The new frontier- fighting cancer from the marrow before it can spread:
Adjuvant ovarian suppression combined with tamoxifen or anastrozole, alone or in combination with zoledronic acid, in premenopausal women with hormone-responsive, stage I and II breast cancer: First efficacy results from ABCSG-12.
Abstract No: LBA4
Citation: J Clin Oncol 26: 2008 (May 20 suppl; abstr LBA4)
Author(s): M. Gnant, B. Mlineritsch, W. Schippinger, G. Luschin-Ebengreuth, S. Poestlberger, C. Menzel, R. Jakesz, E. Kubista, C. Marth, R. Greil, On behalf of the ABCSG
Abstract: Background: Zoledronic acid (ZOL) has demonstrated antitumor and antimetastatic activity in preclinical and early clinical studies. The Austrian Breast and Colorectal Cancer Study Group Trial 12 (ABCSG-12) examined the efficacy of ovarian suppression using the gonadotropin-releasing hormone analogue goserelin in combination with anastrozole (ANA) or tamoxifen (TAM) ± ZOL in premenopausal women with endocrine-responsive breast cancer (BC). Methods: 1,801 premenopausal women with endocrine-responsive BC were randomized to goserelin (3.6 mg q 28 d SC) and TAM (20 mg/d PO) ± ZOL (4 mg IV q 6 mo) or goserelin and ANA (1 mg/d PO) ± ZOL for 3 yr. Primary endpoint was disease-free survival (DFS) for both the comparison of TAM vs ANA and ZOL vs no ZOL, respectively. Relapse-free survival (RFS) and overall survival (OS) were secondary endpoints. Exploratory endpoints included bone-metastases-free survival and safety. Results: With median follow-up of 60 mo (March 31, 2008), 137 (7.6%) DFS events and 42 (2.3%) deaths have occurred. There was no significant difference in DFS between patients who received TAM alone vs ANA alone (HR = 1.10 [95% CI = 0.79, 1.54]; P = 0.59). However, endocrine therapy plus ZOL significantly reduced the risk of DFS events by 36% compared with endocrine therapy alone (HR = 0.64 [0.46, 0.91]; P = 0.01). The addition of ZOL significantly reduced the risk of RFS events by 35% (HR = 0.65 [0.46, 0.92]; P = 0.015) compared with endocrine therapy alone. For OS, there was a nonsignificant trend favoring ZOL treatment (HR = 0.60 [0.32, 1.11]; P = 0.10). Treatment was generally well tolerated among the 4 groups and consistent with known safety profiles of the drugs. Conclusions: There was no significant difference in DFS between TAM and ANA. The addition of ZOL (4 mg q 6 mo) to adjuvant endocrine therapy significantly prolonged DFS and RFS compared with adjuvant endocrine therapy alone in premenopausal women with endocrine-responsive BC. This large clinical trial demonstrates that the antitumor activity of adjuvant ZOL improves outcomes beyond the effect of endocrine therapy alone
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So simple, so easy to remedy. Get your D level checked then supplement to get your blood values to where they should be.
Frequency of vitamin D (Vit D) deficiency at breast cancer (BC) diagnosis and association with risk of distant recurrence and death in a prospective cohort study of T1-3, N0-1, M0 BC.
