Rebecca Aft - Academia.edu (original) (raw)

Papers by Rebecca Aft

Research paper thumbnail of Therapeutic management of intracystic papillary carcinoma of the breast: the roles of radiation and endocrine therapy

The American Journal of Surgery, 2007

The role of radiation and endocrine therapy in the treatment of intracystic papillary carcinoma (... more The role of radiation and endocrine therapy in the treatment of intracystic papillary carcinoma (IPC) remains unclear. The aim of the current study was to review the management of IPC in order to determine factors associated with use of adjuvant therapies. Methods: A retrospective review of our surgical and pathology databases from 1995-2006 identified 45 women with IPC. These patients were further divided into those with pure IPC (n ϭ 21), IPC with associated ductal carcinoma in situ (DCIS) (n ϭ 18), and IPC with associated microinvasion with or without DCIS (n ϭ 6). Patient characteristics were compared between groups using the chi-square test. Results: Patients with IPC and microinvasion were more likely to undergo an axillary staging procedure (6/6, 100%) compared to patients with pure IPC (6/21, 29%) or IPC with DCIS (5/18, 28%) (P Ͻ .001). Patients with pure IPC were less likely to have radiation therapy than patients with IPC and DCIS or microinvasion (P Ͻ .001). However, within the subset of patients with pure IPC, women less than 50 years of age were more likely to have radiation therapy than those older than 50 years (P Ͻ .001). Patients with IPC and DCIS or microinvasion had significantly increased use of endocrine therapy versus patients with pure IPC (P Ͻ .01). Conclusions: In our patient population, those patients with IPC and associated DCIS or microinvasion are treated with adjuvant radiation and endocrine therapy on the basis of this associated pathology. The use of adjuvant radiation and/or endocrine therapy should be considered in patients with pure IPC who are of young age (Ͻ50 years).

Research paper thumbnail of Paired-like Homeodomain Transcription factor 2 expression by breast cancer bone marrow disseminated tumor cells is associated with early recurrent disease development

Breast cancer research and treatment, Jan 23, 2015

The presence of disseminated tumor cells (DTCs) in the bone marrow (BM) of breast cancer patients... more The presence of disseminated tumor cells (DTCs) in the bone marrow (BM) of breast cancer patients is prognostic for early relapse. In the present study, we analyzed the gene expression profiles from BM cells of breast cancer patients to identify molecular signatures associated with DTCs and their relevance to metastatic outcome. We analyzed BM from 30 patients with stage II/III breast cancer by gene expression profiling and correlated expression with metastatic disease development. A candidate gene, PITX2, was analyzed for expression and phenotype in breast cancer cell lines. PITX2 was knocked down in the MDAMB231 cell lines for gene expression analysis and cell invasiveness. Expression of various signaling pathway molecules was confirmed by RT-PCR. We found that the expression of Paired-like Homeobox Transcription factor-2 (PITX2) is absent in the BM of normal healthy volunteers and, when detected in the BM of breast cancer patients, is significantly correlated with early metastati...

Research paper thumbnail of Disparities related to socioeconomic status and access to medical care remain in the United States among women who never had a mammogram

Cancer causes & control : CCC, 2003

This study examined whether disparities in mammography use between women of differing socioeconom... more This study examined whether disparities in mammography use between women of differing socioeconomic status (SES; income and education) and varying access to medical care (healthcare insurance and routine medical check-up) remained over time despite overall increased breast cancer screening. Analysis of changes over time were made using data from the 1992, 1996, and 2000 Behavioral Risk Factor Surveillance System data from 53,846 women 50-69 years of age. Women who reported that they never had a mammogram were compared with those who ever had a mammogram. Multivariate logistic regression was used to determine whether and to what extent disparities between subgroups of women changed over time. The percentage of women 50-69 years of age who had never had a mammogram declined 65% from 22.1% in 1992 to 7.7% in 2000. Racial and ethnic differences in mammography prevalence disappeared over time. However, disparities among women of differing SES and among those with varying access to medica...

Research paper thumbnail of 2-Deoxy-D-glucose-induced cytotoxicity and radiosensitization in tumor cells is mediated via disruptions in thiol metabolism

Cancer research, Jan 15, 2003

Exposure to ionizing radiation is believed to cause cell injury via the production of free radica... more Exposure to ionizing radiation is believed to cause cell injury via the production of free radicals that are thought to induce oxidative damage. It has been proposed that exposure to agents that enhance oxidative stress-induced injury by disrupting thiol metabolism may sensitize cells to the cytotoxic effects of ionizing radiation. Recently, it has been shown that glucose deprivation selectively induces cell injury in transformed human cells via metabolic oxidative stress (J. Biol. Chem., 273: 5294-5299; Ann. N.Y. Acad. Sci., 899: 349-362), resulting in profound disruptions in thiol metabolism. Because 2-deoxy-D-glucose (2DG) is a potent inhibitor of glucose metabolism thought to mimic glucose deprivation in vivo, the hypothesis that exposure to 2DG might be capable of inducing radiosensitization in transformed cells via perturbations in thiol metabolism was tested. When HeLa cells were exposed to 2DG (4-10 mM) for 4-72 h, cell survival decreased (20-90%) in a dose- and time-depende...

