Faculty Bibliography

UNLABELLED:The presence of estrogen receptor (ER) in breast cancer is a prognostic indicator for both disease-free and overall survival. 16α-(18)F-fluoro-17β-estradiol ((18)F-FES) with PET is a noninvasive test for evaluation of ER expression and has been used for predicting response to endocrine therapy in patients with ER-positive metastatic breast cancer. The purpose of this study was to correlate (18)F-FES PET and ER expression in patients with primary, operable breast cancer. METHODS:Forty-eight patients were prospectively enrolled in an institutional review board-approved protocol and signed an informed consent form. All patients had undergone (18)F-FES PET preoperatively. Clinical characteristics, tumor characteristics, and treatment outcomes were recorded. Immunohistochemical analysis for ER and progesterone receptor (PgR) percentage expression (46 surgical, 2 core biopsy specimens) was performed. (18)F-FES PET standardized uptake value (SUV) of the breast lesion was correlated with percentage immunohistochemistry ER and PgR expression. (18)F-FES PET SUV was quantified, with a value of 1.5 or more considered positive, and ER and PgR was quantified, with 1% or more considered positive. Formalin-fixed paraffin-embedded tissue was available for 44 patients (42 surgical, 2 core biopsy specimens). We used a microarray platform, and estrogen-related gene expression data (ESR1, ESR2, and PGR) were compared with (18)F-FES PET SUV (Spearman rank correlation). Tumor size, ductal histology, grade, HER2-neu overexpression, PgR expression, estradiol level, body mass index (BMI), and lean BMI were compared with (18)F-FES PET uptake using univariate and multivariate analysis. RESULTS:Forty-eight patients completed our protocol, and 2 patients did not undergo surgery because bone metastases were identified preoperatively on (18)F-FES PET. Eighty-three percent of our patients were stage I or II, with a median tumor size of 1.9 cm. Forty-one patients underwent a sentinel node biopsy. Twenty-one patients had nodal involvement. (18)F-FES PET identified 5 patients with axillary nodal uptake (median SUV, 3.0; range, 1.7-6.9). These 5 patients had ER-positive breast cancer, and all had more than 4 positive nodes at the time of axillary node dissection. (18)F-FES PET SUV was associated with immunohistochemistry ER expression. The sensitivity and specificity of the (18)F-FES PET for the breast lesion were 0.85 and 0.75, respectively. Estrogen and progesterone gene expression (ESR1, ESR2, and PGR) was not associated with (18)F-FES PET SUV (Spearman rank correlation). We found a significant correlation between (18)F-FES PET SUV and tumor size (P = 0.0015) but not with ductal histology, grade, HER2-neu overexpression, PgR, estradiol, BMI, or lean BMI (logistic regression). ER expression (P < 0.001) and tumor size (P < 0.0001) were significant on multivariate regression analysis. CONCLUSION/CONCLUSIONS:(18)F-FES PET SUV correlated with ER immunohistochemistry expression but not gene expression in our patients with early breast cancer. We found that size of primary tumor was significantly associated with (18)F-FES PET SUV. (18)F-FES PET is highly predictive for metastatic disease and helped in the identification of patients with metastatic disease in a preoperative setting.

BACKGROUND:Pregnancy-associated breast cancer (PABC) may be defined as breast cancer diagnosed during pregnancy or within 1 year of giving birth. Conflicting data exist regarding the impact of pregnancy on clinical features and prognosis of breast cancer. METHODS:A single-institution retrospective chart review was performed of 99 patients identified with PABC between 1992 and 2007. Non-PABC controls were matched 2:1 to PABC cases by year of diagnosis and age. The differences in clinical features were compared between cases and controls using chi-square tests. Univariate and multivariate analyses were performed to assess the effect of PABC on survival. RESULTS:Of the 99 PABC cases, breast cancer was diagnosed during pregnancy in 36 patients, and after delivery in 63. PABC cases were more likely than controls to be negative for estrogen receptor (59% vs 31%, P < .0001) and negative for progesterone receptor (72% vs 40%, P < .0001). Cases were also more likely to have advanced T class (P = .0271) and N class (P = .0104) and higher grade tumors (P = .0115). With a median follow-up of 6.3 years for cases and 4.7 years for controls, overall survival did not differ between cases and controls (P = .0787). On multivariate analysis, the independent prognostic factors for overall survival were estrogen receptor status (P = .0031) and N class (P = .0003). The diagnosis of PABC was not an independent prognostic factor (P = .1317). CONCLUSIONS:PABC is associated with more adverse tumor features than non-PABC matched for age and year of diagnosis. After correcting for pathologic features, the diagnosis of PABC is not in itself an adverse prognostic factor for survival.

