Breast Neoplasms: El Saghir NS

El Saghir NS, Eniu A, Carlson RW, Aziz Z, Vorobiof D, Hortobagyi GN, Anonymous00023. · Division of Hematology-Oncology, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon. nagi.saghir@ aub.edu.lb · Cancer. · Pubmed #18837023 No free full text.

Abstract: The management of locally advanced breast cancer (LABC) is guided by scientific advances but is limited by local resources and expertise. LABC remains very common in low-resource countries. The Systemic Therapy Focus Group met as part of the Breast Health Global Initiative (BHGI) Summit in Budapest, Hungary, in October 2007 to discuss management and implementation of primary systemic therapy (PST) for LABC. PST is standard treatment for large operable breast cancer in enhanced-resource settings and, in all resource settings, should be standard treatment for inoperable breast cancer and for LABC. Standard PST includes anthracycline-based chemotherapy. The addition of sequential taxanes after anthracycline improves pathologic responses and breast-conservation rates and is appropriate at enhanced-resource levels; however, costs and lack of clear survival benefit do not justify their use at limited-resource levels. It remains to define better the role of endocrine therapy as PST, but it is acceptable in elderly women. Aromatase inhibitors have produced better results than tamoxifen in postmenopausal patients and are used in enhanced-resource settings. The less expensive tamoxifen remains useful in low-resource countries. Trastuzumab combined with chemotherapy yields high pathologic response rates in patients with HER2/neu-overexpressing tumors; its use in low-resource countries is limited by high costs. Most studies on PST of LABC were conducted in countries with enhanced resources. BHGI encourages conducting clinical trials in countries with limited resources.

Eniu A, Carlson RW, El Saghir NS, Bines J, Bese NS, Vorobiof D, Masetti R, Anderson BO, Anonymous00019. · Department of Breast Tumors, Cancer Institute Ion Chiricuta, Cluj-Napoca, Romania. · Cancer. · Pubmed #18837019 No free full text.

Abstract: A key determinant of breast cancer outcome is the degree to which newly diagnosed cancers are treated correctly in a timely fashion. Available resources must be applied in a rational manner to optimize population-based outcomes. A multidisciplinary international panel of experts addressed the implementation of treatment guidelines and developed process checklists for breast surgery, radiation treatment, and systemic therapy. The needed resources for stage I, stage II, locally advanced, and metastatic breast cancer were outlined, and process metrics were developed. The ability to perform modified radical mastectomy is the mainstay of locoregional treatment at the basic level of breast healthcare. Radiation therapy allows for consideration of breast-conserving therapy, postmastectomy chest wall irradiation, and palliation of painful or symptomatic metastases. Systemic therapy with cytotoxic chemotherapy is effective in the treatment of all biologic subtypes of breast cancer, but its provision is resource intensive. Although endocrine therapy requires few specialized resources, it requires knowledge of hormone receptor status. Targeted therapy against human epidermal growth factor receptor 2 (anti-HER-2) is very effective in tumors that overexpress HER-2/neu receptors, but cost largely prevents its use in resource-limited environments. Incremental allocation of resources can help address economic disparities and ensure equity in access to care. Checklists and allocation tables can support the objective of offering optimal care for all patients. The use of process metrics can facilitate the development of multidisciplinary, integrated, fiscally responsible, continuously improving, and flexible approaches to the global enhancement of breast cancer treatment.

El Saghir NS, Khalil MK, Eid T, El Kinge AR, Charafeddine M, Geara F, Seoud M, Shamseddine AI. · Division of Hematology, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon. <> · Int J Surg. · Pubmed #17660128 No free full text.

Abstract: BACKGROUND: Registries and research on breast cancer in Arabic and developing countries are limited. METHODS: We searched PubMed, Medline, WHO and IAEA publications, national, regional, hospital tumor registries and abstracts. We reviewed and analyzed available data on epidemiological trends and management of breast cancer in Arab countries, and compared it to current international standards of early detection, surgery and radiation therapy. RESULTS: Breast cancer constitutes 13-35% of all female cancers. Almost half of patients are below 50 and median age is 49-52 years as compared to 63 in industrialized nations. A recent rise of Age-Standardized Incidence Rates (ASR) is noted. Advanced disease remains very common in Egypt, Tunisia, Saudi Arabia, Syria, Palestinians and others. Mastectomy is still performed in more than 80% of women with breast cancer. There are only 84 radiation therapy centers, 256 radiation oncologists and 473 radiation technologists in all Arab countries, as compared with 1875, 3068 and 5155, respectively, in the USA, which has an equivalent population of about 300 million. Population-based screening is rarely practiced. Results from recent campaigns and studies show a positive impact of clinical breast examination leading to more early diagnosis and breast-conserving surgery. CONCLUSIONS: Breast cancer is the most common cancer among women in Arab countries with a young age of around 50 years at presentation. Locally advanced disease is very common and total mastectomy is the most commonly performed surgery. Awareness campaigns and value of clinical breast examination were validated in the Cairo Breast Cancer Screening Trial. More radiation centers and early detection would optimize care and reduce the currently high rate of total mastectomies. Population-based screening in those countries with affluent resources and accessible care should be implemented.

de Castro Junior G, Puglisi F, de Azambuja E, El Saghir NS, Awada A. · Medical Oncology Clinic, Institut Jules Bordet, Brussels, Belgium. · Crit Rev Oncol Hematol. · Pubmed #16600618 No free full text.

