Sentinel Lymph Node Biopsy in Breast Cancer: A Validation Study and Preliminary Results

Aviram Nissan, Ram M. Spira, Roland Chisin, Oded Zamir, Diana Prus, Martin Klein, Mahmoud Badriyyah, Herbert R. Freund

Departments of Surgery. Biophysics and Nuclear Medicine, and Pathology. Hadassah University Hospital Mount Scopus and Hebrew University - Hadassah Medical School, Jerusalem

Introduction: Sentinel lymph node biopsy (SLNB) has been recently proven to be an accurate staging method for breast cancer, replacing axillary lymph node dissection (ALND) in selected cases. We present our initial experience and the process of introduction and implementation of SLNB in a University Hospital setting.

Material and methods: 46 SLNB were performed in 42 consecutive female patients with invasive breast cancer. Treatment included 0.4mCi-2mCi of Tc-99m rhenium colloid injected either 2 hours before surgery (0.4 mCi) or the night before surgery (2 mCi). Four milliliters of Patent Blue V were injected peritumoral 10 minutes prior to skin incision in all patients. Following SLNB all women underwent subsequent ALND. Sentinel nodes were processed both with multiple (10-15) H&E sections and immunohistochemistry with cytokeratin antibodies stain.

Results: Blue dye, isotope or the combination of both identified 43/46 (93%) of the sentinel lymph nodes. ALND was performed only unilaterally in 4 patients with bilateral breast cancer bringing the total evaluable SLNB to 39. In the 39 patients in whom the sentinel node was successfully identified and underwent ALND, the SLNB was true positive (TP) in 17/39 (44%) true negative (TN) in 20/39 (51%) and false negative in 2/39 [(5%), both T2 lesions] with overall accuracy of 95%. In the last 10 cases all sentinel nodes were successfully identified with 70% TP and 30% TN.

Conclusions: Experience with at least 30-40 consecutive cases for safe implementation of SLNB in clinical practice. Specific training and dedication is required for the entire team involved, including surgeons, nuclear medicine physicians and technicians and pathologists.  

למעלה מ- 40,000 נשים נפטרו בשנה האחרונה מסרטן השד בארצות הברית. עובדה זו מעמידה את סרטן השד כסרטן השכיח ביותר בנשים והשני כגורם לתמותה מסרטן בנשים. נשים מעל גיל 60 הן בעלות הסיכון הגבוה ביותר ללקות בסרטן השד ואוכלוסייה זו היא אוכלוסיית המטרה לרוב המחקרים הקליניים שמטרתם טיפול מונע. הסיכון במהלך שנות החיים ללקות בסרטן שד פולשני הוא בשיעור של 12%, ולכן כל טיפול שיפחית או יגדיל את הסיכון הנ"ל, הוא בעל השפעה חשובה על בריאות האשה. טיפולים המשפיעים על עלייה או ירידה בסיכון לסרטן השד בנשים בעת חדלון הווסת כוללים: טיפול הורמוני חלופי, כריתת שד כטיפול מונע, ומתן טמוקסיפן וראלוקסיפן. בשנה האחרונה, פורסמו מספר מחקרים בנושא, אותם נסקור במאמר זה.

Systemic Mastocytosis

K. Sade, I. Dotan, Y. Levo

Depts. of Pulmonary and Allergy Diseases and of Medicine T, Tel Aviv-Sourasky Medical Center

Mastocytosis has a highly variable clinical expression, and systemic mastocytosis is occasionally associated with a myeloproliferative or a myelodysplastic disorder. These patients often present without skin involvement and have a very poor prognosis. We report a 72-year-old man with this condition who had spells of flushing and dyspnea, myelo-fibrosis, and high serum and urine histamine levels.

Breast Tumors Demonstrated by Tc-99m Sestamibi Scintimammography 

Itzhak Pappo, Tifha Horne, Herbert Merdad, Ruben Orda

Dept. of Surgery A, Institute of Nuclear Medicine and Dept. of Pathology, Assaf Harofeh Medical Center, Zrifin; and Sackler Faculty of Medicine, Tel Aviv University

Breast cancer can be detected by scintimammography using Tc-99m sestamibi (MIBI). The method is highly accurate, sensitive and specific. Histologically, most of the tumors have been adenocarcinomas.

We present 2 women with rare breast tumors, primary squamous cell carcinoma and malignant phyllodes tumor. In both, mammography and cytological biopsy were not diagnostic, but MIBI scintimammography demonstrated focal uptake in the diseased breast.

