L. Mauriac

Fulvestrant, Formerly ICI 182,780, Is as Effective as Anastrozole in Postmenopausal Women With Advanced Breast Cancer Progressing After Prior Endocrine Treatment

PURPOSEnTo compare the efficacy and tolerability of fulvestrant (formerly ICI 182,780) and anastrozole in postmenopausal women with advanced breast cancer progressing after prior endocrine treatment.nnnPATIENTS AND METHODSnPatients (n = 451) with advanced breast cancer were randomized to receive fulvestrant 250 mg as a once-monthly (one x 5 mL) intramuscular injection or an oral dose of anastrozole 1 mg in this open, parallel-group, multicenter trial. The primary end point was time to progression (TTP). Secondary end points included objective response (OR) rates, defined as complete response (CR) or partial response (PR), duration of response (DOR), and tolerability.nnnRESULTSnPatients were followed for a median period of 14.4 months. In terms of TTP, fulvestrant was as effective as anastrozole (hazard ratio, 0.98; confidence interval [CI], 0.80 to 1.21; P =.84). Median TTP was 5.5 months for fulvestrant and 5.1 months for anastrozole. OR rates showed a numerical advantage for fulvestrant (20.7%) over anastrozole (15.7%) (odds ratio, 1.38; CI, 0.84 to 2.29; P =.20). Clinical benefit rates (CR + PR + stable disease > or = 24 weeks) were 44.6% for fulvestrant and 45.0% for anastrozole. Median DOR was 14.3 months for fulvestrant and 14.0 months for anastrozole. Both treatments were well tolerated, with 3.2% and 1.3% of fulvestrant- and anastrozole-treated patients, respectively, withdrawn from treatment because of an adverse event.nnnCONCLUSIONnFulvestrant was as effective as anastrozole. These data confirm that fulvestrant is an additional, effective, and well-tolerated treatment for advanced breast cancer in postmenopausal women whose disease progressed on prior endocrine therapy.

Magnetic resonance imaging of the breast: Recommendations from the EUSOMA working group

The use of breast magnetic resonance imaging (MRI) is rapidly increasing. EUSOMA organised a workshop in Milan on 20-21st October 2008 to evaluate the evidence currently available on clinical value and indications for breast MRI. Twenty-three experts from the disciplines involved in breast disease management - including epidemiologists, geneticists, oncologists, radiologists, radiation oncologists, and surgeons - discussed the evidence for the use of this technology in plenary and focused sessions. This paper presents the consensus reached by this working group. General recommendations, technical requirements, methodology, and interpretation were firstly considered. For the following ten indications, an overview of the evidence, a list of recommendations, and a number of research issues were defined: staging before treatment planning; screening of high-risk women; evaluation of response to neoadjuvant chemotherapy; patients with breast augmentation or reconstruction; occult primary breast cancer; breast cancer recurrence; nipple discharge; characterisation of equivocal findings at conventional imaging; inflammatory breast cancer; and male breast. The working group strongly suggests that all breast cancer specialists cooperate for an optimal clinical use of this emerging technology and for future research, focusing on patient outcome as primary end-point.

Fulvestrant (Faslodex™) versus anastrozole for the second-line treatment of advanced breast cancer in subgroups of postmenopausal women with visceral and non-visceral metastases: combined results from two multicentre trials

The efficacy of fulvestrant (Faslodex), a novel oestrogen receptor (ER) antagonist that downregulates the ER and has no known agonist effects, was compared with the aromatase inhibitor anastrozole (Arimidex) for the second-line treatment of advanced breast cancer in postmenopausal women with visceral and non-visceral metastases. Assessment was by means of a retrospective subgroup analysis of combined data from two randomised, phase III trials. Objective response (OR) rates were similar in patients treated with fulvestrant and anastrozole, respectively (21.9% versus 19.3%-patients with no visceral metastases; 15.7% versus 13.2%-all of the patients with visceral metastases; 18.8% versus 14.0%-patients with visceral metastases only). The proportion of patients with clinical benefit (CB) was also similar between treatments and between subgroups with and without visceral disease. Fulvestrant is at least as effective as anastrozole, providing a valuable treatment option for advanced breast cancer in postmenopausal women with visceral metastases who have failed on prior endocrine therapy.