Abstract No: 511
Citation: J Clin Oncol 26: 2008 (May 20 suppl; abstr 511)
Author(s): P. J. Goodwin, M. Ennis, K. I. Pritchard, J. Koo, N. Hood
Abstract: Background: Vit D acts through a nuclear transcription factor to regulate many aspects of cellular growth and differentiation. Low levels have been associated with increased BC risk. We examined Vit D levels and prognostic effects in an existing BC cohort. Methods: 512 consecutive women with newly diagnosed BC were enrolled at 3 U of Toronto hospitals between 1989 and 1995. A blood specimen obtained at diagnosis was stored at -80°C. The Block questionnaire was used to measure diet intake. Clinical and pathology data were obtained from medical and pathology records. 25-OH Vit D was measured by radioimmunoassay. Women were followed prospectively to 2006. Results: Mean age was 50.4±9.7 yrs. 288 women had T1 tumors, 164 T2 and 24 T3/4. 356 tumors were N0. 342 were estrogen receptor (ER) positive. 73 tumors were grade 1, 202 grade 2 and 173 grade 3. 199 women received adjuvant chemotherapy (CXT) and 200 received tamoxifen. 116 women (22.7%) had distant recurrences and 106 (20.7%) died during a median follow-up of 11.6 yrs. Mean 25-OH Vit D was 58.1±23.4 nmol/L. Vit D levels were deficient (<50 nmol/L) in 192 (37.5%), insufficient (50-72 nmol/L) in 197 (38.5%) and adequate (>72 nmol/L) in 123 (24.0%). Low Vit D levels were associated with premenopausal status, high body mass index (BMI), high insulin and high tumor grade (all p<0.03). Low Vit D levels were associated with low dietary intake of retinol, Vitamin E, grains and alcohol (all p<0.02). Vit D was marginally lower when drawn in winter (Oct-Mar) vs summer (Apr-Sept) months (56.7 vs 59.5 nmol/L, p=0.07). Distant disease-free survival (DDFS) was significantly worse in women with deficient (vs adequate) Vit D levels (HR 1.94, 95% CI 1.16-3.24, p=0.02) as was overall survival (OS) (HR 1.73, 95% CI 1.05-2.86, p=0.02). Vit D associations with DDFS were independent of age, BMI, insulin, T and N stage, ER and grade (all HR >1.55 Q1 vs Q4, all p < 0.04); they were not significantly modified by ER, adjuvant CXT or tamoxifen. Vit D associations with OS were attenuated by grade and were absent in ER negative BC. Conclusions: Vit D deficiency is common at BC diagnosis and is associated with poor prognosis. This research was funded by the Breast Cancer Research Foundation.
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Protect your bones, protect your future.
Effect of zoledronic acid (ZA) on bone mineral density (BMD) in premenopausal women who develop ovarian failure (OF) due to adjuvant chemotherapy (AdC): First results from ASCO 2008 meeting
Abstract No: 512
Citation: J Clin Oncol 26: 2008 (May 20 suppl; abstr 512)
Author(s): C. L. Shapiro, S. Halabi, G. Gibson, D. J. Weckstein, J. Kirshner, W. M. Sikov, E. P. Winer, C. A. Hudis, C. Isaacs, D. Weckstein, R. L. Schilsky, E. Paskett
Abstract: Background: OF causes accelerated bone loss in premenopausal women receiving AdC of greater magnitude than natural menopause or aromatase inhibitor therapy in postmenopausal women. CALGB 79809 compared the effect of early ZA (with AdC) or late (one year after AdC) on change in BMD in the lumbar spine (LS). We report the effect of early ZA versus no ZA (Control) at 12 months after randomization. Methods: Eligible women (> 40 years; stages I-III breast cancer; and last menstrual period < 6 months prior to entry) were randomized to either ZA 4 mg IV every 3 months beginning 1-3 months (Arm A) after the start of AdC or no ZA. BMD of LS, serum FSH, estradiol, and ß-HCG were performed at baseline (< 28 days prior to randomization) and repeated at 12 months. OF was prospectively defined at the 12 month study visit as > 3 months of amenorrhea with an FSH > 30. All women were told to take 1,000 mg of calcium and 400 IU of vitamin D and compliance (by self-report) and toxicity were assessed every 3 months. Assuming an attrition rate of 20% and that only 50% of women would develop OF, a sample size of 200 per arm was required to have 80% power to detect a mean difference of 0.09 g/cm2 in LS BMD at 12 months with at a two-sided significance level of 0.05. A prespecified boundary for early stopping for superiority was crossed at the first interim analysis. Results: From 12/01 to 12/06, 439 women enrolled and 166 (38%) met the criteria for OF at 12 months. Median age was 47 years (range 40-58); white-92%; performance status 0-91%; stage I-25%; and stage II- 56%. Compliance with calcium and vitamin D was nearly 100%. The majority of ZA-related toxicities were grades 1 or 2; grade 3 included fever- 3%, fatigue-2%, and pain-3%. There was 1(0.5%) woman with possible jaw osteonecrosis after trauma to the jaw and 2 doses of ZA. The results are described in the Table. Conclusions: ZA adds minimal toxicity and prevents the accelerated bone loss that occurs in women who develop OF receiving AdC.
