Studies on prognostic factors in patients with MBC vary considerably and are sometimes contradictory with respect to the selection of patients, availability of biological and clinical parameters, patients’ follow-up and methods of analysis. In the present analysis of 1038 patients treated in our institution from 1980 to 2005, we have shown that hormonal status receptor, site of metastasis, adjuvant chemotherapy, patient age, size of primary tumor and SBR grade constituted independent prognostic factors which were significant in multivariate analysis, while metastatic diagnosis period and MFI were significant only in the univariate analysis.
Among these factors, the site of metastasis seems to be the most significant independent prognostic factor. As previously described, multiple or visceral site of metastasis seems to be predictor of poor-specific survival with a median survival not exceeding 22 months, while nonvisceral sites are associated with better-specific survival with a median survival of >33 months [11
]. Patients with metastatic bone disease were associated with a relatively better survival [13
] and bone is the most frequently reported site of metastasis with 40% in our study and >30% described in other reports [11
]. Other studies have already investigated the relationship between the site of metastasis and survival [17
] but few of them have included enough patients to allow a powerful multivariate analysis to be carried out. It is interesting to note that these observations were more significant when considering hormonal status. Thus, whatever the metastasis site, survival after metastatic recurrence for HR+ patients was better than for HR− patients. Some groups have suggested a relationship between HR status and the site of recurrence. Our study confirms this trend and shows that positive HRs were more likely to recur in bone while negative receptor status occurred more often in brain and multiple sites.
As previously reported by Andre et al. [19
], univariate analysis in the present study has shown that survival of breast cancer patients developing metastases was improved in the time period from 1980 to 2005 with median survival ranging from 16 months for the first metastatic diagnosis period (1980–1985) to 31 months for the last period (2000–2005). This result, however, was not confirmed by a multivariate analysis indicating that the survival improvement appears to be more closely linked to other independent prognostic factors studied (site of metastasis, age, HR status, previous chemotherapy and tumor size) than to time period. The present study also demonstrates that several types of therapeutic management have improved the survival of metastatic HR+ breast cancer patients while the improvement of HR− patients has remained unchanged for the past 25 years. It is generally accepted that young age at diagnosis is associated with more aggressive disease and relative poor survival from diagnosis. Risk of recurrence, however, is significantly increased in older women [20
]. In our study, women aged >50 years had significantly lower survival rates. One can explain this observation more precisely: postmenopausal patients were found to have a lower response rate to chemotherapy. The increase in side-effects inducing dose reduction and loss of efficiency in older women may also explain this observation.
Some studies have already considered adjuvant chemotherapy or axillary lymph node involvement at first diagnosis as survival prognostic factors following first recurrence. Results and conclusions differed [11
]. In our population and in most of the others, adjuvant chemotherapy and axillary lymph node status were correlated and administration of adjuvant chemotherapy was more frequent in patients with positive lymph node status. It is difficult to distinguish the respective influence of each of these two factors. Nevertheless, adjuvant chemotherapy appears to be an unfavorable independent prognostic factor for survival.
Some studies have shown that early recurrence is an independent predictor of survival and that desease-free interval (DFI) is one of the strongest prognostic factors reflecting the aggressiveness of the disease [17
]. In the present study, disease-free interval appeared to be related to survival in the univariate analysis, but when performing a multivariate Cox model, the other previously described parameters were more powerful for predicting specific survival. Nevertheless, it appears that MFI may be considered an easily and immediately available multifactorial prognostic index reflecting the multiparametric variability of the disease.
In summary, this study on a particularly large number of patients with breast carcinoma shows that prognostic factors of the initial primary tumor and metastastic disease are associated with specific survival after recurrence. These findings are consistent with the hypothesis that the intrinsic tumor biology of the primary tumor plays a critical role in determining outcome following recurrence [22
]. The aim of the present study was dual: first, to draw up a list of factors easily available in usual clinical practice requiring no sophisticated or costly methods. Secondly, to provide results from a large cohort of women who underwent diagnostic and treatment at a single institution. It is presently shown that age at initial diagnosis, HR status, site of metastasis and DFI are the most relevant prognostic factors for predicting survival from the time of metastatic occurrence. These three fundamental factors may enable physicians to evaluate more easily the survival potential at individual level and guide them in their therapeutic decision.