Sally M. Knox

Preliminary Outcome Analysis in Patients With Breast Cancer and a Positive Sentinel Lymph Node Who Declined Axillary Dissection

Background:This retrospective study was designed to provide a preliminary outcome analysis in patients with positive sentinel nodes who declined axillary dissection.Methods:A review was conducted of patients who underwent lumpectomy and sentinel lymph node excision for invasive disease between January 1998 and July 2000. Those who were found to have sentinel lymph node metastasis without completion axillary dissection were selected for evaluation. Follow-up included physical examination and mammography.Results:Thirty-one patients were identified who met inclusion criteria. Primary invasive cell types included infiltrating ductal carcinoma, infiltrating lobular carcinoma, and mixed cellularity. Most primary tumors were T1. Nodal metastases were identified by hematoxylin and eosin stain and immunohistochemistry. Twenty-seven of the metastases were microscopic (<2 mm), and the remaining four were macroscopic. All patients received adjuvant systemic therapy. With a mean follow-up of 30 months, there have been no patients with axillary recurrence on physical examination or mammographic evaluation.Conclusions:We have presented patients with sentinel lymph nodes involved by cancer who did not undergo further axillary resection and remain free of disease at least 1 year later. This preliminary analysis supports the inclusion of patients with subclinical axillary disease in trials that randomize to observation alone.

Clinical recognition and management of depression in node negative breast cancer patients treated with tamoxifen

SummaryDepression is not an uncommon complaint of women with breast cancer and is usually assumed to be related to the cancer diagnosis itself or its treatment. As part of a prospective clinical trial of adjuvant therapy of node negative breast cancer, 301 patients treated and assessed by one oncologist (SEJ) were serially questioned for symptoms of depression in the first 6–12 months after completing initial treatment (surgery, radiation therapy, and/or chemotherapy). Two hundred and fifty-seven patients were evaluable for assessment of depression; 155 were receiving tamoxifen and 102 were not. Twenty-six patients had symptoms of depression including 23 (15%) treated with tamoxifen compared to 3 (3%) in the group not placed on tamoxifen (p < 0.005). Of the 23 patients with depression in the tamoxifen group, symptoms were temporally related to the initiation of therapy and occurred generally in the first 2 months of treatment. Eight patients had mild symptoms not requiring a dose reduction, 8 had significant depression requiring a dose reduction to relieve symptoms, and 7 required discontinuation of tamoxifen. We conclude that clinical depression as a side effect of tamoxifen therapy may be more common than previously believed and should be further rigorously investigated to confirm or deny our clinical impressions.

Circulating Tumor Cells in Patients Undergoing Surgery for Primary Breast Cancer: Preliminary Results of a Pilot Study

IntroductionCirculating tumor cells (CTCs) have recently been shown to be an independent predictor of progression-free and overall survival in patients undergoing treatment for metastatic breast cancer. This study evaluates the presence and significance of CTCs in patient undergoing surgical resection of clinically localized primary breast cancer.MethodsPatients undergoing surgery for clinically localized primary breast cancer were enrolled into a prospective study. Thirty milliliters of blood was drawn and studied using the CellSearch assay.ResultsForty-one patients were enrolled at a single tertiary referral center. Ten patients (24.4%) had detectable CTCs preoperatively (PreOp). Nine (30%) patients were found to have CTCs postoperatively (PostOp). Overall, 16 (39%) were found to have CTCs either PreOp or PostOp. Hormone-negative patients were significantly more likely to have CTCs than hormone-positive patients. No other pathologic factor was predictive of the presence of CTCs.ConclusionCTCs are detectable and quantifiable in breast surgery patients. CTCs were more likely to be found in hormone receptor negative patients. Further study will allow correlation with other pathological variables and clinical outcome.

Survival analysis following sentinel lymph node biopsy: a validation trial demonstrating its accuracy in staging early breast cancer.

Few long-term follow-up studies prove sentinel lymph node biopsy (SLNB) effectively stages breast cancer without the further evaluation of a completion axillary dissection. Our prospective study addressed this issue, enrolling 345 women with clinically node-negative breast cancer who underwent SLNB from October 1997 through December 2000. The median age of the patients in the study was 56.7 years. Average primary tumor size was 1.42 cm. Ninety-three patients had a positive sentinel lymph node (27%); 70 (75.3%) of these patients underwent completion axillary dissection, while 23 patients (24.7%) declined further surgery. Most (91.3%) of the patients who declined further surgery had evidence of micrometastatic disease only. The median follow-up period for all patients was 60 months. No tumor recurrences in the axilla were reported in either sentinel nodenegative or -positive patients. The local and systemic recurrence rates were 3.1% and 4% in node-negative patients and 2.2% and 4.3% in node-positive patients. Two patients (0.9%) in the node-negative group and 6 (6.5%) in the node-positive group died of their disease. Estimated 5-year disease-free survival rates were 96% for node-negative patients and 87% for node-positive patients (P = 0.02). The clinical false-negative rate of the SLNB in this study was 0%. This long-term validation trial proves the accuracy of the SLNB and its extremely low false-negative rate. The findings indicate that patients with a positive SLNB have significantly different survival rates than patients with a negative SLNB.

