Association of Insulin Resistance and Higher Oncotype DX™ Recurrence Score

Annals of Surgical Oncology - Black women with breast cancer have a worse overall survival compared with White women; however, no difference in Oncotype DX? (ODX) recurrence scores has been...     

George Peters Award: How does breast-specific gamma imaging affect the management of patients with newly diagnosed breast cancer?

Background

We sought to determine the number of patients with known breast cancer who were found to have an additional, mammographically occult lesion detected on breast-specific gamma imaging (BSGI).

Methods

An institutional review board-approved review of all patients who underwent BSGI at Beth Israel Medical Center from 2006 to 2008 was performed.

Results

A total of 82 patients underwent BSGI for newly diagnosed breast cancer. Of these, 18 had an additional abnormality, and 17 were biopsied. There were 4 cases of invasive ductal carcinoma, 1 invasive lobular carcinoma, 1 ductal carcinoma in situ, 1 lobular carcinoma in situ, 2 papillomas, and 8 benign biopsies. One patient proceeded directly to mastectomy and an area of ductal carcinoma in situ was found, corresponding to the BSGI.

Conclusions

In our study group, 22% of patients had a surgical change in management based on BSGI findings. BSGI detected additional carcinoma in 9%. BSGI plays an important role in the clinical management of patients with known breast cancer.     

A Nomogram for Predicting the Likelihood of Additional Nodal Metastases in Breast Cancer Patients With a Positive Sentinel Node Biopsy

Background:The standard of care for breast cancer patients with sentinel lymph node (SLN) metastases includes complete axillary lymph node dissection (ALND). However, many question the need for complete ALND in every patient with detectable SLN metastases, particularly those perceived to have a low risk of non-SLN metastases. Accurate estimates of the likelihood of additional disease in the axilla could assist greatly in decision-making regarding further treatment.Methods:Pathological features of the primary tumor and SLN metastases of 702 patients who underwent complete ALND were assessed with multivariable logistic regression to predict the presence of additional disease in the non-SLNs of these patients. A nomogram was created using pathological size, tumor type and nuclear grade, lymphovascular invasion, multifocality, and estrogen-receptor status of the primary tumor; method of detection of SLN metastases; number of positive SLNs; and number of negative SLNs. The model was subsequently applied prospectively to 373 patients.Results:The nomogram for the retrospective population was accurate and discriminating, with an area under the receiver operating characteristic (ROC) curve of 0.76. When applied to the prospective group, the model accurately predicted likelihood of non-SLN disease (ROC, 0.77).Conclusions:We have developed a user-friendly nomogram that uses information commonly available to the surgeon to easily and accurately calculate the likelihood of having additional, non-SLN metastases for an individual patient.Drs. Manasseh and Bevilacqua contributed equally to the work.Dr. Bevilacqua is currently affiliated with Hospital Sírio Libanes, Instituto Brasileiro de Controle do Câncer, and Disciplina de Cirurgia Geral, Departamento de Cirurgia, Faculdade de Medicina da Univerdidade de Sao Paulo. São Paulo, Brazil; Dr. Boolbol is currently affiliated with Beth Israel Medical Center, New York, New York.     

Randomized clinical trials in breast cancer

Before the second half of this century, treatment approaches to breast cancer were radical and disfiguring. In the past four decades, however, multiple prospective randomized trials have made highly significant advances in the management of patients with this disease. These trials have established, in select patients, breast conservation therapy as a primary therapeutic procedure, and radiation therapy as a means to improve local control and survival. This article provides an overview of some of these trials.     

The Role of Mammary Ductoscopy in Breast Cancer: a Review of the Literature

Breast cancer is the most frequently diagnosed malignancy among American women. It is the second most common cause of cancer death. Genetic analysis using comparative genetic hybridization (CGH) has shown evidence that the majority of breast cancers, approximately 85%, begin in the ductal epithelium with normal cells progressing to atypia and finally to carcinoma. Mammary ductoscopy, also referred to as the intraductal approach, is a new tool that allows direct visualization of the breast ductal system. It enables one to sample the ductal epithelium and may allow identification of early changes cytologically as well as potentially play an important role in aiding surgical excision. This may aid in detection of breast masses long before they are palpable or visible via mammography. Mammary ductoscopy may have a role in the evaluation of women with nipple discharge, high-risk women, or limiting the amount of tissue removed in breast conservation surgery for cancer.     