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The arbitrary five year time table now tested.
aTTom (adjuvant Tamoxifen--To offer more?): Randomized trial of 10 versus 5 years of adjuvant tamoxifen among 6,934 women with estrogen receptor-positive (ER+) or ER untested breast cancer--Preliminary results.
Abstract No: 513
Citation: J Clin Oncol 26: 2008 (May 20 suppl; abstr 513)
Author(s): R. G. Gray, D. W. Rea, K. Handley, A. Marshall, M. G. Pritchard, P. Perry, H. M. Earl, C. J. Poole, A. Salman, M. Lee, aTTom Collaborators
Abstract: Background: In ER+ early breast cancer, 5 years of tamoxifen substantially reduces the annual recurrence rate throughout the first decade (years 0-9). Despite this, appreciable risks of recurrence remain, with similar annual recurrence risks for ER+ disease during years 0-4, 5-9 and 10-14 following surgery. It is not reliably known how 10 years duration of adjuvant tamoxifen compares with the current standard of 5 years. Methods: Between 1991 and 2005, 6,934 women with ER+ (39%), or ER untested (61%) invasive breast cancer (53% node negative, 31% node positive, 16% node status unspecified) from 176 UK centers, who had completed 4+ years of adjuvant tamoxifen, were randomized between continuing for another 5 years and stopping. Information on compliance, hospital admission(s), breast cancer recurrence (including new contralateral disease), other new primary cancer, death and cause of death was sought annually. Results: 78% of those allocated to continue and 3% of those allocated to stop were taking adjuvant tamoxifen at 3 years following randomization; fewer than 1% switched to any other adjuvant hormone treatment. With a median follow-up of 4.2 years, there were fewer recurrences (415 vs 442; RR=0.94, 95% CI 0.81-1.09; p=0.4) among those allocated to 10yrs than 5yrs tamoxifen. Although breast cancer mortality was lower among those allocated 10yrs, with just 374 deaths from breast cancer recorded, data remain immature. Despite a doubling in the risk of endometrial cancer (76 vs 35) with 10yrs tamoxifen, there was no increase in deaths from endometrial cancer (10 vs 12) or from any other non-breast cancer cause. Conclusions: Although no significant reduction in recurrence has yet been seen in aTTom, the results are consistent with preliminary findings from the ATLAS trial, which reported a DFS but not overall survival advantage to longer tamoxifen (Peto et al SABCS 2007). Combining results from these two large studies indicate that continuation of tamoxifen beyond the first 5 years reduces recurrence over the next few years, but further follow-up is needed to assess reliably the longer-term effects on recurrence and the net effects, if any, on mortality.
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Heart health while undergoing chemotherapy.
Preliminary safety results of dose-dense (dd) doxorubicin and cyclophosphamide (AC) followed by weekly paclitaxel (P) with trastuzumab (T) and lapatinib (L) in HER2 overexpressed/amplified breast cancer (BCA).
Abstract No: 518
Citation: J Clin Oncol 26: 2008 (May 20 suppl; abstr 518)
Author(s): C. T. Dang, N. U. Lin, D.