Predictors for nonsentinel node involvement in breast cancer patients with micrometastases in the sentinel lymph node.

Sentinel lymph node (SLN) biopsy in breast cancer allows for a more thorough pathologic assessment with serial sectioning and cytokeratin staining. This has resulted in increased detection of micrometastatic disease (tumor size <2 mm) in the SLN. Unfortunately, the value of completion axillary dissection after finding micrometastatic disease in the SLN remains poorly defined. Over a 2-year period, a prospective database of 305 patients who underwent SLN biopsy for breast cancer at Baylor University Medical Center was reviewed. Eighty-four (27.5%) of the patients had evidence of metastatic disease in the SLN. Twenty-four of the 41 patients identified as having micrometastatic disease in the SLN underwent completion axillary lymph node dissection. In these patients, all nonsentinel nodes were further studied by serial sectioning and immunohistochemistry. The median age of these 24 patients was 52 years (range, 34–83). Their primary tumor stages were T1a and T1b (n = 5), T1c (n = 15), and T2 (n = 4). A total of 328 nonsentinel lymph nodes were examined, including 225 from patients with infiltrating ductal carcinoma (n = 17) and 103 from patients with infiltrating lobular carcinoma (n = 7). In the patients with infiltrating ductal carcinoma, no additional nodal metastases were identified, while in those with infiltrating lobular carcinoma, additional nodal disease was found in 5 lymph nodes (2 of 12 patients, 17%). Primary tumor characteristics were not predictive of additional nodal disease. These data suggest that patients with micrometastasis in the SLN from infiltrating lobular carcinoma have a significant risk of harboring additional nodal disease and should undergo completion axillary dissection. However, those with micrometastatic disease from infiltrating ductal carcinoma have a very low incidence of additional metastasis and may not need completion axillary dissection.

Tumor hormone receptor status and recurrences in premenopausal patients with node-negative breast carcinoma

To ascertain the prognostic significance of tumor hormone receptor status in premenopausal patients with node‐negative breast cancer, a retrospective review of 199 patients who met these criteria was conducted. Of these 199 patients, estrogen receptor (ER) data were available for 147. One hundred four patients (71%) had ER‐negative disease and 22 (21%) exhibited local or distant recurrence with a median follow‐up time of 85.4 months. Thirteen patients in this group had died of breast cancer. Of the 43 patients who had ER‐positive disease, 5 (12%) had recurrences and 2 died of breast cancer. After observing patients for a longer period of time (median follow‐up time, 85.4 months), no statistically significant differences in disease‐free survival (DFS) or overall survival (OS) were demonstrated. However, as seen in our first analysis of this group at 45 months, tumor size after a median follow‐up time of 85.4 months continues to have significant prognostic implications, regardless of ER status. Cancer 1992; 69:984–987.

Clinical utility of breast magnetic resonance imaging in patients presenting with primary breast cancer

Since magnetic resonance imaging (MRI) of the breast has been shown to be sensitive in identifying the extent of the primary tumor and other foci of cancer, we examined its clinical utility in the surgical management of breast cancer patients. From January 2004 to April 2007, 117 patients with newly diagnosed breast cancer underwent bilateral MRI prior to definitive surgical management. Additional lesions were found in 27 patients (23.1%) in the ipsilateral breast and 19 patients (16.2%) in the contralateral breast. Twelve patients (10.3%) had more than one new lesion identified. Six patients (5.1%) had a larger area of tumor than detected by mammography or ultrasound. Additional biopsies were performed in 27 patients (23.1%). Additional foci of cancer were identified in 17 patients (14.5%): 12 (10.2%) in the ipsilateral breast and 5 (4.3%) in the contralateral breast. This information changed the clinical management in 23 cases (19.7%). Further studies are needed to confirm the benefits of MRI relative to its costs and to further identify the appropriate patients to undergo this imaging procedure.

Phase I trial of adjuvant chemotherapy with cyclophosphamide, epirubicin and 5-fluorouracil (CEF) for stage II breast cancer

SummaryEpirubicin is a new anthracycline with a potentially more favorable toxicity profile than the parent compound, doxorubicin. Accordingly, the feasibility and toxicity of 6 courses of adjuvant chemotherapy with cyclophosphamide (C), epirubicin (E), and 5-fluorouracil (F) were assessed in 10 patients with Stage 2 (node positive) breast cancer. Doses of C and F were 600 mg/m2 and E was 75 mg/m2. Moderate granulocytopenia (median count = 610/mm3) occurred on day 14 of the first 21 day treatment course and was the main toxicity encountered with treatment, although there were no episodes of granulocytopenic fever. Grade 3 or 4 vomiting occurred in 40% and significant alopecia in 30% of patients. Four patients experienced transient asymptomatic decreases in calculated radionuclide cardiac ejection fraction of ≥ 10% but no signs or symptoms of cardiac failure were observed. If epirubicin proves to be less cardiotoxic than doxorubicin, this combination would merit further evaluation as potential adjuvant therapy for early breast cancer.

Magnetic Resonance Imaging of the Breast: Present and Future Roles

New magnetic resonance imaging (MRI) methods have been developed for imaging a variety of breast disorders. Researchers at Baylor University Medical Center have established a world leadership posit...