Prognostic factors of breast cancer

OBJECTIVES: Characterization of breast cancers by various tumour markers which are appropriate for the identification of high risk groups. Markers related to the metastasis cascade and tumour recurrence have been investigated. MATERIALS AND METHODS: RT-PCR was used to determine the expression of cytokeratin 20 in the bone marrow and sentinel lymph node of breast cancer patients (n=45). The expression of HER2, Cadherin E, Cyclin D, Bcl2 and Bax has been evaluated by Western blot (n=744 invasive ductal carcinomas and 117 invasive lobular carcinomas, 124 recurrent breast cancers). Mutations of p53, APC and beta Catenin genes were detected by PCR-SSCP method. RESULTS: Expression of cytokeratin 20 was found in 30% of the bone marrow samples indicating the presence of micrometastasis. The level of Cyclin D, HER2 and Bcl2 is elevated four-fold in the recurrent breast cancers. The metastasis of invasive ductal carcinomas is accompained by high frequency of p53 mutations (24%) and APC mutations (18%). The invasive lobular carcinomas could be characterized with low frequency of p53 mutation (3%), low level of Cadherin E and high level of catenin beta. CONCLUSIONS: Identification of micrometastasis can promote the development of therapeutic strategy. Evaluation of HER2 level and determination of p53 mutations contribute to the identification of high risk patients. Our results suggest that the progression of invasive ductal carcinomas depends on the APC mutations, while metastasis of invasive lobular carcinomas depends on beta catenin mutations.     

Prognostic factors for recurrence and survival in axillary node-negative breast cancer

The question of which node-negative breast cancer patients should be treated with adjuvant systemic therapy is a debatable topic. Our approach in San Antonio is to examine the risk profile for an individual patient and attempt to classify the patient into a good risk group or a high risk group in terms of disease recurrence. Features such as small tumor size (less than 2 cm), diploid tumors with low proliferative rate, and nuclear grade I, all indicate a good prognosis with a disease-free survival of approx. 90% at 5 yr. Examination of the cost vs benefits in this category of patients suggest that routine treatment with systemic adjuvant therapy is not appropriate.     

Evaluation of a cytological scoring system for predicting histological grade and disease-free survival in primary breast cancer

A simple cytological scoring system was evaluated as a method of predicting histological grade and disease-free survival in 79 patients with primary breast cancer. the mitotic activity index and oestrogen receptor status were also assessed for their predictive value. the concordance between cytological scores and histological grades was good (80%) for low-grade lesions, but poor (45%) for high-grade lesions. Similar results were found using the mitotic activity index as a prognostic indicator. Cytological grading was not found to be an independent prognostic indicator after a median follow up of 8 years.     

Prognostic factors and survival in metastatic breast cancer: A single institution experience

Background

The current retrospective study aims to identify some determinants of survival in metastatic breast cancer.

Methods

The study concerned 332 patients with synchronous (SM) or metachronous (MM) metastatic breast cancer treated between January 2000 and December 2007. Statistical comparison between subgroups of patients concerning survival was carried out employing log-rank test for the invariable analysis and Cox model for the multivariable analysis. Factors included: age group (≤50 years vs. >50; ≤70 years vs. >70; ≤35 years vs. >35), menopausal status, presentation of metastatic disease (SM vs. MM), disease free interval (DFI) (≤24 months vs. >24 months; ≤60 months vs. >60 months), performance status at diagnosis of metastatic disease (PS) (0–1 vs. >1), hormone receptors (HR), number of metastatic sites (1 site vs. >1), nature of the metastatic site (visceral vs. non visceral), first line therapy, surgery of the primary tumor (SPT), locoregional radiotherapy (LRRT) and use or not of bisphosphonates.

Results

Overall survival at 5 years was 12%. Positive prognostic factors in univariate analysis were: age ≤ 70 years, hormono-dependence of the tumor, good PS (PS 0–1), less than two metastatic sites, no visceral metastases, DFI ≥ 24 months, SPT or LRRT. In multivariate analysis, favorable independent prognostic factors included: good PS (PS 0–1), absence of visceral metastases (liver, lung, brain) and age ≤ 70 years.

Conclusion

Many of the prognostic factors in metastatic breast cancer found in our study are known in the literature but some of them, like the application of locoregional treatment (radiotherapy or surgery) and the use of bisphosphonates, need to be further investigated in randomized clinical trials.     

Prognostic factors in human primary breast cancer: comparison of c-myc and HER2/neu amplification.

Amplification of oncogenes in primary tumours may have prognostic and/or therapeutic significance for patients with breast cancer. We have studied HER2/neu and c-myc amplification together with steroid receptors in human primary breast tumours and related the outcome with (relapse-free) survival. A strong inverse correlation was found between HER2/neu amplification and the presence of oestrogen and progesterone receptors. Actuarial 5-years survival showed that breast cancer patients with c-myc amplification in their primary tumours experience a shorter relapse-free survival, especially in node-negative and in receptor-positive tumours, whereas HER2/neu amplification may be of prognostic value for overall survival in receptor-negative tumours. Overall, in our hands, c-myc amplification appeared to be a more potent prognosticator than HER2/neu amplification in human primary breast cancer.     

Solitary primary CNS lymphoma: long term survival following total resection

Primary non-Hodgkin's CNS lymphoma is rare, constituting 0.3–1.5% of all intracranial neoplasms in patients without AIDS. In the past 10 years the incidence has tripled in this population. The role of surgery is commonly limited to obtaining adequate tissue for diagnosis. This has precluded the evaluation of total surgical resection for a surgically accessible solitary lesion. We have encountered a 36-year-old healthy white male with primary CNS lymphoma who is HIV-negative and who has survived over five years disease free after total surgical resection of his lymphoma.     