Research paper thumbnail of Metastatic disease to the breast: the Washington University experience

World Journal of Surgical Oncology, 2007

Background: Metastases to the breast occur rarely, but may be increasing in incidence as patients... more Background: Metastases to the breast occur rarely, but may be increasing in incidence as patients live longer with malignant diseases. The aim of this study is to characterize metastatic disease to the breast and to describe the management and prognosis of patients who present with this diagnosis.

Research paper thumbnail of Estimated Effects of Potential Interventions to Prevent Decreases in Self-Rated Health Among Breast Cancer Survivors

Annals of Epidemiology, 2012

Purpose-To estimate the effect of hypothetical changes in modifiable predictors on the incidence ... more Purpose-To estimate the effect of hypothetical changes in modifiable predictors on the incidence of fair-poor self-rated health (SRH) in breast cancer survivors.

Research paper thumbnail of Predictors of Primary Breast Abscesses and Recurrence

World Journal of Surgery, 2009

Background We investigated the patients and microbiological risk factors that predispose to the d... more Background We investigated the patients and microbiological risk factors that predispose to the development of primary breast abscesses and subsequent recurrence. Methods Patients with a primary breast abscess requiring surgical therapy between January 1, 2000 and December 31, 2006 were reviewed. Recurrent breast abscess was defined by the need for repeated drainage within 6 months. Patient characteristics were compared to the general population and between groups. Results A total of 89 patients with a primary breast abscess were identified; 12 (14%) were lactational and 77 (86%) were nonlactational. None of the lactational abscesses recurred, whereas 43 (57%) of the nonlactational abscesses did so (P \ 0.01). Compared to the general population, patients with a primary breast abscess were predominantly African American (64% vs. 12%), had higher rates of obesity (body mass index [ 30: 43% vs. 22%), and were tobacco smokers (45% vs, 23%) (P \ 0.01 for all). The only factor significantly associated with recurrence in the multivariate logistic regression analysis was tobacco smoking (P = 0.003). Compared to patients who did not have a recurrence, patients with recurrent breast abscesses had a higher incidence of mixed bacteria (20.5% vs. 8.9%), anaerobes (4.5% vs. 0%), and Proteus (9.1% vs. 4.4%) but lower incidence of Staphylococcus (4.6% vs. 24.4%) (P \ 0.05 for each). Conclusions Risk factors for developing a primary breast abscess include African American race, obesity, and tobacco smoking. Patients with recurrent breast abscesses are more likely to be smokers and have mixed bacterial and anaerobic infections. Broader antibiotic coverage should be considered for the higher risk groups.

Research paper thumbnail of Predictors of complete pathological response after neoadjuvant systemic therapy for breast cancer

The American Journal of Surgery, 2009

BACKGROUND: The aim of the current study was to identify predictors of pathologic complete respon... more BACKGROUND: The aim of the current study was to identify predictors of pathologic complete response (pCR) following neoadjuvant therapy. METHODS: From 2000 to 2007, 518 breast cancer patients received neoadjuvant therapy. Data were compared using 2 and Fisher's exact tests and multivariate analysis of variance, as appropriate. RESULTS: Of 518 breast cancer patients receiving neoadjuvant therapy, 81 (16%) had pCR (77 of 456 [17%] with chemotherapy, 4 of 62 [6%]

Research paper thumbnail of Impact of neoadjuvant chemotherapy on rate of tissue expander/implant loss and progression to successful breast reconstruction following mastectomy

The American Journal of Surgery, 2008

PURPOSE: We examined the frequency and causes of tissue expander (TE) and permanent implant (PI) ... more PURPOSE: We examined the frequency and causes of tissue expander (TE) and permanent implant (PI) reconstruction failure in patients undergoing neoadjuvant chemotherapy.

Research paper thumbnail of Patterns of local breast cancer recurrence after skin-sparing mastectomy and immediate breast reconstruction

The American Journal of Surgery, 2007

Background: Local recurrence rates after skin-sparing mastectomy and immediate reconstruction are... more Background: Local recurrence rates after skin-sparing mastectomy and immediate reconstruction are similar to recurrence rates after conventional mastectomy. We investigated the pattern of local recurrences and risk factors associated with them. Methods: We identified 206 patients who underwent 210 skin-sparing mastectomies with immediate reconstruction from 1998 to 2006 in our database. Results: Eleven patients had local recurrences (5.3%). Nine developed in the quadrant of the corresponding primary tumor. There were no significant differences between patients who recurred and those who did not with respect to tumor size/stage, margin status, estrogen receptor/progesterone receptor/Her2neu status, lymph node metastases, or radiation therapy (P Ͼ .05). Patients with grade 3 invasive tumors or high-grade ductal carcinoma in situ were more likely to recur than patients with grade 1 or 2 invasive tumors or low-or intermediate-grade ductal carcinoma in situ (P ϭ .0035). Those patients who recurred had a significantly decreased overall survival compared to patients who did not recur (P ϭ .0006). Conclusions: Skin-sparing mastectomy and immediate reconstruction has a low local recurrence rate. Recurrences occur most commonly in the same quadrant as the primary tumor and treatment approaches include surgery, chemotherapy, and radiation therapy. Local recurrence portends a poorer overall survival.