Breast Cancer after Mantle Field Irradiation for Hodgkin's Disease 

A. Katz, B. Brenner, A. Sulkes, H. Luria, G. Marshak, E. Fenig

Oncology Institute, Rabin Medical Center, Beilinson Campus, Petah Tikva and Sackler Faculty of Medicine, Tel Aviv University

Effective use of modern therapeutic modalities results in the cure of 75%-80% of Hodgkin's disease patients, regardless of stage. The major threat to continued survival is, therefore, not recurrent disease but development of second malignancies. Recent reports have firmly established the increased risk of breast cancer developing in women treated with mantle field irradiation.

We describe 3 women who developed breast carcinoma following mantle field irradiation for Hodgkin's disease. Their clinical course was consistent with that reported in larger series. They were relatively young when irradiated and there was a long interval between radiation therapy and the diagnosis of breast cancer.

Review of the literature shows that there may be a role for prophylactic mastectomy after irradiation for Hodkgin's disease.

Hemophagocytic Syndrome

I. Morag, M. Goldman, T. Bistrizer, C. Kaplinsky

Pediatric Division, Assaf Harofeh Medical Center, Zerifin and Pediatric Hematology-Oncology Dept., Chaim Sheba Medical Center, Tel Hashomer and Sackler Faculty of Medicine, Tel Aviv University

Hemophagocytic syndrome is a rare, fulminant disease characterized by generalized histiocytic proliferation associated with phagocytosis of erythrocytes, platelets, and to a lesser extent, of white blood cells. We report a 2-year-old boy admitted with high fever and irritability, with a rash, marked hepatomegaly and generalized lymphadenopathy. Liver function tests were abnormal and there was thrombocytopenia and hyperlipidemia. Bone marrow aspiration revealed hemophagocytosis. Despite intensive treatment with steroids, intravenous immunoglobulin and cytotoxic drugs, he died within 10 weeks.

Breast Conservation: Safe for Early Breast Cancer

Gil Bar-Sella, Georgetta Fried, Zipora Brotman, Anna Ravkin, Riva Borovik, Abraham Kuten

Dept. of Oncology, Rambam Medical Center; Dept. of Oncology, Lin Medical Center; and Rappaport Faculty of Medicine, Technion, Haifa

Between 1981-1993 581 women with primary breast cancer were treated by breast conservation. Their mean age was 56‏12 years and 63% were postmenopausal and 37% pre- or perimenopausal. The median follow-up time was 56 months. 45% had pathological Stage I disease, 49% Stage II, 2.5% Stage III and 3.5% clinical Stage I-II disease. 54% of lesions were excised with good margins, 10% with close margins (<0.5 cm), 9% with microscopic residual, 3% with macroscopic residual, and in 24% margins were not reported. Adjuvant therapy, consisting of combination chemotherapy and/or hormones, was given to 69%.

Radiotherapy, usually 50 Gy tangential photon irradiation to the whole breast, was given to 564 (97%); an electron or photon "boost" to the tumor with a median dose of 17.5 Gy was given to 378 (65%). Most of those with positive nodes received 50 Gy to the lymphatic drainage system.

1 year after radiotherapy cosmetic results were rated as "good" or "excellent" in 80%, "moderate" in 17% and "poor" in 3%. The 5-year actuarial survival was 97% in Stage I and 88% in Stage II. 37 patients (6.5%) developed breast recurrence; 11 of these (2%) had simultaneous distant metastases. 5 (<1%) developed axillary or supraclavicular lymph node metastases, and 81 (14%) developed distant metastases. Most local recurrences were in those younger than 40, and in those with primary tumors >1.75 cm.

The satisfactory level of local control achieved is attributed to the high doses of radiation (up to 75 Gy) administered to those with high risk lesions.

Risk of Transmission of Viral Disease by Needle Puncture in Health Care Workers

Yosef Mishal, Chaim Yosefy, Emil Hay, Dalia Catz, Elisia Ambon, Roza Schneider

Infectious Disease Unit, Emergency Dept. and Microbiology Lab, Barzilai Medical Center, Ashkelon (Affiliated with Ben-Gurion University of the Negev)

The accidental exposure of the health care workers (HCW) to blood and blood products constitutes a danger for transmission of blood-borne pathogens and the development of severe diseases. Most attention is focused on exposure to the viruses of hepatitis B, C and human immunodeficiency. The objectives of this prospective study were to determine the rate of exposure of our HCW to blood and blood products; to define the high risk groups; and to establish recommendations to prevent transmission or reduce the risk of exposure to these viruses.

During the year 1996, 103 injuries from needle-puncture or other sharp objects were reported to our infectious diseases control unit. Most of those injured were women. 58.4% of the events occurred in the vicinity of the patient. The source of exposure was known in 60% of the cases. 73.8% of those injured had already been immunized against hepatitis B. The departments in which most exposures occurred were the operating theater (12.5%), medical departments A (10.6%) and B (9.6%), and the emergency department (7.7%). Nurses were at highest risk, constituting 47% of those injured.

