ASCO 2009 News
Comparison of neoadjuvant paclitaxel and carboplatin with neoadjuvant letrozole in postmenopausal patients with receptor-positive locally advanced breast cancer (LABC).
Sub-category: Local-Regional Therapy
Category: Breast Cancer--Local-Regional and Adjuvant Therapy
Meeting: 2009 ASCO Annual Meeting
Citation: J Clin Oncol 27:15s, 2009 (suppl; abstr 608)
Abstract No: 608
Author(s): D. Sinha, A. K. Bahadur, K. Singh, A. K. Rathi; Maulana Azad Medical College, Delhi, India
Abstract:
Background: For the treatment of LABC using a regimen with the highest likelihood of shrinking the tumor should improve the outcome. Paclitaxel was the first taxane to show activity in breast cancer. The advent of endocrine therapy in the neoadjuvant setting allows downstaging of tumors with less morbidity. The aromatase inhibitors are now the treatment of choice in neoadjuvant setting for elderly patients with estrogen receptor-positive breast cancer. Methods: This prospective, randomized, comparative study assessed the effect of three cycles of neoadjuvant chemotherapy vs. three months of neoadjuvant hormonal therapy in terms of loss of clinical and pathological primary tumor size. Inclusion criteria required postmenopausal patients with non-metastatic, ER and/or PR positive LABC with no co-morbidity. Forty eligible patients were randomly assigned into 2 groups of 20 patients each: Group A treated with 3 cycles of 3 weekly injections of paclitaxel (175 mg/m2) and carboplatin (AUC 6) assessed after each cycle; group B received oral Letrozole 2.5mg once daily for 3 months assessed every 4 weeks. Surgery was done and primary specimen was pathologically examined. Results: Clinically mean loss in primary residual tumor compared to volume at presentation in group A vs. group B at 1st review was 45% vs. 35% (p: 0.536), 63% vs. 57% at second (p: 0.176), and 71% vs. 74% at third review (p: 0.062).Clinical complete response (WHO criteria) and stable disease each were seen in 14% in either group of patients (p: 0.632), partial response in 65% group A and in 72% group B (p: 0.117); no progressive disease was seen in either. All patients underwent surgery. The mean pathological primary cell kill in group A vs. group B was 81% vs.78 %(p:0.918). Resected nodes were pathologically positive for tumor in 47% group A and 60% group B patients (p: 0.269). Conclusions: Neoadjuvant hormonal therapy using oral Letrozole in receptor positive LABC in post menopausal women is as effective as three weekly paclitaxel and carboplatin in downstaging the tumor.
Targeted Therapy Shows Promise in Treatment of Triple-negative Breast Cancer
According to the results of a Phase II clinical trial presented at a plenary session of the 2009 annual meeting of the American Society of Clinical Oncology (ASCO), treatment with chemotherapy plus the investigational drug BSI-201—a type of targeted therapy known as a PARP inhibitor—improved outcomes among women with triple-negative breast cancer.
Triple-negative breast cancer refers to breast cancer that is estrogen receptor-negative, progesterone receptor-negative, and HER2-negative. These cancers tend to be more aggressive than other types of breast cancer and do not respond to treatment with hormonal therapy or HER2-targeted therapy. Chemotherapy provides effective treatment for some women with triple-negative breast cancer, but more targeted and more effective treatments are clearly needed.
PARP stands for “poly (ADP-ribose) polymerase.” The PARP enzyme plays a role in DNA repair, including the repair of DNA damage from chemotherapy. Drugs that inhibit this enzyme may contribute to cancer cell death and increased sensitivity to chemotherapy.
The investigational PARP inhibitor BSI-201 was evaluated in a Phase II clinical trial among 116 women with metastatic, triple-negative breast cancer.[1] Study participants were assigned to receive chemotherapy alone or chemotherapy plus BSI-201. Chemotherapy consisted of Gemzar® (gemcitabine) and Paraplatin® (carboplatin).
* 62% of women treated with chemotherapy plus BSI-201 experienced a clinical benefit compared with 21% of women treated with chemotherapy alone. Clinical benefit refers to either a reduction in detectable cancer or stable disease of at least six months.
* Median overall survival was 9.2 months among women treated with chemotherapy plus BSI-201 compared with 5.7 months among women treated with chemotherapy alone.
* Median survival without cancer progression was 6.9 months among women treated with chemotherapy plus BSI-201 compared with 3.3 months among women treated with chemotherapy alone.
* The occurrence of side effects was similar in the two groups.
The results of this study suggest that the addition of BSI-201 to chemotherapy improves outcomes among women with metastatic, triple-negative breast cancer.
In a separate Phase II clinical trial also presented at ASCO, the investigational PARP inhibitor olaparib was evaluated among 54 women with BRCA1 or BRCA2 mutations and previously treated, advanced breast cancer.[2] All study participants were treated with olaparib alone, and more than one-third experienced tumor shrinkage.
References:
[1] O’Shaughnessy J, Osborne C, Pippen J et al. Efficacy of BSI-201, a poly (ADP-ribose) polymerase-1 (PARP1) inhibitor, in combination with gemcitabine/carboplatin (G/C) in patients with metastatic triple negative breast cancer (TNBC): Results of a randomized phase II trial. Presented at the 2009 annual meeting of the American Society of Clinical Oncology, May 29-June 2, 2009, Orlando, FL. Abstract P3.
[2] Tutt A, Robson M, Garber JE et al. Phase II trial of the oral PARP inhibitor olaparib in BRCA-deficient advanced breast cancer. Presented at the 2009 annual meeting of the American Society of Clinical Oncology, May 29-June 2, 2009, Orlando, FL. Abstract CRA501.
Effective treatment of triple-negative breast cancer with targeted cytotoxic somatostatin analogue AN-162 (AEZS-124).