Abstract: Background: We showed that dd q 2 weekly (w) AC ? P + T x 1 year (y) as adjuvant treatment (Rx) for patients (pts) with HER2 (+) BCA is safe with a congestive heart failure (CHF) rate of 1/70 pts (in press, JCO 2008). Lapatinib (L) is effective in HER2/neu (+) pts w/ Stage IV BCA and is being tested in randomized adjuvant trials. We are conducting a pilot study of dd AC ? w P + T + L to determine the cardiac safety and feasibility of this combination. The 1° endpoint is cardiac safety defined as discontinuation of T + L due to 1) cardiac death or 2) CHF. The 2° endpoints are to evaluate toxicities, time to recurrence, overall survival, and to explore the use of serial troponin I and C-reactive protein as predictors of cardiac toxicity. Methods: Pts must have HER2 IHC 3+ or FISH-amplified BCA, LVEF > 50% and no active cardiac disease. Rx consists of AC at 60/600 mg/m2 x 4 q 2 w (w/ pegfilgrastim 6 mg on day 2) ? P at 80 mg/m2 x 12 q w + T x 1 y (H 4 mg/kg load and 2 mg/kg q w during P and 6 mg/kg q 3 w after all chemotherapy is completed); L (1,000 mg daily is begun w/ P +T and continued for 1 y). MUGA is obtained at baseline and at months (mo) 2, 6, 9, and 18. Pts with significant asymptomatic LVEF decline after dd AC based on mo 2 MUGA do not receive T + L; pts with significant asymptomatic LVEF decline during T + L may have T + L held permanently. Results: From March 2007 to January 2008, we enrolled 63 of 100 planned pts. Median (med) age is 45 years (range, 28-73). Med baseline LVEF is 68 % (range, 52-79 %). As of January 5, 2008, 44 pts have had mo 2 MUGA after dd AC w/ a med LVEF of 70% (52-81%) and there have been no significant LVEF declines. 10/63 pts are off study (5 G 3 diarrhea, 1 G 2 diarrhea, 1 G 2 rash, 1 POD, 1 death after AC # 2 from adenovirus, 1 G 2 fatigue after AC # 4). Conclusions: This is the first report demonstrating cardiac safety and feasibility of dd AC ? w P + T + L. These are the first safety results for the combination arm in the ALLTO trial. Updated results will be available.
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More toxic but also more effective
Randomized phase III trial comparing the sequential administration of docetaxel followed by epirubicin plus cyclophosphamide versus FE75C as adjuvant chemotherapy in axillary lymph node-positive breast cancer.
Abstract No: 521
Citation: J Clin Oncol 26: 2008 (May 20 suppl; abstr 521)
Author(s): D. Mavroudis, N. Malamos, P. Papakotoulas, A. Adamou, C. Christophyllakis, N. Ziras, K. Syrigos, S. Kakolyris, C. Kouroussis, V. Georgoulias
Abstract: Background: The role of adding docetaxel to an anthracycline-based regimen in the adjuvant setting of node-positive early breast cancer was investigated in this multicenter study. Methods: Women with axillary node-positive operable breast cancer who had lumpectomy or mastectomy with axillary lymph node dissection, performance status 0-2 (WHO) and good organ function were randomized to receive either docetaxel 100 mg/m2 every 21 days for 4 cycles followed by epirubicin 75 mg/m2 plus cyclophosphamide 700 mg/m2 on day 1 every 21 days for 4 cycles (T-EC) or FEC (5-fluorouracil 700 mg/m2 plus epirubicin 75 mg/m2 plus cyclophosphamide 700 mg/m2) every 21 days for 6 cycles without primary growth factor support. This was a prospective, randomized, stratified study with 5-year relapse-free survival (RFS) rate as the primary endpoint. Planned sample size was 376 women/arm with power 0.8 and alpha error 0.05. Results: A total of 756 women were randomized to T-EC (n=378) and FEC (n=378). 30% and 27% of women were premenopausal while 37% and 32% had 1-3 positive axillary nodes on T-EC and FEC groups. Treatment was completed as per protocol for 98.1% and 98.4% of patients on the T-EC and FEC arms, respectively. Median follow-up was 62.5 (range 3.4-132.7) months for T-EC and 52.7 (range 2.8-136.2) for FEC patients. The 5-year RFS rate was 74.8% vs 68.9% (log-rank test; p=0.029) for T-EC and FEC patients, respectively. There were 94 (24.9%) vs 115 (30.4%) relapses (p=0.08) and 69 (18%) vs 64 (17%) deaths (p=0.6) in T-EC vs FEC patients, respectively. Severe toxicity included grade 3-4 neutropenia 72% vs 42% (p=0.0001), febrile neutropenia 8% vs 3% (p=0.003), diarrhea 3.7% vs 0% (p=0.0001) for T-EC and FEC patients, respectively. Secondary G-CSF support was used in 342 (90.5%) T-EC and 281 (74.3%) FEC patients (p=0.0001). Conclusions: T-EC is more effective and more toxic than FEC as adjuvant chemotherapy for women with axillary node-positive early breast cancer.