MRI Versus Breast-Specific Gamma Imaging (BSGI) in Newly Diagnosed Ductal Cell Carcinoma-in-situ: A Prospective Head-to-Head Trial

Background  

Mammography remains the standard imaging technique for the diagnosis of ductal carcinoma-in-situ (DCIS). Functional breast imaging, including breast magnetic resonance imaging (MRI), has known limitations in evaluating DCIS. To date, there are limited data on the utility of breast-specific gamma imaging (BSGI) in DCIS. We sought to prospectively compare the sensitivity of BSGI to MRI in newly diagnosed DCIS patients.     

Intraoperative Touch Preparation Cytology for Margin Assessment in Breast-Conservation Surgery: Does It Work for Lobular Carcinoma?

Background Breast carcinoma is the most frequently diagnosed malignancy in women of the North America. The combination of breast-conservation surgery and radiotherapy has become a standard of treatment for most breast cancers. It is critical to obtain clear margins to minimize local recurrence. The literature suggests that intraoperative touch preparation cytology (IOTPC) can be useful in evaluation of margins. Invasive lobular carcinoma (ILC) accounts for 10% to 15% of all breast cancers. Obtaining clear margins in ILC can be more challenging. Literature shows the positive margin rate for ILC to be as high as 60%. This report describes our experience with IOTPC for margin assessment in ILC by a single surgeon at Beth Israel Medical Center. The purpose of this study is to determine whether IOTPC is reliable for ILC. Methods A prospective review of 73 patients who underwent breast-conservation surgery with the use of IOTPC for margin assessment at Beth Israel Medical Center was performed. Pathology revealed ILC in 12 of these patients (16.4%), who are the subjects of this study. The lumpectomy specimens were oriented by the surgeon intraoperatively and were submitted fresh to pathology for cytologic assessment. IOTPC consisted of touching the corresponding margin onto the glass slide. The principle of this technique is that if cancer cells are present, they will stick to the slide, whereas fat cells will not. Six slides were prepared for each lumpectomy specimen. Air-dried samples were stained immediately by the Diff-Quik method and examined under the microscope by a cytopathologist. Results Twelve patients with ILC underwent breast-conservation surgery with IOTPC for assessment of 72 margins. Ten patients had lobular carcinoma only, and the remaining two patients had a combination of lobular and ductal carcinoma. There was a correlation between IOTPC and final pathology in 60 of 72 margins, which accounted for 83.3% of the cases. IOTPC for assessment of margins in patients undergoing breast-conservation surgery for ILC has a sensitivity of 8.3%, specificity of 98.3%, positive predictive value of 50%, and negative predictive value of 84.3%. Conclusions On the basis of our experience, IOTPC is of limited value for intraoperative assessment of margins for ILC. Poster presentation at the Sixth Annual Meeting of the American Society of Breast Surgeons, March 16–20, 2005, Los Angeles, California.     

Consensus Guidelines on Genetic` Testing for Hereditary Breast Cancer from the American Society of Breast Surgeons

Background

The purpose of this consensus guideline is to outline recommendations for genetic testing that medical professionals can use to assess hereditary risk for breast cancer.

Methods

Literature review included large datasets, basic and clinical science publications, and recent updated national guidelines. Genetic testing to assess hereditary risk of cancer is a complex, broad, and dynamic area of medical research. The dominant focus of this guideline is limited in scope to breast cancer.

Results

There is a lack of consensus among experts regarding which genes among many should be tested in different clinical scenarios. There is also variation in the degree of consensus regarding the understanding of risk and appropriate clinical management of mutations in many genes.

Conclusions

Genetic testing should be made available to all patients with a personal history of breast cancer. Recent data are reviewed that support genetic testing being offered to each patient with breast cancer (newly diagnosed or with a personal history). If genetic testing is performed, such testing should include BRCA1/BRCA2 and PALB2, with other genes as appropriate for the clinical scenario and family history. For patients with newly diagnosed breast cancer, identification of a mutation may impact local treatment recommendations. Patients who had genetic testing previously may benefit from updated testing. Genetic testing should be made available to patients without a history of breast cancer who meet National Comprehensive Cancer Network guidelines. Finally, variants of uncertain significance are not clinically actionable and these patients should be managed based on their individual risk factors.