Sub-category: Local-Regional Therapy
Category: Breast Cancer--Local-Regional and Adjuvant Therapy
Meeting: 2009 ASCO Annual Meeting
Citation: J Clin Oncol 27:15s, 2009 (suppl; abstr 619)
Abstract No: 619
Author(s): S. Seitz, A. V. Schally, S. Gluck, F. Rick, L. Szalontay, F. Hohla, A. Papadia, F. Köster, O. Ortmann, S. Buchholz; University of Regensburg, Regensburg, Germany; VA Medical Center, Miami, FL; University of Miami, Miami, FL; General Hospital Oberndorf, Oberndorf, Austria; University of Lübeck, Lübeck, Germany
Abstract:
Background: Triple negative breast cancers (TNBC) represent a distinct subtype of breast cancer being negative to ER, PR and HER2 and are associated with poor prognosis. Limited systemic treatment options exist for TNBC. TNBC cells express somatostatin receptors (SSTR). Therefore, to investigate preclinical characteristics of TNBC we used a novel targeted cytotoxic somatostatin analogue AN-162 containing doxorubicin (DOX) which binds to the subtypes 2, 3 and 5 of SSTR. Methods: The expression of SSTR in HCC 1806 human TNBC cell line was detected by RT-PCR. Cytotoxic effect of AN-162 in vitro was visualized by ethidium bromide staining fluorescence microscopy. Internalization of AN-162 into HCC 1806 cells was tested by 125Iodide-labeled AN-162 uptake assays and the presence of DOX in the nucleus was measured by fluorescence assays after separating the nucleus from the cytoplasm. For in vivo experiments, HCC 1806 TNBC cells were xenografted subcutaneously into nude mice which were then randomized into four groups receiving AN-162, DOX, an unconjugated mixture of DOX and somatostatin analogue RC-160 at the same equimolar dose of 2.5 µmol/kg (1.45 mg/kg Dox equivalent) i.v. (q7d 4x) and vehicle solution control. Results: HCC 1806 TNBC cell line was positive for the expression of all five SSTR receptor subtypes. Ethidum bromide staining of cells treated with 2.5 µM of AN-162 for 30 min demonstrated cell death after 24h by fluorescence microscopy. Uptake assays with AN-162 showed specific internalization of AN-162 into the cells mediated through the sstrs. After treatment of the cells with 2.5 µM AN-162 for 10 or 30 min, DOX could be detected in the nucleus by fluorescence assays. In vivo, AN-162 significantly (p<0.05) inhibited tumor growth of HCC 1806 xenografts compared to Control, DOX and the unconjugated mixture of DOX+RC-160 from day 14 and the inhibition remained significant until the end of the study on day 35. Conclusions: Our results indicate that treatment with targeted cytotoxic somatostatin analogue AN-162 produces a greater inhibition of tumor growth than DOX alone in somatostatin receptor positive TNBC. Our findings support the concept of targeted chemotherapy based on cytotoxic peptide analogues for the treatment of breast cancer and other cancers.
Neoadjuvant platinum-based chemotherapy (CT) for triple-negative locally advanced breast cancer (LABC): Retrospective analysis of 125 patients.
Sub-category: Local-Regional Therapy
Category: Breast Cancer--Local-Regional and Adjuvant Therapy
Meeting: 2009 ASCO Annual Meeting
Citation: J Clin Oncol 27:15s, 2009 (suppl; abstr 625)
Abstract No: 625
Author(s): J. P. Leone, V. Guardiola, A. Venkatraman, M. D. Pegram, C. Welsh, O. Silva, R. Larrieux, D. Franchesci, C. Gomez, J. Hurley; University of Miami, Jackson Memorial Hospital, Miami, FL
Abstract:
Background: Triple-negative breast cancer (TNBC), defined by lack of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2, accounts for 15-20% of all breast cancers and is associated with poor prognosis. There is no consensus regarding optimal CT for treatment of such patients. Preclinical data suggests TNBC may be sensitive to platinums because of deficiencies in BRCA-associated DNA repair. The aim of this study was to evaluate pathologic complete response (pCR) and overall survival (OS) in patients with TNBC treated with neoadjuvant platinum-based CT. Methods: We identified 674 patients with LABC who received neoadjuvant CT between January 1999 and June 2008 at University of Miami. Of these, 125 (18.5%) had histopathologic confirmation of TNBC. All patients received neoadjuvant platinum salts + docetaxel. 76 (61%) also received neoadjuvant AC, while 42 (34%) received adjuvant AC. pCR was defined as no residual invasive disease in breast and axilla. OS was calculated according to Kaplan-Meier. Results: Demographics: median age 50 (28-86 years). 60% premenopausal. TNM stage distribution: T1 0.9%, T2 5.2%, T3 53.4%, T4 40.5%, N0 25.0%, N1 36.2%, N2 35.4%, N3 3.4%, M0 100%, inflammatory 11%, median tumor size = 9.5 cm. Follow up duration ranged from 0.3 to 8.9 years. pCR was observed in 42 of 125 patients (34%; 95% CI 26-43%). Among patients receiving neoadjuvant AC, 30 of 76 (40%; 95% CI 28-51%) had pCR, while amongst those receiving adjuvant AC, 12 of 42 (29%, 95% CI 16-45%) had pCR at the time of definitive surgery. Patients achieving pCR had significantly higher OS (5-yr rate = 73% in pCR, vs. 49% in non-pCR; p < 0.001). OS in TNBC patients receiving cisplatin/docetaxel was significantly superior to those receiving carboplatin/docetaxel (11 mortality events out of 78 patients receiving cisplatin based CT vs 24 out of 47 receiving carboplatin based CT logrank p = 0.001). Conclusions: To date, this is the largest single institution cohort of locally advanced TNBC uniformly treated with platinum+docetaxel-based CT regimens. Platinum/docetaxel-based neoadjuvant CT provided high rates of pCR and excellent OS for women with locally advanced TNBC.
Effect of mTOR inhibition on sensitivity of triple-negative breast cancer cells to epidermal growth factor inhibition.
Sub-category: Metastatic Breast Cancer
Category: Breast Cancer--Metastatic Breast Cancer
Meeting: 2009 ASCO Annual Meeting
Citation: J Clin Oncol 27:15s, 2009 (suppl; abstr 1055)
Abstract No: 1055
Author(s): T. Liu, R. Yacoub, T. Graham, L. Yang, M. Tighiouart, R. M. O'Regan; Emory University, Atlanta, GA
Abstract:
Background: The outcome for patients with triple negative (TN) cancers is poor at least in part because of a lack of targeted therapies. Although 50% of TN breast cancers over-express EGFR, the use of EGFR inhibitors as single agents in patients with unselected and TN metastatic breast cancers has produced disappointing results. Likewise, mTOR inhibitors have modest activity as single agents in metastatic breast cancer. mTOR inhibitors have been demonstrated to activate the Akt pathway by a possible feedback mechanism, which could potentially sensitize TN breast cancer cells to upstream inhibitors. We have previously demonstrated that EGFR inhibitors in combination with rapamycin (RAPA) decrease cell survival, increase apoptosis, and are synergistic in TN breast cancer cells, compared to any of the agents alone (AACR 2008). We, therefore, evaluated the combination of mTOR and EGFR inhibition in vivo. Methods: Athymic mice were inoculated with TN (MDA-MB-231) breast cancer cells. One week after cell inoculation, mice were treated with vehicle, lapatinib 75mg/kg by mouth daily, RAPA 3mg/kg IP biweekly, or the combination. After 4 weeks of treatment, mice were sacrificed and tumors were assessed for target proteins by Western blotting and immunohistochemistry Results: The combination of RAPA and lapatinib resulted in a significant decrease in TN breast tumor volume (76 mm3), compared to rapamycin alone (133 mm3, p = 0.01), lapatinib alone (183 mm3, p < 0.0001) or control (188 mm3, p = 0.005). Neither lapatinib nor RAPA alone inhibited tumor growth significantly compared to control (p > 0.05). Interestingly, in contrast to our findings in vitro, the increase in pAkt noted in RAPA treated tumors was not decreased by lapatinib, despite the significant decrease in tumor size in tumors treated with the combination. Conclusions: These studies demonstrate that the combination of mTOR inhibition and lapatinib significantly inhibit TN breast cancer growth, compared with either agent alone. Given the lack of targeted therapies in TN breast cancers, these data support the possibility that mTOR inhibition can sensitize TN breast cancers to EGFR inhibitors. A clinical trial evaluating the combination of lapatinib and RAD001 as second-line therapy for TN metastatic breast cancer is planned.
