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The Influence Of Preoperative MRI On Breast Cancer Treatment
220
ASSOCIATION FOR ACADEMIC SURGERY AND SOCIETY OF UNIVERSITY SURGEONS—ABSTRACTS
21.10. Breast Cancer Histology And The Influence Of The Hormonal Milieu. J. R. Nitzkorski,1 F. Zhu,2 C. E. Loveland-Jones,3 L. Sesa,1 E. A. Ross,2 E. R. Sigurdson,1 R. J. Bleicher1; 1Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, PA; 2Department of Biostatistics, Fox Chase Cancer Center, Philadelphia, PA; 3 Department of Surgery, Temple University Hospital, Philadelphia, PA Introduction: Although greater exposure to endogenous hormones and to hormone replacement therapy (HRT) increases the risk of developing breast cancer, and HRT usage is associated with pathologic findings, little is known about the impact of differences in the length of HRT use and chronology of exposure on the innate characteristics of the primary tumor. Methods: A prospectively collected IRBapproved breast cancer database containing 4,257 breast cancer patients was retrospectively reviewed. Patients having oophorectomies were eliminated. Demographics, HRT usage and chronology, and menopausal status were reviewed. Innate primary tumor characteristics alone were correlated to avoid the confounders of screening differences, lead time, and length bias upon stage. Charts were rereviewed for the date of menarche and menopause. Total hormonal exposure (THX) was defined as the time from menarche to menopause plus any time on HRT. Results: There were 403 postmenopausal patients identified between 2004 and 2008, among whom 75.6% of tumors were ER positive (+), 61.5% PR+, and 22.1% high grade. HER2/neu was overexpressed on IHC in 18.6% of patients and invasive ductal and lobular carcinomas comprised 76.9% and 16.4% of cases, respectively. Median duration of endogenous hormonal (menarche to natural menopause) and HRT exposure was 38y and 5y, respectively. Median THX was 39y in both ER+ and ER- tumors (p¼0.58). HRT exposure was similar prior to developing primary tumors that were ER+ and ER- (4 and 5 years, respectively, p¼0.28). Univariate predictors of ER positivity included white race (p<0.0001), lobular histology (p<0.0001), and lack of HER2/neu overexpression (p<0.0001). ER-positive tumors were more likely to be present in patients having HRT when on HRT at diagnosis (p¼0.03). When adjusted for age and race, no differences were found in histology, ER positivity, PR positivity, grade and HER2/neu status based upon the duration of THX, or the duration of HRT. In contrast, in those using HRT, use at diagnosis predicted ER-positivity (p¼0.011) but not PR status, HER2/neu overexpression, grade, or histology. These factors were also not affected by an increasing duration between the end of THX and diagnosis, during which there was no hormonal exposure. Conclusion: Although longer hormonal exposure (natural or HRT) increases the risk of breast cancer development, the duration of THX, the duration of HRT, and the interval between hormonal exposure and cancer diagnosis did not affect the innate characteristics of the tumor. These findings may affect HRT decision making in those without breast cancer who have chosen to have HRT, and may assist in preoperative discussions with those who develop breast cancer regarding its impact upon the expected pathology.
ONCOLOGY 2: CLINICAL OUTCOMES & BIOMARKERS 22.1. The Influence Of Preoperative MRI On Breast Cancer Treatment. B. T. Miller, A. M. Abbott, T. M. Tuttle; Department of Surgery, University of Minnesota, Minneapolis, MN Introduction: The use of breast magnetic resonance imaging (MRI) for preoperative imaging and operation planning has been increasing. The aims of this study were to evaluate the rates of mastectomy and breast conserving surgery (BCS) in patients who undergo preoperative MRI for early stage breast cancer, and to determine patient and tumor characteristics that predicted treatment choice. Methods: We con-
ducted a retrospective review of 418 patients who underwent initial surgical treatment for breast cancer at the University of Minnesota Medical Center between 2002 and 2009. Exclusion criteria included: stage IV disease, previous breast cancer, lobular carcinoma in situ, Hodgkin’s lymphoma, or positive BRCA status.Univariate analysis was used to evaluate differences in patient demographics, surgical management, and tumor characteristics of women who received mastectomy compared to BCS. Multiple logistic regression was used to identify independent predictors for mastectomy. Results: Among the 418 patients that met inclusion criteria, 222 (53%) patients received preoperative MRI and 196 (47%) patients did not receive MRI. We found that patients who received MRI had higher rates of mastectomy than patients who did not have MRI (44% vs 29%; p¼0.001). Multivariate analysis of 406 patients with known estrogen receptor (ER) status revealed that tumor size, lymph node status, infiltrating lobular carcinoma, and pretreatment MRI were independent predictors for mastectomy (p<0.01) (Table). Patients who had an MRI were 1.78 times more likely to have a mastectomy than patients without an MRI (95% CI 1.13 to 2.79) Family history of breast cancer, ER status, and invasive (vs. noninvasive) carcinoma were not significantly predictive for mastectomy. Patients who had a preoperative MRI were more likely to have additional biopsies than patients who did not receive MRI (p<0.001), and MRI detected occult contralateral breast cancer in 2.7% of patients. Additionally, among patients treated with BCS, those with no preoperative MRI did not have higher re-excision rates or increased ipsilateral breast tumor recurrences than patients with preoperative MRI. Conclusion: The use of preoperative MRI significantly influences breast cancer treatment; we found that preoperative MRI was associated with higher rates of mastectomy, synchronous contralateral breast cancers, and additional breast biopsies.
