Predictive power of progesterone receptor status in early breast carcinoma

Progesterone receptor status (PgR) and oestrogen receptor status (ER) were examined in 332 women with stage I-II breast carcinoma treated at a single centre either by simple mastectomy with (n = 283) or without (n = 6) axillary clearance, or by segmental mastectomy with (n = 18) or without (n = 25) axillary clearance and radiotherapy; median follow-up time was 40 (range 10-60) months. Neither the concentration nor the presence of PgR related to either disease-free interval or survival. However both the presence and the concentration of ER were found to be associated with a longer disease-free interval amongst patients with stage II tumours (P less than 0.01). From this study it appears that progesterone receptor status does not predict outcome in early breast carcinoma.     

Survival patterns in hormone treated advanced breast cancer

This study investigates a series of factors, all recordable by the time of presentation of distant metastases from primary breast cancer and relates these to survival after the initiation of endocrine therapies. One hundred and ninety-one patients have received endocrine therapy as initial treatment for distant metastases. In all patients both the histological grade and oestrogen receptor (ER) status of primary tumour tissue; the lymph node stage and menopausal status at mastectomy and the disease-free interval and sites of initial metastases are available for analysis. Four of these factors have been found to contribute independently towards prolonged survival after the initiation of treatment: tumour grade, ER status, disease-free interval and sites of metastases. Employing a multivariate analysis incorporating these four factors, three groups of patients have been identified with survivals of 67, 37 and 0 per cent at 18 months on therapy. These three groups of patients contain 37, 41 and 22 per cent of the patient population respectively.     

Value of steroid hormone receptor analysis in predicting time to treatment failure in operable breast cancer

An analysis of prognostic factors for predicting time to treatment failure (TTF) was performed on 246 patients who were referred for adjuvant chemotherapy after mastectomy. Oestrogen receptor (ER) and progesterone receptor (PgR) analyses were carried out on 172 and 102 patients respectively. Prognostic factors predicting for TTF were, in decreasing order of significance: nodal status, tumour size, ER status and age of the patient. Comparison of TTF for ER+ and ER- (without categories of other prognostic factors) showed that ER status is prognostic irrespective of nodal status. ER is prognostically significant within both categories of PgR. PgR predicted significantly for TTF only in patients without nodal involvement.     

The prognostic significance of single hormone receptor positive metastatic breast cancer: An analysis of three randomised phase III trials of aromatase inhibitors

We analysed the outcomes of women with metastatic breast cancer (MBC) from three randomised phase III trials of aromatase inhibitors according to oestrogen receptor (ER) and progesterone receptor (PgR) status. Both receptors were analysed in 1010 of the 1870 women (54%), including 31 that were ER-/PgR-, which were excluded. Of the remaining 979, 726 (74%) were ER+/PgR+ but 253 were single hormone receptor positive (213 ER+/PgR-, 40 ER-/PgR+). Although there were no differences in clinical benefit or time to progression, the median overall survival of women with ER+/PgR+ tumours was significantly longer than those with single HR positive tumours (800 versus 600 days, p = 0·01). In women with ER+ tumours, the median overall survival of those with tumours that were also PgR+ was significantly longer than those that were PgR- (800 versus 625 days, p = 0·02). The PgR status is an important prognostic factor for survival in MBC.     

Prognostic significance of the DNA content of human breast cancer

The DNA content of paraffin embedded primary tumour tissue has been measured by flow cytometry in 354 patients with operable breast cancer. Tumour ploidy significantly correlated with tumour size, histological grade, and with menopausal status. No significant correlation with oestrogen receptor status or lymph node involvement was found. Patients with diploid cancers had a significantly improved short term survival and disease-free interval (DFI) compared with patients having aneuploid tumours. However, no difference in survival or DFI was shown after longer term follow-up (median 84 months). Multivariate analysis showed no independently significant prognostic value for tumour ploidy. No patient in this study received adjuvant therapy.     