Research paper thumbnail of Perioperative outcomes and complications of laparoscopic ventral hernia repair

Surgery, 2005

Laparoscopic techniques are being used increasingly in the repair of ventral hernias and offer th... more Laparoscopic techniques are being used increasingly in the repair of ventral hernias and offer the potential benefits of a shorter hospital stay, decreased wound complications, and possibly a lower recurrence rate. Despite good results from high-volume centers, significant complications may occur with this approach and the morbidity of incisional hernia repair may be underestimated. The purpose of this study was to review our experience with laparoscopic ventral hernia repair (LVHR) since its inception at our institution. Medical records of all patients who underwent LVHR at a single institution from May 2000 through December 2003 were reviewed. Preoperative and postoperative variables including complications were analyzed. Follow-up evaluation was by office visit and phone survey with assessment of patient satisfaction scores. Data are expressed as mean +/- SD. A total of 121 LVHR were performed in 116 patients (52 men, 64 women; mean age, 57 +/- 13 y; mean body mass index, 35 +/- 8). Hernias were recurrent in 35 cases (28.9%), with a mean of 1.4 prior repairs (range, 1-7). The mean defect size was 109 +/- 126 cm2 and the average mesh size used was 256 +/- 192 cm2. Operating time was 147 +/- 45 minutes, and the hospital stay averaged 1.7 +/- 1 days. Twelve cases (9.9%) were converted to open operation, most commonly because of extensive adhesions. Extensive laparoscopic adhesiolysis was necessary in 29 cases (26.6%). Overall, perioperative complications occurred in 33 cases (27.3%), 13 of which (39.3%) were persistent seromas. Major complications were seen in 9 cases (7.4%). There were 4 enterotomies (3.3%): 3 occurred as a result of adhesiolysis and 1 resulted from a trocar injury; 2 were detected intraoperatively and were converted to open operation and 2 presented postoperatively. One of these patients developed sepsis and died. Follow-up evaluation was available for 83.6% of cases at a mean interval of 22 +/- 16 months after repair. The hernia recurrence rate was 9.3% (9 cases) and was detected at a median of 6 months postoperatively. The overall patient satisfaction score was high at 4.3 +/- 1.1 (scale, 1-5). Laparoscopic repair is effective for the vast majority of patients with primary or recurrent ventral hernias and results in hernia recurrence rates of less than 10%, with high patient satisfaction scores. Although seroma is the most common complication, major morbidity occurred in 7.4% of the patients in our series. Enterotomy is the most common serious complication and may result in sepsis and death.

Research paper thumbnail of Genome remodelling in a basal-like breast cancer metastasis and xenograft

Nature, 2010

Using a paired-end sequencing strategy, we generated 130.7, 124.9, 111.8 and 149.2 billion base p... more Using a paired-end sequencing strategy, we generated 130.7, 124.9, 111.8 and 149.2 billion base pairs of sequence data from genomic DNA derived from blood, primary tumour, brain metastasis and *These authors contributed equally to this work.

Research paper thumbnail of Effect of zoledronic acid on disseminated tumour cells in women with locally advanced breast cancer: an open label, randomised, phase 2 trial

The Lancet Oncology, 2010

Treatment with bisphosphonates decreases bone loss and can increase disease-free survival in pati... more Treatment with bisphosphonates decreases bone loss and can increase disease-free survival in patients with breast cancer. The aim of our study was to assess the effect of zoledronic acid on clearance of disseminated tumour cells (DTCs) from the bone marrow in women undergoing neoadjuvant chemotherapy for breast cancer. Patients were recruited for this open-label, phase 2 randomised trial between March 17, 2003, and May 19, 2006, at a single centre. Eligible patients had clinical stage II-III (> or = T2 and/or > or = N1) newly diagnosed breast cancer, Eastern Cooperative Oncology Group performance status of 0 or 1, and normal cardiac, renal, and liver function. 120 women were randomly assigned, using allocation concealment, to receive 4 mg zoledronic acid intravenously every 3 weeks (n=60), or no zoledronic acid (n=60), for 1 year concomitant with four cycles of neoadjuvant epirubicin (75 mg/m(2)) plus docetaxel (75 mg/m(2)) and two cycles of adjuvant epirubicin plus docetaxel. The primary endpoint was the number of patients with detectable DTCs at 3 months. Final analysis was done 1 year after the last patient was enrolled. Analyses were done for all patients with available data at 3 months. This study is registered with ClinicalTrials.gov, number NCT00242203. Of the 120 patients initially enrolled, one withdrew after signing consent and one patient's baseline bone marrow was not available. Both of these patients were in the control group. At 3 months, 109 bone-marrow samples were available for analysis. In the zoledronic acid group, bone marrow was not collected from one patient because of disease…

Research paper thumbnail of Area-Level Poverty Is Associated with Greater Risk of Ambulatory–Care–Sensitive Hospitalizations in Older Breast Cancer Survivors

Journal of the American Geriatrics Society, 2000

Mario Schootman, Ph.D.

Research paper thumbnail of The impact of breast MRI on surgical decision-making: Are patients at risk for mastectomy?