Effect of modest delays in primary surgical treatment on progression of tumor size in breast cancer patients.
Sub-category: Local-Regional Therapy
Category: Breast Cancer--Local-Regional and Adjuvant Therapy
Meeting: 2009 ASCO Annual Meeting
Citation: J Clin Oncol 27:15s, 2009 (suppl; abstr 622)
Abstract No: 622
Author(s): J. L. Wagner, C. Warneke, I. Bedrosian, E. Mittendorf, G. Babiera, H. Kuerer, K. Hunt, W. Yang, A. Sahin, F. Meric-Bernstam, F. Meric-Bernstam; Plaza Medical Center, Fort Worth, TX; M. D. Anderson Cancer Center, Houston, TX
Abstract:
Background: Evaluation of medical co-morbidities, coordination of reconstructive surgery and referral to tertiary care centers can delay surgical treatment in breast cancer. These delays raise concerns for tumor progression in the interim. We evaluated the time from initial imaging at a cancer center to surgical treatment and the change in tumor size. Methods: We identified 823 patients who underwent surgery as their first therapeutic modality for invasive breast cancer diagnosed from December 2003 to September 2005. Baseline tumor size was determined by mammogram (MMG) and ultrasound (US) reports, and tumor size at surgery was determined by pathology reports. Results: The median time from imaging at our facility to surgery was 0.69 months (range 0.03 to 4.34). Multivariate modeling indicated that older patient age, undergoing total mastectomy, and undergoing reconstruction predicted a longer time from initial imaging to surgery. Comparing radiographic to pathologic size, a moderate correlation was demonstrated for both MMG (Spearman r = 0.58; p < 0.0001) and US (Spearman r = 0.66, p < 0.0001). Pathologic size was the same as MMG size in 14%, smaller in 49%, and larger in 37% of patients. Differences in tumor size estimates were not significantly associated with time lapse between MMG and surgery, but in a multivariate model, MMG tumor size , tumor histology, and tumor grade were significant predictors (p < 0.0001 for all) of differences in mammographic and pathologic size. The pathologic tumor size was the same as US in 10%, smaller in 38%, and larger in 52% of patients. Time lapse to surgery was not significantly associated with differences in US and pathologic tumor size. In a multivariate model, US tumor size (p < 0.0001), tumor histology (p = 0.0006) and tumor grade (p = 0.005) were significant predictors of differences in US and pathologic tumor size estimates. Conclusions: There is no evidence that time lapse from initial imaging to surgical intervention leads to significant changes in tumor size thus allowing patients to complete preoperative workup and planning without significant clinical disease progression.
Results of a multicenter pilot study of weekly nab-paclitaxel, carboplatin with bevacizumab, and trastuzumab as neoadjuvant therapy in HER2+ locally advanced breast cancer with SPARC correlatives.
Sub-category: Local-Regional Therapy
Category: Breast Cancer--Local-Regional and Adjuvant Therapy
Meeting: 2009 ASCO Annual Meeting
Citation: J Clin Oncol 27:15s, 2009 (suppl; abstr 527)
Abstract No: 527
Author(s): D. A. Yardley, E. Raefsky, R. Castillo, A. Lahiry, R. LoCicero, D. Thompson, M. Shastry, V. Trieu, D. Knauer, N. Desai; Sarah Cannon Research Institute, Nashville, TN; Tennessee Oncology, Nashville, TN; Florida Hospital Cancer Institute, Orlando, FL; Northeast Georgia Medical Center, Gainesville, GA; Abraxis BioScience, Los Angeles, CA
Abstract:
Background: The addition of targeted therapies to standard chemotherapy has resulted in improved outcomes in metastatic, neoadjuvant and early stage breast cancer. A phase III study in MBC demonstrated improved efficacy with nab paclitaxel (nab-P) compared with standard solvent-based paclitaxel. The secreted protein acidic rich in cysteine (SPARC) is a poor prognostic factor for survival and may mediate enhanced intratumoral accumulation of nab-P via an interaction with albumin. This multicenter phase II pilot study was designed to evaluate the feasibility, safety, and preliminary efficacy of dual VEGF and HER-2 monoclonal antibodies of bevacizumab (B) and trastuzumab (T) administered in with neoadjuvant nab-P and carboplatin (C) with SPARC tumor correlatives. Methods: Eligibility: clinical T1c-T4d and/or N0-3, M0 (T1N0M0 excluded) chemo naive, ECOG PS 0-2, normal LVEF, adequate organ function. Treatment: nab-P 125 mg/m2 D1, 8, 15 with C AUC 6 D1 q28 days plus T 4 mg/kg load followed by 2 mg/kg/wk and B 5 mg/kg/wk x 6 cycles followed by surgery. Post surgery T and B continued for 52 wks. SPARC tumor expression was measured by immunohistochemistry. Results: 29 pts are enrolled and evaluable for safety. Median age: 52 years (29-76), ECOG PS 0-93%, median tumor size 3.2 cm, 54% ER-/PR-, 72% node positive. G3/4 neutropenia was 38% with no febrile neutropenia. Nonheme toxicity: G3/4 hyperglycemia 10%, proteinuria and hypertension, each in 7%. 8 pts were hospitalized (infection-4, ↓LVEF-1, wound dehiscence-1 pt, other-2). 5 pts did not complete neoadjuvant therapy (↓LVEF-1, noncompliance-1, pt request-3) and 10 pts did not complete post op therapy ((pt request-2, toxicity-3, wound-2, unk-3). Pathologic responses are available for 20 pts. pCR was noted in 13/20 pts (65%) and PR was noted in 7/20 pts (35%). 77% of the pCR pts (10/13) and 86% of the PR pts (6/7) were positive for SPARC. Conclusions: Neoadjuvant B, T with nab-P and C is feasible and highly active with a remarkable pCR of 65%. SPARC tumor correlations with pathologic response data reveal a concordance between the high response rate and high incidence of SPARC positivity.
Value of adjuvant radiation therapy in breast cancer patients with one to three positive lymph nodes undergoing a modified radical mastectomy and systemic therapy.