Influence of postoperative morbidity on long-term survival following liver resection for colorectal metastases

BACKGROUND: Survival after resection of colorectal liver metastases may be influenced by the patient, the primary tumour and the liver metastases. Postoperative morbidity is associated with poor survival in several cancers. The aim of this retrospective study was to evaluate prognostic factors of survival after resection of colorectal liver metastases, including postoperative morbidity. METHODS: From 1985 to 2000, 311 consecutive patients with liver metastases from colorectal cancer underwent resection with curative intent. Univariate and multivariate analyses were performed to assess the influence of age, sex, site and stage of the colorectal tumour, disease-free interval, number, size and distribution of metastases, type of hepatectomy, pedicular clamping, resection margin, blood transfusion, postoperative morbidity and adjuvant chemotherapy on overall and disease-free survival. RESULTS: The postoperative mortality and morbidity rates were 3 and 30 per cent respectively. The 3- and 5-year overall survival rates were 53 and 36 per cent respectively. Both overall and disease-free survival rates were independently associated with nodal status of the colorectal tumour, number of metastases and postoperative morbidity. Patients with postoperative morbidity had an overall and disease-free 5-year survival rate half that of patients with no morbidity: 21 versus 42 per cent for overall survival (P < 0.001) and 12 versus 28 per cent for disease-free survival (P = 0.001) respectively. CONCLUSION: Long-term survival can be altered by postoperative morbidity after resection of colorectal liver metastases by increasing the risk of tumour recurrence. This justifies optimizing the surgical treatment of colorectal liver metastases to decrease postoperative morbidity and the use of efficient adjuvant treatments in patients with postoperative morbidity.     

Clinicopathological significance of microscopic abscess formation at the invasive margin of advanced low rectal cancer

BACKGROUND: The aim of this study was to evaluate the clinicopathological significance of microscopic abscess formation (MAF) at the invasive front of advanced low rectal cancer. METHODS: The clinicopathological features of 226 consecutive patients with low rectal cancer, who underwent curative resection between May 1997 and December 2002, were analysed. RESULTS: Fifty-seven (25.2 per cent) of the 226 tumours had MAF and 169 (74.8 per cent) did not. Patients with tumours showing MAF were more likely to have extended surgery than those without MAF: 47 versus 31.4 per cent respectively underwent non-sphincter-preserving surgery (P=0.029) and 82 versus 60.9 per cent underwent lateral lymph node dissection (P=0.003). The incidence of lymph node metastases was lower in patients with MAF (30 versus 53.3 per cent; P=0.002). Univariable analysis of disease-free survival revealed that depth of invasion (P<0.001), lymph node status (P<0.001), histological type (P=0.035), lymphatic invasion (P<0.001), venous invasion (P<0.001), perineural invasion (P<0.001), focal dedifferentiation (P<0.001) and MAF (P<0.001) were significant prognostic factors. Multivariable analysis showed that lymph node status (P<0.001), perineural invasion (P=0.002), venous invasion (P=0.033) and MAF (P=0.012) remained independent prognostic factors. CONCLUSION: MAF may reflect indolent tumour behaviour and a more favourable outcome in patients with advanced low rectal cancer.     

Progesterone receptor status provides predictive value for adjuvant endocrine therapy in older estrogen receptor-positive breast cancer patients

Estrogen receptor (ER) status can predict the efficacy of endocrine therapy. However, the predictive significance of the progesterone receptor (PgR) is controversial in an adjuvant setting. Records of 758 ER+ breast cancer patients who received adjuvant tamoxifen (TAM) for 3-5 years were reviewed to evaluate the predictive value of PgR for TAM treatment in ER+/PgR+ and ER+/PgR- groups. By a median of 40 months' follow-up, there was no significant difference between the two groups with regard to disease-free-survival (DFS). On the basis of STEPP analysis showing the tendency of age effect on DFS in both the ER+/PgR- and ER+/PgR+ groups, we classified the ER+ patients into three strata by age (<45, 45-60, and >or=60 years). There was no significant difference in DFS and overall survival (OS) between the two groups in the <45 stratum and the 45-60 stratum. In contrast, the ER+/PgR- group had a worse prognosis in the >or=60 stratum with regard to both DFS (P=0.0484) and OS (P=0.0009). The results suggest that PgR status might be a predictive factor of benefit to be gained from adjuvant TAM for older ER+ patients with regard to DFS and OS. This should take into account older ER+/PgR- patients who tend to be resistant to TAM.     

