High dose toremifene in advanced breast cancer resistant to or relapsed during tamoxifen treatment

Summary Fifty patients with advanced breast cancer refractory to prior tamoxifen therapy were assigned to investigational treatment with high-dose toremifene administered 120 mg orally twice a day. Treatment was generally well tolerated. The majority (80%) of the patients had no side effects, and among the remaining 10 patients reported side effects were mostly mild and/or transient. Two objective tumor responses were observed: one complete response (CR), duration 6.2 months, and one partial response (PR), duration 8 months. The response rate was thus 4% (95% CI: 0.5 to 14%). In addition 3 patients experienced a mixed response, some metastatic sites responding, while at other sites disease progressed; 22 patients had disease stabilization for > 2 months. A subset analysis disclosed that a small subgroup of patients, including 7 patients in this study, who had achieved CR at some of the sites during preceding tamoxifen therapy, experienced a long progressionfree time during high dose toremifene treatment. The median time to progression in this subgroup of patients was 9.4 months (95% CI: 3.8 to 9.4) as opposed to 2.1 months (95% CI: 2.0 to 2.8) for all the remaining 43 patients, which is a significant decrease in disease progression (p < 0.03). Such results reveal that although this kind of second-line hormonal treatment with high dose toremifene cannot be recommended for all tamoxifen failures, there might be a subset of patients, i.e. those who achieve CR in some lesion during tamoxifen therapy, who benefit from this type of treatment.     

High dose toremifene (240 mg daily) is effective as first line hormonal treatment in advanced breast cancer an ongoing phase II multicenter Finnish-Latvian cooperative study

The efficacy of high dose toremifene (240 mg daily) in postmenopausal women with advanced breast cancer is investigated in this ongoing study. At present, 38 patients are fully evaluable. Ten patients have CR (26%), 16 PR (42%) (objective response rate 68%), 8 NC (21%), and 4 PD (11%). Most objective responses are in soft tissue tumors (14/17, 82%). The response rate is equally high in patients with positive or unknown estrogen receptor (ER) status. Median duration of responses and survival are not yet evaluable. Of 48 patients evaluable for side-effects, 22 (46%) experienced some kind of toxicity, which was mild in 64% of cases, moderate in 29%, and mostly of estrogenic type. The study will continue to confirm the results thus far obtained.     

Phase II trials with toremifene in advanced breast cancer: A review

The antitumor activity of the new triphenylethylene drug toremifene has been studied in advanced breast cancer of postmenopausal women as first line treatment at dose levels of 20, 60, and 240 mg, and as second line or later treatment at high dose levels of 200–240 mg. The response rates (complete + partial response) have been 21% with 20 mg (14 patients), 52% with 60 mg (93 patients in three separate trials), and 68% with 240 mg (38 patients) as first line treatment. After failure on previous therapy (hormonal or chemotherapy) the response rates have been about 10% with 200 mg of toremifene (71 patients in two different trials). In patients whose disease had previously responded to tamoxifen with at least stabilization, the response rate with toremifene has been 23%; but among unselected patients, including patients progressing during adjuvant tamoxifen, the response rate (CR + PR) with toremifene in tamoxifen failures has been 3%. If long lasting (more than 5 months) stabilization of the disease is also considered, a further 20% of previously treated patients have benefitted from toremifene. The treatment has been well tolerated at all dose levels. The most reported side effects have been hot flushes (8–19%) and nausea (8%). 0–6% of patients in different trials have interrupted the treatment because of side effects     

Tamoxifen and toremifene treatment of breast cancer and risk of subsequent endometrial cancer: a population-based case-control study

