Tatiana Prowell - Academia.edu (original) (raw)

Papers by Tatiana Prowell

Breast Diseases: A Year Book Quarterly, 2014

Breast Cancer and Molecular Medicine, 2006

... Oncotype DX is a 21-gene recurrence score (RS) assay that has been recently vali-dated to qua... more ... Oncotype DX is a 21-gene recurrence score (RS) assay that has been recently vali-dated to quantify the risk of distant recurrence in ... Stoica, GE, Franke, TF, Wellstein, A., Czubayko, F., List, HJ, Reiter, R., Morgan, E., Martin, MB, and Stoica, A. Estradiol rapidly activates Akt via ...

The Oncologist, 2010

This report summarizes the U.S. Food and Drug Administration (FDA)&am... more This report summarizes the U.S. Food and Drug Administration (FDA)'s approval of temsirolimus (Torisel), on May 30, 2007, for the treatment of advanced renal cell carcinoma (RCC). Information provided includes regulatory history, study design, study results, and literature review. A multicenter, three-arm, randomized, open-label study was conducted in previously untreated patients with poor-prognosis, advanced RCC. The study objectives were to compare overall survival (OS), progression-free survival (PFS), objective response rate, and safety in patients receiving interferon (IFN)-alpha versus those receiving temsirolimus alone or in combination with IFN-alpha. In the second planned interim analysis of the intent-to-treat population (n = 626), there was a statistically significant longer OS time in the temsirolimus (25 mg) arm than in the IFN-alpha arm (median, 10.9 months versus 7.3 months; hazard ratio [HR], 0.73; p = .0078). The combination of temsirolimus (15 mg) and IFN-alpha did not lead to a significant difference in OS compared with IFN-alpha alone. There was also a statistically significant longer PFS time for the temsirolimus (25 mg) arm than for the IFN-alpha arm (median, 5.5 months versus 3.1 months; HR, 0.66, p = .0001). Common adverse reactions reported in patients receiving temsirolimus were rash, asthenia, and mucositis. Common laboratory abnormalities were anemia, hyperglycemia, hyperlipidemia, and hypertriglyceridemia. Serious but rare cases of interstitial lung disease, bowel perforation, and acute renal failure were observed. Temsirolimus has demonstrated superiority in terms of OS and PFS over IFN-alpha and provides an additional treatment option for patients with advanced RCC.

The Oncologist, 2004

Ovarian ablation has been used for more than a century in the treatment of breast cancer. Methods... more Ovarian ablation has been used for more than a century in the treatment of breast cancer. Methods of irreversible ovarian ablation include surgical oophorectomy and ovarian irradiation. Potentially reversible castration can be accomplished medically using luteinizing hormone releasing hormone (LHRH) analogues. In addition, cytotoxic chemotherapy unpredictably produces amenorrhea and primary ovarian failure in 10%-95% of premenopausal women as a function of patient age, cumulative dose, and the specific agents used. In the metastatic setting, ovarian ablation and tamoxifen monotherapies produce comparable outcomes and may be more effective when used together. While many early adjuvant trials of ovarian ablation were methodologically flawed, a more recent meta-analysis by the Early Breast Cancer Trialists' Collaborative Group of 12 properly designed randomized trials found significantly greater disease-free and overall survival rates for women under the age of 50, regardless of nodal status, receiving ovarian ablation as a single adjuvant therapy. Several important issues regarding the role of ovarian ablation in the treatment of breast cancer remain unresolved. Data suggest that ovarian ablation followed by some years of tamoxifen produces similar The Oncologist 2004;9:507-517 www.TheOncologist.com The Oncologist ®

Seminars in Oncology, 2006

Most women with breast cancer that overexpresses either estrogen (ER؉) or progesterone receptors ... more Most women with breast cancer that overexpresses either estrogen (ER؉) or progesterone receptors (PR؉) will be treated with an endocrine agent. Although ER and PR are the only validated predictive markers of response to hormonal therapy, many women with hormone receptor-positive (HR؉) tumors will fail to respond to endocrine treatment or develop hormone resistant disease. Another tumor marker, HER-2/neu, is an oncogene whose amplification or protein overexpression predicts response to a monoclonal antibody targeting HER-2/neu, as well as to anthracycline-based chemotherapy. Preclinical and some clinical data suggest that HER-2/neu positivity may also predict for relative resistance to endocrine therapy. Interpretation of clinical data addressing this issue is confounded by largely retrospective study designs and considerable heterogeneity in patient populations and methods of marker detection and interpretation. At this writing, HER-2/neu expression should not influence the decision to use endocrine therapy. Semin Oncol 33:681-687