Clinical Significance of Biological Markers at Primary Operation for Metastatic Breast Cancer

Purpose: To identify the prognostic value of biological markers at initial operation for metastatic breast cancer, we measured the presence of estrogen receptor-alpha (ERα), progesterone receptor (PgR) and human epidermal growth factor receptor type 2 (HER2),and histological grade (HG) of tumors. Methods: One-hundred and seventy-six patients, aged 29 to 90 (median: 51 years), with recurrent breast cancer underwent primary operation at our department during the period from 1983 to 2000. Clinicopathological factors examined at primary operation included menopausal symptoms, presence of axillary lymph node metastasis, tumor size, HG, HER2, ERα and PgR.Factors examined at recurrence included site of primary recurrence, disease-free interval(DFI) and tumor markers, such as CEA and CA15-3. The relationship between these factors and prognosis following recurrence was assessed. Results: Menopausal status, axillary lymph node metastasis and tumor size at primary operation had no significant effect on prognosis. Patients with low HG, positive expession of ERα and PgR, and low HER2 expression had a good prognosis, similar to those with long DFI and distant metastases. After distant metastases, HER2 was found to be the most important prognostic factor following recurrence and in predicting response to drug therapy.Conclusion: Biological factors indicating tumor malignancy at the time of the first operation are also important prognostic factors following tumor recurrence.     

Prognostic significance of DNA ploidy in colorectal cancer: a prospective flow cytometric study

A prospective study of prognostic factors has been carried out in a group of 123 consecutive patients with colorectal cancer. The fate of all patients is known at 3 years after operation. Clinical and pathological data were recorded at the time of presentation and operation, and the patients have been subject to regular postoperative review. DNA ploidy status was determined by flow cytometry. In all, 39 (33 per cent) patients had DNA diploid tumours and 80 (67 per cent) patients had DNA aneuploid tumours. In four cases, tumour material was not obtained. The patients with DNA aneuploid tumours had a worse prognosis than those with DNA diploid tumours, but this was only seen in those patients classified as Dukes' B. In a Cox's regression analysis, the surgeon's assessment of operability was the strongest predictor of survival, followed by the pathological classification and the patient's age. After these factors had been considered, the DNA ploidy status conferred no independent survival value.     

Estimation of prognosis after hepatectomy for hepatocellular carcinoma

BACKGROUND: The preferred means of treatment for hepatocellular carcinoma is surgical resection. However, the tumour recurrence rate is high. Accurate estimation of the risk of tumour recurrence after hepatectomy may facilitate the administration of adjuvant therapy after hepatectomy to patients with a high likelihood of tumour recurrence. METHODS: The clinical and pathological profiles of 176 patients undergoing hepatectomy for hepatocellular carcinoma from March 1992 to August 1998 were reviewed. The Kaplan--Meier method and log rank test were used to analyse univariate prognostic factors. The Cox proportional hazard model was used for multivariate analysis. Disease-free and overall cumulative survival rates were estimated with respect to the number of prognostic factors. RESULTS: Independent factors associated with a lower disease-free survival included the presence of venous infiltration, presence of daughter tumours, absence of tumour encapsulation and tumour size exceeding 5 cm. Factors decreasing the overall survival rate included the presence of venous infiltration, absence of tumour encapsulation and surgical resection margin less than 1 cm. The 1-year disease-free survival rate decreased from 77.5(s.e. 5.6) to 14.0(8.5) per cent when the number of risk factors present increased from zero to three. The 5-year survival rate decreased from 60.2(11.7) per cent to zero when the number of risk factors increased from zero to three. CONCLUSION: The deterioration of disease-free or overall survival of patients with hepatocellular carcinoma after hepatectomy correlates with increasing number of risk factors. The number of risk factors can be employed to accurately estimate disease-free and overall survival.     

