Publications (358) View all
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Article: Impact of chemotherapy sequencing on local-regional failure risk in breast cancer patients undergoing breast-conserving therapy.
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ABSTRACT: : This study was performed to evaluate long-term local-regional control rates after breast-conserving therapy (BCT) for patients undergoing surgery before or after neoadjuvant chemotherapy. : There were 2983 patients who underwent segmental mastectomy with whole-breast irradiation from 1987 to 2005. Clinicopathological and outcome data were reviewed, and comparisons were made between those undergoing surgery before and those undergoing surgery after neoadjuvant chemotherapy. : There were 2331 patients (78%) who underwent surgery first and 652 (22%) received neoadjuvant chemotherapy. Patients receiving neoadjuvant chemotherapy had more advanced disease at baseline and more adverse clinicopathological features. The 5- and 10-year local-regional recurrence (LRR)-free survival rates were 97% [95% confidence interval (CI), 96-98) and 94% (95% CI, 93-95) for surgery first and 93% (95% CI, 91-95) and 90% (95% CI, 87-93) after neoadjuvant chemotherapy (P < 0.001). However, there were no differences in LRR-free survival rates when comparing the presenting clinical stage (P = NS). Of 607 patients presenting with clinical stage II/III disease, chemotherapy downstaged 313 patients (52%) to pathological stage 0/I disease; 294 (48%) had residual stage II/III disease. In multivariate analysis, an age less than 50 years, clinical stage III, grade 3, estrogen receptor (ER)-negative disease, estrogen receptor-positive disease without receipt of endocrine therapy, lymphovascular invasion, multifocal disease on pathology, and close/positive margins were associated with LRR. Use of neoadjuvant chemotherapy was not significant when added to the model. Adjusting for adverse factors, there were no differences in LRR between patients who underwent surgery before and those who underwent neoadjuvant chemotherapy after surgery. : LRR after BCT is driven by tumor biology and disease stage. Appropriately selected patients can achieve high rates of local-regional control with BCT with either upfront surgery or surgery after neoadjuvant chemotherapy.Annals of surgery 02/2013; 257(2):173-9. · 7.90 Impact Factor -
Article: Elafin, an inhibitor of elastase, is a prognostic indicator in breast cancer.
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ABSTRACT: INTRODUCTION: Elafin is an elastase-specific inhibitor with increased transcription in normal mammary epithelial cells compared to mammary carcinoma cells. In this report, we test the hypothesis that inhibition of elastase, through induction of elafin leads to inhibition of human breast cancer cell viability and therefore predicts survival in breast cancer patients. METHODS: Panels of normal and immortalized breast epithelial cells, along with breast carcinoma cells, were used to examine the impact of adenoviral-mediated elafin expression or shRNA-mediated inhibition of elastase on the growth of cells and xenografts in nude mice. To determine the prognostic significance of decreased elafin in patients with invasive breast cancer, previously published gene array datasets were interrogated. RESULTS: Elafin expression had no effect on non-tumorigenic cells but resulted in marked inhibition of cell growth in breast cancer cell lines. Control-treated xenografts generated a tumor burden that necessitated sacrifice within 1 month of initial treatment, whereas xenograft-bearing mice treated with Ad-Elafin were alive at 8 months with marked reduction in tumor growth. Elastase inhibition mimicked these results, showing decreased tumor cell growth in vitro and in vivo. Low expression of elafin gene correlated with significantly reduced time to relapse, and when combined with high expression of elastase gene was associated with decreased survival in breast cancer patients. CONCLUSION: Our data suggest that elafin plays a direct role in the suppression of tumors through inhibition of elastase and thus serves as a prognostic indicator for breast cancer patients.Breast cancer research: BCR 01/2013; 15(1):R3. · 5.24 Impact Factor -
Article: Primary Tumor Extirpation in Breast Cancer Patients Who Present with Stage IV Disease is Associated with Improved Survival.