A population-based case-control study was performed to evaluate the risk of endometrial cancer related to tamoxifen or toremifene treatment. All patients with breast cancer diagnosis since 1980 in Finland who subsequently developed an endometrial cancer by the end of 1995 and 3 matched controls were identified among the 38,000 breast cancer patients of the Finnish Cancer Registry database. Detailed information on treatment of breast cancer and potential confounders was collected from hospital records. The OR for tamoxifen treatment (59 cases), adjusted for significant cofactors (increased risk associated with obesity, low parity and PR positivity) was 2.9 (95% CI 1.8-4.7). The OR for toremifene (3 cases) was 0.9 (95% CI 0.3-3.9). The OR related to adjuvant tamoxifen treatment reached its maximum 2-5 years after the beginning of treatment (OR 5.1, 95% CI 2.1-13), while the OR for tamoxifen used for palliative treatment of advanced breast cancer was especially high after a lag of over 5 years (OR 9.5, 95% CI 2.5-36). The risk increase due to tamoxifen was slightly higher if the age at initiation was below 55, and risk was more pronounced among patients with well-differentiated endometrial cancer than patients with cancers of clinical grades 2 or 3. According to our results, treatment with tamoxifen increases the risk of endometrial cancer. Due to the rare use of toremifene up to the mid-1990s, the risk assessment concerning it was inconclusive.     

Paclitaxel and mitoxantrone in metastatic breast cancer: a phase II trial of the Italian Oncology Group for Cancer Research

Background: In a previous dose-finding trial, in previously treated patients with metastatic breast cancer (MBC), we showed that the combination of Mitoxantrone (M) and Paclitaxel (P) may be an interesting (response rate: 69%) and well-tolerated regimen. On the basis of these results, our group started a new trial in chemotherapy-naive patients with MBC. Patients and Method: Forty-six women entered in this trial, and all patients were evaluated for response and toxicity. Schedule of treatment was P 175 mg/m² over 3 hr day 1 and M 12 mg/m² day 1, every 3 weeks. Patients were reevaluated every 3 months and chemotherapy was continued unless tumor progression or unacceptable toxicity occurred. Result: The intent-to-treat objective response was 61% (95% confidence interval: 49%-78%). Five patients (11%) obtained complete response and 23 (50%) partial response with a median time to failure of 14 months. The median survival was 22 months (range 1-39). The principal toxicity was hematological: 38 (82%) patients had grade 3 to 4 leukopenia; only 2 patients had grade 4 anemia and one grade 4 thrombocytopenia. Nonhematological toxicity (grade 3-4) was mild and cardiotoxicity was infrequent. Conclusion: This trial suggests the combination of M and P is an active palliative regimen for patients with MBC. Toxicity was moderate. The infrequent development of cardiotoxicity suggests this combination may not share the problems reported with P plus doxorubicin combinations.     

Randomized trial of tamoxifen alone or combined with fluoxymesterone as adjuvant therapy in postmenopausal women with resected estrogen receptor positive breast cancer. North Central Cancer Treatment Group Trial 89-30-52

SummaryPurpose This clinical trial evaluated the addition of fluoxymesterone (Flu) to tamoxifen (Tam) in women with resected early stage breast cancer and attempted to corroborate the findings of superiority for the combination over Tam alone seen in a previous randomized trial in metastatic disease.Patients and methods Postmenopausal women with early stage breast cancer that was known to be estrogen receptor (ER) positive were randomized to treatment with Tam (20 mg per day orally for 5 years) alone or combined with Flu (10 mg orally twice per day for 1 year). The primary endpoint was relapse-free survival (RFS) defined as local-regional or distant recurrence including ductal carcinoma in situ of the ipsilateral, but not contralateral breast, and death from any cause.Results There were 541 eligible patients entered between 1991 and 1995 and the treatment arms were balanced with respect to patient characteristics. The median follow up of patients still alive was 11.4 years. No significant difference was found between Tam plus Flu and Tam alone in terms of RFS or overall survival. The adjusted hazard ratio (Tam+Flu/Tam) for relapse or death without relapse was estimated to be 0.84 (95% CI: 0.64–1.10) and that for death was 0.89 (95% CI: 0.67–1.18). As expected there was more virilization in women who received Flu.Conclusions This clinical trial did not demonstrate superiority of Tam plus Flu over Tam alone as adjuvant therapy for postmenopausal women with resected early breast cancer known to be ER positive.     