JNCI Journal of the National Cancer Institute, 2007

Journal of Clinical Oncology, 2006

REFERENCES 1. Bonovas S, Filioussi K, Tsavaris N, et al: Use of statins and breast cancer: A meta... more REFERENCES 1. Bonovas S, Filioussi K, Tsavaris N, et al: Use of statins and breast cancer: A meta-analysis of seven randomized clinical trials and nine observational studies. J Clin Oncol 23:8606-8612, 2005 2. Strandberg TE, Pyorala K, Cook TJ, et al: Mortality and incidence of cancer during 10-year follow-up of the Scandinavian Simvastatin Survival study (4S). Lancet 364:771-777, 2004 3. Downs JR, Clearfield M, Weis S, et al: Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: Results of AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study.

Cancer Prevention Research, 2011

Factors associated with an increased risk of breast cancer include prior breast cancer, high circ... more Factors associated with an increased risk of breast cancer include prior breast cancer, high circulating estrogens, and increased breast density. Adjuvant aromatase inhibitors are associated with a reduction in incidence of contralateral breast cancer. We conducted a prospective, single-arm, single-institution study to determine whether use of anastrozole is associated with changes in contralateral breast density and circulating estrogens. Eligible patients included postmenopausal women with hormone receptor-positive early-stage breast cancer who had completed local therapy, had an intact contralateral breast, and were recommended an aromatase inhibitor as their only systemic therapy. Participants received anastrozole 1 mg daily for 12 months on study. We assessed contralateral breast density and serum estrogens at baseline, 6, and 12 months. The primary endpoint was change in contralateral percent breast density from baseline to 12 months. Secondary endpoints included change in serum estrone sulfate from baseline to 12 months. Fifty-four patients were accrued. At 12 months, compared with baseline, there was a nonstatistically significant reduction in breast density (mean change: -16%, 95% CI: -30 to 2, P = 0.08) and a significant reduction in estrone sulfate (mean change: -93%, 95% CI: -94 to -91, P < 0.001). Eighteen women achieved 20% or greater relative reduction in contralateral percent density at 12 months compared with baseline; however, no measured patient or disease characteristics distinguished these women from the overall population. Large trials are required to provide additional data on the relationship between aromatase inhibitors and breast density and, more importantly, whether observed changes in breast density correlate with meaningful disease-specific outcomes.

Breast Cancer Research and Treatment, 2012

Observational studies have demonstrated a decreased incidence of cancers among users of HMG CoA r... more Observational studies have demonstrated a decreased incidence of cancers among users of HMG CoA reductase inhibitors (statins) and a reduced risk of recurrence among statin users diagnosed with early stage breast cancer. We initiated a prospective study to identify potential biomarkers of simvastatin chemopreventive activity that can be validated in future trials. The contralateral breast of women with a previous history of breast cancer was used as a high-risk model. Eligible women who had completed all planned treatment of a prior stage 0-III breast cancer received simvastatin 40 mg orally daily for 24-28 weeks. At baseline and end-of-study, we measured circulating concentrations of high-sensitivity C-reactive protein (hsCRP), estrogens, and fasting lipids; breast density on contralateral breast mammogram; and quality of life by Rand Short Form 36-Item health survey. Fifty women were enrolled with a median age of 53 years. Total cholesterol, LDL cholesterol, triglyceride, and hsCRP fell significantly during the study (P values < 0.001, <0.001, 0.003, and 0.05, respectively). Estrone sulfate concentrations decreased with simvastatin treatment (P = 0.01 overall), particularly among post-menopausal participants (P = 0.006). We did not observe a significant change in circulating estradiol or estrone concentrations, contralateral mammographic breast density, or reported physical functioning or pain scores. This study demonstrates the feasibility of short-term biomarker modulation studies using the contralateral breast of high-risk women. Simvastatin appears to modulate estrone sulfate concentrations and its potential chemopreventive activity in breast cancer warrants further investigation.