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ABSTRACT: PURPOSE: Previous evaluation of our institutional experience with stage IV breast cancer patients with an intact primary tumor (IPT) did not reveal an overall survival (OS) benefit for surgery at 32.1 months median follow-up. We assessed the impact of surgery after 74.2 months median follow-up, and the effect of systemic therapy and local radiotherapy (RT). METHODS: We reviewed the records of all patients presenting from 1997 to 2002 with stage IV disease with an IPT. Cox proportional hazards modeling was used to assess differences in survival between treatment groups. RESULTS: Seventy-four (35.6 %) of 208 patients underwent resection of the IPT. After adjustment for covariates, surgery was associated with improved OS (p = 0.04). Multivariable analysis revealed that estrogen receptor (ER) positivity (p = 0.002) and having only a single focus of metastatic disease (p = 0.05) were also associated with improved OS. Surgery was highly associated with receipt of RT (p = 0.0003). RT was significantly associated with improved survival (p = 0.015) in an exploratory analysis. CONCLUSIONS: Stage IV breast cancer patients with an IPT treated surgically had significantly improved OS. Radiation to the primary was also associated with improved survival, but this was evident only with adjustment for the effect of surgery. These findings may be limited by selection bias. Completion of ongoing prospective randomized trials is needed to conclusively determine whether stage IV patients with an IPT should be offered aggressive locoregional therapy.Annals of Surgical Oncology 01/2013; · 4.17 Impact Factor -
Article: Long-Term Outcomes in Patients with Radiation-Associated Angiosarcomas of the Breast Following Surgery and Radiotherapy for Breast Cancer.
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ABSTRACT: BACKGROUND: Radiation-associated angiosarcoma (RAAS) is a devastating disease occasionally observed in breast cancer patients treated with radiation. Due to its rarity, our knowledge-of disease risk factors, epidemiology, treatment, and outcome-is extremely limited. Therefore, we sought to identify clinicopathologic factors associated with local and distant recurrence and disease-specific survival (DSS). METHODS: Radiation-associated angiosarcoma was defined as pathologically confirmed breast or chest wall angiosarcoma arising within a previously irradiated field. A comprehensive search of our institutional tumor registry (1/1/93 through 2/28/11) was used to identify patients (n = 95 females). Patient, original tumor, RAAS treatment, and outcome variables were retrospectively retrieved and assembled into a database. RESULTS: The median follow-up for all RAAS patients was 10.3 (range, 2.4-31.8) years. The latency period following radiation exposure ranged from 1.4 to 26 (median, 7) years. One-year and 5-year DSS rates were 93.5 and 62.6 %, respectively. Reduced risk of local recurrence was observed in patients who received chemotherapy (P = 0.0003). In multivariable analysis, size was found to be an independent predictor of adverse outcome (P = 0.015). CONCLUSIONS: Our study demonstrates that RAAS exhibits high recurrence rates. It also highlights the need for well-designed, multicenter, clinical trials to inform the true utility of chemotherapy in this disease.Annals of Surgical Oncology 12/2012; · 4.17 Impact Factor -
Article: Other Primary Malignancies in Breast Cancer Patients Treated with Breast Conserving Surgery and Radiation Therapy.
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ABSTRACT: BACKGROUND: Our purpose was to examine the incidence and impact on survival of other primary malignancies (OPM) outside of the breast in breast cancer patients and to identify risk factors associated with OPM. METHODS: Patients with stage 0-III breast cancer treated with breast conserving therapy at our center from 1979 to 2007 were included. Risk factors were compared between patients with/without OPM. Logistic regression was used to identify factors that were associated with OPM. Standardized incidence ratios (SIRs) were calculated. RESULTS: Among 4,198 patients in this study, 276 (6.6 %) developed an OPM after breast cancer treatment. Patients with OPM were older and had a higher proportion of stage 0/I disease and contralateral breast cancer compared with those without OPM. In a multivariate analysis, older patients, those with contralateral breast cancer, and those who did not receive chemotherapy or hormone therapy were more likely to develop OPM after breast cancer. Patients without OPM had better overall survival. The SIR for all OPM sites combined after a first primary breast cancer was 2.91 (95 % confidence interval: 2.57-3.24). Significantly elevated risks were seen for numerous cancer sites, with SIRs ranging from 1.84 for lung cancer to 5.69 for ovarian cancer. CONCLUSIONS: Our study shows that breast cancer patients have an increased risk of developing OPM over the general population. The use of systemic therapy was not associated with increased risk of OPM. In addition to screening for a contralateral breast cancer and recurrences, breast cancer survivors should undergo screening for other malignancies.Annals of Surgical Oncology 12/2012; · 4.17 Impact Factor