Journal of Surgical Oncology, 2009

The goal of the current study was to determine whether MRI impacts multidisciplinary treatment pl... more The goal of the current study was to determine whether MRI impacts multidisciplinary treatment planning and if it leads to increased mastectomy rates. A retrospective review was conducted of 441 patients treated for breast cancer between January 2005 and May 2008 who underwent breast MRI. Data included number of additional findings and their imaging and pathologic work-up. This was analyzed to determine impact of MRI on treatment planning. Of 441 patients, 45% had > or =1 additional finding on MRI. Of 410 patients with complete records, 29% had changes in the treatment plan, including 36 patients who were initially considered for breast conservation but proceeded directly to mastectomy based on MRI findings of suspected multicentricity. Twenty-three of those patients did not have a biopsy of the MRI lesion, with 87% having unicentric disease on final pathology. Overall, the mastectomy rate was 44%, which was significantly increased compared to patients not undergoing MRI (32%, P < 0.05). Breast MRI alters the treatment planning for many patients with newly diagnosed breast cancer. Mastectomy rates are increased when MRI results alone direct surgical planning. Biopsy of MRI-identified lesions should be performed to avoid over-treatment.

Research paper thumbnail of Patient and tumor characteristics associated with increased mortality in young women (≤40 years) with breast cancer

Journal of Surgical Oncology, 2009

The goal of the current study is to identify predictors responsible for mortality disparities bet... more The goal of the current study is to identify predictors responsible for mortality disparities between young (< or =40 years) and older (>40 years) women with breast cancer. From 1998 to 2006, 344 patients < or =40 years were treated for breast cancer. Cox regression models calculated adjusted hazard ratios (aHR) and 95% confidence intervals (CI) to determine differences in breast cancer mortality in women < or =40 years versus >40 years (n = 3,252), controlling for potential confounders in univariate tests. From 1998 to 2006, 3,596 patients were treated for breast cancer; 9.6% were < or =40 years and 90.4% were >40 years. Young women were more likely to be African-American, with a family history of breast cancer, diagnosed at advanced stage, and treated by mastectomy (P < 0.05). Tumors in young women were more likely to be bilateral, T2/T3, grade III, ER/PR negative, and lymph-node positive (P < 0.01). Overall, young women (< or =40 years) with breast cancer were more likely to die compared with older women (>40 years) (aHR 1.52, CI 1.37-1.74). Young women (< or =40 years) with breast cancer are diagnosed at a more advanced stage and have tumors with poor prognostic features. Young women (< or =40 years) are 52% more likely to die from breast cancer compared to older women (>40 years).

Research paper thumbnail of Self-report by elderly breast cancer patients was an acceptable alternative to surveillance, epidemiology, and end results (SEER) abstract data

Journal of Clinical Epidemiology, 2005

Background and Objectives: The purpose of this study was to compare breast cancer patients' self-... more Background and Objectives: The purpose of this study was to compare breast cancer patients' self-report and surveillance, epidemiology, and end results (SEER) abstract data regarding type of treatment received (radiation, chemotherapy, and hormonal therapies).

Research paper thumbnail of Could targeting bone delay cancer progression? Potential mechanisms of action of bisphosphonates

Critical Reviews in Oncology/Hematology, 2012

Although dissemination may occur early in the course of many cancers, the development of overt me... more Although dissemination may occur early in the course of many cancers, the development of overt metastases depends upon a variety of factors inherent to the cancer cells and the tissue(s) they colonize. The time lag between initial dissemination and established metastases could be several years, during which period the bone marrow may provide an unwitting sanctuary for disseminated tumor cells (DTCs). Survival in a dormant state within the bone marrow may help DTCs weather the effects of anticancer therapies and seed posttreatment relapses. The importance of the bone marrow for facilitating DTC survival may vary depending on the type of cancer and mechanisms of tumor cell dissemination. By altering the bone microenvironment, bisphosphonates may reduce DTC viability. Moreover, some bisphosphonates have demonstrated multiple anticancer activities. These multiple mechanisms may help explain the improvement in disease outcomes with the use of zoledronic acid in malignancies like breast cancer and multiple myeloma.

Research paper thumbnail of Isolation and Molecular Profiling of Bone Marrow Micrometastases Identifies TWIST1 as a Marker of Early Tumor Relapse in Breast Cancer Patients

Clinical Cancer Research, 2007

Purpose-Micrometastatic cells detected in the bone marrow have prognostic significance in breast ... more Purpose-Micrometastatic cells detected in the bone marrow have prognostic significance in breast cancer. These cells are heterogeneous and likely do not exhibit uniform biological behavior. To understand the molecular diversity of disseminated cancer cells that reside in bone marrow, we enriched this cell population and did global gene expression profiling in the context of a prospective clinical trial involving women with clinical stage II/III breast cancer undergoing neoadjuvant chemotherapy.

Research paper thumbnail of National estimates of racial disparities in health status and behavioral risk factors among long-term cancer survivors and non-cancer controls

Cancer Causes & Control, 2010

Objective-We examined racial disparities (White, African American, and other race) in health stat... more Objective-We examined racial disparities (White, African American, and other race) in health status (self-rated health, lower-body functional limitations, psychological distress, and body mass index [BMI]) and behaviors (smoking, alcohol use, and physical activity) of long-term cancer survivors (≥5 years) when compared to non-cancer controls.