Expanded phase II trial of paclitaxel in metastatic breast cancer: A Southwest Oncology Group study

Background. The study was designed to evaluate the efficacy of paclitaxel in metastatic breast cancer patients. The design was motivated by a report from FDA and NCI staff proposing assessment of pre- and post-treatment symptoms as a means of evaluating treatment effectiveness [1]. Methods. Patients with symptomatic and/or measurable metastatic breast cancer with prior treatment received paclitaxel 210 mg/m2 as a 3 hour infusion every three weeks until toxicity or progression. A unique endpoint was subjective symptomatic response, defined as an improvement in the Symptom Distress Scale score by 3 points at two successive evaluations before treatment failure. Patients were also evaluated for objective response and toxicity. Results. Of 135 patients registered, 123 were eligible and treated. The subjective symptomatic response rate for 93 symptomatic patients who completed forms was 40%, 95% confidence interval 29–51%. The objective response rate in 77 patients with measurable disease was 19%, 95% confidence interval 11–30%. In patients with both measurable and symptomatic disease, 37% had symptomatic and 13% had objective responses. Median times to treatment failure and death were 4 and 11 months, respectively. Toxicity was greater than anticipated: 12% discontinued treatment due to toxicity, 29% developed at least one Grade 3 neuromuscular toxicity, and two patients died of sepsis while neutropenic. Conclusion. Paclitaxel by 3 hour infusion at a dose of 210 mg/m2 produced excessive neurotoxicity in patients with previously treated metastatic breast cancer. Both sustained subjective symptom reduction and objective responses were demonstrated, but dose reduction for routine practice is recommended.     

Phase II study of sequential hormonal therapy with anastrozole/exemestane in advanced and metastatic breast cancer

Hormonal therapy is the preferred systemic treatment for recurrent or metastatic, post-menopausal hormone-receptor-positive breast cancer. Previous studies have shown that there is no cross-resistance between exemestane and reversible aromatase inhibitors. Exposure to hormonal therapy does not hamper later response to chemotherapy. Patients with locally advanced or metastatic, hormonal receptor positive or unknown, breast cancer were treated with oral anastrozole, until disease progression, followed by oral exemestane until new evidence of disease progression. The primary end point of the study was clinical benefit, defined as the sum of complete responses (CR), partial responses (PR) and > 24 weeks stable disease (SD). In all, 100 patients were enrolled in the study. Anastrozole produced eight CR and 19 PR for an overall response rate of 27% (95% CI: 18.6-36.8%). An additional 46 patients had long-term (> 24 weeks) SD for an overall clinical benefit of 73% (95% CI: 63.2-81.4). Median time to progression (TTP) was 11 months (95% CI: 10-12). A total of 50 patients were evaluated for the second-line treatment: exemestane produced one CR and three PR; 25 patients had SD which lasted > or = 6 months in 18 patients. Median TTP was 5 months. Toxicity of treatment was low. Our study confirms that treatment with sequential hormonal agents can extend the period of time during which endocrine therapy can be used, thereby deferring the decision to use chemotherapy.     

A phase II trial of tamoxifen,premarin, methotrexate and 5-fluorouracil in metastatic breast cancer

Complete remissions in patients with metastatic breast cancer using endocrine therapy or chemotherapy are infrequent. Breast tumors are known to be heterogeneous with respect to estrogen receptor status, and the low complete remission rate may be related to this biochemical heterogeneity. Based on laboratory experiments using human breast cancer cells in tissue culture, a phase II protocol was designed using tamoxifen, premarin, methotrexate, and 5-fluorouracil. Thus far, twenty-nine (29) patients have been entered into this study and twenty-five (25) are currently evaluable for response. Overall response rate was 72%, and 14 of 25 (56%) attained a complete remission. Toxicity was minimal. Median nadir white blood cell count was 5,800 and median nadir platelet count was 252,000. In summary, this combination chemo-hormonal therapy regimen is effective with a more than 50% complete remission rate and minimal toxicity.     