Sub-category: Local-Regional Therapy
Category: Breast Cancer--Local-Regional and Adjuvant Therapy
Meeting: 2009 ASCO Annual Meeting
Citation: J Clin Oncol 27:15s, 2009 (suppl; abstr 507)
Abstract No: 507
Author(s): S. Dawood, A. M. Gonzalez-Angulo, W. Woodward, F. Meric-Bernstam, K. Hunt, A. Buzdar, G. Hortobagyi, T. Buchholz; Dubai Hospital, Dubai, United Arab Emirates; UT M. D. Anderson Cancer Center, Houston, TX
Abstract:
Background: Whether adjuvant radiation therapy should be utilized for patients (pts) with early stage breast cancer with up to 3 positive axillary lymph nodes treated with mastectomy and systemic therapy is controversial. This retrospective study was performed to determine if adjuvant radiation therapy had an impact on survival for this cohort of pts. Methods: 4240 pts with T1-2N0-1 breast cancers, diagnosed between 1980-2007, who underwent either mastectomy without adjuvant radiation therapy or segmental mastectomy with adjuvant radiation therapy were identified. All pts received systemic treatment. Women with >3 positive axillary lymph nodes were excluded. Overall (OS) and distant disease free survival (DDFS) were estimated using the Kaplan-Meir product method. Cox proportional hazards were used to determine associations between OS/DDFS and type of surgery after controlling for pt and disease characteristics. Results: 1336 (18.8%) had T1N0 disease, 1114 (26.27%) had T2N0 disease, 989 (23.33%) had T1N1 disease and 801 (18.89%) had T2N1 disease. Median follow-up was 54 months.5- year DDFS among women who underwent mastectomy and segmental mastectomy was 81% (95% 78%-83%) and 86% (95% CI 84%-87%), respectively (p < 0.0001). In the Cox analysis, pts who had mastectomy without radiation had a significantly increased risk of distant recurrence (HR = 1.39, 95% CI 1.14-1.70, p = 0.0013) than pts treated with segmental mastectomy and radiation. When looking at subgroups, no significant difference in DDFS was observed between the two groups in pts with lymph node negative disease. However, for pts with 1-3 positive lymph nodes, pts treated with mastectomy without radiation had significantly increased risk of distant recurrence compared to pts treated with segmental mastectomy with radiation (HR=1.614, 95% CI 1.198-2.177, p = 0.002). This difference was most pronounce in the subset of patients with T2N1 disease (HR = 1.794, 95% CI 1.220-2.637, p=0.003). Similar trends were observed for OS. Conclusions: This study provides provocative evidence for benefit of radiation therapy among pts with 1-3 positive axillary lymph nodes who are treated with surgery and systemic therapy.
Effect of modest delays in primary surgical treatment on progression of tumor size in breast cancer patients.
Sub-category: Local-Regional Therapy
Category: Breast Cancer--Local-Regional and Adjuvant Therapy
Meeting: 2009 ASCO Annual Meeting
Citation: J Clin Oncol 27:15s, 2009 (suppl; abstr 622)
Abstract No: 622
Author(s): J. L. Wagner, C. Warneke, I. Bedrosian, E. Mittendorf, G. Babiera, H. Kuerer, K. Hunt, W. Yang, A. Sahin, F. Meric-Bernstam, F. Meric-Bernstam; Plaza Medical Center, Fort Worth, TX; M. D. Anderson Cancer Center, Houston, TX
Abstract:
Background: Evaluation of medical co-morbidities, coordination of reconstructive surgery and referral to tertiary care centers can delay surgical treatment in breast cancer. These delays raise concerns for tumor progression in the interim. We evaluated the time from initial imaging at a cancer center to surgical treatment and the change in tumor size. Methods: We identified 823 patients who underwent surgery as their first therapeutic modality for invasive breast cancer diagnosed from December 2003 to September 2005. Baseline tumor size was determined by mammogram (MMG) and ultrasound (US) reports, and tumor size at surgery was determined by pathology reports. Results: The median time from imaging at our facility to surgery was 0.69 months (range 0.03 to 4.34). Multivariate modeling indicated that older patient age, undergoing total mastectomy, and undergoing reconstruction predicted a longer time from initial imaging to surgery. Comparing radiographic to pathologic size, a moderate correlation was demonstrated for both MMG (Spearman r = 0.58; p < 0.0001) and US (Spearman r = 0.66, p < 0.0001). Pathologic size was the same as MMG size in 14%, smaller in 49%, and larger in 37% of patients. Differences in tumor size estimates were not significantly associated with time lapse between MMG and surgery, but in a multivariate model, MMG tumor size , tumor histology, and tumor grade were significant predictors (p < 0.0001 for all) of differences in mammographic and pathologic size. The pathologic tumor size was the same as US in 10%, smaller in 38%, and larger in 52% of patients. Time lapse to surgery was not significantly associated with differences in US and pathologic tumor size. In a multivariate model, US tumor size (p < 0.0001), tumor histology (p = 0.0006) and tumor grade (p = 0.005) were significant predictors of differences in US and pathologic tumor size estimates. Conclusions: There is no evidence that time lapse from initial imaging to surgical intervention leads to significant changes in tumor size thus allowing patients to complete preoperative workup and planning without significant clinical disease progression.
Comparison of neoadjuvant paclitaxel and carboplatin with neoadjuvant letrozole in postmenopausal patients with receptor-positive locally advanced breast cancer (LABC).
Sub-category: Local-Regional Therapy
Category: Breast Cancer--Local-Regional and Adjuvant Therapy
Meeting: 2009 ASCO Annual Meeting
Citation: J Clin Oncol 27:15s, 2009 (suppl; abstr 608)
Abstract No: 608
Author(s): D. Sinha, A. K. Bahadur, K. Singh, A. K. Rathi; Maulana Azad Medical College, Delhi, India
Abstract:
Background: For the treatment of LABC using a regimen with the highest likelihood of shrinking the tumor should improve the outcome. Paclitaxel was the first taxane to show activity in breast cancer. The advent of endocrine therapy in the neoadjuvant setting allows downstaging of tumors with less morbidity. The aromatase inhibitors are now the treatment of choice in neoadjuvant setting for elderly patients with estrogen receptor-positive breast cancer. Methods: This prospective, randomized, comparative study assessed the effect of three cycles of neoadjuvant chemotherapy vs. three months of neoadjuvant hormonal therapy in terms of loss of clinical and pathological primary tumor size. Inclusion criteria required postmenopausal patients with non-metastatic, ER and/or PR positive LABC with no co-morbidity. Forty eligible patients were randomly assigned into 2 groups of 20 patients each: Group A treated with 3 cycles of 3 weekly injections of paclitaxel (175 mg/m2) and carboplatin (AUC 6) assessed after each cycle; group B received oral Letrozole 2.5mg once daily for 3 months assessed every 4 weeks. Surgery was done and primary specimen was pathologically examined. Results: Clinically mean loss in primary residual tumor compared to volume at presentation in group A vs. group B at 1st review was 45% vs. 35% (p: 0.536), 63% vs. 57% at second (p: 0.176), and 71% vs. 74% at third review (p: 0.062).Clinical complete response (WHO criteria) and stable disease each were seen in 14% in either group of patients (p: 0.632), partial response in 65% group A and in 72% group B (p: 0.117); no progressive disease was seen in either. All patients underwent surgery. The mean pathological primary cell kill in group A vs. group B was 81% vs.78 %(p:0.918). Resected nodes were pathologically positive for tumor in 47% group A and 60% group B patients (p: 0.269). Conclusions: Neoadjuvant hormonal therapy using oral Letrozole in receptor positive LABC in post menopausal women is as effective as three weekly paclitaxel and carboplatin in downstaging the tumor.