Research paper thumbnail of Therapeutic management of intracystic papillary carcinoma of the breast: the roles of radiation and endocrine therapy

The American Journal of Surgery, 2007

The role of radiation and endocrine therapy in the treatment of intracystic papillary carcinoma (... more The role of radiation and endocrine therapy in the treatment of intracystic papillary carcinoma (IPC) remains unclear. The aim of the current study was to review the management of IPC in order to determine factors associated with use of adjuvant therapies. Methods: A retrospective review of our surgical and pathology databases from 1995-2006 identified 45 women with IPC. These patients were further divided into those with pure IPC (n ϭ 21), IPC with associated ductal carcinoma in situ (DCIS) (n ϭ 18), and IPC with associated microinvasion with or without DCIS (n ϭ 6). Patient characteristics were compared between groups using the chi-square test. Results: Patients with IPC and microinvasion were more likely to undergo an axillary staging procedure (6/6, 100%) compared to patients with pure IPC (6/21, 29%) or IPC with DCIS (5/18, 28%) (P Ͻ .001). Patients with pure IPC were less likely to have radiation therapy than patients with IPC and DCIS or microinvasion (P Ͻ .001). However, within the subset of patients with pure IPC, women less than 50 years of age were more likely to have radiation therapy than those older than 50 years (P Ͻ .001). Patients with IPC and DCIS or microinvasion had significantly increased use of endocrine therapy versus patients with pure IPC (P Ͻ .01). Conclusions: In our patient population, those patients with IPC and associated DCIS or microinvasion are treated with adjuvant radiation and endocrine therapy on the basis of this associated pathology. The use of adjuvant radiation and/or endocrine therapy should be considered in patients with pure IPC who are of young age (Ͻ50 years).

Research paper thumbnail of Paired-like Homeodomain Transcription factor 2 expression by breast cancer bone marrow disseminated tumor cells is associated with early recurrent disease development

Breast cancer research and treatment, Jan 23, 2015

The presence of disseminated tumor cells (DTCs) in the bone marrow (BM) of breast cancer patients... more The presence of disseminated tumor cells (DTCs) in the bone marrow (BM) of breast cancer patients is prognostic for early relapse. In the present study, we analyzed the gene expression profiles from BM cells of breast cancer patients to identify molecular signatures associated with DTCs and their relevance to metastatic outcome. We analyzed BM from 30 patients with stage II/III breast cancer by gene expression profiling and correlated expression with metastatic disease development. A candidate gene, PITX2, was analyzed for expression and phenotype in breast cancer cell lines. PITX2 was knocked down in the MDAMB231 cell lines for gene expression analysis and cell invasiveness. Expression of various signaling pathway molecules was confirmed by RT-PCR. We found that the expression of Paired-like Homeobox Transcription factor-2 (PITX2) is absent in the BM of normal healthy volunteers and, when detected in the BM of breast cancer patients, is significantly correlated with early metastati...

Research paper thumbnail of Disparities related to socioeconomic status and access to medical care remain in the United States among women who never had a mammogram

Cancer causes & control : CCC, 2003

This study examined whether disparities in mammography use between women of differing socioeconom... more This study examined whether disparities in mammography use between women of differing socioeconomic status (SES; income and education) and varying access to medical care (healthcare insurance and routine medical check-up) remained over time despite overall increased breast cancer screening. Analysis of changes over time were made using data from the 1992, 1996, and 2000 Behavioral Risk Factor Surveillance System data from 53,846 women 50-69 years of age. Women who reported that they never had a mammogram were compared with those who ever had a mammogram. Multivariate logistic regression was used to determine whether and to what extent disparities between subgroups of women changed over time. The percentage of women 50-69 years of age who had never had a mammogram declined 65% from 22.1% in 1992 to 7.7% in 2000. Racial and ethnic differences in mammography prevalence disappeared over time. However, disparities among women of differing SES and among those with varying access to medica...

Research paper thumbnail of 2-Deoxy-D-glucose-induced cytotoxicity and radiosensitization in tumor cells is mediated via disruptions in thiol metabolism

Cancer research, Jan 15, 2003

Exposure to ionizing radiation is believed to cause cell injury via the production of free radica... more Exposure to ionizing radiation is believed to cause cell injury via the production of free radicals that are thought to induce oxidative damage. It has been proposed that exposure to agents that enhance oxidative stress-induced injury by disrupting thiol metabolism may sensitize cells to the cytotoxic effects of ionizing radiation. Recently, it has been shown that glucose deprivation selectively induces cell injury in transformed human cells via metabolic oxidative stress (J. Biol. Chem., 273: 5294-5299; Ann. N.Y. Acad. Sci., 899: 349-362), resulting in profound disruptions in thiol metabolism. Because 2-deoxy-D-glucose (2DG) is a potent inhibitor of glucose metabolism thought to mimic glucose deprivation in vivo, the hypothesis that exposure to 2DG might be capable of inducing radiosensitization in transformed cells via perturbations in thiol metabolism was tested. When HeLa cells were exposed to 2DG (4-10 mM) for 4-72 h, cell survival decreased (20-90%) in a dose- and time-depende...