Arsenic Trioxide in Recurrent Urothelial Cancer: A Cancer and Leukemia Group B Phase II Trial (CALGB 99903)

Background

Arsenic trioxide is highly active in patients with acute promyelocytic leukemia. There are also preclinical data to suggest that this drug might be active in nonhematopoietic malignancies, and transitional cell carcinoma cell lines are particularly sensitive to this agent.

Patients and Methods

Twelve evaluable patients with metastatic urothelial cancer were treated with arsenic trioxide in a phase II trial conducted by the Cancer and Leukemia Group B. Eligible patients were required to have measurable urothelial cancer and a maximum of 1 previous chemotherapy regimen. Arsenic trioxide was given at a dose of 0.3 mg/kg daily for 5 days every 28 days.

Results

No major responses were observed; 4 patients achieved stable disease. The median survival was 6.5 months (95% CI, 3.9-13.4 months). The most commonly observed toxicities included fatigue and malaise, anemia, nausea, emesis, and constipation.

Conclusion

Arsenic trioxide at this dose and schedule does not have significant activity in previously treated urothelial cancer and has substantial toxicity in this patient population.     

Monitoring the chemosensitizing effects of toremifene with flow cytometry in estrogen receptor negative multidrug resistant human breast cancer cells

Summary The clinical study of compounds that modulate multidrug resistance in cancer cells has been hindered by both the toxicities of these agents and the inability to monitor their effectiveness at a cellular level. The non-steroidal triphenylethylene toremifene is well tolerated clinically and can sensitize multidrug resistant cells to the effects of doxorubicin in vitro. The chemosensitizing properties of toremifene in estrogen receptor negative, multidrug resistant MDA-A1 human breast cancer cells were studied using flow cytometric analysis. Cell cycle kinetics of MDA-A1 cells were not significantly affected by treatment with either toremifene or doxorubicin alone, as the majority of cells remained in G₀/G₁. However, preincubation with toremifene for 70 hours followed by treatment with doxorubicin caused a marked shift of cells to G₂, as cells appeared to be blocked in that phase of the cell cycle. This result was nearly identical to the effect of doxorubicin alone on doxorubicin-sensitive MDA-MB-231 breast cancer cells and can be interpreted as a "resensitization" by toremifene of MDA-A1 cells to doxorubicin. This chemosensitizing effect of toremifene was accompanied by an enhanced accumulation of doxorubicin in MDA-A1 cells (+110% after 70 hours pre-incubation with toremifene), and by a depression in protein kinase C activity in MDA-A1 cells that was maximal following 70 hours incubation with toremifene. Flow cytometry is a widely available technique that might be applied clinically to monitor at the cellular level the chemosensitizing effects of toremifene and other modulators of multidrug resistance.     

A phase II clinical trial of weekly paclitaxel and carboplatin in combination with panitumumab in metastatic triple negative breast cancer

Purpose: Women with metastatic triple negative breast cancer (TNBC) can have a poor prognosis with treatment limited to cytotoxic chemotherapy. The identification of effective therapies that may limit exposure to cytotoxic chemotherapy and lead to prolonged survival is an unmet medical need. We tested an inhibitor of the epidermal growth factor receptor, panitumumab in combination with chemotherapy. Methods: We conducted a single arm clinical trial in women with metastatic or locally advanced TNBC to paclitaxel 80 mg/m2 and carboplatin AUC of 2 on days 1, 8, and 15 and panitumumab 6 mg/kg on days 1 and 15 for a cycle length of 28 days. The objectives were to evaluate the response rate and safety of the combination in comparison to historical controls. Results: Fourteen patients with TNBC were enrolled with a median age of 53 years. The majority of women were African American (64.3%) with visceral metastasis (64.2%). Hematologic toxicities, particularly neutropenia and thrombocytopenia, were a major cause of missed chemotherapy and delayed treatment in this study. The overall response rate (complete and partial response) of the 13 evaluable patients was 46%. The median time to best response was 2.4 months and the median time to disease progression was 3.6 months. We were able to perform the PAM50 analysis on tumors from 7 of our subjects. All the samples tested clustered within the basal-like subtype. Conclusions: In our experience the response rate of carboplatin, paclitaxel and panitumumab was consistent with other reports of response for cytotoxic chemotherapy in metastatic TNBC.     