Our recommendations are that a continuous teaching program be established for the high risk groups; that HCW be urged to report every event of exposure; and to encourage HCW to undergo active immunization against hepatitis B.

The Surgeon and the Emperor: a Humanitarian on the Battlefield

M. Feinsod

Dept. of Neurosurgery, Rambam (Maimonides) Medical Center; B. Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa

The Baron Dominique-Jean Larrey, one of the greatest names in military surgery, participated as Chief Surgeon in all the Napoleonic campaigns. He developed the concept of early evacuation from the battlefield, and of immediate treatment of the wounded, even under fire. He implemented improved surgical techniques and improved wound care that were followed by surgeons all over Europe. His devotion to wounded soldiers crossed national boundaries and became a way of life. Here is an account of Larrey's involvement in the aftermath of the Battles of Lutzen and Bautzen (May-June 1813), when many soldiers were accused of self-mutilation and were about to be executed. He dared to oppose, singlehanded, the Emperor, the highest military authorities and their concurring physicians and surgeons, armed only by his undisputed honesty, professional authority and exceptional reputation won over years of devotion to wounded soldiers. Larrey saved the lives of many soldiers and set an example of unbent ethical integrity.

Oncogenetic Counseling and Genetic Testing of Those at High Risk for Breast and Ovarian Cancer

Livia Theodor, Ronit Shiri-Sverdlov, Galit Hirsch Yechezkel, Revital Bruchim Bar-Sade, Eva Gak, Irit Friedman, Anna Kruglikova, Gilad Ben-Baruch, Shulamit Risel, Moshe Z. Papa, Boleslav Goldman, Eitan Friedman

Oncogenetics Unit, Dept. of Clinical Epidemiology, Institute of Genetics, and Gynecology, Oncology, and Surgical Depts., Chaim Sheba Medical Center, Tel Hashomer

There is inherited predisposition to breast and ovarian cancer in 5-10% of all women with these diseases. Germline mutations in BRCA1 and BRCA2 presumably account for most of the genetically susceptible individuals. We summarize 2 years of experience in counseling and testing for inherited predisposition to these cancers.

597 women (from 320 families) have been evaluated since August 1995. 242 were evaluated for inherited predisposition to breast and ovarian cancer. One-third had clear-cut evidence of familial background. 74 families were of Ashkenazi origin; the age range of breast cancer was 30-35, of ovarian cancer 40-45. In 80% of families other cancers were also noted in first degree family members, including lung, colon, and prostate cancer and leukemia.

Genetic testing revealed that 45% of affected and 25% of unaffected women were carriers of a mutation in BRCA1 or BRCA2: 67/90 185delAG (BRCA1), 12/90 6174delT (BRCA2), and 4/90 of 5382insC (BRCA1). In addition, a novel mutation in exon 11 of BRCA1 was detected, carried by 7/90 women. The experience gained in oncogenetic counseling and genetic testing for inherited cancer predisposition will eventually enable determining an optimal, rational therapeutic regimen in carriers of mutations.

Taxol as Second-Line Therapy in Recurrent Breast and Ovarian Cancer

R. Borovik, M. Steiner, J. Atad, B. Sneiderman, T. Rosenberg, S. Palti

Oncology Depts., Lin Medical Center and Carmel Medical Center, Haifa

Results of chemotherapy with Taxol (paclitaxel) in 55 patients with recurrent breast and ovarian cancer were reviewed. Taxol was given as a 3-hour infusion, every 3 weeks, on an outpatient basis. There was complete or partial response in 8 patients (23%) with breast cancer and 10 (50%) with ovarian cancer. Performance status and previous response to adriamycin were important prognostic factors. Toxicity was manageable. Treatment had to be stopped for hypersensitivity reactions in only 2 patients. Taxol given in an ambulatory clinic is safe and effective.

Fibrosarcoma after Silicone Breast Augmentation: Associated?

Anabel Aharon-Maor, Yair Levy, Yehuda Schoenfeld

Medical Dept. B, Chaim Sheba Medical Center and Sackler Faculty of Medicine, Tel Aviv University

We describe a 42-year-old woman in whom bilateral fibrosarcoma of the breast was diagnosed 15 years after bilateral breast augmentation with silicone implants. 3 years prior to admission the implants were replaced and 2 years prior to admission mammography showed a nodule in the left breast which biopsy showed to be fibrosarcoma. The implants were removed from both breasts and she was given chemotherapy but later that year underwent bilateral mastectomy. Despite chemotherapy, as well as adjuvant radiotherapy, the disease progressed, with involvement of the lungs and the skin of the left hemithorax. She was admitted repeatedly for severe anemia caused by bleeding from the malignant skin lesions, and died less than 2 years after diagnosis of the disease.