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Celebrex to the rescue?
Reduced risk of bone metastases in breast cancer patients treated with Cox-2 inhibitors.
Abstract No: 526
Citation: J Clin Oncol 26: 2008 (May 20 suppl; abstr 526)
Author(s): W. J. Tester, M. Valsecchi, S. Pomerantz, R. Jaslow
Abstract: Background: Approximately 40-70% of women diagnosed with breast cancer will develop bone metastases. The level of cyclooxygenase-2 (Cox-2) is overexpressed in human bone metastases and correlates with the occurrence of bone metastases in animal models. We hypothesize that the use of Cox-2 inhibitors in early phases of breast cancer could protect against the development of bone metastases. Methods: The medical charts of all patients treated for stage II and III breast cancer between 1999-2005 were reviewed. Patients were subsequently subdivided into those who took Cox-2 inhibitors (celecoxib, rofecoxib or valdecoxib) for at least 6 months following the diagnosis of breast cancer and those who did not. The diagnosis of bone metastases required conclusive radiologic imaging. Fisher's exact test and a multivariate logistic regression were used to analyze the data. Results: A total of 692 patients were included in this analysis. The patients' mean age was 59 and the mean follow up was 3.9 years. Eleven percent (74/644) of patients who did not take Cox-2 inhibitors developed bone metastasis compared to two percent (1/48) of those who did (Fisher's exact test p = 0.05). Significant predictors for developing bone metastases using a multivariate logistic regression model were: 3 or more positive nodes (p<0.001; Odds Ratio = 3.19, 95% CI = 1.79 - 5.70), stage IIb-IIIc (p = 0.001; OR = 4.61, 95% CI = 2.19-9.72) and use of Cox-2 inhibitors (p = 0.025; OR = 0.10, 95% CI = 0.013-0.75). Adjusting for TNM stage, of the 327 patients in stages IIb-IIIc, 21.5% (63/293) had bone metastasis in the non-Cox-2 group vs. 3% (1/34) in the Cox-2 group (p = 0.006). In this high-risk group of patients, the calculated odds ratio for development of bone metastases associated with the use of Cox-2 inhibitors was 0.10 (95% CI = 0.014-0.78). There was no significant difference between the groups in the number of patients that received adjuvant radiotherapy, chemotherapy, or hormone therapy. Conclusions: This retrospective study suggests that the use of Cox-2 inhibitors can reduce the risk of bone metastases in patients with stage II and III breast cancer. Prospective randomized trials of adjuvant Cox-2 inhibitors in patients with high-risk breast cancer are needed to validate this conclusion.
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Diabetic patients and metformin
The effects of metformin on pathologic complete response (pCR) rates in diabetic breast cancer (BC) patients receiving neoadjuvant systemic therapy (NST).