The Multivariate Prognostic Index and nuclear DNA content are independent prognostic factors in primary breast cancer patients

The predictive value of a previously described Multivariate Prognostic Index (which incorporates weighted values of the mitotic activity index, tumor size, and the axillary lymph node status), and the nuclear DNA content (DNA) was evaluated in 156 patients with primary invasive ductal breast cancer, diagnosed between 1980 and 1983. The results were analysed with respect to the occurrence of distant recurrence and survival of the patients after at least 3 yr of follow-up (range 36-73 months; median 44 months). Known prognostic factors such as lymph node status, tumor size, and the mitotic activity index correlated independently with distant recurrence. Furthermore, in respect to survival, the investigated prognostic factors (except DNA content) were significantly correlated. The results indicate that the predictive value of the Multivariate Prognostic Index (MPI) is stronger (P less than 0.001) than of the nuclear DNA content (P less than 0.005) with respect to distant recurrence. In a Cox multivariate regression analysis DNA ploidy turned out to be an independent prognostic factor once the MPI was selected. Furthermore, in Cox's analysis, DNA ploidy was the fourth selected variable after lymph node status, mitotic activity index, and tumor size in individual parameter analysis. The results of this study indicate that, with respect to breast cancer screening programs, it seems worthwhile to integrate morphometric features, the MPI, and DNA ploidy in a new prognostic model.     

The favorable prognostic significance of surgery-induced hyperprolactinemia in node-positive breast cancer patients: ten-year disease-free survival results

It has been shown that each manipulation of the mammary region, including breast surgery, may stimulate prolactin secretion. However, it has also been observed that in more than 50% of breast cancer patients surgical removal of the tumor is not followed by enhanced prolactin secretion. This might be indicative of an altered psychoneuroendocrine control of the mammary gland, which could lead to the onset of more biologically aggressive breast cancer. In fact, surgery-induced hyperprolactinemia has been proven to be associated with a better prognosis in terms of survival in node-negative breast cancer patients. The present study was performed to investigate the impact of postoperative hyperprolactinemia on the disease-free survival (DFS) of breast cancer patients with axillary node involvement. The study included 100 consecutive node-positive breast cancer patients who were followed for at least 10 years. Surgery-induced hyperprolactinemia occurred in 45/100 (45%) patients without any significant correlation with the main prognostic variables including number of involved nodes and ER status. The two groups of patients received the same adjuvant therapies. After a median follow-up of 151 months, the recurrence rate in patients with surgery-induced hyperprolactinemia was significantly lower than in patients with no postoperative hyperprolactinemia (23/45 vs 43/55, p<0.01). Moreover, DFS was significantly longer in hyperprolactinemic patients than in patients who had no enhanced secretion of prolactin postoperatively. In agreement with the results described previously in node-negative breast cancer, our study demonstrates the favorable prognostic significance of surgery-induced hyperprolactinemia in terms of DFS duration also in breast cancer patients with axillary node involvement, independent of the other well-known prognostic variables, thereby confirming that the psychoneuroendocrine status of cancer patients may influence the prognosis of their disease.     

Bilateral breast cancer in northern Alberta: risk factors and survival patterns.

Of 2231 women with stage I, II or III breast cancer who were registered and seen between 1971 and 1979 and followed to the end of 1981, 48 (2.2%) had synchronous and 58 (2.6%) asynchronous bilateral breast cancer. The unadjusted incidence rate for a second breast cancer was 6.4/1000 breast-years at risk, compared with a rate of 0.70 for the risk of a first breast cancer in women. When calculated from the date of diagnosis of the first breast cancer the survival rate was better for the group with asynchronous disease than for the group with synchronous disease or for a group with unilateral disease, but when calculated from the date of diagnosis of the second cancer the rate was the same in all three groups. Comparison of known risk factors showed a significant association between the development of bilateral cancer and a later age at the birth of the first child and a longer interval between menarche and that birth. There was a trend towards greater age and more stage III cancer in the group with synchronous disease. There was no correlation between receiving radiotherapy for the first breast cancer and development of the second cancer. Annual mammography and clinical examination of asymptomatic women at a cancer centre resulted in the detection of a significantly higher proportion of minimal breast cancers in the second breast compared with the first. Such screening practices should be even more valuable in the earlier detection of unilateral breast cancer in asymptomatic women who have not had breast cancer.     

Treatment and survival on advanced breast cancer.

The final results of a clinical trial comparing endocrine with cytotoxic drug treatment for advanced breast cancer were analysed. Although cytotoxic treatment gave a significantly higher response rate with a remission duration comparable to that obtained with endocrine treatment, the sequence in which the two treatments were given did not appear to influence survival--except possibly in women with rapidly progressing disease, when cytotoxic treatment is preferred.     

Second primary cancer following treatment for cervical cancer.

A follow-up study of 7535 women in Ontario was carried out to assess the occurrence of second primary cancers following the treatment of invasive carcinoma of the cervix between 1960 and 1975. The study was part of a larger international investigation of late radiation effects in patients with cervical cancer. Data were collected on the date and the type of treatment for cervical cancer and on the occurrence of second primary cancers diagnosed before 1980. Observed and expected numbers of second primary cancers, the latter determined according to Ontario incidence rates, were compared for individual sites and for all sites combined. There were significantly more primary cancers of the lung than expected (64 v. 15.52) but significantly fewer second primary cancers of the breast (56 v. 105.01) and colon (27 v. 43.31). Overall, there were significantly fewer (p less than 0.05) observed second primary cancers than expected (280 v. 394). Although the median follow-up period was less than 10 years there was no marked evidence of an excess of radiation-induced second primary cancers.