TABLE Multivariate Logistic Regression Results for Predictors of Mastectomy
Family History Positive v negative Unknown v negative LN status Positive v negative ER status Negative v positive Tumor size <2 cm v 2-5 cm 2-5 cm v>5 cm MRI Yes v no Infiltrating carcinoma Yes v no ILC Yes v no
Odds Ratio
95% CI
P
1.4 0.7
0.9 to 2.3 0.1 to 6.6
0.17 0.75
2.5
1.5 to 4.2
<0.001
1.3
0.8 to 2.3
0.30
0.6 20.1
0.4 to 0.9 2.5 to 165
0.03 0.005
1.8
1.1 to 2.8
0.01
1.2
0.6 to 2.5
0.55
0.3
0.1 to 0.6
<0.001
Abbreviations: CI, confidence interval; LN, lymph node; ER, estrogen receptor; MRI, magnetic resonance imaging; ILC, infiltrating lobular carcinoma.
22.2. Is There a Molecular Basis for Cancer Gender Disparity? R. Rahbari, L. Zhang, E. Kebebew; National Cancer Institute, Bethesda, MD Introduction: Cancer gender disparity in incidence, disease aggressiveness, response to therapy, and prognosis has been observed for a variety of cancers, but the cause of the disparity is poorly understood. Thyroid cancer is one such cancer for which gender disparity in incidence, aggressiveness and prognosis is well established.
ASSOCIATION FOR ACADEMIC SURGERY AND SOCIETY OF UNIVERSITY SURGEONS—ABSTRACTS
21.10. Breast Cancer Histology And The Influence Of The Hormonal Milieu. J. R. Nitzkorski,1 F. Zhu,2 C. E. Loveland-Jones,3 L. Sesa,1 E. A. Ross,2 E. R. Sigurdson,1 R. J. Bleicher1; 1Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, PA; 2Department of Biostatistics, Fox Chase Cancer Center, Philadelphia, PA; 3 Department of Surgery, Temple University Hospital, Philadelphia, PA Introduction: Although greater exposure to endogenous hormones and to hormone replacement therapy (HRT) increases the risk of developing breast cancer, and HRT usage is associated with pathologic findings, little is known about the impact of differences in the length of HRT use and chronology of exposure on the innate characteristics of the primary tumor. Methods: A prospectively collected IRBapproved breast cancer database containing 4,257 breast cancer patients was retrospectively reviewed. Patients having oophorectomies were eliminated. Demographics, HRT usage and chronology, and menopausal status were reviewed. Innate primary tumor characteristics alone were correlated to avoid the confounders of screening differences, lead time, and length bias upon stage. Charts were rereviewed for the date of menarche and menopause. Total hormonal exposure (THX) was defined as the time from menarche to menopause plus any time on HRT. Results: There were 403 postmenopausal patients identified between 2004 and 2008, among whom 75.6% of tumors were ER positive (+), 61.5% PR+, and 22.1% high grade. HER2/neu was overexpressed on IHC in 18.6% of patients and invasive ductal and lobular carcinomas comprised 76.9% and 16.4% of cases, respectively. Median duration of endogenous hormonal (menarche to natural menopause) and HRT exposure was 38y and 5y, respectively. Median THX was 39y in both ER+ and ER- tumors (p¼0.58). HRT exposure was similar prior to developing primary tumors that were ER+ and ER- (4 and 5 years, respectively, p¼0.28). Univariate predictors of ER positivity included white race (p<0.0001), lobular histology (p<0.0001), and lack of HER2/neu overexpression (p<0.0001). ER-positive tumors were more likely to be present in patients having HRT when on HRT at diagnosis (p¼0.03). When adjusted for age and race, no differences were found in histology, ER positivity, PR positivity, grade and HER2/neu status based upon the duration of THX, or the duration of HRT. In contrast, in those using HRT, use at diagnosis predicted ER-positivity (p¼0.011) but not PR status, HER2/neu overexpression, grade, or histology. These factors were also not affected by an increasing duration between the end of THX and diagnosis, during which there was no hormonal exposure. Conclusion: Although longer hormonal exposure (natural or HRT) increases the risk of breast cancer development, the duration of THX, the duration of HRT, and the interval between hormonal exposure and cancer diagnosis did not affect the innate characteristics of the tumor. These findings may affect HRT decision making in those without breast cancer who have chosen to have HRT, and may assist in preoperative discussions with those who develop breast cancer regarding its impact upon the expected pathology.