Abstract No: 528
Citation: J Clin Oncol 26: 2008 (May 20 suppl; abstr 528)
Author(s): S. Jiralerspong, S. H. Giordano, F. Meric-Bernstam, C. M. Barnett, S. Kau, M. C. Hung, G. N. Hortobagyi, A. M. Gonzalez-Angulo
Abstract: Background: Recent epidemiologic studies suggest that metformin use in diabetic patients decreases cancer incidence and cancer-related mortality. Metformin inhibits the growth of breast cancer cell lines by activating AMP kinase and thereby inhibiting the mTOR pathway/protein translation. We hypothesized that the antiproliferative effects of metformin might increase the efficacy of NST in diabetic BC patients. Methods: From the M.D. Anderson Breast Medical Oncology database, we identified 2,529 patients that received NST for early- stage BC. Patients' characteristics were compared by groups: non-diabetic (ND), diabetics taking metformin (DM) during NST, and diabetics not taking metformin (DN) during NST. pCR was defined as no residual disease in breast and nodes. Recurrence-free survival (RFS) and overall survival (OS) were estimated by the Kaplan-Meier product. Results: There were 2,374 (94%) ND, 68 (2.7%) DM, and 87 (3.4%) DN patients. Median age was 49 (range 21-87). 1,513 (60%) were stage I-II; 1,004 (40%) were stage III. 64% of tumors were hormone- receptor (HR) and 25% were HER2-positive. Prognostic factors were balanced overall in the 3 groups, though ND patients were more frequently white and pre-menopausal. pCR was seen in 16% ND, 24% DM, and 8% DN patients (p=0.03). At a median follow-up of 39 months, there have been 622 recurrences and 500 deaths. RFS was not statistically different between the three groups (p=0.84). The 3-year OS was significantly better in the ND (85.9%) group compared to the DM (80.9%) and DN (77.6%) groups (p=0.02). After adjustment for stage, grade, HR and HER2 status, ethnicity, and menopausal status, the odds ratio for achieving pCR was 1.32 (95% CI=0.69, 2.51; p=0.08) for DM and 0.45 (95%CI = 0.20, 1.02; p=0.03) for DN, as compared to ND patients. We are currently expanding our analysis cohorts. Conclusions: Diabetic BC patients receiving NST and metformin have higher pCR rates than those not receiving metformin. As metformin has a novel mechanism of action, further studies to evaluate its potential as an antitumor agent are warranted.
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A way to make Femara even more effective?
Improved clinical and cell cycle response with an mTOR inhibitor, daily oral RAD001 (everolimus) plus letrozole versus placebo plus letrozole in a randomized phase II neoadjuvant trial in ER+ breast cancer.
Abstract No: 530
Citation: J Clin Oncol 26: 2008 (May 20 suppl; abstr 530)
Author(s): J. Baselga, P. A. van Dam, R. Greil, H. Gardner, R. Bandaru, B. Molloy, J. Steinseifer, P. Phillips, J. M. Dixon, H. S. Rugo
Abstract: Background: Activation of the mTOR pathway is a key adaptive change driving endocrine resistance. RAD001, an oral mTOR inhibitor, and letrozole synergistically inhibit proliferation in breast cancer cells. Methods: 270 postmenopausal women with > T2 ER+ tumors were randomized to receive 4 mo of letrozole 2.5mg QD + RAD001 10mg QD or letrozole 2.5mg plus placebo. The primary endpoint was overall clinical response. Mandatory needle biopsies were collected immediately prior to initial treatment, and at day 15 after treatment initiation. Samples were assessed at baseline for Her2 by FISH and mutation of exons 9 and 20 of PIK3CA and exons 5-8 of TP53, and at baseline and day 15 for Ki67, phospho-Akt S473, phospho-S6, PTEN, CyclinD1, ER, PR, p53, and total Akt and S6 by immunohistochemistry. A total of 207 patients (77%) were primary marker evaluable and clinical outcome evaluable; 186 patients had an evaluable second biopsy. Results: The clinical response rate with RAD001 + letrozole was significantly superior to letrozole alone at the preplanned Alpha of 0.1 (68 vs 59%, p=0.062). This was confirmed by ultrasound (OR 58% vs 47 %, p=0.035). Pharmacodynamic changes in each treatment arm were observed. Marked downregulation in progesterone receptor and cyclin D1 were seen in response to letrozole. Phospho- S6 levels showed dramatic down-regulation only in response to RAD001. Cell cycle response, as defined by either % reduction in Ki67 at day 15 or by proportion of patients with Ki67<2 at day 15, was also significantly higher in the RAD001 + letrozole arm (57% vs 30% for Ki67<2 at day 15, p<0.01). The rate of grade 3/4 adverse events (Aes) was 22.6% in the RAD001 + letrozole arm vs 3.8% in the placebo + letrozole arm. Most frequent grade 3/4 Aes with RAD001 + letrozole were hyperglycemia (n=7), stomatitis (3), interstitial lung disease/pneumonitis (3) and infections (3). Conclusions: RAD001 significantly increases the efficacy of letrozole in newly diagnosed ER+ breast cancer, with regard to both clinical and cell cycle response. The increased cell cycle response rate in the RAD001 arm was found in all subsets of tumors, including PTEN-positive, PIK3CA wild-type tumors.
