The analysis of prognostic factors in stage III-B non-inflammatory breast cancer.

AIMS: To evaluate factors predicting disease recurrence in patients treated for stage III-B breast cancer by neoadjuvant chemotherapy followed by surgery. METHODS: A retrospective study of 52 patients who responded to neoadjuvant chemotherapy followed by modified radical mastectomy was carried out. The parameters studied included pre-treatment tumour size, clinical axillary status, grade, lymphatic-vascular invasion, pathological axillary status, number of metastatic lymph nodes, menopausal status and oestrogen receptor status. RESULTS: In the univariate analysis, number of metastatic lymph nodes, primary tumour size, pathological axillary status and histological grade were statistically significant factors associated with recurrence of disease. Multivariate analysis demonstrated that the number of metastatic lymph nodes (relative hazard 6.1) and primary tumour size (related hazard 2.5) were the most important independent prognostic factors for recurrence. CONCLUSIONS: These results indicate that the number of involved lymph nodes after neoadjuvant chemotherapy, independent of the clinical response of primary tumour, had a most significant impact on disease free survival. Additionally primary tumour size had a marked prognostic significance in spite of clinical changes in tumours following chemotherapy.     

Treatment toxicity reduction: breast cancer

Since curative treatment of advanced breast cancer is still beyond our reach, the importance of reducing overall toxicity of systemic treatment must be stressed. This seems to be possible by adapting the form and intensity of therapy to the prognosis and stage of disease and by using drugs exhibiting high antitumoral efficacy combined with low systemic toxicity. In 475 patients with metastatic breast cancer, we initiated a prognosis-oriented therapeutic strategy. We developed a prognostic score so as to classify patients into 'high' and 'low' risk groups. In this way we were able to separate patients into two groups with statistically different survival times. In addition, we found that the impact of the first polychemotherapy on survival is different when comparing patient with favourable and unfavourable prognostic scores. Patients with favourable prognostic factors had exactly the same survival time independent of tumour progression, stable disease or even partial remission. Only patients achieving a complete remission survived longer. In contrast, patients with unfavourable prognostic factors apparently benefited from chemotherapy. Patients achieving stable disease or objective tumour remission had a significantly longer survival time than those patients with immediate tumour progression. Additionally, for most of the patients in this group, chemotherapy induced a transient stabilization or improvement of tumour induced symptoms. Therefore, we conclude that chemotherapy of advanced breast cancer is necessary. However, to reduce overall toxicity, it must be planned and administered according to the prognostic picture of the individual patient.     

A multivariate analysis of tumour biological factors predicting response to cytotoxic treatment in advanced breast cancer.

The study was designed to identify factors that could predict response to chemotherapy in breast cancer. A total of 173 patients with measurable or evaluable metastatic breast cancer were enrolled in a randomized trial between November 1987 and January 1991 to receive a monthly dose of 5-fluorouracil (500 mg m(-2)), epirubicin (60 mg m(-2)) and cyclophosphamide (500 mg m(-2)) either administered in four weekly doses or in an every-4-week dose as first-line cytotoxic treatment. In 103 evaluable patients we performed a multivariate analysis of the tumour biological factors, i.e. histological grade, oestrogen receptor (ER), progesterone receptor (PR), S-phase fraction (SPF), ploidy, p53, c-erbB-2, Bcl-2 and Bax expression, which showed significance in the univariate analysis according to treatment response, time to progression (TTP) or overall survival (OS). In the univariate analysis only SPF, grade and the proapoptotic protein Bax correlated with the response to cytotoxic treatment. In the multivariate analysis SPF had the strongest correlation, followed by grade and Bax. In the univariate analysis grade, PR, Bax and Bcl-2 correlated significantly with TTP, whereas in the multivariate analysis only PR showed a statistically significant correlation. In the univariate analysis PR and Bax correlated with OS and both retained its significance in the multivariate analysis. The factors that correlated significantly with the response to cytotoxic treatment in the univariate analysis, i.e. grade, SPF and Bax, seemed to predict independently the response to treatment in the multivariate analysis also. TTP and OS could be predicted partly by the same factors, although the association was quite weak. More studies and new tumour biological factors are needed to identify the group of breast cancer patients who get the most benefit from chemotherapy.     