The Lancet, 2014

Pathological complete response has been proposed as a surrogate endpoint for prediction of long-t... more Pathological complete response has been proposed as a surrogate endpoint for prediction of long-term clinical benefit, such as disease-free survival, event-free survival (EFS), and overall survival (OS). We had four key objectives: to establish the association between pathological complete response and EFS and OS, to establish the definition of pathological complete response that correlates best with long-term outcome, to identify the breast cancer subtypes in which pathological complete response is best correlated with long-term outcome, and to assess whether an increase in frequency of pathological complete response between treatment groups predicts improved EFS and OS. We searched PubMed, Embase, and Medline for clinical trials of neoadjuvant treatment of breast cancer. To be eligible, studies had to meet three inclusion criteria: include at least 200 patients with primary breast cancer treated with preoperative chemotherapy followed by surgery; have available data for pathological complete response, EFS, and OS; and have a median follow-up of at least 3 years. We compared the three most commonly used definitions of pathological complete response--ypT0 ypN0, ypT0/is ypN0, and ypT0/is--for their association with EFS and OS in a responder analysis. We assessed the association between pathological complete response and EFS and OS in various subgroups. Finally, we did a trial-level analysis to assess whether pathological complete response could be used as a surrogate endpoint for EFS or OS. We obtained data from 12 identified international trials and 11 955 patients were included in our responder analysis. Eradication of tumour from both breast and lymph nodes (ypT0 ypN0 or ypT0/is ypN0) was better associated with improved EFS (ypT0 ypN0: hazard ratio [HR] 0·44, 95% CI 0·39-0·51; ypT0/is ypN0: 0·48, 0·43-0·54) and OS (0·36, 0·30-0·44; 0·36, 0·31-0·42) than was tumour eradication from the breast alone (ypT0/is; EFS: HR 0·60, 95% CI 0·55-0·66; OS 0·51, 0·45-0·58). We used the ypT0/is ypN0 definition for all subsequent analyses. The association between pathological complete response and long-term outcomes was strongest in patients with triple-negative breast cancer (EFS: HR 0·24, 95% CI 0·18-0·33; OS: 0·16, 0·11-0·25) and in those with HER2-positive, hormone-receptor-negative tumours who received trastuzumab (EFS: 0·15, 0·09-0·27; OS: 0·08, 0·03, 0·22). In the trial-level analysis, we recorded little association between increases in frequency of pathological complete response and EFS (R(2)=0·03, 95% CI 0·00-0·25) and OS (R(2)=0·24, 0·00-0·70). Patients who attain pathological complete response defined as ypT0 ypN0 or ypT0/is ypN0 have improved survival. The prognostic value is greatest in aggressive tumour subtypes. Our pooled analysis could not validate pathological complete response as a surrogate endpoint for improved EFS and OS. US Food and Drug Administration.

Breast Diseases: A Year Book Quarterly, 2014

Breast Cancer and Molecular Medicine, 2006

... Oncotype DX is a 21-gene recurrence score (RS) assay that has been recently vali-dated to qua... more ... Oncotype DX is a 21-gene recurrence score (RS) assay that has been recently vali-dated to quantify the risk of distant recurrence in ... Stoica, GE, Franke, TF, Wellstein, A., Czubayko, F., List, HJ, Reiter, R., Morgan, E., Martin, MB, and Stoica, A. Estradiol rapidly activates Akt via ...

The Oncologist, 2010

This report summarizes the U.S. Food and Drug Administration (FDA)&am... more This report summarizes the U.S. Food and Drug Administration (FDA)'s approval of temsirolimus (Torisel), on May 30, 2007, for the treatment of advanced renal cell carcinoma (RCC). Information provided includes regulatory history, study design, study results, and literature review. A multicenter, three-arm, randomized, open-label study was conducted in previously untreated patients with poor-prognosis, advanced RCC. The study objectives were to compare overall survival (OS), progression-free survival (PFS), objective response rate, and safety in patients receiving interferon (IFN)-alpha versus those receiving temsirolimus alone or in combination with IFN-alpha. In the second planned interim analysis of the intent-to-treat population (n = 626), there was a statistically significant longer OS time in the temsirolimus (25 mg) arm than in the IFN-alpha arm (median, 10.9 months versus 7.3 months; hazard ratio [HR], 0.73; p = .0078). The combination of temsirolimus (15 mg) and IFN-alpha did not lead to a significant difference in OS compared with IFN-alpha alone. There was also a statistically significant longer PFS time for the temsirolimus (25 mg) arm than for the IFN-alpha arm (median, 5.5 months versus 3.1 months; HR, 0.66, p = .0001). Common adverse reactions reported in patients receiving temsirolimus were rash, asthenia, and mucositis. Common laboratory abnormalities were anemia, hyperglycemia, hyperlipidemia, and hypertriglyceridemia. Serious but rare cases of interstitial lung disease, bowel perforation, and acute renal failure were observed. Temsirolimus has demonstrated superiority in terms of OS and PFS over IFN-alpha and provides an additional treatment option for patients with advanced RCC.