Comparison of neoadjuvant paclitaxel and carboplatin with neoadjuvant letrozole in postmenopausal patients with receptor-positive locally advanced breast cancer (LABC).
Sub-category: Local-Regional Therapy
Category: Breast Cancer--Local-Regional and Adjuvant Therapy
Meeting: 2009 ASCO Annual Meeting
Citation: J Clin Oncol 27:15s, 2009 (suppl; abstr 608)
Abstract No: 608
Author(s): D. Sinha, A. K. Bahadur, K. Singh, A. K. Rathi; Maulana Azad Medical College, Delhi, India
Abstract:
Background: For the treatment of LABC using a regimen with the highest likelihood of shrinking the tumor should improve the outcome. Paclitaxel was the first taxane to show activity in breast cancer. The advent of endocrine therapy in the neoadjuvant setting allows downstaging of tumors with less morbidity. The aromatase inhibitors are now the treatment of choice in neoadjuvant setting for elderly patients with estrogen receptor-positive breast cancer. Methods: This prospective, randomized, comparative study assessed the effect of three cycles of neoadjuvant chemotherapy vs. three months of neoadjuvant hormonal therapy in terms of loss of clinical and pathological primary tumor size. Inclusion criteria required postmenopausal patients with non-metastatic, ER and/or PR positive LABC with no co-morbidity. Forty eligible patients were randomly assigned into 2 groups of 20 patients each: Group A treated with 3 cycles of 3 weekly injections of paclitaxel (175 mg/m2) and carboplatin (AUC 6) assessed after each cycle; group B received oral Letrozole 2.5mg once daily for 3 months assessed every 4 weeks. Surgery was done and primary specimen was pathologically examined. Results: Clinically mean loss in primary residual tumor compared to volume at presentation in group A vs. group B at 1st review was 45% vs. 35% (p: 0.536), 63% vs. 57% at second (p: 0.176), and 71% vs. 74% at third review (p: 0.062).Clinical complete response (WHO criteria) and stable disease each were seen in 14% in either group of patients (p: 0.632), partial response in 65% group A and in 72% group B (p: 0.117); no progressive disease was seen in either. All patients underwent surgery. The mean pathological primary cell kill in group A vs. group B was 81% vs.78 %(p:0.918). Resected nodes were pathologically positive for tumor in 47% group A and 60% group B patients (p: 0.269). Conclusions: Neoadjuvant hormonal therapy using oral Letrozole in receptor positive LABC in post menopausal women is as effective as three weekly paclitaxel and carboplatin in downstaging the tumor.
Targeted Therapy Shows Promise in Treatment of Triple-negative Breast Cancer
According to the results of a Phase II clinical trial presented at a plenary session of the 2009 annual meeting of the American Society of Clinical Oncology (ASCO), treatment with chemotherapy plus the investigational drug BSI-201—a type of targeted therapy known as a PARP inhibitor—improved outcomes among women with triple-negative breast cancer.
Triple-negative breast cancer refers to breast cancer that is estrogen receptor-negative, progesterone receptor-negative, and HER2-negative. These cancers tend to be more aggressive than other types of breast cancer and do not respond to treatment with hormonal therapy or HER2-targeted therapy. Chemotherapy provides effective treatment for some women with triple-negative breast cancer, but more targeted and more effective treatments are clearly needed.
PARP stands for “poly (ADP-ribose) polymerase.” The PARP enzyme plays a role in DNA repair, including the repair of DNA damage from chemotherapy. Drugs that inhibit this enzyme may contribute to cancer cell death and increased sensitivity to chemotherapy.
The investigational PARP inhibitor BSI-201 was evaluated in a Phase II clinical trial among 116 women with metastatic, triple-negative breast cancer.[1] Study participants were assigned to receive chemotherapy alone or chemotherapy plus BSI-201. Chemotherapy consisted of Gemzar® (gemcitabine) and Paraplatin® (carboplatin).
* 62% of women treated with chemotherapy plus BSI-201 experienced a clinical benefit compared with 21% of women treated with chemotherapy alone. Clinical benefit refers to either a reduction in detectable cancer or stable disease of at least six months.
* Median overall survival was 9.2 months among women treated with chemotherapy plus BSI-201 compared with 5.7 months among women treated with chemotherapy alone.
* Median survival without cancer progression was 6.9 months among women treated with chemotherapy plus BSI-201 compared with 3.3 months among women treated with chemotherapy alone.
* The occurrence of side effects was similar in the two groups.
The results of this study suggest that the addition of BSI-201 to chemotherapy improves outcomes among women with metastatic, triple-negative breast cancer.
In a separate Phase II clinical trial also presented at ASCO, the investigational PARP inhibitor olaparib was evaluated among 54 women with BRCA1 or BRCA2 mutations and previously treated, advanced breast cancer.[2] All study participants were treated with olaparib alone, and more than one-third experienced tumor shrinkage.
References:
[1] O’Shaughnessy J, Osborne C, Pippen J et al. Efficacy of BSI-201, a poly (ADP-ribose) polymerase-1 (PARP1) inhibitor, in combination with gemcitabine/carboplatin (G/C) in patients with metastatic triple negative breast cancer (TNBC): Results of a randomized phase II trial. Presented at the 2009 annual meeting of the American Society of Clinical Oncology, May 29-June 2, 2009, Orlando, FL. Abstract P3.
[2] Tutt A, Robson M, Garber JE et al. Phase II trial of the oral PARP inhibitor olaparib in BRCA-deficient advanced breast cancer. Presented at the 2009 annual meeting of the American Society of Clinical Oncology, May 29-June 2, 2009, Orlando, FL. Abstract CRA501.
Effective treatment of triple-negative breast cancer with targeted cytotoxic somatostatin analogue AN-162 (AEZS-124).