Oestrogen receptor D5 antibody is an independent negative prognostic factor in gastric cancer

Recent studies have demonstrated oestrogen receptors in tissues other than those considered to be sex hormone responsive, for instance in gastric cancer. In vitro experiments have shown oestradiol to be trophic to gastric cancer cell lines. The effect of D5 (an oestrogen receptor-related protein) status on survival was therefore studied in a group of 188 consecutive patients undergoing surgery for gastric cancer. Ninety-two patients (49 per cent) were positive for the D5 antibody. There were no differences between the D5-positive and D5-negative groups for age or adverse prognostic features such as high grade tumours or advanced stage. The D5-negative patients had a significant survival advantage over the D5-positive patients. The 95 per cent confidence interval for survival in the patients with D5-negative tumours was 63-101 weeks compared with 39-66 weeks for the patients with D5-positive tumours (Mantel-Cox statistic = 4.15, P = 0.042). Prognostic factor analysis with a Cox proportional hazards model showed tumour stage (P = 0.001) and D5 status (P = 0.003) to be significant independent factors in gastric cancer. Laurén type, grade and gender were not significant independent factors in this small series.     

Population-based study of prognostic factors in stage II colonic cancer

BACKGROUND: Adjuvant chemotherapy in stage II colorectal cancer may be considered for patients whose tumours have poor prognostic features. The aim of this study was to evaluate the prognostic significance of commonly reported clinical and pathological features of stage II colonic cancer. METHODS: A population-based observational study of all patients with stage II colonic cancer diagnosed in the state of Western Australia from 1993 to 2003 was performed. A total of 1306 patients treated by surgery alone were identified, with a median follow-up of 59 (range 0-145) months. RESULTS: Multivariable analysis revealed that the only independent prognostic factors for disease-specific survival were stage T4 (hazard ratio (HR) 1.75 (95 per cent confidence interval (c.i.) 1.32 to 2.32); P < 0.001) and vascular invasion (HR 1.63 (95 per cent c.i. 1.15 to 2.30); P < 0.001). In younger patients (aged 75 years or less), who are more likely to be considered for chemotherapy, these two features showed independent prognostic significance but with higher HR values (1.96 for stage T4 and 2.73 for vascular invasion). Stage T4 and/or the presence of vascular invasion identified a 'poor' prognostic group, comprising 26.6 per cent of younger patients and with a 5-year survival rate of 71.2 per cent. The remaining 'good' prognostic group had a survival rate of 84.3 per cent at 5 years' follow-up. CONCLUSION: This study highlights the importance of accurate pathological assessment of tumour stage and vascular invasion for the prognostic stratification of patients with stage II colonic cancer. The results provide clarification of guidelines for the management of stage II disease in relation to recommendations for chemotherapy.     

Prognostic factors influencing surgical management and outcome of gastrointestinal stromal tumours

BACKGROUND: The purpose of this study was to review surgical experience with gastrointestinal stromal tumours (GISTs) at a single tertiary university hospital, and to identify morphological and genetic prognostic markers of tumour progression. METHODS: Forty-eight GISTs from 39 patients were reviewed retrospectively. The prognostic significance of DNA copy number changes, measured by comparative genomic hybridization (CGH), and morphological markers in low-risk and high-risk tumours were investigated. RESULTS: Significantly more patients died from disease after incomplete tumour resection than after complete primary resection (P = 0.020). Tumour size of 5 cm or greater, mitotic count of 2 or more, and proliferative activity greater than 10 per cent were significantly associated with a shorter recurrence-free survival (P = 0.020, P = 0.001 and P = 0.002 respectively). Patients with low-risk tumours had a significantly better outcome than those with high-risk GISTs, both in terms of overall and recurrence-free survival (P < or = 0.001). CGH performed on 16 tumours revealed fewer DNA sequence copy number changes in low-risk than in high-risk GISTs. Non-progressive GISTs contained significantly fewer genetic alterations than recurrent or metastatic tumours (P < 0.001). Only tumours with more than five changes showed disease progression. CONCLUSION: Complete surgical resection is the most important means of cure for GISTs. DNA copy number changes are related to the behaviour of these tumours and may serve as additional prognostic markers.     