Cyclin A as a marker for prognosis and chemotherapy response in advanced breast cancer

We wanted to study cyclin A as a marker for prognosis and chemotherapy response. A total of 283 women with metastatic breast cancer were initially enrolled in a randomised multicentre trial comparing docetaxel to sequential methotrexate-fluorouracil (MF) in advanced breast cancer after anthracycline failure. Paraffin-embedded blocks of the primary tumour were available for 96 patients (34%). The proportion of cells expressing cyclin A was determined by immunohistochemistry using a mouse monoclonal antibody to human cyclin A. Response evaluation was performed according to WHO recommendations. The median cyclin A positivity of tumour cells was 14.5% (range 1.2-45.0). Cyclin A correlated statistically significantly to all other tested proliferation markers (mitotic count, histological grade and Ki-67). A high cyclin A correlated significantly to a shorter time to first relapse, risk ratio (RR) 1.94 (95% CI 1.24-3.03) and survival from diagnosis, RR 2.49 (95% CI 1.45-4.29), cutoff point for high/low proliferation group 10.5%. Cyclin A did not correlate to chemotherapy response or survival after anthracycline, docetaxel or MF therapy. Of all tumour biological factors tested (mitotic count, histological grade and Ki-67), cyclin A seemed to have the strongest prognostic value. Cyclin A is a good marker for tumour proliferation and prognosis in breast cancer. In the present study, cyclin A did not predict chemotherapy response.     

Prognostic role of p27Kip1 and apoptosis in human breast cancer

Human breast carcinoma is biologically heterogeneous, and its clinical course may vary from an indolent slowly progressive one to a course associated with rapid progression and metastatic spread. It is important to establish prognostic factors which will define subgroups of patients with low vs high risk of recurrence so as to better define the need for additional therapy. Additional characterization of the molecular make-up of breast cancer phenotypes should provide important insights into the biology of breast cancer. In the present study, we investigated apoptosis, expression of p27Kip1 and p53 retrospectively in 181 human breast cancer specimens. In addition, their relevance to the biological behaviour of breast cancer was examined. Our studies found a significant association among high histological grade, high p53, low apoptosis and low p27. Our results also demonstrated that, in human breast cancer, low levels of p27 and apoptotic index (AI) strongly correlated with the presence of lymph node metastasis and decreased patient survival. In node-negative patients, however, p27 also had prognostic value for relapse-free and overall survival in multivariate analysis. Furthermore p27 and AI had predictive value for the benefits of chemotherapy. These latter observations should prompt prospective randomized studies designed to investigate the predictive role of p27 and AI in determining who should receive chemotherapy in node-negative patients.     

Vascular grading of angiogenesis: prognostic significance in breast cancer

The study aimed to evaluate the prognostic value of angiogenesis by vascular grading of primary breast tumours, and to evaluate the prognostic impact of adding the vascular grade to the Nottingham Prognostic Index (NPI). The investigation included 836 patients. The median follow-up time was 11 years and 4 months. The microvessels were immunohistochemically stained by antibodies against CD34. Angiogenesis was graded semiquantitatively by subjective scoring into three groups according to the expected number of microvessels in the most vascular tumour area. The vascular grading between observers was moderately reproduced (kappa = 0.59). Vascular grade was significantly associated with axillary node involvement, tumour size, malignancy grade, oestrogen receptor status and histological type. In univariate analyses vascular grade significantly predicted recurrence free survival and overall survival for all patients (P < 0.0001), node-negative patients (P < 0.0001) and node-positive patients (P < 0.0001). Cox multivariate regression analysis showed that vascular grading contributed with independent prognostic value in all patients (P < 0.0001). A prognostic index including the vascular grade had clinical impact for 24% of the patients, who had a shift in prognostic group, as compared to NPI, and implied a better prognostic dissemination. We concluded that the angiogenesis determined by vascular grading has independent prognostic value of clinical relevance for patients with breast cancer.     