Toremifene and tamoxifen are equally effective for early-stage breast cancer: first results of International Breast Cancer Study Group Trials 12-93 and 14-93.

BACKGROUND: Toremifene is a chlorinated derivative of tamoxifen, developed to improve its risk-benefit profile. The International Breast Cancer Study Group (IBCSG) conducted two complementary randomized trials for peri- and postmenopausal patients with node-positive breast cancer to compare toremifene versus tamoxifen as the endocrine agent and simultaneously investigate a chemotherapy-oriented question. This is the first report of the endocrine comparison after a median follow-up of 5.5 years. PATIENTS AND METHODS: 1035 patients were available for analysis: 75% had estrogen receptor (ER)-positive primary tumors, the median number of involved axillary lymph nodes was three and 81% received prior adjuvant chemotherapy. RESULTS: Toremifene and tamoxifen yielded similar disease-free (DFS) and overall survival (OS): 5-year DFS rates of 72% and 69%, respectively [risk ratio (RR)=0.95; 95% confidence interval (CI)=0.76-1.18]; 5-year OS rates of 85% and 81%, respectively (RR = 1.03; 95% CI = 0.78-1.36). Similar outcomes were observed in the ER-positive cohort. Toxicities were similar in the two treatment groups with very few women (<1%) experiencing severe thromboembolic or cerebrovascular complications. Quality of life results were also similar. Nine patients developed early stage endometrial cancer (toremifene, six; tamoxifen, three). CONCLUSIONS: Toremifene is a valid and safe alternative to tamoxifen in postmenopausal women with endocrine-responsive breast cancer.     

Efficacy and tolerability of toremifene and tamoxifen therapy in premenopausal patients with operable breast cancer: a retrospective analysis

Background

Given the use of tamoxifen as standard treatment for hormone receptor–positive breast cancer, the use of toremifene as an adjuvant endocrine therapy has not been widely examined. The present retrospective study compared the efficacy and safety of toremifene and tamoxifen in the treatment of operable hormone receptor–positive breast cancer in premenopausal women.

Methods

Premenopausal patients with hormone receptor– positive operable breast cancer were eligible. Enrolled patients (n = 1847) received either 60 mg toremifene (n = 396) or 20 mg tamoxifen (n = 1451) daily for a minimum of 5 years after surgery. Disease-free survival (dfs) was the primary endpoint. Overall survival (os) and time to distant recurrence were secondary endpoints.

Results

Treatment with toremifene and tamoxifen resulted in no between-group differences in dfs (p = 0.659) or os (p = 0.364). Mean dfs was 10.3 years for both groups. Mean os was 11.2 years for the toremifene group and 11.1 years for tamoxifen group. The 5-year dfs rate was 87.0% in the toremifene group and 85.0% in the tamoxifen group. The 5-year survival rate was 94.3% in the toremifene group and 93.5% in the tamoxifen group. Adverse events rates were similar in the two groups, with the exception of irregular menses, which occurred at a higher rate in the tamoxifen group than in the toremifene group (10.0% vs. 6.3%, p = 0.025).

Conclusions

In this retrospective study, the efficacy and safety profiles of toremifene and tamoxifen for the treatment of operable hormone receptor–positive breast cancer in premenopausal women were similar.     