Not all reports in the literature find a significant connection between silicone implants and subsequent development of breast cancer, but there are reports that do connect them. Breast fibrosarcoma is not significantly more frequent after silicone augmentation, but still there is controversy as to whether there is a connection between silicone implants and breast malignancy. In the patient we present, the prolonged exposure to silicone may have been a predisposing factor for the development of bilateral fibrosarcoma, since other known risk factors for breast cancer were denied.

Screening Tests for Detecting Breast Cancer: Performance Rates and Characteristics of Patients

Netta Bentur, Revital Gross, Ayelet Berg

JDC-Brookdale Institute of Gerontology and Human Development, Jerusalem

Screening tests including mammograms for early detection of breast cancer are in the basket of services provided under the National Health Insurance Law. The law also defines the population groups entitled to mammograms, and sets the frequency of the test as once every 2 years. The aim of this study was to examine the screening rates for early detection of breast cancer at the inception of the law, in order to monitor future changes in performance rates, and identify the characteristics of those unlikely to undergo these tests, in order to promote the use of screening tests by them. This study is part of a comprehensive survey examining the effect of the National Health Insurance Law on the Israeli population.

The survey, carried out in the summer of 1995, included a sample of 1,400 Israeli residents aged 22 and over. To determine performance rates for clinical breast examinations a subgroup of 515 women aged 30 and over was sampled. To determine performance rates for mammograms, 173 women were aged 50-74 (the entitlement ages under the law), were sampled. 54% of women aged 30+ reported having had at least 1 clinical breast examination during their lifetime, and 56% of women aged 50-74 reported having had a mammogram during the past 2 years. Variables with an independent effect on the likelihood of having had a clinical breast examination by a physician during the past 2 years were: being over the age of 50, having at least 9 years of education, being a veteran resident of Israel (as opposed to a new immigrant), and being Jewish. Variables with an independent effect on the likelihood of having a mammogram during the past 2 years were: being a veteran resident of Israel, and having a high income צ which was found to have a borderline effect. The findings of the survey emphasize the importance of changing the behavior patterns of both women and physicians, informing women about their entitlement to the tests, and raising consciousness of the importance of having repeated clinical examinations by a physician, as well as mammograms.

Paroxysmal Nocturnal Hemoglobinuria

Haim Ben-Ami, Yehuda Edoute

Medical Dept. C, Rambam Medical Center and Bruce Rappaport Faculty of Medicine, The Technion, Haifa

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired disorder of blood cells which originate from an abnormal hematopoietic stem cell. The condition is characterized by nocturnal hemoglobinuria, chronic hemolytic anemia, and thrombosis. We describe a 60-year-old woman with PNH admitted with abdominal pain and jaundice, who had dark urine on arising after a night's sleep. The diagnosis was established by the typical clinical story and a positive Ham test. She was successfully treated with Halotestin and folic acid. Although PNH is rare, it should be considered in the differential diagnosis of hemolytic anemia. Early diagnosis and treatment are important.

Accessibility of Information and Informed Consent: Experiences of Breast Cancer Patients

Ephraim Tabory, Susan Sered

Dept. of Sociology and Anthropology, Bar-Ilan University, Ramat Gan

We studied the social and cultural frameworks that impact on breast cancer patients in the medical system. The subjects were 98 Jewish women who had undergone mastectomy or lumpectomy for cancer 6 months to 3 years prior to the interview. They emanated from a variety of socioeconomic and ethnic backgrounds, and reflected the age range of women with breast cancer in the general Jewish population of Israel. Patients were asked about each stage of the medical process they had experienced: diagnosis, surgery, oncological care, and follow-up care. The interview revealed a general perception of having received insufficient information regarding their medical condition and treatment. The problem tended to be most severe during the diagnostic stage, when women had not yet been officially included as patients within the system. The problem was relatively severe during follow-up care, when they often did not have an address for their questions. Few women received a schedule of follow-up care that allowed them to carry on with the many necessary tests in an orderly and comprehensive manner. Most important, systematic absence of informed consent also characterized the decision-making process regarding surgery and oncological treatment. Few women felt they had been informed about treatment options, side-effects, or long-term implications of the treatment offered. We found no indication of inequitable medical treatment that would suggest a manifest pattern of discrimination, but we did find some social variables related to a feeling of insufficient personal care and information. In particular, older women said they received less attention, support, and information from the medical staff relative to the younger women.