Postmenopausal Women who Progress on Fulvestrant ('Faslodex') Remain Sensitive to Further Endocrine Therapy

AbstractPurpose. This retrospective evaluation of data from two randomized, multicenter trials examined whether tumor responses to further endocrine therapy were seen in postmenopausal women with advanced breast cancer who had progressed on both initial endocrine therapy, usually tamoxifen, and on the estrogen receptor (ER) antagonist fulvestrant (Faslodex).nPatients and methods. A combined total of 423 patients received fulvestrant 250 mg as a monthly intramuscular injection. After progression on fulvestrant, some patients received another endocrine therapy. Responses to subsequent endocrine therapy were assessed using a questionnaire sent to the trial investigators. Best responses were classified as a complete or partial response (CR or PR), stable disease (SD) lasting ≥24 weeks, or disease progression.nResults. Follow-up data were available for 54 patients who derived clinical benefit (CB, defined as CR, PR or SD) from fulvestrant and who received subsequent endocrine therapy, resulting in a PR in 4 patients, SD in 21 patients, and disease progression in 29 patients. Data were available for 51 patients who derived no CB from fulvestrant and who received further endocrine therapy, resulting in a PR in 1 patient, SD in 17 patients, and disease progression in 33 patients. Aromatase inhibitors were used as subsequent endocrine therapy in >80% of patients.nConclusions. After progression on fulvestrant, patients may retain sensitivity to other endocrine agents. Fulvestrant provides an additional option to existing endocrine therapies for the treatment of advanced or metastatic breast cancer in postmenopausal women, and may provide the opportunity to extend the sequence of endocrine regimens before cytotoxic chemotherapy is required.

Breast cancer and in vitro fertilization. About 32 cases.

Because of the increased risk of breast cancer for infertile nulliparous women, the suspected promoter role of estradiol in mammary carcinogenesis and the high frequency of ovulation inducer treatments, it was interesting to focus on the risk of breast cancer after such a treatment. We reviewed 32 cases during a retrospective survey in Assisted Reproductive Techniques (ART) centers in France. Because of the small sample size and the few cases published so far, no statistical study could be made. However, many observations may have gone unnoticed or were not published. Two hypotheses can be proposed: (1) the facilitating role of stimulation on potential infra-clinical or un-diagnosed cancers; (2) the initiation of new cancers. Consequently, we propose to establish a register for the follow-up of treated women to monitor the advent of new cancers and to increase the follow-up of patients with other associated risk factors.

First-line chemotherapy for metastatic breast cancer in patients ≥75 years: A retrospective single-centre analysis

Data on chemotherapy for elderly patients with metastatic breast carcinoma (MBC) are limited. We performed a 7-year retrospective analysis of MBC patients at our institution receiving first-line chemotherapy aged ≥75 years. Of 117 patients, 103 received monotherapy (67 capecitabine, 29 vinorelbine, 5 docetaxel, 2 liposomal doxorubicin) and 14 received polychemotherapy (12 anthracycline-based, 2 vinorelbine-gemcitabine). Chemotherapy demonstrated acceptable tolerability. Median progression-free survival (PFS) and overall survival (OS) from initiation of chemotherapy were 6.2 months and 13.8 months, respectively. At 2 years, 25% of patients were alive; however, 25% died within 3 months of beginning chemotherapy. Independent prognostic factors for longer PFS were good performance status, absence of visceral disease and capecitabine treatment. Good performance status and lack of visceral disease were also significant for OS. These results suggest that palliative chemotherapy should not be systematically excluded in this setting, but should be carefully discussed as it appears to be feasible with apparent benefit in selected patients.

Docetaxel rechallenge after a first response in non-resistant metastatic breast cancer: significant activity with manageable toxicity

Docetaxel is a major drug in metastatic breast cancer (MBC) treatment. At progression, rechallenge with docetaxel can be discussed, according to previous efficacy and tolerance, as long as it was stopped for reasons other than progression. Currently, no data are available outlining outcomes after this pragmatic approach in MBC. We retrospectively identified 72 patients with the following criteria: (i) objective response or stable disease with a previous line of treatment with docetaxel in the metastatic setting, (ii) discontinuation for a reason other than progression, (iii) rechallenge with docetaxel after a minimal docetaxel-free interval of 3xa0months. The main objectives were to evaluate overall response (ORR), time to progression (TTP), overall survival (OS) and toxicity at reintroduction of docetaxel. Median patient age was 57xa0years (range: 34–84). Docetaxel was reintroduced as a 2nd, 3rd, or ≥4th line of chemotherapy in the metastatic setting in 21, 46 and 33xa0% of cases, respectively. Previous agents used included capecitabine, anthracycline, and vinorelbine in 54, 40 and 21xa0% of cases, respectively. The median number of docetaxel cycles was 6 (range: 1–18). Among the 33 patients with disease assessed according to RECIST criteria, 14 (42.5xa0%) had a partial response and 11 (33.5xa0%) a stable disease >6xa0weeks. Among the 46 patients with an initial CA 15-3 increase, 34 (74xa0%) had a ≥50xa0% decrease of the value. Globally, 55 patients (76xa0%) obtained a benefit from the treatment. The median TTP and OS were 5.7xa0months (95xa0% CI: 5.0–6.3) and 10.2xa0months (95xa0% CI: 8.6–11.8), respectively. Forty-six patients (64xa0%) reported grade 1/2 toxicity, 23 patients (32xa0%) experienced grade 3/4 toxicity, mostly neutropenia (17xa0%) and fluid retention (10xa0%). There was no difference in median TTP after subsequent docetaxel in subgroup analyses. This retrospective analysis supports the pragmatic strategy to retreat patients with MBC with docetaxel when this drug has shown previous activity and was stopped for other causes than progression.