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As more of us surpass the five year mark, and then the ten year mark, it is time to develop new ways to calculate how well we are doing.
Is overall survival an appropriate endpoint in early breast cancer studies? Data from the ATAC study at 100-month median follow-up.
Abstract No: 552
Citation: J Clin Oncol 26: 2008 (May 20 suppl; abstr 552)
Author(s): A. U. Buzdar, J. Cuzick
Abstract: Background: As the length of follow-up increases, competing causes of death are a major confounder of survival findings in studies of women with early breast cancer. Recent data from women with node-negative, estrogen receptor-positive primary breast cancer treated with adjuvant tamoxifen reported a five-fold higher risk of dying from causes other than breast cancer (Hanrahan et al. J Clin Oncol 2007; 25: 4952-60). At 100-month median follow-up in the ATAC trial, statistically significant reductions in recurrences and an advantage in disease-free survival were observed for patients treated with initial adjuvant anastrozole (A) compared with tamoxifen (T). However, no statistically significant difference in overall survival (OS) was noted. Methods: Key OS and efficacy data from the hormone receptor-positive population in ATAC at 100-month median follow-up, mean age 72 years, are presented. Results: There was significant advantage in time to recurrence in the anastrozole group (HR 0.76 [95 % CI 0.67-0.87], p=0.0001) and a 16% lower risk of distant recurrence (HR 0.84 [95 % CI 0.72-0.97], p=0.022) but no statistically significant difference was found in OS between treatment groups (HR 0.97 [95% CI 0.86-1.11], p=0.7). The number of deaths in each group was similar (A 18.0%; T 18.4%). In both groups death without recurrence (DWR) accounted for nearly half of these (A48%, T44%). From the 33-month analysis to the 100-month analysis, there was a greater increase in DWR in both groups than in deaths following recurrence. Conclusions: The impact of treatment on OS is confounded by the increasing number of deaths from other causes. Time to distant recurrence is the best measure of breast cancers that would lead to death without intercurrent intervention and should be used in preference to OS. With initial adjuvant anastrozole treatment, a greater proportion of patients avoid disease recurrence and the need for subsequent intervention. New data with respect to competing causes of mortality and survival findings in the study will be presented.
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Zometa: Hope?
Zoledronic acid as adjuvant therapy for women with early stage breast cancer and disseminated tumor cells in bone marrow.
Abstract No: 559
Citation: J Clin Oncol 26: 2008 (May 20 suppl; abstr 559)
Author(s): A. Y. Lin, J. W. Park, J. Scott, M. Melisko, A. Goga, M. M. Moasser, D. H. Moore, H. S. Rugo
Abstract: Background: DTC in BM is associated with an increased risk of distant recurrence (DR) and death in patients (pts) with ESBC, particularly when these cells are detected after adjuvant therapy. Bisphosphonates can act as antitumor agents by various mechanisms including induction of tumor cell apoptosis. Clodronate in pts with DTC at BC diagnosis reduced the incidence of metastases and improved survival. ZA is significantly more potent than clodronate in inhibiting bone resorption. We designed a pilot study to evaluate ZA in pts with ESBC with DTC. Decrease in DTC could serve as a surrogate marker of antitumor effect. Methods: DTCs are detected by immunomagnetic enrichment + flow cytometry (FC): BM is enriched with anti-EpCAM-conjugated iron particles, DTC are detected with EpCAM, CD45, and nucleic acid content. Pts with stage
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