P. Schiavone

Molecularly targeted endocrine therapies for breast cancer

The identification of the estrogen receptor (ER) provided the first target for antiestrogenic therapeutic agents. Endocrine therapies, either by blocking or downregulating the receptor or by suppressing the estrogen production, inhibit the proliferative effect of estradiol on ER. While the activity on ER is considered a real target-mediated therapy, the effect on enzymatic activity involved in estrogen production (mainly inhibition of aromatase by aromatase inhibitors, AIs, and ovarian ablation) could be considered an indirect targeted strategy. In addiction to the direct ligand-ER signal, the complexity of endocrine and non endocrine pathways has led to combination therapies against different targets. Tamoxifen is the widely investigated, most used and representative of drugs blocking the ER and has been introduced in the advanced disease, in neoadjuvant and adjuvant setting and for chemo-prevention of high risk women. Its role has been challenged in the last years by the introduction of third generation aromatase inhibitors that have proven a higher activity than tamoxifen and different toxicity. Several other SERMs (selective estrogen receptor modulators) have been investigated, but none of them was clearly superior to tamoxifen. SERDs (selective estrogen receptor downregulators) act as pure estrogen antagonist. They are used in the treatment of advanced breast cancers and their role in other settings still needs further investigation. Here we discuss the well established data with SERMs, SERDs and AIs, mechanisms underlying resistance and rationale for recycling endocrine compounds and for simultaneously targeting different pathways.

22 ADHERENCE TO AND PERSISTENCE WITH AN ORAL METRONOMIC CHEMOTHERAPY WITH CAPECITABINE IN HEAVILY PRETREATED METASTATIC BREAST CANCER (MBC) PATIENTS

s / Cancer Treatment Reviews 36S3 (2010) S95–S119 S101 histochemical expression of HER-2 growth factor. With a median follow-up of 18 months (range 11–35) there were 16 pts (70%) with no evidence of disease; 4 patients (17%) were alive with disease; and 3 patients (13%) died of the disease. Relapse was detected in 7 women (30%), lung, brain, and chest wall recurrence being the most common sites of metastasis. Among those 7 cases, 5 are triple negative and one patient had obtained a complete pathological response. Conclusions: Our data suggest an improvement in locoregional control in patients treated by surgery, in conjunction with chemotherapy based on antracycline and radiotherapy, for LABD. Moreover, patients with triple-negative disease are a poor prognosis and at high incidence of early metastatic recurrence. 21 DUCTAL CARCINOMA IN SITU OF BREAST: ANALYSIS OF 232 CASES T.P. Latiano, C. D’Addetta, L. Lombardi, M. Morritti, A. Piano, R. Murgo, M. El Jaouni, M. Copetti, E. Maiello. Oncology Unit, Surgery Unit, Unit of Radiotherapy, Unit of Biostatistics, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy Background: Ductal carcinoma in situ (DCIS) is a heterogeneous, unicentric precursor of invasive breast cancer, which is frequently identified through mammographic breast screening programs. The prognostic factors of DCIS include anatomo-pathologic factors, age and molecular factors. Methods: Two-hundred-thirty-two woman with DCIS were retrospectively reviewed between 1996 and 2009 in our Institution. The main characteristics of these pts were: median age 53 years (range 23–78), menopause 154 pts (66.3%), fertility 192 pts (82.7%); 50 pts (21.5%) were treated with mastectomy, 182 (78.4%) with breast conservation, and 171 (93.3%) received radiotherapy. Moreover, 106 pts (45.6%) received tamoxifen. Results: With median follow-up of 55 months (range 4–170), recurrence rate was 4.7% (11 pts: 8 ipsilateral, 2 controlateral and 1 ipsilateral + controlateral synchronous). Median relapse free survival was 44.5 months (range 23–68). Approximately 90% of these recurrence have received a breast conservation developing invasive cancer. All these pts had more than 40 years (range 40–66; median 49) and 6/11 were between 40 and 50 yrs. Histologically, 10/11 pts presented comedocarcinoma and 8/11 positive surgical margins. Nine of these woman underwent breast irradiation (90%) and only four pts (36%) ormonal therapy with tamoxifen. The overall survival of all group was 98.2%. Conclusions: Our retrospective analysis confirm the usefulness of mastectomy for patients with DCIS: in fact, breast radical surgery was associated with optimal local control. Furthermore, we observed that pts with 40–50 yrs and comedocarcinoma histology might be considered at high risk of local recurrence and therefore the age and the histology might be considerate as predictors of