ONCOLOGY 2: CLINICAL OUTCOMES & BIOMARKERS 22.1. The Influence Of Preoperative MRI On Breast Cancer Treatment. B. T. Miller, A. M. Abbott, T. M. Tuttle; Department of Surgery, University of Minnesota, Minneapolis, MN Introduction: The use of breast magnetic resonance imaging (MRI) for preoperative imaging and operation planning has been increasing. The aims of this study were to evaluate the rates of mastectomy and breast conserving surgery (BCS) in patients who undergo preoperative MRI for early stage breast cancer, and to determine patient and tumor characteristics that predicted treatment choice. Methods: We con-
ducted a retrospective review of 418 patients who underwent initial surgical treatment for breast cancer at the University of Minnesota Medical Center between 2002 and 2009. Exclusion criteria included: stage IV disease, previous breast cancer, lobular carcinoma in situ, Hodgkin’s lymphoma, or positive BRCA status.Univariate analysis was used to evaluate differences in patient demographics, surgical management, and tumor characteristics of women who received mastectomy compared to BCS. Multiple logistic regression was used to identify independent predictors for mastectomy. Results: Among the 418 patients that met inclusion criteria, 222 (53%) patients received preoperative MRI and 196 (47%) patients did not receive MRI. We found that patients who received MRI had higher rates of mastectomy than patients who did not have MRI (44% vs 29%; p¼0.001). Multivariate analysis of 406 patients with known estrogen receptor (ER) status revealed that tumor size, lymph node status, infiltrating lobular carcinoma, and pretreatment MRI were independent predictors for mastectomy (p<0.01) (Table). Patients who had an MRI were 1.78 times more likely to have a mastectomy than patients without an MRI (95% CI 1.13 to 2.79) Family history of breast cancer, ER status, and invasive (vs. noninvasive) carcinoma were not significantly predictive for mastectomy. Patients who had a preoperative MRI were more likely to have additional biopsies than patients who did not receive MRI (p<0.001), and MRI detected occult contralateral breast cancer in 2.7% of patients. Additionally, among patients treated with BCS, those with no preoperative MRI did not have higher re-excision rates or increased ipsilateral breast tumor recurrences than patients with preoperative MRI. Conclusion: The use of preoperative MRI significantly influences breast cancer treatment; we found that preoperative MRI was associated with higher rates of mastectomy, synchronous contralateral breast cancers, and additional breast biopsies.
TABLE Multivariate Logistic Regression Results for Predictors of Mastectomy
Family History Positive v negative Unknown v negative LN status Positive v negative ER status Negative v positive Tumor size <2 cm v 2-5 cm 2-5 cm v>5 cm MRI Yes v no Infiltrating carcinoma Yes v no ILC Yes v no
Odds Ratio
95% CI
P
1.4 0.7
0.9 to 2.3 0.1 to 6.6
0.17 0.75
2.5
1.5 to 4.2
<0.001
1.3
0.8 to 2.3
0.30
0.6 20.1
0.4 to 0.9 2.5 to 165
0.03 0.005
1.8
1.1 to 2.8
0.01
1.2
0.6 to 2.5
0.55
0.3
0.1 to 0.6
<0.001
Abbreviations: CI, confidence interval; LN, lymph node; ER, estrogen receptor; MRI, magnetic resonance imaging; ILC, infiltrating lobular carcinoma.
22.2. Is There a Molecular Basis for Cancer Gender Disparity? R. Rahbari, L. Zhang, E. Kebebew; National Cancer Institute, Bethesda, MD Introduction: Cancer gender disparity in incidence, disease aggressiveness, response to therapy, and prognosis has been observed for a variety of cancers, but the cause of the disparity is poorly understood. Thyroid cancer is one such cancer for which gender disparity in incidence, aggressiveness and prognosis is well established.