the breast and adjuvant hormone therapy were protective. Cancer in situ was not associated with a higher risk of local recurrence than invasive cancer (odds ratio 1.0, 95 per cent confidence interval 0.8 to 1.3). NHG and NPI were not helpful in determining risk of local recurrence. CONCLUSION: Margin status, age, tumour multicentricity, and use of radiotherapy and adjuvant hormone therapy were important determinants of risk of local recurrence. With the exception of surgical margin, variables related to the quality of surgical management did not predict risk of local recurrence.

Local recurrence in the breast after conservative surgery--a study of prognosis and prognostic factors in 391 women.

In a population-based cohort of 6613 women with invasive breast cancer, who had breast-conserving surgery between 1981 and 1990, 391 recurrences in the operated breast were identified. The main aim of this study was to examine the prognosis and prognostic factors in different subgroups of local recurrences, characterised by the time to recurrence, location of recurrence and previously given radiotherapy. The median follow-up for women who had a local recurrence was 7.9 years. The life-table estimates for breast cancer-specific survival in women with local recurrences were 84.5% (standard error (S.E.) 1.8) at 5 years and 70.9% (S.E. 2.7) at 10 years. The risk of breast cancer death was highest among women who had an early (

Consequences of axillary recurrence after conservative breast surgery.

BACKGROUND: The aim was to study the incidence, time course and prognosis of patients who developed axillary recurrence after breast-conserving surgery, and to evaluate possible risk factors for axillary recurrence and prognostic factors after axillary recurrence. METHODS: In a population-based cohort of 6613 women with invasive breast cancer who had breast-conserving surgery between 1981 and 1990, 92 recurrences in the ipsilateral axilla were identified. Risk factors for axillary recurrence were studied in a case-control study nested in the cohort, and late survival was documented in the women with axillary recurrence. RESULTS: The overall risk of axillary recurrence was 1.0 per cent at 5 years and 1.7 per cent at 10 years. The risk of axillary recurrence increased with tumour size (P = 0.033) and was highest in younger women (odds ratio (OR) 3.9 for women aged less than 40 years compared with those aged 50-59 years). Radiotherapy to the breast reduced the risk of axillary recurrence (OR 0.1 (95 per cent confidence interval 0.1 to 0.4)). The breast cancer-specific survival rate after axillary recurrence, as measured from primary treatment, was 78.0 per cent at 5 years and 52.3 per cent at 10 years. Tumour size and node status had a statistically significant effect on death from breast cancer. CONCLUSION: Axillary recurrence is rare, although more common in younger women with large tumours. Radiotherapy to the breast was protective. Tumour size and node status were the most important prognostic factors in women with axillary recurrence.

Pulmonary complications following different radiotherapy techniques for breast cancer, and the association to irradiated lung volume and dose.

PURPOSE: This study investigates the incidence of short-term pulmonary complications following radiotherapy (RT) for breast cancer (BC) with different treatment techniques/incidentally irradiated lung volumes and the importance of confounding factors on RT-induced pulmonary complications. PATIENTS AND METHODS: Prospectively, 475 patients with BC were followed for pulmonary complications 1, 4 and 7 months post-RT. Mean lung dose volume histograms (MDVH) were constructed and compared for the different RT-techniques. Among a subset of the mastectomized patients treated with loco-regional (LR-) RT, who had undergone complete three-dimensional (3-D) dose planning (n = 43), MDVH for asymptomatic patients was compared with MDVH for patients experiencing both radiological and clinical pulmonary side-effects. RESULTS: Moderate pulmonary complications, that is requiring treatment with corticosteroids, were rare following local RT (< 1%), but were diagnosed among 11% of the patients treated with LR-RT. A correlation between increasing irradiated lung volumes at the >20 Gy-level (V20), based on MDVH for the RT-techniques, and pulmonary complications was found (P < 0.001). Furthermore, increasing age and reduced pre-RT functional level were independently associated with a higher rate of pulmonary complications (P = 0.005 and P = 0.018). Among the subgroup of mastectomized patients treated with LR-RT, who had undergone complete 3-D dose planning, a difference in mean V20 was found between patients experiencing both clinical and radiological pulmonary side-effects compared to patients experiencing neither of the two side-effects (P = 0.007). CONCLUSION: Moderate pulmonary complications following local RT for BC are rare. The incidence of short-term moderate pulmonary complications in LR-RT is, however, clinically significant and to define quality assurance guidelines for these RT-techniques, 3-D RT planning can be used.

Time trends in the results of breast conservation in 4694 women.

In a population-based cohort of 4694 women with invasive breast cancer, operated upon with breast conserving surgery (BCS) in 1981--1990 and followed through to 1997, we studied how this technique had been adopted into clinical practice, especially with reference to the use of radiotherapy (RT). Our main aim was to see whether there was a drift in the risk of local recurrence and breast cancer death over time. During the 30,151 person-years of observation in the cohort, there were 582 local recurrences, 456 breast cancer deaths and 438 deaths due to other causes. Postoperative RT was given to 70.2%, but usage increased over the period. The women not receiving RT were mostly elderly, but also in women <70 years, 20.4% did not receive RT. The risk for local recurrence after RT were 7.6 and 17.8% at 5 and 10 years, respectively. Without RT, more than 30% had a local recurrence at 10 years. Thus, the choice not to irradiate failed to target women at a low risk. In a multivariate Cox analysis taking tumour size, nodal status, age at operation and RT into account, there was a trend for a higher risk of local recurrence in the later time period, relative hazard 1.5 (95% confidence interval (CI) 1.0--2.1). Corrected survival was 93.3 and 85.2% at 5 and 10 years, respectively.

The clinical significance of thymidine kinase 1 measurement in serum of breast cancer patients using anti-TK1 antibody.

The activity of total thymidine kinase in serum (S-TK) has been used as a tumor maker for decades. To date such activity has been determined using [125]I-iodo-deoxyuridine as a substrate. The aim of this study was to develop a new, antibody-based technique for the measurement of cytoplasmic thymidine kinase (TK1) in serum. Both mono- and polyclonal antibodies against S-TK1 were used in dot blot assay. S-TK1 was characterized by SDS and IEF techniques. Sixty-five breast cancer patients were studied, including 17 preoperative and 38 postoperative tumor-free patients and 10 patients with metastases to the lymph nodes (N1-2). They were compared to patients with benign tumors (n=21) and healthy volunteers (n=11). S-TK1 was low (0-1.0 pM) in healthy volunteers, while in preoperative patients the level was increased 6-110-fold. Significant differences were observed between preoperative patients and healthy volunteers (p=0.005), preoperative patients and patients with benign tumors (p<0.001), and preoperative patients and postoperative patients without metastases (p<0.001). No significant difference was observed between preoperative patients and postoperative patients with metastases (p=0.191). The S-TK activity in preoperative patients was also high in serum, but no decrease was observed following surgery. In conclusion, the anti-TK1 antibody could be a good marker for monitoring the response of breast cancer patients to therapy.