The Oncologist, 2004

Ovarian ablation has been used for more than a century in the treatment of breast cancer. Methods... more Ovarian ablation has been used for more than a century in the treatment of breast cancer. Methods of irreversible ovarian ablation include surgical oophorectomy and ovarian irradiation. Potentially reversible castration can be accomplished medically using luteinizing hormone releasing hormone (LHRH) analogues. In addition, cytotoxic chemotherapy unpredictably produces amenorrhea and primary ovarian failure in 10%-95% of premenopausal women as a function of patient age, cumulative dose, and the specific agents used. In the metastatic setting, ovarian ablation and tamoxifen monotherapies produce comparable outcomes and may be more effective when used together. While many early adjuvant trials of ovarian ablation were methodologically flawed, a more recent meta-analysis by the Early Breast Cancer Trialists' Collaborative Group of 12 properly designed randomized trials found significantly greater disease-free and overall survival rates for women under the age of 50, regardless of nodal status, receiving ovarian ablation as a single adjuvant therapy. Several important issues regarding the role of ovarian ablation in the treatment of breast cancer remain unresolved. Data suggest that ovarian ablation followed by some years of tamoxifen produces similar The Oncologist 2004;9:507-517 www.TheOncologist.com The Oncologist ®

Seminars in Oncology, 2006

Most women with breast cancer that overexpresses either estrogen (ER؉) or progesterone receptors ... more Most women with breast cancer that overexpresses either estrogen (ER؉) or progesterone receptors (PR؉) will be treated with an endocrine agent. Although ER and PR are the only validated predictive markers of response to hormonal therapy, many women with hormone receptor-positive (HR؉) tumors will fail to respond to endocrine treatment or develop hormone resistant disease. Another tumor marker, HER-2/neu, is an oncogene whose amplification or protein overexpression predicts response to a monoclonal antibody targeting HER-2/neu, as well as to anthracycline-based chemotherapy. Preclinical and some clinical data suggest that HER-2/neu positivity may also predict for relative resistance to endocrine therapy. Interpretation of clinical data addressing this issue is confounded by largely retrospective study designs and considerable heterogeneity in patient populations and methods of marker detection and interpretation. At this writing, HER-2/neu expression should not influence the decision to use endocrine therapy. Semin Oncol 33:681-687

JNCI Journal of the National Cancer Institute, 2007

Journal of Clinical Oncology, 2006

REFERENCES 1. Bonovas S, Filioussi K, Tsavaris N, et al: Use of statins and breast cancer: A meta... more REFERENCES 1. Bonovas S, Filioussi K, Tsavaris N, et al: Use of statins and breast cancer: A meta-analysis of seven randomized clinical trials and nine observational studies. J Clin Oncol 23:8606-8612, 2005 2. Strandberg TE, Pyorala K, Cook TJ, et al: Mortality and incidence of cancer during 10-year follow-up of the Scandinavian Simvastatin Survival study (4S). Lancet 364:771-777, 2004 3. Downs JR, Clearfield M, Weis S, et al: Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: Results of AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study.

Cancer Prevention Research, 2011

Factors associated with an increased risk of breast cancer include prior breast cancer, high circ... more Factors associated with an increased risk of breast cancer include prior breast cancer, high circulating estrogens, and increased breast density. Adjuvant aromatase inhibitors are associated with a reduction in incidence of contralateral breast cancer. We conducted a prospective, single-arm, single-institution study to determine whether use of anastrozole is associated with changes in contralateral breast density and circulating estrogens. Eligible patients included postmenopausal women with hormone receptor-positive early-stage breast cancer who had completed local therapy, had an intact contralateral breast, and were recommended an aromatase inhibitor as their only systemic therapy. Participants received anastrozole 1 mg daily for 12 months on study. We assessed contralateral breast density and serum estrogens at baseline, 6, and 12 months. The primary endpoint was change in contralateral percent breast density from baseline to 12 months. Secondary endpoints included change in serum estrone sulfate from baseline to 12 months. Fifty-four patients were accrued. At 12 months, compared with baseline, there was a nonstatistically significant reduction in breast density (mean change: -16%, 95% CI: -30 to 2, P = 0.08) and a significant reduction in estrone sulfate (mean change: -93%, 95% CI: -94 to -91, P < 0.001). Eighteen women achieved 20% or greater relative reduction in contralateral percent density at 12 months compared with baseline; however, no measured patient or disease characteristics distinguished these women from the overall population. Large trials are required to provide additional data on the relationship between aromatase inhibitors and breast density and, more importantly, whether observed changes in breast density correlate with meaningful disease-specific outcomes.