Sub-category: Local-Regional Therapy
Category: Breast Cancer--Local-Regional and Adjuvant Therapy
Meeting: 2009 ASCO Annual Meeting
Citation: J Clin Oncol 27:15s, 2009 (suppl; abstr 619)
Abstract No: 619
Author(s): S. Seitz, A. V. Schally, S. Gluck, F. Rick, L. Szalontay, F. Hohla, A. Papadia, F. Köster, O. Ortmann, S. Buchholz; University of Regensburg, Regensburg, Germany; VA Medical Center, Miami, FL; University of Miami, Miami, FL; General Hospital Oberndorf, Oberndorf, Austria; University of Lübeck, Lübeck, Germany
Abstract:
Background: Triple negative breast cancers (TNBC) represent a distinct subtype of breast cancer being negative to ER, PR and HER2 and are associated with poor prognosis. Limited systemic treatment options exist for TNBC. TNBC cells express somatostatin receptors (SSTR). Therefore, to investigate preclinical characteristics of TNBC we used a novel targeted cytotoxic somatostatin analogue AN-162 containing doxorubicin (DOX) which binds to the subtypes 2, 3 and 5 of SSTR. Methods: The expression of SSTR in HCC 1806 human TNBC cell line was detected by RT-PCR. Cytotoxic effect of AN-162 in vitro was visualized by ethidium bromide staining fluorescence microscopy. Internalization of AN-162 into HCC 1806 cells was tested by 125Iodide-labeled AN-162 uptake assays and the presence of DOX in the nucleus was measured by fluorescence assays after separating the nucleus from the cytoplasm. For in vivo experiments, HCC 1806 TNBC cells were xenografted subcutaneously into nude mice which were then randomized into four groups receiving AN-162, DOX, an unconjugated mixture of DOX and somatostatin analogue RC-160 at the same equimolar dose of 2.5 µmol/kg (1.45 mg/kg Dox equivalent) i.v. (q7d 4x) and vehicle solution control. Results: HCC 1806 TNBC cell line was positive for the expression of all five SSTR receptor subtypes. Ethidum bromide staining of cells treated with 2.5 µM of AN-162 for 30 min demonstrated cell death after 24h by fluorescence microscopy. Uptake assays with AN-162 showed specific internalization of AN-162 into the cells mediated through the sstrs. After treatment of the cells with 2.5 µM AN-162 for 10 or 30 min, DOX could be detected in the nucleus by fluorescence assays. In vivo, AN-162 significantly (p<0.05) inhibited tumor growth of HCC 1806 xenografts compared to Control, DOX and the unconjugated mixture of DOX+RC-160 from day 14 and the inhibition remained significant until the end of the study on day 35. Conclusions: Our results indicate that treatment with targeted cytotoxic somatostatin analogue AN-162 produces a greater inhibition of tumor growth than DOX alone in somatostatin receptor positive TNBC. Our findings support the concept of targeted chemotherapy based on cytotoxic peptide analogues for the treatment of breast cancer and other cancers.
Neoadjuvant platinum-based chemotherapy (CT) for triple-negative locally advanced breast cancer (LABC): Retrospective analysis of 125 patients.
Sub-category: Local-Regional Therapy
Category: Breast Cancer--Local-Regional and Adjuvant Therapy
Meeting: 2009 ASCO Annual Meeting
Citation: J Clin Oncol 27:15s, 2009 (suppl; abstr 625)
Abstract No: 625
Author(s): J. P. Leone, V. Guardiola, A. Venkatraman, M. D. Pegram, C. Welsh, O. Silva, R. Larrieux, D. Franchesci, C. Gomez, J. Hurley; University of Miami, Jackson Memorial Hospital, Miami, FL
Abstract:
Background: Triple-negative breast cancer (TNBC), defined by lack of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2, accounts for 15-20% of all breast cancers and is associated with poor prognosis. There is no consensus regarding optimal CT for treatment of such patients. Preclinical data suggests TNBC may be sensitive to platinums because of deficiencies in BRCA-associated DNA repair. The aim of this study was to evaluate pathologic complete response (pCR) and overall survival (OS) in patients with TNBC treated with neoadjuvant platinum-based CT. Methods: We identified 674 patients with LABC who received neoadjuvant CT between January 1999 and June 2008 at University of Miami. Of these, 125 (18.5%) had histopathologic confirmation of TNBC. All patients received neoadjuvant platinum salts + docetaxel. 76 (61%) also received neoadjuvant AC, while 42 (34%) received adjuvant AC. pCR was defined as no residual invasive disease in breast and axilla. OS was calculated according to Kaplan-Meier. Results: Demographics: median age 50 (28-86 years). 60% premenopausal. TNM stage distribution: T1 0.9%, T2 5.2%, T3 53.4%, T4 40.5%, N0 25.0%, N1 36.2%, N2 35.4%, N3 3.4%, M0 100%, inflammatory 11%, median tumor size = 9.5 cm. Follow up duration ranged from 0.3 to 8.9 years. pCR was observed in 42 of 125 patients (34%; 95% CI 26-43%). Among patients receiving neoadjuvant AC, 30 of 76 (40%; 95% CI 28-51%) had pCR, while amongst those receiving adjuvant AC, 12 of 42 (29%, 95% CI 16-45%) had pCR at the time of definitive surgery. Patients achieving pCR had significantly higher OS (5-yr rate = 73% in pCR, vs. 49% in non-pCR; p < 0.001). OS in TNBC patients receiving cisplatin/docetaxel was significantly superior to those receiving carboplatin/docetaxel (11 mortality events out of 78 patients receiving cisplatin based CT vs 24 out of 47 receiving carboplatin based CT logrank p = 0.001). Conclusions: To date, this is the largest single institution cohort of locally advanced TNBC uniformly treated with platinum+docetaxel-based CT regimens. Platinum/docetaxel-based neoadjuvant CT provided high rates of pCR and excellent OS for women with locally advanced TNBC.
Effect of mTOR inhibition on sensitivity of triple-negative breast cancer cells to epidermal growth factor inhibition.
Sub-category: Metastatic Breast Cancer
Category: Breast Cancer--Metastatic Breast Cancer
Meeting: 2009 ASCO Annual Meeting
Citation: J Clin Oncol 27:15s, 2009 (suppl; abstr 1055)
Abstract No: 1055
Author(s): T. Liu, R. Yacoub, T. Graham, L. Yang, M. Tighiouart, R. M. O'Regan; Emory University, Atlanta, GA
Abstract:
Background: The outcome for patients with triple negative (TN) cancers is poor at least in part because of a lack of targeted therapies. Although 50% of TN breast cancers over-express EGFR, the use of EGFR inhibitors as single agents in patients with unselected and TN metastatic breast cancers has produced disappointing results. Likewise, mTOR inhibitors have modest activity as single agents in metastatic breast cancer. mTOR inhibitors have been demonstrated to activate the Akt pathway by a possible feedback mechanism, which could potentially sensitize TN breast cancer cells to upstream inhibitors. We have previously demonstrated that EGFR inhibitors in combination with rapamycin (RAPA) decrease cell survival, increase apoptosis, and are synergistic in TN breast cancer cells, compared to any of the agents alone (AACR 2008). We, therefore, evaluated the combination of mTOR and EGFR inhibition in vivo. Methods: Athymic mice were inoculated with TN (MDA-MB-231) breast cancer cells. One week after cell inoculation, mice were treated with vehicle, lapatinib 75mg/kg by mouth daily, RAPA 3mg/kg IP biweekly, or the combination. After 4 weeks of treatment, mice were sacrificed and tumors were assessed for target proteins by Western blotting and immunohistochemistry Results: The combination of RAPA and lapatinib resulted in a significant decrease in TN breast tumor volume (76 mm3), compared to rapamycin alone (133 mm3, p = 0.01), lapatinib alone (183 mm3, p < 0.0001) or control (188 mm3, p = 0.005). Neither lapatinib nor RAPA alone inhibited tumor growth significantly compared to control (p > 0.05). Interestingly, in contrast to our findings in vitro, the increase in pAkt noted in RAPA treated tumors was not decreased by lapatinib, despite the significant decrease in tumor size in tumors treated with the combination. Conclusions: These studies demonstrate that the combination of mTOR inhibition and lapatinib significantly inhibit TN breast cancer growth, compared with either agent alone. Given the lack of targeted therapies in TN breast cancers, these data support the possibility that mTOR inhibition can sensitize TN breast cancers to EGFR inhibitors. A clinical trial evaluating the combination of lapatinib and RAD001 as second-line therapy for TN metastatic breast cancer is planned.
