Endocrine Therapies for Patients with Recurrent Breast Cancer: Predictive Factors for Responses to First- and Second-Line Endocrine Therapies

Abstract

Breast cancer patients have been treated with four different hormonal agents, antiestrogen, progestin, luteinizing hormone-releasing hormone agonist and aromatase inhibitor, during the past 7 years in Japan. To investigate the efficacy of these agents for the treatment of recurrent breast cancer patients, we conducted a retrospective multi-institute survey in Japan. The clinico-pathological data of 131 patients, who received endocrine therapy as first-line treatment between 1993 and 1998, were collected from seven institutes. The median age of the patients was 55 (range 27–92) years, 75% of their primary tumors were estrogen receptor (ER)-positive or unknown, and 95% of the dominant metastatic sites were bone, soft tissue or lungs. The objective response rate to first-line endocrine therapy was 42.7%, and that to second-line therapy 42.5% (17 of 40 patients). Multiple regression analyses of predictive factors for a response to first- and second-line endocrine therapies indicated two independent factors, ER status of the primary tumors and dominant site of metastasis, for the former, and one independent factor, a response to first-line endocrine therapy, for the latter. Analysis of relationships between sequences of use of hormonal agents and objective response rates revealed that the choice of first-line hormonal agent did not influence the overall efficacy of first- and second-line endocrine therapies. Overall survival after first recurrence in patients with tumors exhibiting an objective response or stable disease to first-line endocrine therapy was significantly better than that in patients with tumors exhibiting progressive disease (p < 0.01). These findings suggest that an adequate selection of recurrent breast cancer patients referring the ER status, dominant site of metastasis and a prior response to endocrine therapy may contribute to better clinical outcomes of the patients.

Different mechanisms of action of 2, 2’, 4, 4’‐tetrabromodiphenyl ether (BDE‐47) and its metabolites (5‐OH‐BDE‐47 and 6‐OH‐BDE‐47) on cell proliferation in OVCAR‐3 ovarian cancer cells and MCF‐7 breast cancer cells

“…Reducing the ER expression by these compounds may indicate the possibility of binding 5-OH-BDE-47 and 6-OH-BDE-47 with oestrogen receptors in place of E2, thus triggering an oestrogenic action in mammary tissue. Kurebayashi et al (2000) showed downregulation of ERα and ERβ during the progression of breast cancer. In MCF-7 cells, similar to the effect observed in OVCAR-3 cells, BDE-47 abolished the inhibitory effect of ICI 182,780 and hydroxylated metabolites enhanced the effects of this anti-oestrogen compound.…”

“…Kurebayashi et al . () showed downregulation of ERα and ERβ during the progression of breast cancer. In MCF‐7 cells, similar to the effect observed in OVCAR‐3 cells, BDE‐47 abolished the inhibitory effect of ICI 182,780 and hydroxylated metabolites enhanced the effects of this anti‐oestrogen compound.…”

Efficacy of Exemestane After Nonsteroidal Aromatase inhibitor Use in Metastatic Breast Cancer Patients

“…The clinical factors that predict a greater likelihood of a response to hormonal therapy are positivity of ER and/or PgR, age, menopausal status, soft-tissue disease, longer DFI, and a previous response to hormonal therapy (Santen et al, 1990;Muss, 1992). Few data are available regarding the response association between exemestane and nSAIs, although tamoxifen responsiveness is thought to be an important predictor of subsequent endocrine responsiveness (Santen et al, 1990;Muss ,1992;Kurebayashi et al, 2000). In a phase II study of exemestane given as the third-or fourth-line therapy, Lønning et al (2000) showed that the efficacy of exemestane in 241 patients depended on their response to the previous hormonal therapy.…”

The evolving role of receptors as predictive biomarkers for metastatic breast cancer

“…For instance, endocrine therapy has been shown to be at least as effective as chemotherapy [37,99] in ER+ MBC. Evidence suggests that treatment with endocrine therapy in the adjuvant setting does not significantly influence the rate of response of subsequent recurrent cancers [100]. Endocrine therapy is now the recommended first option for treatment of ER+ MBC, except in cases with visceral involvement, which warrant the administration of chemotherapy instead [94,101,102].…”