c-erbB-2 positivity is a factor for poor prognosis in breast cancer and poor response to hormonal or chemotherapy treatment in advanced disease

The aim of this work was to evaluate the prognostic and predictive values of c-erbB-2 in breast cancer. 650 patients were enrolled. The amplification/overexpression of c-erbB-2 from fresh frozen or paraffin-embedded breast tumour tissue samples was analysed by polymerase chain reaction (PCR) technique (75%), immunohistochemically (17%) or by Southern blot analysis (8%). 126 patients (19%) were positive for c-erbB-2. 148 patients developed metastatic disease, but only 35 were positive for c-erbB-2. Positivity for c-erbB-2 was significantly associated with node positivity, large tumour size, high grade of malignancy, low receptor status, postmenopausal status, and with a shorter overall survival. In multivariate regression analysis, only tumour size and nodal involvement were risk factors for poor survival when analysed separately together with c-erbB-2 and receptor status. Metastatic patients with c-erbB-2 positivity had a significantly shorter survival and disease-free survival (DFS) than the c-erbB-2-negative patients. 29 advanced patients with c-erbB-2 positivity showed a poor response rate to hormonal, non-anthracycline-based and anthracycline-based therapies. Positivity for the c-erbB-2 is a poor prognostic factor in breast cancer, but it also emerges as predictive of the response to hormonal or chemotherapy treatment once the disease has recurred.     

Meningeal carcinomatosis in breast cancer: prognostic factors and outcome

Meningeal carcinomatosis (MC) occurs in up to 5% of breast cancer patients. Few studies have evaluated prognostic markers in breast cancer patients with MC. Our aim was to describe the treatment of breast cancer patients with MC, and identify prognostic factors related to survival. Sixty breast cancer patients that had a diagnosis of MC between January 2003 and December 2009 were included. The median age was 46 years (range 27–76). Most patients had invasive ductal carcinoma (78.3%) and high histological/nuclear grade (61.7/53.3%). Estrogen and progesterone receptors were positive in 51.7 and 43.3% of patients, respectively, and 15% were HER-2-positive. Symptoms at presentation were headache, cranial nerve dysfunction, seizures, and intracranial hypertension signals. Diagnosis was made by CSF cytology in 66.7% of cases and by MRI in 71.7%. Intrathecal (IT) chemotherapy was used in 68.3% of patients, and 21.6% received a new systemic treatment (chemo- or hormone therapy). Median survival was 3.3 months (range 0.03–90.4). There was no survival difference according to age, nuclear grade, hormonal and HER-2 status, CSF features, sites of metastasis, systemic and IT chemotherapy, or radiotherapy. However, histological grade and performance status had a significant impact on survival in the multivariate analysis. Only four papers have addressed prognostic factors in breast cancer patients with MC in the last two decades. The results of those reports are discussed here. High histological grade and poor performance status seem to impact survival of breast cancer patients with MC. Prospective studies are necessary to clarify the role of IT and systemic treatment in the treatment of those patients.     

The significance of nuclear morphometric variables as prognostic predictors in breast cancer.