Research paper thumbnail of Metastatic disease to the breast: the Washington University experience

World Journal of Surgical Oncology, 2007

Background: Metastases to the breast occur rarely, but may be increasing in incidence as patients... more Background: Metastases to the breast occur rarely, but may be increasing in incidence as patients live longer with malignant diseases. The aim of this study is to characterize metastatic disease to the breast and to describe the management and prognosis of patients who present with this diagnosis.

Research paper thumbnail of Estimated Effects of Potential Interventions to Prevent Decreases in Self-Rated Health Among Breast Cancer Survivors

Annals of Epidemiology, 2012

Purpose-To estimate the effect of hypothetical changes in modifiable predictors on the incidence ... more Purpose-To estimate the effect of hypothetical changes in modifiable predictors on the incidence of fair-poor self-rated health (SRH) in breast cancer survivors.

Research paper thumbnail of Predictors of Primary Breast Abscesses and Recurrence

World Journal of Surgery, 2009

Background We investigated the patients and microbiological risk factors that predispose to the d... more Background We investigated the patients and microbiological risk factors that predispose to the development of primary breast abscesses and subsequent recurrence. Methods Patients with a primary breast abscess requiring surgical therapy between January 1, 2000 and December 31, 2006 were reviewed. Recurrent breast abscess was defined by the need for repeated drainage within 6 months. Patient characteristics were compared to the general population and between groups. Results A total of 89 patients with a primary breast abscess were identified; 12 (14%) were lactational and 77 (86%) were nonlactational. None of the lactational abscesses recurred, whereas 43 (57%) of the nonlactational abscesses did so (P \ 0.01). Compared to the general population, patients with a primary breast abscess were predominantly African American (64% vs. 12%), had higher rates of obesity (body mass index [ 30: 43% vs. 22%), and were tobacco smokers (45% vs, 23%) (P \ 0.01 for all). The only factor significantly associated with recurrence in the multivariate logistic regression analysis was tobacco smoking (P = 0.003). Compared to patients who did not have a recurrence, patients with recurrent breast abscesses had a higher incidence of mixed bacteria (20.5% vs. 8.9%), anaerobes (4.5% vs. 0%), and Proteus (9.1% vs. 4.4%) but lower incidence of Staphylococcus (4.6% vs. 24.4%) (P \ 0.05 for each). Conclusions Risk factors for developing a primary breast abscess include African American race, obesity, and tobacco smoking. Patients with recurrent breast abscesses are more likely to be smokers and have mixed bacterial and anaerobic infections. Broader antibiotic coverage should be considered for the higher risk groups.

Research paper thumbnail of Predictors of complete pathological response after neoadjuvant systemic therapy for breast cancer

The American Journal of Surgery, 2009

BACKGROUND: The aim of the current study was to identify predictors of pathologic complete respon... more BACKGROUND: The aim of the current study was to identify predictors of pathologic complete response (pCR) following neoadjuvant therapy. METHODS: From 2000 to 2007, 518 breast cancer patients received neoadjuvant therapy. Data were compared using 2 and Fisher's exact tests and multivariate analysis of variance, as appropriate. RESULTS: Of 518 breast cancer patients receiving neoadjuvant therapy, 81 (16%) had pCR (77 of 456 [17%] with chemotherapy, 4 of 62 [6%]

Research paper thumbnail of Impact of neoadjuvant chemotherapy on rate of tissue expander/implant loss and progression to successful breast reconstruction following mastectomy

The American Journal of Surgery, 2008

PURPOSE: We examined the frequency and causes of tissue expander (TE) and permanent implant (PI) ... more PURPOSE: We examined the frequency and causes of tissue expander (TE) and permanent implant (PI) reconstruction failure in patients undergoing neoadjuvant chemotherapy.

Research paper thumbnail of Patterns of local breast cancer recurrence after skin-sparing mastectomy and immediate breast reconstruction

The American Journal of Surgery, 2007

Background: Local recurrence rates after skin-sparing mastectomy and immediate reconstruction are... more Background: Local recurrence rates after skin-sparing mastectomy and immediate reconstruction are similar to recurrence rates after conventional mastectomy. We investigated the pattern of local recurrences and risk factors associated with them. Methods: We identified 206 patients who underwent 210 skin-sparing mastectomies with immediate reconstruction from 1998 to 2006 in our database. Results: Eleven patients had local recurrences (5.3%). Nine developed in the quadrant of the corresponding primary tumor. There were no significant differences between patients who recurred and those who did not with respect to tumor size/stage, margin status, estrogen receptor/progesterone receptor/Her2neu status, lymph node metastases, or radiation therapy (P Ͼ .05). Patients with grade 3 invasive tumors or high-grade ductal carcinoma in situ were more likely to recur than patients with grade 1 or 2 invasive tumors or low-or intermediate-grade ductal carcinoma in situ (P ϭ .0035). Those patients who recurred had a significantly decreased overall survival compared to patients who did not recur (P ϭ .0006). Conclusions: Skin-sparing mastectomy and immediate reconstruction has a low local recurrence rate. Recurrences occur most commonly in the same quadrant as the primary tumor and treatment approaches include surgery, chemotherapy, and radiation therapy. Local recurrence portends a poorer overall survival.