Sequential or alternating administration of docetaxel (Taxotere) combined with FEC in metastatic breast cancer: a randomised phase II trial

The aim of this study, using a Fleming single-stage design, was to explore the efficacy and safety of Taxotere 100 x mg x m(-2) docetaxel and FEC 75 cyclophosphamide 500 mg x m(-2), fluorouracil 500 x mg x m(-2) and epirubicin 75 mg x m(-2), in alternating and sequential schedules for the first-line treatment of metastatic breast cancer. One hundred and thirty-six women were randomly allocated, to one of three treatment regimens: DTX 100 plus FEC 75, alternated for eight courses (ALT); four courses of DTX 100 followed by four courses of FEC 75 (SEQ T); or four courses of FEC 75 followed by four courses of DTX 100 (SEQ F). One hundred and thirty-one women were evaluable for tumour response. Although the treatment outcome was equivalent in the two sequential arms and the alternating regimen (P=0.110, not significant), the response rate was less encouraging in the SEQ F arm (52.3%) than in the other two arms (71.1% for ALT and 70.5% for SEQ T), in which docetaxel was administered first. Time to progression was similar in the ALT, SEQ T and SEQ F arms (9.5, 9.3 and 10.4 months respectively). Grade 3-4 neutropenia was observed in nearly all patients; febrile neutropenia occurred in 9% (ALT), 16% (SEQ T) and 2% (SEQ F) of patients. Few patients (< or =9%) developed grade 3-4 non-haematological toxicities. Relative dose intensity was 97-99% for all regimens. All treatment regimens were active and well tolerated.     

Monthly docetaxel and weekly gemcitabine in metastatic breast cancer: A?phase II trial

Background:Docetaxel and gemcitabine are active againstbreast cancer. The purpose of this phase II study was to evaluate theefficacy and safety of monthly docetaxel combined with weeklygemcitabine in patients with chemotherapy-pretreated metastatic breastcancer. Patients and methods:Thirty-nine patients were enrolled, ofwhom thirty had received prior chemotherapy in the adjuvant setting,seven for metastatic disease, and two for both, including prioranthracycline in 33 patients. Treatment was gemcitabine 800mg/m² days 1, 8, 15 and docetaxel 100 mg/m² on day1, with cycles repeated every four weeks. Results:Response rate was 79% (95% confidenceinterval (CI): 63%–91%), with 2 complete and 29partial responses. Twenty-five of the responders remainedprogression-free for more than six months. Median survival was 24.5months. Delivered dose intensity of gemcitabine was lower than expected(63% of planned). The predominant hematologic toxicity was grade4 neutropenia in 36 patients, complicated by fever in three patients.With the exception of asthenia, severe non-hematological toxicities wereinfrequent. Conclusions:Monthly docetaxel, combined with weeklygemcitabine, has significant but manageable hematologic toxicity.Despite frequent dose adjustments, this doublet is very active inmetastatic breast cancer, producing a high proportion of durableresponses associated with favorable survival.     

Crossover trial for lipid abnormality in postmenopausal breast cancer patients during selective estrogen receptor modulators (SERMs) administrations

The objective of this study was to evaluate the different profiles of serum lipids resulting from the administration of selective estrogen receptor modulators (SERMs). Postmenopausal primary breast cancer patients (n=197) with node-negative, hormone receptor-positive who were treated at our department or in other related medical institutions from April 1997 through March 2001 were given adjuvant therapy. The adjuvant therapy included 1 year's administration of tamoxifen (TAM) 20 mg or toremifene (TOR) 40 mg. The profiles of serum lipids such as total cholesterol (TC), high-density lipoprotein cholesterol (HDL) and triglyceride (TG) were observed. After 1 year administration TC had significantly decreased (p < 0.001) both in the TAM group and the TOR group, but no significant difference was found between these groups (p=0.249). HDL had significantly decreased in the TAM group (p < 0.001), while it had significantly increased in the TOR group (p < 0.001), and a significant difference was found between the groups (p < 0.001). TG had significantly increased in the TAM group (p < 0.001) but significantly decreased in the TOR group (p < 0.001). The medication was switched in those who still had abnormal lipid metabolism and given to them for another year. After 1 year from the crossover TC and HDL had increased to the levels of before administration (p < 0.001) and TG had decreased in those (n=57) whose medication was switched from TAM to TOR. While TC had decreased and TG had increased in those (n=23) whose medication was switched from TOR to TAM (p < 0.001). The above findings have suggested that TOR provides better profiles of lipid metabolism than TAM.     