Effect of modest delays in primary surgical treatment on progression of tumor size in breast cancer patients.
Sub-category: Local-Regional Therapy
Category: Breast Cancer--Local-Regional and Adjuvant Therapy
Meeting: 2009 ASCO Annual Meeting
Citation: J Clin Oncol 27:15s, 2009 (suppl; abstr 622)
Abstract No: 622
Author(s): J. L. Wagner, C. Warneke, I. Bedrosian, E. Mittendorf, G. Babiera, H. Kuerer, K. Hunt, W. Yang, A. Sahin, F. Meric-Bernstam, F. Meric-Bernstam; Plaza Medical Center, Fort Worth, TX; M. D. Anderson Cancer Center, Houston, TX
Abstract:
Background: Evaluation of medical co-morbidities, coordination of reconstructive surgery and referral to tertiary care centers can delay surgical treatment in breast cancer. These delays raise concerns for tumor progression in the interim. We evaluated the time from initial imaging at a cancer center to surgical treatment and the change in tumor size. Methods: We identified 823 patients who underwent surgery as their first therapeutic modality for invasive breast cancer diagnosed from December 2003 to September 2005. Baseline tumor size was determined by mammogram (MMG) and ultrasound (US) reports, and tumor size at surgery was determined by pathology reports. Results: The median time from imaging at our facility to surgery was 0.69 months (range 0.03 to 4.34). Multivariate modeling indicated that older patient age, undergoing total mastectomy, and undergoing reconstruction predicted a longer time from initial imaging to surgery. Comparing radiographic to pathologic size, a moderate correlation was demonstrated for both MMG (Spearman r = 0.58; p < 0.0001) and US (Spearman r = 0.66, p < 0.0001). Pathologic size was the same as MMG size in 14%, smaller in 49%, and larger in 37% of patients. Differences in tumor size estimates were not significantly associated with time lapse between MMG and surgery, but in a multivariate model, MMG tumor size , tumor histology, and tumor grade were significant predictors (p < 0.0001 for all) of differences in mammographic and pathologic size. The pathologic tumor size was the same as US in 10%, smaller in 38%, and larger in 52% of patients. Time lapse to surgery was not significantly associated with differences in US and pathologic tumor size. In a multivariate model, US tumor size (p < 0.0001), tumor histology (p = 0.0006) and tumor grade (p = 0.005) were significant predictors of differences in US and pathologic tumor size estimates. Conclusions: There is no evidence that time lapse from initial imaging to surgical intervention leads to significant changes in tumor size thus allowing patients to complete preoperative workup and planning without significant clinical disease progression.
Results of a multicenter pilot study of weekly nab-paclitaxel, carboplatin with bevacizumab, and trastuzumab as neoadjuvant therapy in HER2+ locally advanced breast cancer with SPARC correlatives.
Sub-category: Local-Regional Therapy
Category: Breast Cancer--Local-Regional and Adjuvant Therapy
Meeting: 2009 ASCO Annual Meeting
Citation: J Clin Oncol 27:15s, 2009 (suppl; abstr 527)
Abstract No: 527
Author(s): D. A. Yardley, E. Raefsky, R. Castillo, A. Lahiry, R. LoCicero, D. Thompson, M. Shastry, V. Trieu, D. Knauer, N. Desai; Sarah Cannon Research Institute, Nashville, TN; Tennessee Oncology, Nashville, TN; Florida Hospital Cancer Institute, Orlando, FL; Northeast Georgia Medical Center, Gainesville, GA; Abraxis BioScience, Los Angeles, CA
Abstract:
Background: The addition of targeted therapies to standard chemotherapy has resulted in improved outcomes in metastatic, neoadjuvant and early stage breast cancer. A phase III study in MBC demonstrated improved efficacy with nab paclitaxel (nab-P) compared with standard solvent-based paclitaxel. The secreted protein acidic rich in cysteine (SPARC) is a poor prognostic factor for survival and may mediate enhanced intratumoral accumulation of nab-P via an interaction with albumin. This multicenter phase II pilot study was designed to evaluate the feasibility, safety, and preliminary efficacy of dual VEGF and HER-2 monoclonal antibodies of bevacizumab (B) and trastuzumab (T) administered in with neoadjuvant nab-P and carboplatin (C) with SPARC tumor correlatives. Methods: Eligibility: clinical T1c-T4d and/or N0-3, M0 (T1N0M0 excluded) chemo naive, ECOG PS 0-2, normal LVEF, adequate organ function. Treatment: nab-P 125 mg/m2 D1, 8, 15 with C AUC 6 D1 q28 days plus T 4 mg/kg load followed by 2 mg/kg/wk and B 5 mg/kg/wk x 6 cycles followed by surgery. Post surgery T and B continued for 52 wks. SPARC tumor expression was measured by immunohistochemistry. Results: 29 pts are enrolled and evaluable for safety. Median age: 52 years (29-76), ECOG PS 0-93%, median tumor size 3.2 cm, 54% ER-/PR-, 72% node positive. G3/4 neutropenia was 38% with no febrile neutropenia. Nonheme toxicity: G3/4 hyperglycemia 10%, proteinuria and hypertension, each in 7%. 8 pts were hospitalized (infection-4, ↓LVEF-1, wound dehiscence-1 pt, other-2). 5 pts did not complete neoadjuvant therapy (↓LVEF-1, noncompliance-1, pt request-3) and 10 pts did not complete post op therapy ((pt request-2, toxicity-3, wound-2, unk-3). Pathologic responses are available for 20 pts. pCR was noted in 13/20 pts (65%) and PR was noted in 7/20 pts (35%). 77% of the pCR pts (10/13) and 86% of the PR pts (6/7) were positive for SPARC. Conclusions: Neoadjuvant B, T with nab-P and C is feasible and highly active with a remarkable pCR of 65%. SPARC tumor correlations with pathologic response data reveal a concordance between the high response rate and high incidence of SPARC positivity.
Value of adjuvant radiation therapy in breast cancer patients with one to three positive lymph nodes undergoing a modified radical mastectomy and systemic therapy.