The preoperative biopsies from primary breast carcinomas of 504 women were subjected to interactive morphometric analysis of a) the mean nuclear area (NA), b) standard deviation of nuclear area (SDNA), c) mean area of the 10 largest nuclei (NAl0), d) nuclear perimeter (PE), e) standard deviation of nuclear perimeter (SPDE), f) largest nuclear diameter (Dmax) and g) shortest nuclear diameter (Dmin), h) histological grade and i) classical prognostic variables. The above data were correlated with the disease outcome during the mean follow-up period of 11.2 years. Tumor size (p less than 0.0001), morphometric variables (p = 0.0001-0.005) and histological grade (p = 0.03) predicted axillary lymph node metastasis at the time of diagnosis. According to multivariate analysis, tumour size and NA predicted the axillary lymph node metastasis independently. Axillary lymph node status (p less than 0.0001) and histological grade (p = 0.01) predicted the tumour recurrence and recurrence-free survival, whereas the morphometric variables had no significant predictive value. Axillary lymph node status (p less than 0.0001), tumour size (p less than 0.0001), histological grade (p = 0.0012) and morphometric variables (p = 0.003-0.035) predicted the disease-related survival. Of the morphometric variables, NA and the Dmin were the two most important predictors of tumour-related survival in univariate analysis. Dmax had independent prognostic information in multivariate survival analysis. In the same analysis, tumour size and axillary lymph node status were more important predictors. In conclusion, the morphometric variables analysed have independent predictive value in female breast cancer. Their value is, however, inferior to that of the tumour size and axillary lymph node status, but equal to that of the histological grade.     

Prognostic value of initial tumor parameters after metastatic relapse

Classical prognostic factors of breast cancer are correlated to disease-free survival and overall survival (OS); their precise role is less known on metastatic disease. A total of 511 breast cancer patients without initial metastasis were treated. OS was divided in time to distant recurrence and metastatic survival (MS). Age, Scarff-Bloom-Richardson (SBR) grade, hormone receptor, axillary node involvement, and Nottingham prognostic index predicted MS in univariate analysis. Multivariate analysis retained age, SBR grade, and axillary lymph node involvement as significant independent prognostic factors. Interactions are still present between initial parameters and MS. The clinician has to take into account for treatment choice.     

Clinical effect of irinotecan in advanced and metastatic breast cancer patients previously treated with doxorubicin- and docetaxel-containing regimens

BACKGROUND: Previous phase II trials in Japan suggested that irinotecan was a promising agent for advanced or metastatic breast cancer pretreated with anthracycline. However, irinotecan has not yet been evaluated in the salvage setting for breast cancer pretreated with both anthracycline and taxane, which are two active agents for breast cancer. METHODS: The efficacy and safety of irinotecan were retrospectively evaluated in patients with breast cancer who had previously been treated with both doxorubicin and docetaxel. From 1996 to 1999, irinotecan was administered to 20 patients, all with a performance status of <2. Irinotecan treatment was repeated in approximately 6 week cycles consisting of the administration of irinotecan once weekly for 4 weeks followed by a 2 week rest. The median dose of irinotecan administered was 100 mg/m(2) weekly. The median number of irinotecan cycles given was 1 (range: 1-8 cycles). The median total dose was 388 mg/m(2) (range: 50-2400 mg/m(2)). RESULTS: Performance status declined to >3 after treatment with irinotecan in four patients. Two patients had grade 3 leukopenia; three had grade 3 anemia and one had a creatinine elevation of grade 4. The objective response rate for all patients was 5.0% (95% CI: 0-15.5%). The median time to progression and overall survival were 35 days (range: 17-285 days) and 124 days (range: 17-667 days), respectively, since the start of the administration of irinotecan. CONCLUSIONS: Salvage chemotherapy with irinotecan may be inactive against advanced and metastatic breast cancer pretreated with doxorubicin and docetaxel. We will evaluate irinotecan for advanced and metastatic breast cancer patients as first- or second-line chemotherapy combined with anthracycline or taxane.     

DNA flow cytometry, nuclear morphometry, mitotic indices and steroid receptors as independent prognostic factors in female breast cancer.