Local recurrence after curative resection for rectal cancer is associated with anterior position of the tumour

BACKGROUND: Mobilization of rectal cancer can be difficult if the tumour is located anteriorly and may result in a higher incidence of local recurrence. The aim of this study was to determine whether local recurrence and survival following curative resection of rectal cancer were associated with the position of the tumour. METHODS: Data were drawn from a comprehensive, prospective hospital registry of all resections for rectal cancer from January 1990 to December 1998, with follow-up to December 2003. RESULTS: The 5-year local recurrence rate was 15.9 (95 per cent confidence interval (c.i.) 11.0 to 22.8) per cent in 176 patients with tumours that had an anterior component compared with 5.8 (95 per cent c.i. 2.8 to 11.9) per cent in 132 patients with tumours without an anterior component (P = 0.009). This association persisted after adjustment for other factors linked to local recurrence (hazard ratio (HR) 2.4 (95 per cent c.i. 1.1 to 5.4)). Similarly, anterior position had a significant negative independent association with survival (HR 1.4 (95 per cent c.i. 1.0 to 2.00)). CONCLUSION: Anterior position is an independent negative prognostic factor for both local recurrence and survival after curative resection of rectal cancer.     

DNA ploidy pattern and tumour spread in gastric cancer

The DNA ploidy pattern of gastric cancer was studied in 58 patients to investigate the heterogeneity between primary tumour and metastases. In both primary tumours and lymph node metastases, diploid patterns accounted for 33 per cent, whereas all liver metastases were aneuploid. The percentage of polyploid cells was higher in the liver metastases than in primary tumours and lymph node metastases. When the heterogeneity of DNA ploidy pattern between primary tumour and metastasis was evaluated, diploid tumours had a significantly lower rate of lymph node metastasis heterogeneity than aneuploid tumours. When the DNA ploidy pattern and survival were evaluated, the patients who had a diploid pattern in both primary tumour and metastasis had a significantly higher survival rate than the patients who had an aneuploid pattern in the primary tumour and metastasis (57 per cent versus 26 per cent at 5 years). These data suggest that cell heterogeneity is a common phenomenon in gastric cancer, and this may be important in the evolution of the disease. Furthermore, the role of the DNA ploidy pattern as a prognostic factor is emphasized.     

Activated oestrogen receptor in human breast cancer: clinical and biochemical correlates

The oestrogen receptor (ER) contains a DNA-binding site, the activity of which can be determined by its binding to oligo(dT)-cellulose. In premenopausal women with breast cancer, 53 per cent of ER-positive tumours were capable of binding to oligo(dT)-cellulose (activated ER): the corresponding proportion in postmenopausal patients was 70 per cent (P less than 0.005). Disease recurrence was significantly increased in patients whose tumours contained non-activated rather than activated ER. The presence of activated ER was associated with a significant increase in the median activity of creatine kinase in premenopausal and postmenopausal patients. In postmenopausal patients the incidence of progesterone receptor was higher in tumours that contained activated ER than in tumours that contained ER not capable of binding to oligo(dT)-cellulose (non-activated). The incidence of activated ER was not related to disease stage or nodal involvement at the time of sampling. The data suggest that ER-positive tumours can be divided, according to the activity of the DNA-binding site, into subgroups with differing biological properties.     