Sub-category: Local-Regional Therapy
Category: Breast Cancer--Local-Regional and Adjuvant Therapy
Meeting: 2009 ASCO Annual Meeting
Citation: J Clin Oncol 27:15s, 2009 (suppl; abstr 507)
Abstract No: 507
Author(s): S. Dawood, A. M. Gonzalez-Angulo, W. Woodward, F. Meric-Bernstam, K. Hunt, A. Buzdar, G. Hortobagyi, T. Buchholz; Dubai Hospital, Dubai, United Arab Emirates; UT M. D. Anderson Cancer Center, Houston, TX
Abstract:
Background: Whether adjuvant radiation therapy should be utilized for patients (pts) with early stage breast cancer with up to 3 positive axillary lymph nodes treated with mastectomy and systemic therapy is controversial. This retrospective study was performed to determine if adjuvant radiation therapy had an impact on survival for this cohort of pts. Methods: 4240 pts with T1-2N0-1 breast cancers, diagnosed between 1980-2007, who underwent either mastectomy without adjuvant radiation therapy or segmental mastectomy with adjuvant radiation therapy were identified. All pts received systemic treatment. Women with >3 positive axillary lymph nodes were excluded. Overall (OS) and distant disease free survival (DDFS) were estimated using the Kaplan-Meir product method. Cox proportional hazards were used to determine associations between OS/DDFS and type of surgery after controlling for pt and disease characteristics. Results: 1336 (18.8%) had T1N0 disease, 1114 (26.27%) had T2N0 disease, 989 (23.33%) had T1N1 disease and 801 (18.89%) had T2N1 disease. Median follow-up was 54 months.5- year DDFS among women who underwent mastectomy and segmental mastectomy was 81% (95% 78%-83%) and 86% (95% CI 84%-87%), respectively (p < 0.0001). In the Cox analysis, pts who had mastectomy without radiation had a significantly increased risk of distant recurrence (HR = 1.39, 95% CI 1.14-1.70, p = 0.0013) than pts treated with segmental mastectomy and radiation. When looking at subgroups, no significant difference in DDFS was observed between the two groups in pts with lymph node negative disease. However, for pts with 1-3 positive lymph nodes, pts treated with mastectomy without radiation had significantly increased risk of distant recurrence compared to pts treated with segmental mastectomy with radiation (HR=1.614, 95% CI 1.198-2.177, p = 0.002). This difference was most pronounce in the subset of patients with T2N1 disease (HR = 1.794, 95% CI 1.220-2.637, p=0.003). Similar trends were observed for OS. Conclusions: This study provides provocative evidence for benefit of radiation therapy among pts with 1-3 positive axillary lymph nodes who are treated with surgery and systemic therapy.
Effect of modest delays in primary surgical treatment on progression of tumor size in breast cancer patients.
Sub-category: Local-Regional Therapy
Category: Breast Cancer--Local-Regional and Adjuvant Therapy
Meeting: 2009 ASCO Annual Meeting
Citation: J Clin Oncol 27:15s, 2009 (suppl; abstr 622)
Abstract No: 622
Author(s): J. L. Wagner, C. Warneke, I. Bedrosian, E. Mittendorf, G. Babiera, H. Kuerer, K. Hunt, W. Yang, A. Sahin, F. Meric-Bernstam, F. Meric-Bernstam; Plaza Medical Center, Fort Worth, TX; M. D. Anderson Cancer Center, Houston, TX
Abstract:
Background: Evaluation of medical co-morbidities, coordination of reconstructive surgery and referral to tertiary care centers can delay surgical treatment in breast cancer. These delays raise concerns for tumor progression in the interim. We evaluated the time from initial imaging at a cancer center to surgical treatment and the change in tumor size. Methods: We identified 823 patients who underwent surgery as their first therapeutic modality for invasive breast cancer diagnosed from December 2003 to September 2005. Baseline tumor size was determined by mammogram (MMG) and ultrasound (US) reports, and tumor size at surgery was determined by pathology reports. Results: The median time from imaging at our facility to surgery was 0.69 months (range 0.03 to 4.34). Multivariate modeling indicated that older patient age, undergoing total mastectomy, and undergoing reconstruction predicted a longer time from initial imaging to surgery. Comparing radiographic to pathologic size, a moderate correlation was demonstrated for both MMG (Spearman r = 0.58; p < 0.0001) and US (Spearman r = 0.66, p < 0.0001). Pathologic size was the same as MMG size in 14%, smaller in 49%, and larger in 37% of patients. Differences in tumor size estimates were not significantly associated with time lapse between MMG and surgery, but in a multivariate model, MMG tumor size , tumor histology, and tumor grade were significant predictors (p < 0.0001 for all) of differences in mammographic and pathologic size. The pathologic tumor size was the same as US in 10%, smaller in 38%, and larger in 52% of patients. Time lapse to surgery was not significantly associated with differences in US and pathologic tumor size. In a multivariate model, US tumor size (p < 0.0001), tumor histology (p = 0.0006) and tumor grade (p = 0.005) were significant predictors of differences in US and pathologic tumor size estimates. Conclusions: There is no evidence that time lapse from initial imaging to surgical intervention leads to significant changes in tumor size thus allowing patients to complete preoperative workup and planning without significant clinical disease progression.
Comparison of neoadjuvant paclitaxel and carboplatin with neoadjuvant letrozole in postmenopausal patients with receptor-positive locally advanced breast cancer (LABC).
Sub-category: Local-Regional Therapy
Category: Breast Cancer--Local-Regional and Adjuvant Therapy
Meeting: 2009 ASCO Annual Meeting
Citation: J Clin Oncol 27:15s, 2009 (suppl; abstr 608)
Abstract No: 608
Author(s): D. Sinha, A. K. Bahadur, K. Singh, A. K. Rathi; Maulana Azad Medical College, Delhi, India
Abstract:
Background: For the treatment of LABC using a regimen with the highest likelihood of shrinking the tumor should improve the outcome. Paclitaxel was the first taxane to show activity in breast cancer. The advent of endocrine therapy in the neoadjuvant setting allows downstaging of tumors with less morbidity. The aromatase inhibitors are now the treatment of choice in neoadjuvant setting for elderly patients with estrogen receptor-positive breast cancer. Methods: This prospective, randomized, comparative study assessed the effect of three cycles of neoadjuvant chemotherapy vs. three months of neoadjuvant hormonal therapy in terms of loss of clinical and pathological primary tumor size. Inclusion criteria required postmenopausal patients with non-metastatic, ER and/or PR positive LABC with no co-morbidity. Forty eligible patients were randomly assigned into 2 groups of 20 patients each: Group A treated with 3 cycles of 3 weekly injections of paclitaxel (175 mg/m2) and carboplatin (AUC 6) assessed after each cycle; group B received oral Letrozole 2.5mg once daily for 3 months assessed every 4 weeks. Surgery was done and primary specimen was pathologically examined. Results: Clinically mean loss in primary residual tumor compared to volume at presentation in group A vs. group B at 1st review was 45% vs. 35% (p: 0.536), 63% vs. 57% at second (p: 0.176), and 71% vs. 74% at third review (p: 0.062).Clinical complete response (WHO criteria) and stable disease each were seen in 14% in either group of patients (p: 0.632), partial response in 65% group A and in 72% group B (p: 0.117); no progressive disease was seen in either. All patients underwent surgery. The mean pathological primary cell kill in group A vs. group B was 81% vs.78 %(p:0.918). Resected nodes were pathologically positive for tumor in 47% group A and 60% group B patients (p: 0.269). Conclusions: Neoadjuvant hormonal therapy using oral Letrozole in receptor positive LABC in post menopausal women is as effective as three weekly paclitaxel and carboplatin in downstaging the tumor.
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