Research paper thumbnail of Perioperative outcomes and complications of laparoscopic ventral hernia repair

Surgery, 2005

Laparoscopic techniques are being used increasingly in the repair of ventral hernias and offer th... more Laparoscopic techniques are being used increasingly in the repair of ventral hernias and offer the potential benefits of a shorter hospital stay, decreased wound complications, and possibly a lower recurrence rate. Despite good results from high-volume centers, significant complications may occur with this approach and the morbidity of incisional hernia repair may be underestimated. The purpose of this study was to review our experience with laparoscopic ventral hernia repair (LVHR) since its inception at our institution. Medical records of all patients who underwent LVHR at a single institution from May 2000 through December 2003 were reviewed. Preoperative and postoperative variables including complications were analyzed. Follow-up evaluation was by office visit and phone survey with assessment of patient satisfaction scores. Data are expressed as mean +/- SD. A total of 121 LVHR were performed in 116 patients (52 men, 64 women; mean age, 57 +/- 13 y; mean body mass index, 35 +/- 8). Hernias were recurrent in 35 cases (28.9%), with a mean of 1.4 prior repairs (range, 1-7). The mean defect size was 109 +/- 126 cm2 and the average mesh size used was 256 +/- 192 cm2. Operating time was 147 +/- 45 minutes, and the hospital stay averaged 1.7 +/- 1 days. Twelve cases (9.9%) were converted to open operation, most commonly because of extensive adhesions. Extensive laparoscopic adhesiolysis was necessary in 29 cases (26.6%). Overall, perioperative complications occurred in 33 cases (27.3%), 13 of which (39.3%) were persistent seromas. Major complications were seen in 9 cases (7.4%). There were 4 enterotomies (3.3%): 3 occurred as a result of adhesiolysis and 1 resulted from a trocar injury; 2 were detected intraoperatively and were converted to open operation and 2 presented postoperatively. One of these patients developed sepsis and died. Follow-up evaluation was available for 83.6% of cases at a mean interval of 22 +/- 16 months after repair. The hernia recurrence rate was 9.3% (9 cases) and was detected at a median of 6 months postoperatively. The overall patient satisfaction score was high at 4.3 +/- 1.1 (scale, 1-5). Laparoscopic repair is effective for the vast majority of patients with primary or recurrent ventral hernias and results in hernia recurrence rates of less than 10%, with high patient satisfaction scores. Although seroma is the most common complication, major morbidity occurred in 7.4% of the patients in our series. Enterotomy is the most common serious complication and may result in sepsis and death.

Research paper thumbnail of Genome remodelling in a basal-like breast cancer metastasis and xenograft

Nature, 2010

Using a paired-end sequencing strategy, we generated 130.7, 124.9, 111.8 and 149.2 billion base p... more Using a paired-end sequencing strategy, we generated 130.7, 124.9, 111.8 and 149.2 billion base pairs of sequence data from genomic DNA derived from blood, primary tumour, brain metastasis and *These authors contributed equally to this work.

Research paper thumbnail of Effect of zoledronic acid on disseminated tumour cells in women with locally advanced breast cancer: an open label, randomised, phase 2 trial

The Lancet Oncology, 2010

Treatment with bisphosphonates decreases bone loss and can increase disease-free survival in pati... more Treatment with bisphosphonates decreases bone loss and can increase disease-free survival in patients with breast cancer. The aim of our study was to assess the effect of zoledronic acid on clearance of disseminated tumour cells (DTCs) from the bone marrow in women undergoing neoadjuvant chemotherapy for breast cancer. Patients were recruited for this open-label, phase 2 randomised trial between March 17, 2003, and May 19, 2006, at a single centre. Eligible patients had clinical stage II-III (> or = T2 and/or > or = N1) newly diagnosed breast cancer, Eastern Cooperative Oncology Group performance status of 0 or 1, and normal cardiac, renal, and liver function. 120 women were randomly assigned, using allocation concealment, to receive 4 mg zoledronic acid intravenously every 3 weeks (n=60), or no zoledronic acid (n=60), for 1 year concomitant with four cycles of neoadjuvant epirubicin (75 mg/m(2)) plus docetaxel (75 mg/m(2)) and two cycles of adjuvant epirubicin plus docetaxel. The primary endpoint was the number of patients with detectable DTCs at 3 months. Final analysis was done 1 year after the last patient was enrolled. Analyses were done for all patients with available data at 3 months. This study is registered with ClinicalTrials.gov, number NCT00242203. Of the 120 patients initially enrolled, one withdrew after signing consent and one patient's baseline bone marrow was not available. Both of these patients were in the control group. At 3 months, 109 bone-marrow samples were available for analysis. In the zoledronic acid group, bone marrow was not collected from one patient because of disease…

Research paper thumbnail of Area-Level Poverty Is Associated with Greater Risk of Ambulatory–Care–Sensitive Hospitalizations in Older Breast Cancer Survivors

Journal of the American Geriatrics Society, 2000

Mario Schootman, Ph.D.

Research paper thumbnail of The impact of breast MRI on surgical decision-making: Are patients at risk for mastectomy?