A phase II trial of circadian-timed paclitaxel and cisplatin therapy in metastatic breast cancer

Purpose: In a phase II study with combination paclitaxel and cisplatin inmetastatic breast cancer using circadian timing, we attempted to maximiseresponse and minimise toxicity.Materials and methods: Forty-one patients with histologically-provenmetastatic breast cancer with or without previous chemotherapy were treatedwith Paclitaxel 135 mg/m² administered as a three-hourinfusion at 06.00 hours followed by cisplatin 75 mg/m² as aone-hour infusion at 18.00 hours utilising circadian timing. Six cycles wereplanned once every 21 days. Response assessment was performed every twocycles, and toxicity was measured using WHO criteria.Results: All patients were evaluable for response and toxicity. There werenine (22%) complete responses (CR), and 24 (59%) partialresponses (PR), for an overall response rate of 80% (95%confidence interval (CI) 69–92). Responses were seen in patientspreviously treated with anthracyclines (75%) (95% CI57–92), and in patients who had had no prior chemotherapy (90%)(95% CI 71–100). Responses were seen in all metastatic sites:liver 80%, lung 76%, bone 69%, and soft tissues71%. The overall median response duration was seven months (range3–26, 95% CI 5.0–9.8), and 14 of the responses(42%), (95% CI 28–62) were durable. A total of 212 cyclesof chemotherapy were given. There were 15 episodes (7%) of grade3–4neutropenia, seven (3.2%) of grade 3–4 neurologic toxicity, andthree(1.4%) of grade 3–4 nephrotoxicity. There were no toxic deaths.Conclusion: The combination of paclitaxel and cisplatin is very effectivein metastatic breast cancer, and with application of circadian timing,toxicity has been acceptable. This combination is being tested as primarytherapy in locally-advanced breast cancer at our institution.     

Exemestane as primary systemic treatment for hormone receptor positive post-menopausal breast cancer patients: a phase II trial of the Austrian Breast and Colorectal Cancer Study Group (ABCSG-17)

Background A multicenter phase II study was conducted to analyze the clinical activity of the steroidal aromatase inhibitor exemestane in the neoadjuvant treatment of post-menopausal women with strongly ER- and/or PgR- positive operable breast cancer. Patients and methods From September 2000 to December 2003, 80 women were recruited for treatment with exemestane 25 mg once daily for 4 months. The primary end-point was the clinical response rate according the WHO criteria; the secondary end-points included toxicity and the number of patients who qualified for breast conserving surgery at the end of treatment, comparability of evaluation methods for response, potential alterations of hormone receptor and Her2/neu status during treatment. Results On an intention to evaluate analysis, according to the prespecified criteria the overall clinical objective response rate was 34%, the pCR rate was 3% and the rate of breast conserving surgery was 76%. When sonographic and mammographic longitudinal measurements were included in patients with missing palpation data, response rates were 38% and 41%, respectively. The tumor response was independent of the Her2/neu status which remained unchanged during treatment. In contrast, while the ER expression remained unaltered, downregulation of the PgR was observed. The treatment was well tolerated with no grade 3 and 4 toxicities except gastrointestinal (one grade 3 case) and hot flushes (two grade 3 cases). Conclusion This study shows that exemestane is effective and safe as a preoperative therapy in post-menopausal patients with strongly hormone receptor-positive breast cancer.