BACKGROUND:Older women are less likely to receive standard of care treatment for breast cancer. METHODS:We examined variables that affected the outcome of elderly patients ≥70 years old among 1,470 patients with invasive cancer with positive sentinel lymph nodes (SLNs). RESULTS:Elderly patients were less likely to undergo mastectomy, completion axillary node dissection (ALND), adjuvant chemotherapy, and radiotherapy (RT) following breast-conserving therapy (BCT) compared with patients <70 years old. The 5-year risk of disease progression and cumulative incidence of breast cancer-specific deaths were not significantly different for both groups. On multivariate analysis, hormone receptor-negative status, number of metastatic lymph nodes, high nuclear grade, and tumor size were the factors independently associated with increased risk of disease progression. CONCLUSIONS:Tumor factors were the primary determinants of breast cancer outcomes in our cohort. Elderly patients are less likely to receive aggressive surgical interventions and adjuvant therapy because of perceived life expectancy.

This article focuses on breast cancer screening in the general population. Using an evidence-based medicine approach, a review of the current literature was undertaken to examine the rationale, risks, and benefits of breast cancer screening. The focus of breast cancer screening is to reduce disease mortality. However, there are additional benefits that are afforded by early detection, such as an early stage of diagnosis and a greater chance of having negative lymph nodes. Currently, we believe mammography offers significant benefits for breast cancer detection and mortality reduction in the general population. Further research is necessary on methods to minimize false-positive results.

OBJECTIVES/OBJECTIVE:We aimed to determine the sentinel lymph node detection rates, accuracy in predicting the status of lymph node metastasis, and if pathologic ultrastaging improves the detection of micrometastases and isolated tumor cells at the time of primary surgery for cervical cancer. METHODS:A prospective, non-randomized study of women with early-stage (FIGO stage IA1 with lymphovascular space involvement--IIA) cervical carcinoma was conducted from June 2003 to August 2009. All patients underwent an intraoperative intracervical blue dye injection. Patients who underwent a preoperative lymphoscintigraphy received a 99m Tc sulfur colloid injection in addition. All patients underwent sentinel lymph node (SLN) identification followed by a complete pelvic node and parametrial dissection. SLN were evaluated using our institutional protocol that included pathologic ultrastaging. RESULTS:SLN mapping was successful in 77 (95%) of 81 patients. A total of 316 SLN were identified, with a median of 3 SLN per patient (range, 0-10 SLN). The majority (85%) of SLN were located at three main sites: the external iliac (35%); internal iliac (30%); and obturator (20%). Positive lymph nodes (LN) were identified in 26 (32%) patients, including 21 patients with positive SLN. Fifteen of 21 patients (71%) had SLN metastasis detected on routine processing. SLN ultrastaging detected metastasis in an additional 6/21 patients (29%). Two patients had grossly positive LN at exploration, and mapping was abandoned. Three of 26 (12%) patients had successful SLN mapping; however, the SLN failed to identify the metastatic LN. Of these 3 false negative cases, 2 patients had a metastatic parametrial node as the only positive LN with multiple negative pelvic nodes including negative SLN. One patient with stage IA1 disease and lymphovascular invasion had unilateral SLN mapping and a metastatic common iliac LN identified on completion lymphadenectomy of the contralateral side that did not map. The 4 (5%) patients with unsuccessful mapping included 1 who had grossly positive nodes identified at the time of laparotomy; the remaining 3 occurred during each surgeon's initial SLN mapping learning phase. CONCLUSION/CONCLUSIONS:SLN mapping in early-stage cervical carcinoma yields high detection rates. Ultrastaging improves micrometastasis detection. Parametrectomy and side-specific lymphadenectomy (in cases of failed mapping) remain important components of the surgical management of selected cases.