Clinical features, 8 histological variables, 7 nuclear morphometric variables, 2 mitotic indices, oestrogen-receptor (ER) and progesterone-receptor content (PR), DNA ploidy and S-phase fraction (SPF) were entered in a Cox's model to assess their independent predictive value in 216 breast-cancer patients followed up for over 9 years. In the whole series, histological type (p = 0.007), volume-corrected mitotic index (M/V index) (p = 0.01), axillary-lymph-node (pN) status (p = 0.024) and the year of treatment (p = 0.045) predicted independently the recurrence-free survival (RFS). In a sub-analysis including SPF (n = 148), the year of treatment (p = 0.003), tumour diameter (p = 0.004), SPF (p = 0.022) and nuclear pleomorphism (p = 0.056) independently predicted the RFS. In a Cox's analysis of the whole series, tumour diameter (p less than 0.001), pN status (p = 0.001), PR status (p = 0.002) and the year of treatment (p = 0.021) were independent predictors of survival. In a separate analysis including also SPF (n = 148), tumour diameter (p less than 0.001), SPF (p = 0.003), pN status (p = 0.008) and the year of treatment (p = 0.015) proved to be independent prognostic factors. The results show that tumour diameter, pN status, M/V-index, histological type, SPF and PR status comprise a sufficient combination of prognostic factors in female breast cancer. In pN patients, age and SDPE may be of additional prognostic significance. The prognostic scores combining the independent prognostic variables reflecting both the proliferative rate and metastatic potential of the tumours are accurate predictors of the RFS and overall survival.     

The DNA labelling index: A prognostic factor in node-negative breast cancer

Summary The DNA labelling index (LI), representing the fraction of S-phase cells, was studied in 76 patients operated on for breast cancer from 1975 to 1979. No patient had lymph node involvement following axillary dissection (N–), and no adjuvant medical treatment was given. Patients were classified in one of two groups according to the median LI. Patient distribution by age, tumour size, and receptor status was identical in both groups. A higher frequency of grade 3 tumours was noted in the group with an LI above the median value. The cell proliferation rate was an important discriminative factor for metastatic potential. The probability of survival at 8 years for patients with a high LI was significantly lower than that of patients with low LI (36% versus 100%;p<0.001). Relapse-free survival at 8 years was respectively 56% and 83% (p<0.02). At 2 years, these values were 75% and 100%, indicating the early occurrence of metastases. By contrast, the LI had no prognostic value concerning loco-regional disease recurrence or survival after the appearance of metastasis. No relationship was found in this study between survival and other prognostic factors, namely tumour size, histological grade, or hormone receptor level. The LI currently appears to be the best prognostic factor for N– breast cancer. High risk patients identified by this method could thus be offered adjuvant medical treatment.Presented in part at the 5th Annual Meeting of the European Society for Therapeutic Radiology and Oncology, September 1986, Baden-Baden, FRG     

p53 overexpression as a prognostic factor for advanced stage bladder cancer

Overexpression of the TP53 gene protein detected by immunohistochemistry appears to identify those patients with superficial bladder cancer at risk of the development of muscle invasive or metastatic disease. However, the role of p53 overexpression in patients with advanced or metastatic bladder cancer is not yet well established. In the present study, 44 specimens from 44 patients with advanced stage bladder tumours (T₂–T₄) undergoing radical cystectomy were investigated for different biological and clinical characteristics as possible prognostic factors: sex, age, depth of tumour infiltration, T-stage, histological grade, lymph node status, application of adjuvant systemic chemotherapy (MVAC), proliferative activity (staining for proliferating cell nuclear antigen (PCNA) by monoclonal antibody (PC10) as well as overexpression of the p53 oncoprotein (monoclonal antibody pAb 1801)). After a median follow-up of 22 months, 16 of the 23 patients (70%) with more than 40% of tumour cells stained positively for p53 (Group B) died from tumour progression compared with 7 of the 21 patients (33%) with less than 40% of tumour cells positive for p53. During univariate analysis, p53 overexpression (P = 0.008), staining for PCNA (80% of cells positive) (P = 0.01) and tumour stage (P = 0.01) were significant prognostic factors for survival, among which p53 overexpression (P = 0.023) as well as T-stage (P = 0.012) remained independent significant predictors during multivariate analysis. Prospective studies are needed to confirm the independent prognostic potential of p53 overexpression in patients with advanced bladder cancer. The availability of more refined prognostic factors should assist decision making regarding the value of more aggressive treatment options, such as adjuvant or neoadjuvant chemotherapy, for prognostically defined subgroups of patients.     

The predictive value of bcl-2, bax, bcl-xL, bag-1, fas, and fasL for chemotherapy response in advanced breast cancer.