Breast Cancer Research and Treatment, 2012

Observational studies have demonstrated a decreased incidence of cancers among users of HMG CoA r... more Observational studies have demonstrated a decreased incidence of cancers among users of HMG CoA reductase inhibitors (statins) and a reduced risk of recurrence among statin users diagnosed with early stage breast cancer. We initiated a prospective study to identify potential biomarkers of simvastatin chemopreventive activity that can be validated in future trials. The contralateral breast of women with a previous history of breast cancer was used as a high-risk model. Eligible women who had completed all planned treatment of a prior stage 0-III breast cancer received simvastatin 40 mg orally daily for 24-28 weeks. At baseline and end-of-study, we measured circulating concentrations of high-sensitivity C-reactive protein (hsCRP), estrogens, and fasting lipids; breast density on contralateral breast mammogram; and quality of life by Rand Short Form 36-Item health survey. Fifty women were enrolled with a median age of 53 years. Total cholesterol, LDL cholesterol, triglyceride, and hsCRP fell significantly during the study (P values < 0.001, <0.001, 0.003, and 0.05, respectively). Estrone sulfate concentrations decreased with simvastatin treatment (P = 0.01 overall), particularly among post-menopausal participants (P = 0.006). We did not observe a significant change in circulating estradiol or estrone concentrations, contralateral mammographic breast density, or reported physical functioning or pain scores. This study demonstrates the feasibility of short-term biomarker modulation studies using the contralateral breast of high-risk women. Simvastatin appears to modulate estrone sulfate concentrations and its potential chemopreventive activity in breast cancer warrants further investigation.

The Lancet, 2014

Pathological complete response has been proposed as a surrogate endpoint for prediction of long-t... more Pathological complete response has been proposed as a surrogate endpoint for prediction of long-term clinical benefit, such as disease-free survival, event-free survival (EFS), and overall survival (OS). We had four key objectives: to establish the association between pathological complete response and EFS and OS, to establish the definition of pathological complete response that correlates best with long-term outcome, to identify the breast cancer subtypes in which pathological complete response is best correlated with long-term outcome, and to assess whether an increase in frequency of pathological complete response between treatment groups predicts improved EFS and OS. We searched PubMed, Embase, and Medline for clinical trials of neoadjuvant treatment of breast cancer. To be eligible, studies had to meet three inclusion criteria: include at least 200 patients with primary breast cancer treated with preoperative chemotherapy followed by surgery; have available data for pathological complete response, EFS, and OS; and have a median follow-up of at least 3 years. We compared the three most commonly used definitions of pathological complete response--ypT0 ypN0, ypT0/is ypN0, and ypT0/is--for their association with EFS and OS in a responder analysis. We assessed the association between pathological complete response and EFS and OS in various subgroups. Finally, we did a trial-level analysis to assess whether pathological complete response could be used as a surrogate endpoint for EFS or OS. We obtained data from 12 identified international trials and 11 955 patients were included in our responder analysis. Eradication of tumour from both breast and lymph nodes (ypT0 ypN0 or ypT0/is ypN0) was better associated with improved EFS (ypT0 ypN0: hazard ratio [HR] 0·44, 95% CI 0·39-0·51; ypT0/is ypN0: 0·48, 0·43-0·54) and OS (0·36, 0·30-0·44; 0·36, 0·31-0·42) than was tumour eradication from the breast alone (ypT0/is; EFS: HR 0·60, 95% CI 0·55-0·66; OS 0·51, 0·45-0·58). We used the ypT0/is ypN0 definition for all subsequent analyses. The association between pathological complete response and long-term outcomes was strongest in patients with triple-negative breast cancer (EFS: HR 0·24, 95% CI 0·18-0·33; OS: 0·16, 0·11-0·25) and in those with HER2-positive, hormone-receptor-negative tumours who received trastuzumab (EFS: 0·15, 0·09-0·27; OS: 0·08, 0·03, 0·22). In the trial-level analysis, we recorded little association between increases in frequency of pathological complete response and EFS (R(2)=0·03, 95% CI 0·00-0·25) and OS (R(2)=0·24, 0·00-0·70). Patients who attain pathological complete response defined as ypT0 ypN0 or ypT0/is ypN0 have improved survival. The prognostic value is greatest in aggressive tumour subtypes. Our pooled analysis could not validate pathological complete response as a surrogate endpoint for improved EFS and OS. US Food and Drug Administration.