Neoadjuvant endocrine treatment in breast cancer: analysis of daily practice in large cancer center to facilitate decision making

BACKGROUNDnTo examine outcomes of neoadjuvant endocrine therapy in daily practice to inform decision making.nnnMETHODSnWe retrospectively selected 204 patients who received neoadjuvant endocrine therapy with T2 (≥30 mm) or T3 tumors, examining subsequent breast-sparing surgery and long-term outcomes.nnnRESULTSnNeoadjuvant endocrine therapy was administered for 7.3 months (median) and breast-sparing surgery was achievable in 53% of patients. Smaller initial tumor size and modified version of the Scarff-Bloom and Richardson grades 1 to 2 were associated with breast-sparing surgery. Disease progression during treatment was 6.9%; actuarial risk of local relapse was 3% at 5 years and 15% at 10 years. Five- and 10-year metastasis relapse-free survival was 78% and 63%, respectively. Grade 3, negative progesterone receptors, and absence or slow response to neoadjuvant therapy were associated prognostic factors.nnnCONCLUSIONnThese daily practice data provide important information about feasibility, efficacy, and long-term results of neoadjuvant endocrine therapy and can be used to inform patients for decision making between mastectomy and endocrine induction therapy.

Genomic score predictive of metastatic evolution in breast cancer.

Abstract #5069 Background: Despite of the existence of clinical and pathological prognostic factors, the metastatic evolution in breast cancer remains uncertain in a substantial proportion of cases. Previous studies have suggested that genome profiling could address this question. In this context we developed a genomic score to evaluate the total level of copy number aberrations in a given tumor, based on data from array-CGH analysis.u2028 Material and Methods: We performed array-CGH analysis in a series of 135 sporadic, operable breast cancers treated at our institution between 1989 and 1992 (more than 10 years follow-up). These cases included 45 invasive ductal carcinomas with metastatic evolution (M + ) and 90 cases that did not relapse at 11 years (M - ). Cases were paired on patients age and initial axillary lymph node status (pN + /pN0), and were equally distributed between the two groups of evolution: 25 pN0/M + , 20 pN + /M + , 50 pN0/M - and 40 pN + /M - . Tumoral DNA was co-hybridized with pooled normal germline DNA from 20 individuals on a 4407 BAC-array (CIT-V6) provided by the CIT program and manufactured by Integragen. Gain, normal and loss status (GNL) were generated from the CapWeb pipeline developped by the bioinformatics plateforme from Institut Curie (Paris). Clinical, pathological and genomic data were retrieved through Annotator, the CIT cancer database and the analysis has been driven by using the R statistical software along with the CIT R packages.u2028 Results: The proposed score of genomic instability is based on two items: (i) the proportion of alteration and (ii) the number of altered genomic regions. By applying a set of appropriate thresholds on these two items we were able to define three highly different prognostic subgroups, 95 % (18/19), 74 % (65/88) and 25 % (7/28) 11 years metastatic-free survival respectively ( p -value = 4.04e −10 ) while univariate analysis of histological parameters such as tumor size and SBR grade showed weaker associations ( p -values of 0.006 and 0.065 respectively). The predictive properties of the genomic score have been assessed by cross-validation but also on other independent large data sets. A signature of genome instability inferred from genomic and gene expression profiles will also be proposed.u2028 Conclusion: Genomic profiling in breast carcinoma is a strong tool for prognostication in breast cancer. We developed a computational method to characterize genome instability of that predict clinical outcome in breast cancer and could be useful for more accurate therapeutic choice but also for identifying new therapeutical targets. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5069.

Métastases vertébrales des cancers du sein

Le cancer du sein est responsable chaque annee en France d’environ 10 000 deces chez la femme. Ce nombre absolu est en augmentation lente et reguliere depuis plusieurs decennies malgre les benefices conjugues du depistage precoce et des traitements adjuvants. L’augmentation du nombre absolu des deces est liee a l’augmentation encore plus forte de la frequence des nouveaux cas de cancer, elle-meme en grande partie liee a l’allongement tres important de l’esperance de vie des femmes.