PURPOSE: The purpose was to evaluate the utility of some bcl-2 family proteins fas and fasL as predictive indicators for chemotherapy response in advanced breast cancer. EXPERIMENTAL DESIGN: Between October 1994 and October 1997, 283 patients with advanced breast cancer were included in a multicenter randomized study comparing docetaxel (D) to sequential methotrexate and 5-fluorouracil (MF) after anthracycline failure. The response rates (complete response + partial response) were 42 and 21% in the D and MF arms, respectively (P < 0.001). In 126 patients, histological blocks of primary tumors were available for immunohistochemical analysis of bax, bcl-2, bcl-xL, bag-1, fas and fasL. RESULTS: Of the investigated factors, bag-1 correlated positively with bax, bcl-2, and fasL, and fasL correlated positively with fas and bax. None of these apoptosis-related factors was associated with a response to chemotherapy either in the whole patient population or in the D or MF arms. Interestingly, low bcl-2 expression was associated with shorter time to progression (P = 0.02) and shorter overall survival (OS; P = 0.001). High fasL expression showed a trend toward shorter OS. In multivariate backwards stepwise Cox analysis, in which histological grade and estrogen receptor status (ER) were also included, bcl-2 (P = 0.01) and fasL (P = 0.005) remained highly significantly associated with OS, whereas histological grade and ER lost their significance. CONCLUSIONS: None of the investigated apoptosis-related factors of primary tumor could predict the later response to either D or MF treatment. However, fasL and bcl-2 were strong prognostic factors. Patients who had tumors with high fasL and low bcl-2 expression had the shortest OS.     

Prognostic scores combining clinical, histological and morphometric variables in assessment of the disease outcome in female breast cancer

Clinical features, 8 histological features, 7 nuclear morphometric variables and 2 mitotic indices were entered in a Cox's model to assess their independent predictive power in a series of 517 breast cancer patients followed up for over 10 years. The volume-corrected mitotic index (M/V index) (p less than 0.001), axillary lymph-node status (p = 0.002), the shortest nuclear axis (p = 0.006) and the degree of tubule formation (p = 0.02) predicted independently the recurrence-free survival. In N- tumours (n = 293), the M/V index (p = 0.005), the degree of tubule formation (p = 0.016) and tumour size (p = 0.023) were independent prognostic predictors, whereas in N+ tumours (n = 224), only the M/V index (p = 0.004) and the maximum nuclear axis (p = 0.004) had independent prognostic value. The corrected survival was predicted independently by the axillary lymph-node status, degree of tubule formation, M/V index, tumour size (p less than 0.001), age (p = 0.002) and year of treatment (p = 0.008). In N- tumours, the degree of tubule formation (p = 0.005) and intraductal growth pattern (p = 0.015) exhibited independent predictive value. In N+ tumours, patient survival was related to the M/V index (p less than 0.001), tumour size (p = 0.005) and patient age (p = 0.005). The results show that the assessment of the M/V index, axillary lymph-node status, tumour size, intraductal growth pattern and tubule formation are reliable factors in predicting the prognosis of breast cancer. The conventional mitotic activity index (MAI) and histological grading should be replaced by the M/V index in histological assessment of malignancy in breast cancer. The prognostic scores combining the independent variables reflecting the proliferative rate and metastatic potential of the tumours are more accurate predictors of the recurrence-free survival and overall survival (p less than 0.0001) than the single variables used alone.     