Journal of Surgical Oncology, 2009

The goal of the current study was to determine whether MRI impacts multidisciplinary treatment pl... more The goal of the current study was to determine whether MRI impacts multidisciplinary treatment planning and if it leads to increased mastectomy rates. A retrospective review was conducted of 441 patients treated for breast cancer between January 2005 and May 2008 who underwent breast MRI. Data included number of additional findings and their imaging and pathologic work-up. This was analyzed to determine impact of MRI on treatment planning. Of 441 patients, 45% had > or =1 additional finding on MRI. Of 410 patients with complete records, 29% had changes in the treatment plan, including 36 patients who were initially considered for breast conservation but proceeded directly to mastectomy based on MRI findings of suspected multicentricity. Twenty-three of those patients did not have a biopsy of the MRI lesion, with 87% having unicentric disease on final pathology. Overall, the mastectomy rate was 44%, which was significantly increased compared to patients not undergoing MRI (32%, P < 0.05). Breast MRI alters the treatment planning for many patients with newly diagnosed breast cancer. Mastectomy rates are increased when MRI results alone direct surgical planning. Biopsy of MRI-identified lesions should be performed to avoid over-treatment.

Research paper thumbnail of Patient and tumor characteristics associated with increased mortality in young women (≤40 years) with breast cancer

Journal of Surgical Oncology, 2009

The goal of the current study is to identify predictors responsible for mortality disparities bet... more The goal of the current study is to identify predictors responsible for mortality disparities between young (< or =40 years) and older (>40 years) women with breast cancer. From 1998 to 2006, 344 patients < or =40 years were treated for breast cancer. Cox regression models calculated adjusted hazard ratios (aHR) and 95% confidence intervals (CI) to determine differences in breast cancer mortality in women < or =40 years versus >40 years (n = 3,252), controlling for potential confounders in univariate tests. From 1998 to 2006, 3,596 patients were treated for breast cancer; 9.6% were < or =40 years and 90.4% were >40 years. Young women were more likely to be African-American, with a family history of breast cancer, diagnosed at advanced stage, and treated by mastectomy (P < 0.05). Tumors in young women were more likely to be bilateral, T2/T3, grade III, ER/PR negative, and lymph-node positive (P < 0.01). Overall, young women (< or =40 years) with breast cancer were more likely to die compared with older women (>40 years) (aHR 1.52, CI 1.37-1.74). Young women (< or =40 years) with breast cancer are diagnosed at a more advanced stage and have tumors with poor prognostic features. Young women (< or =40 years) are 52% more likely to die from breast cancer compared to older women (>40 years).

Research paper thumbnail of Self-report by elderly breast cancer patients was an acceptable alternative to surveillance, epidemiology, and end results (SEER) abstract data

Journal of Clinical Epidemiology, 2005

Background and Objectives: The purpose of this study was to compare breast cancer patients' self-... more Background and Objectives: The purpose of this study was to compare breast cancer patients' self-report and surveillance, epidemiology, and end results (SEER) abstract data regarding type of treatment received (radiation, chemotherapy, and hormonal therapies).

Research paper thumbnail of Could targeting bone delay cancer progression? Potential mechanisms of action of bisphosphonates

Critical Reviews in Oncology/Hematology, 2012

Although dissemination may occur early in the course of many cancers, the development of overt me... more Although dissemination may occur early in the course of many cancers, the development of overt metastases depends upon a variety of factors inherent to the cancer cells and the tissue(s) they colonize. The time lag between initial dissemination and established metastases could be several years, during which period the bone marrow may provide an unwitting sanctuary for disseminated tumor cells (DTCs). Survival in a dormant state within the bone marrow may help DTCs weather the effects of anticancer therapies and seed posttreatment relapses. The importance of the bone marrow for facilitating DTC survival may vary depending on the type of cancer and mechanisms of tumor cell dissemination. By altering the bone microenvironment, bisphosphonates may reduce DTC viability. Moreover, some bisphosphonates have demonstrated multiple anticancer activities. These multiple mechanisms may help explain the improvement in disease outcomes with the use of zoledronic acid in malignancies like breast cancer and multiple myeloma.

Research paper thumbnail of Isolation and Molecular Profiling of Bone Marrow Micrometastases Identifies TWIST1 as a Marker of Early Tumor Relapse in Breast Cancer Patients

Clinical Cancer Research, 2007

Purpose-Micrometastatic cells detected in the bone marrow have prognostic significance in breast ... more Purpose-Micrometastatic cells detected in the bone marrow have prognostic significance in breast cancer. These cells are heterogeneous and likely do not exhibit uniform biological behavior. To understand the molecular diversity of disseminated cancer cells that reside in bone marrow, we enriched this cell population and did global gene expression profiling in the context of a prospective clinical trial involving women with clinical stage II/III breast cancer undergoing neoadjuvant chemotherapy.

Research paper thumbnail of National estimates of racial disparities in health status and behavioral risk factors among long-term cancer survivors and non-cancer controls

Cancer Causes & Control, 2010

Objective-We examined racial disparities (White, African American, and other race) in health stat... more Objective-We examined racial disparities (White, African American, and other race) in health status (self-rated health, lower-body functional limitations, psychological distress, and body mass index [BMI]) and behaviors (smoking, alcohol use, and physical activity) of long-term cancer survivors (≥5 years) when compared to non-cancer controls.