Factors responsible for long-term survival in metastatic breast cancer

Abstract

BackgroundAlthough survival of patients with metastatic breast cancer (MBC) has been significantly prolonged over the past decade due to improvement of anti-cancer therapeutics, only a few patients survive for more than 10 years. It has not been determined which patients can have long-term survival with treatment.MethodsTo determine prognostic factors responsible for long-term survival, we retrospectively compared clinicopathologic factors of patients with MBC who survived for 50 months or more after diagnosis with patients who did not. Of 70 patients with MBC who received chemotherapy between November 2005 and September 2011, 23 patients who survived for 50 months or more after diagnosis and 28 patients who died within 50 months after diagnosis were assessed for their clinicopathologic factors and outcomes.ResultsThe proportion of patients with hormone receptor-positive (HR+) tumors was significantly higher and the proportion of patients with triple negative tumors (TN) was lower in long-term survivors than in non-long-term survivors (HR+: 87% versus 28.6%, P = 0.000037; TN: 13.1% versus 53.6%, P = 0.0028). Metastatic site, number of disease sites, prior chemotherapeutic regimens and human epidermal growth factor receptor-2 (HER2) status did not differ between the two groups. The proportion of patients who received metronomic regimens was significantly higher in long-term survivors than in non-long-term survivors (65.2% versus 35.7%, P = 0.034) when the most effective regimen among regimens that were received in metastatic settings was compared between the two groups. Overall response rate was significantly higher (82.6% versus 17.9%, P <0.00001) and time to treatment failure after receiving the most effective regimen was longer in long-term survivors than in non-long-term survivors (26 versus 5 months, P = 0.0001). The number of chemotherapeutic regimens for breast cancer and that for MBC did not differ between the two groups.ConclusionsPatients with luminal-type MBC who benefit at least once from chemotherapy including metronomic regimens, or patients who continued to receive the most effective regimen for more than two years can be expected to have long-term survival after diagnosis of MBC, regardless of the number of chemotherapeutic regimens they had received.

Melanoma growth effects on molecular clearance from tumors and biodistribution into systemic tissues versus draining lymph nodes

“…The deleterious effects of cancer are not limited to the primary tumor itself, as evidenced by the sentinel lymph node's role in tumor immune suppression [3, 9] as well as the high number of cancer-associated complications and mortalities associated with both metastasis [25, 26] and thrombosis [27, 28]. Distant intercellular signaling can occur even prior to metastasis to precipitate such effects, for example via remodeling of sentinel lymph nodes [29], VEGFR1 + haematopoietic progenitor cell recruitment to pre-metastatic niches [14], and secretion of tumor-derived pro-coagulants and cytokines driving thrombosis [30].…”

Indication of metronomic chemotherapy for metastatic breast cancer: Clinical outcomes and responsive subtypes

“…Metronomic chemotherapy, which is defined as continuous or frequent treatment with low doses of anticancer agents, has been reported to result in favorable tumor responses and prolonged survival (13). We previously reported that the proportion of patients who received a metronomic regimen as the most effective regimen was two-thirds of the long-term survivors (65.3%), who survived for ≥50 months after diagnosis with MBC, which was double that of the non-long-term survivors, who succumbed to the disease within 50 months (12). The mechanisms of inhibition of tumor growth by metronomic chemotherapy remain to be determined.…”

“…We also demonstrated that more MBC patients who survived for ≥60 months following MBC diagnosis had received metronomic chemotherapy, compared with patients exhibiting shorter survival (12). Metronomic chemotherapy, which is defined as continuous or frequent treatment with low doses of anticancer agents, is commonly used as palliative care in patients who have been heavily pretreated with cytotoxic drugs or who have poor performance status (13).…”

Clinical overview of metronomic chemotherapy in breast cancer

“…A large group of patients might have a prolonged survival after the diagnosis of advanced disease. [47][48][49] In such circumstances, one could consider a therapeutic strategy with a low toxi city profile, good tumour control and economically viable for the healthcare system. Moreover, management of metastatic disease must be driven by multiple considerations that include not only the heterogeneity of breast cancer subtypes, but also the heterogeneity of breast cancer patients, such as patient age, preferences, frailty, co-morbidities and potential contraindications to more-intensive regimens.…”