Metastatic breast cancer with liver metastases: a registry analysis of clinicopathologic, management and outcome characteristics of 500 women

SummaryIntroduction Breast cancer patients developing liver metastases have traditionally been considered to make up a poor prognosis group with median survival rates of less than 6 months. We retrospectively analysed clinicopathologic characteristics of 500 women with metastatic breast cancer and liver deposits upon administration of first-line chemotherapy in the 90s. We sought to examine the epidemiology, clinical course, outcome and prognostic factors of this cohort with the hope to identify changing patterns, facilitate cost-effective follow-up and rationalize therapy of these patients.Materials and methods Among 1426 metastatic breast cancer patients enrolled with the Hellenic Cooperative Oncology Group (HeCOG) chemotherapy registry from 1988 to 2004, 500 (35%) had liver deposits when first-line chemotherapy was administered and were the subject of this retrospective analysis. These patients had been treated with single-agent or combination chemotherapy either in the context of clinical trials or outwith trials according to standard HeCOG protocols.Results Median age at diagnosis was 54.5 years, with the majority of women being fit (Performance Status PS 0–1 76%), postmenopausal (53%) harbouring hormone-receptor positive (54%) invasive ductal, lobular or mixed carcinomas (76%). High-grade tumours were present in 35% of patients, while the extent of systemic relapse was confined to the liver plus none or one additional organ site in 59% of women. Half of the patients had received adjuvant chemotherapy and two-thirds relapsed later than 12 months from initial diagnosis of localized disease. First-line palliative chemotherapy included an anthracycline and/or a taxane in 88% of cases with an objective response rate of 34% (95% Confidence Interval CI: 29.1–37.5), while 79% of patients were able to proceed to second-line chemotherapy based mostly on non-anthracycline non-taxane containing regimens with objective responses seen in 16% of them (95% CI: 11.6–21.9). At a median follow-up of 47.5 months, disease progression occurred solely in the liver in one-third of patients and median overall survival was 16.3 months, with projected 5-year survival of 8.5%. Type of palliative chemotherapy was not a predictive factor for response, though non-anthracycline non-taxane regimens were associated with lower tumour regression rates. Positive hormonal receptor status of the primary, low histological grade, malignant relapse in the liver only or liver plus one organ site and good performance status were significant prognostic factors for improved outcome in univariate analysis, the latter two retaining significance in multivariate analysis as well.Conclusions In comparison to historical series, adjuvant therapy, stricter follow up and imaging technology advances result in earlier diagnosis of fitter breast cancer patients with low-volume hepatic and systemic relapse. Cost-effectiveness of close monitoring for early diagnosis of relapse should be further studied. With availability of effective modern chemotherapy, prolonged survival is feasible and aggressive multidisciplinary management of selected patients may be warranted.     

Clinical trials of Herceptin(R) (trastuzumab)

This report summarises the clinical efficacy and safety findings from clinical trials of the new anti-HER2 monoclonal antibody Herceptin(R) (trastuzumab). Data from pivotal trials indicate that trastuzumab is active when added to chemotherapy in patients with advanced metastatic breast cancer. In particular, the combination significantly prolonged the median time to disease progression, increased the overall response rate, increased the duration of response, and improved median survival time by approximately 25% compared with chemotherapy alone. Furthermore, trastuzumab is active as a single agent in women with HER2-positive metastatic breast cancer, inducing durable objective tumour responses. In total, 15% of patients who had received extensive prior treatment for metastatic disease had an objective response. The median duration of response was 9.1 months following administration of single-agent trastuzumab. Notably, 2% of patients were free of disease progression at 6 months. The safety profile of trastuzumab either given alone or in combination was favourable.     

Clinical trials of Herceptin(trastuzumab)

This report summarises the clinical efficacy and safety findings from clinical trials of the new anti-HER2 monoclonal antibody Herceptin(trastuzumab). Data from pivotal trials indicate that trastuzumab is active when added to chemotherapy in patients with advanced metastatic breast cancer. In particular, the combination significantly prolonged the median time to disease progression, increased the overall response rate, increased the duration of response, and improved median survival time by approximately 25% compared with chemotherapy alone. Furthermore, trastuzumab is active as a single agent in women with HER2-positive metastatic breast cancer, inducing durable objective tumour responses. In total, 15% of patients who had received extensive prior treatment for metastatic disease had an objective response. The median duration of response was 9.1 months following administration of single-agent trastuzumab. Notably, 2% of patients were free of disease progression at 6 months. The safety profile of trastuzumab either given alone or in combination was favourable.