BACKGROUND:Modern surgical and pathological techniques can detect small-volume axillary metastases in breast cancer with unknown clinical significance. METHODS:A retrospective database review from 1996 through 2004 identified all patients with immunohistochemical (IHC)-only sentinel node (IHC-SN) metastases and compared them with negative controls (Neg-SN). RESULTS:When comparing the 232 IHC-SN patients with the 252 Neg-SN controls, the IHC-SN patients had larger tumors, more lobular histology, a higher grade, and more HER2/neu positivity. They also received more systemic therapy. With a median follow-up of 5 years, there were no differences in recurrence-free survival or overall survival. In 123 IHC-SN patients treated with axillary dissection (axillary lymph node dissection), 16% had positive non-SLNs. Patients with positive non-SLNs tended to have worse outcomes. CONCLUSIONS:IHC-only sentinel lymph node (SLN) metastases were associated with worse prognostic features and higher rates of systemic therapy. However, no outcomes differences were noted.

OBJECTIVES/OBJECTIVE:Planar lymphoscintigraphy (LSG) is frequently performed for the assessment of the sentinel lymph nodes (SLN) in gynecologic malignancies. Planar imaging helps to localize hot nodes but lacks accuracy of the anatomic location of those nodes. In this study, we compared SPECT-CT to planar LSG in endometrial and cervical cancer to assess its ability to localize SLN. METHODS:We conducted a prospective nonrandomized study of SLN mapping in women with endometrial and cervical cancer. Forty patients with endometrial cancer and 10 with cervical cancer underwent pre-operative LSG with 1 or 4 mCi of (99m)Tc sulfur colloid administered as injections into the cervix. All patients were scanned immediately with planar LSG obtained in the anterior and lateral views. SPECT-CT imaging was obtained following the planar imaging. RESULTS:Planar LSG alone localized SLN in 30/40 (75%) endometrial cancer patients while SPECT-CT localized SLN in all 40 patients (100%). In the 10 cases where SLN was not identified with planar imaging, SPECT-CT localized nodes in the external iliac, internal iliac, common iliac and obturator groups. In cervical cancer, planar LSG alone localized sentinel lymph nodes in 8/10 patients (80%) as compared to SPECT-CT, which localized nodes in all 10 patients (100%). SPECT-CT imaging was especially useful in delineating external iliac versus internal iliac or obturator nodes, and the parametrial nodal uptake. CONCLUSIONS:SPECT-CT appears to improve sentinel lymph node detection and anatomic localization as compared to planar imaging in cervical and uterine cancer.

BACKGROUND:Axillary lymph node dissection (ALND) in patients with immunohistochemistry (IHC)-determined metastases to the sentinel lymph node (SLN) is controversial. The goal of this study was to examine factors associated with ALND in IHC-only patients. METHODS:Retrospective review of an institutional SLN database from July 1997 to July 2003 was performed. We compared sociodemographic, pathologic, and therapeutic variables between IHC-only patients who had SLN biopsy alone and those that had ALND. RESULTS:Our study group consisted of 171 patients with IHC-only metastases to the SLN. Young age, estrogen receptor negative status, high Memorial Sloan-Kettering Cancer Center nomogram score, and chemotherapy were associated with ALND. Among patients who had ALND (n = 95), 18% had a positive non-SLN. Rates of systemic therapy were similar between those with and without positive non-SLNs at ALND. No axillary recurrences were observed in this series with a median follow-up of 6.4 years. The percentage of patients who were recurrence-free after 5 years was 97% (95% confidence interval, 92.1-98.6). CONCLUSIONS:On the basis of our findings and the lack of prospective randomized data, the practice of selectively limiting ALND to IHC-only patients thought to be at high risk and to patients for whom the identification of additional positive nodes may change systemic therapy recommendations seems to be a safe and reasonable approach.