     

A novel automated assay for the rapid identification of metastatic breast carcinoma in sentinel lymph nodes

BACKGROUND:

The authors prospectively evaluated the performance of a proprietary molecular testing platform using one‐step nucleic acid amplification (OSNA) for the detection of metastatic carcinoma in sentinel lymph nodes (SLNs) in a large multicenter trial and compared the OSNA results with the results from a detailed postoperative histopathologic evaluation (reference pathology) and from intraoperative imprint cytology (IC).

METHODS:

In total, 1044 SLN samples from 496 patients at 11 clinical sites were analyzed. Alternate 1‐mm sections were subjected to either detailed histopathologic evaluation with hematoxylin and eosin and pancytokeratin immunostaining or the OSNA Breast Cancer System, which was calibrated to detect tumor deposits >0.2 mm by measuring cytokeratin 19 messenger RNA. At 7 sites, IC was performed before permanent section. The OSNA results were classified as negative (<250 copies/μL), micrometastases (from ≥250 to <5000 copies/μL), or macrometastases (≥5000 copies/μL).

RESULTS:

The sensitivity and specificity of the OSNA breast cancer system compared with reference pathology were 77.5% (95% confidence interval, 69.7%‐84.2%) and 95.8% (95% confidence interval, 94.3%‐97.0%), respectively, before discordant case analyses (DCA). Sensitivity and specificity after DCA were 82.7% and 97.7%, and final concordance was 95.8%. Performance for invasive lobular carcinoma demonstrated 88.2% sensitivity (95% confidence interval, 63.6%‐98.5%) and 98.5% specificity (95% confidence interval, 92%‐100%). The sensitivity of OSNA was significantly better than that of IC (80% vs 63%; P = .0229).

CONCLUSIONS:

The OSNA breast cancer system proved to be highly accurate for the detection of metastatic breast cancer in axillary SLNs. Sensitivity was comparable to that predicted for conventional postoperative histologic examination at 2‐mm intervals and was significantly more sensitive than IC. Automation, semiquantitative results enabling the differentiation of macrometastasis and micrometastasis, and rapid results render the assay suitable for intraoperative and/or permanent evaluation of SLNs. Cancer 2011. © 2011 American Cancer Society.     

Comparative acute toxicity from whole breast irradiation using 3-week accelerated schedule with concomitant boost and the 6.5-week conventional schedule with sequential boost for early-stage breast cancer

BackgroundWe aimed to evaluate the incidence of acute toxicity in a 3-week accelerated radiation therapy (RT) schedule with a concomitant boost compared with the 6.5-week conventional schedule with a sequential boost for early-stage, node-negative breast cancer.Materials and MethodsThis study included the first 50 patients treated on protocol using the accelerated schedule as well as 74 patients with comparable stages of disease treated over the same period using the conventional schedule. An accelerated schedule of 40.5 Gy × 2.7 Gy/fraction to the whole breast with 4.5 Gy × 0.3 Gy/fraction concomitant boost, for a delivered total dose of 45.0 Gy × 3.0 Gy/fraction in 15 fractions to the lumpectomy site. The conventional schedule used 46.8 Gy × 1.8 Gy to the whole breast with a sequential boost of 14.0 Gy × 2.0 Gy/fraction, delivering a total dose of 60.8 Gy × 33 fractions to the lumpectomy site. The side effects observed during RT and through the initial 8 weeks after treatment were scored for acute toxicity.ResultsA lower incidence of ≥ grade 2 skin toxicity was observed among patients treated on the accelerated schedule compared with those treated on the conventional schedule (p = .0015). There was a higher incidence of breast pain among patients receiving the conventional schedule (p = .045). No significant difference in the incidence of breast edema, fatigue, or hematologic side effects was observed between the 2 groups.ConclusionOur observations suggest that there is acceptable toxicity with the accelerated schedule as used in this study. Further, it is not associated with a higher risk of acute toxicity when compared with the conventional schedule. Patients in the study are being followed, and clinical outcomes will be reported as the data mature.