Retrospective analysis of prognostic factors after liver resection and transplantation for cholangiocellular carcinoma

BACKGROUND: Cholangiocellular carcinoma is an uncommon primary liver cancer, which may be mixed with hepatocellular carcinoma. A retrospective analysis was undertaken to evaluate the results of surgical treatment and to identify prognostic factors. METHODS: Between 1978 and 1996, 162 patients underwent surgery for cholangiocellular carcinoma: liver resection (n = 95), liver transplantation (n = 24) and exploratory laparotomy with and without drainage (n = 43). Univariate and multivariate analyses of prognostic factors were performed. RESULTS: Overall survival was 47 per cent at 1 year, 28 per cent at 2 years and 13 per cent at 5 years. Survival rates for patients with resectable tumours were 64, 43 and 21 per cent respectively, and for those who underwent liver transplantation 21, 8 per cent and zero respectively. Univariate analysis showed that the following variables had an effect on survival: age, jaundice, liver resection, T, N and M stage in the tumour node metastasis classification, Union Internacional Contra la Cancrum (UICC) tumour stage, tumour-free margins, vascular infiltration, tumour number, tumour size and serum level of carcinoembryonic antigen. Multivariate analysis identified jaundice, N and M category, and UICC tumour stage as independent prognostic factors. CONCLUSION: The data underscore the importance and prognostic value of the UICC tumour classification for cholangiocellular carcinoma. The prognosis of mixed tumours is no different. Liver resection remains the treatment of choice; transplantation offers no solution for otherwise unresectable tumours.     

Factors influencing survival after resection of pulmonary metastases from colorectal cancer

BACKGROUND: Selection of patients for resection of lung metastases from colorectal cancer is problematic. The aim of this study was to evaluate clinically relevant prognostic factors and to define a subgroup of patients who would most benefit from such surgery. PATIENTS: Seventy-five patients (median age 58 (range 33-82) years) with pulmonary metastases from colorectal cancer underwent 104 R0 lung resections. Median follow-up was 33 (range 4-116) months. Patients who had no evidence of recurrent extrathoracic disease, no more than three metastases on either side, lobectomy as the maximal surgical procedure, and adequate cardiorespiratory function were eligible for surgery. Univariate and multivariate Cox regression, and classification and regression tree subgroup analyses were performed. RESULTS: Overall median survival was 33 months, with 3- and 5-year survival rates of 47 and 27 per cent respectively. Size of metastases (relative risk (RR) 2.6) and extent of resection (RR 0.4) were identified as independent prognostic factors. Primary tumour stage was significant in univariate analysis. Subgroup analysis defined two statistically relevant prognostic groups: patients with a maximum metastasis size of 3.75 cm or less with a disease-free interval of more than 10 months and patients with larger metastases and a shorter disease-free interval. Median survival and 5-year survival were 45 months and 39 per cent in the former group, and 24 months and less than 11 per cent in the latter. CONCLUSION: Subgroup analysis provided criteria for the selection of patients for R0 resection of lung metastases from colorectal cancer and differentiated between those at high or low risk of early tumour progression; the latter patients would benefit most from surgery.     

Prediction of survival from first recurrence of breast carcinoma in Japanese women

The clinical courses of patients with recurrent breast carcinoma vary greatly. We retrospectively examined data on 1863 Japanese patients treated for a breast carcinoma from 1981 to 2000. Among them, 345 (18.5%) who had clearly died of recurrence were reviewed. Patients died most frequently (63.2%) up to 30 months after the first recurrence. Based on multivariate analysis, the four factors that were most predictive of survival after the first recurrence were disease-free interval, site of recurrence, progesterone receptor (PgR) status, and vascular involvement. These findings showed that the intrinsic tumor biology of the initial primary tumor plays a critical role in determining survival after the first recurrence in patients with a breast carcinoma. The combined analysis of disease-free interval, site of recurrence, PgR status, and vascular involvement may assist in estimating the median survival after first recurrence, and may assist with the designing of new therapeutic strategies for patients with recurrence for whom there is an unfavorable prognosis.