Abstract: Angiogenesis plays a crucial role in facilitating tumor growth and the metastatic process, and it is the result of a dynamic balance between pro-angiogenic factors, like vascular endothelial growth factor (VEGF) and platelet-derived growth factor, and antiangiogenic factors, like thrombospondin-1 and angiostatin. Many drugs that target human tumors, like bevacizumab and some VEGF-receptor tyrosine-kinase inhibitors (e.g., BAY 43-9006, SU11248 and PTK787/ZK222584) have been studied in clinical trials, with favorable toxicity reports and encouraging results in advanced colorectal cancer, renal cell cancer, breast cancer and non-squamous non-small cell lung cancer, either combined with chemotherapy, or in monotherapy. Another potential approach to inhibiting angiogenesis is through metronomic chemotherapy (low doses of chemotherapy for long periods of time). This review describes the mechanisms of the angiogenic process and evaluates the recent data about antiangiogenic therapies in clinical trials.

Shamseddine AI, Taher A, Dabaja B, Dandashi A, Salem Z, El Saghir NS. · Division of Hematology-Oncology, American University of Beirut Medical Center, Lebanon. · Am J Clin Oncol. · Pubmed #10362341 No free full text.

Abstract: The purpose of this study was to evaluate the combination of cisplatin and vinorelbine (PVn) for relapsed and chemotherapy-pretreated metastatic breast cancer. Twenty-three patients with metastatic breast cancer and prior chemotherapy were entered in a phase II study between June 1993 and December 1994. Eleven patients were premenopausal and 12 were postmenopausal. Follow-up data up to June 1997 are presented. All patients received cisplatin at a dose of 90 mg/m2 divided over 3 days as 30 mg/m2 infused over 4 hours. Intravenous vinorelbine 25 mg/m2 was given on days 1 and 8 or 15 according to patients' blood counts. Cycles were given every 3 to 4 weeks. An overall response rate of 61% (16/23 patients) was observed. Complete remission was obtained in six patients (26%) and partial remission was obtained in nine patients (35%). The duration of response ranged from 3 to 9 months, with an average of 4 months. Stable disease was noted in 29.1% and progressive disease in 8.3%. Overall survival at 12 months was 50%, and at 36 months it was 8%. Five of 12 patients (42%) who had prior doxorubicin therapy responded well to cisplatin-vinorelbine. Of those 12, seven were refractory and progressive on a doxorubicin-containing regimen, one had complete remission, and four had partial remission. Hematologic toxicity was acceptable. Treatment was delayed because of neutropenia in nine cycles (9.2%) and grade 2 leukopenia occurred in 54% of cycles. Febrile neutropenia occurred in seven cycles (7.1%), and five cycles were complicated by documented sepsis (5.1%). No treatment-related mortality occurred. Thrombocytopenia (grade 3) was seen in 27% of cycles, with no patient having a platelet count below 50,000 or bleeding episodes. Other toxicities were not major or dose-limiting. In conclusion, the combination of cisplatin and vinorelbine produced good responses: 61% response rate (16 of 23 patients) in relapsed, refractory, and heavily pretreated metastatic breast cancer, with 50% survival at 1 year, 12% at 2 years, and 8% at 3 years. In addition, a response rate of 42% (5 of 12 patients) was seen in patients resistant to anthracyclines.

El Saghir NS, Seoud M, Khalil MK, Charafeddine M, Salem ZK, Geara FB, Shamseddine AI. · Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon. · BMC Cancer. · Pubmed #16857060 links to  free full text

Abstract: BACKGROUND: Young age remains a controversial issue as a prognostic factor in breast cancer. Debate includes patients from different parts of the world. Almost 50% of patients with breast cancer seen at the American University of Beirut Medical Center (AUBMC) are below age 50. METHODS: We reviewed 1320 patients seen at AUBMC between 1990 and 2001. We divided them in three age groups: Below 35, 35-50, and above 50. Data and survival were analyzed using Chi-square, Cox regression analysis, and Kaplan Meier. RESULTS: Mean age at presentation was 50.8 years. 107 patients were below age 35, 526 between 35-50 and 687 patients above age 50. Disease stages were as follows: stage I: 14.4%, stage II: 59.9%, stage III: 20% and stage IV: 5.7%. Hormone receptors were positive in 71.8% of patients below 35, in 67.6% of patients 35-50 and in 78.3% of patients above 50. Grade of tumor was higher as age at presentation was lower. More young patients received anthracycline-based adjuvant chemotherapy. Of hormone receptor-positive patients, 83.8% of those below age 35 years, 87.76% of those aged 35-50 years, and 91.2% of those aged above 50 years received adjuvant tamoxifen. The mean follow up time was 3.7 +/- 2.9 years. Time to death was the only variable analyzed for survival analysis. Excluding stage IV patients, tumor size, lymph node, tumor grade and negative hormone receptors were inversely proportional to survival. Higher percentage of young patients at presentation developed metastasis (32.4% of patients below 35, as compared to 22.9% of patients 35-50 and 22.8% of patients above 50) and had a worse survival. Young age had a negative impact on survival of patients with positive axillary lymph nodes, and survival of patients with positive hormonal receptors, but not on survival of patients with negative lymph nodes, or patients with negative hormonal receptors. CONCLUSION: Young age at presentation conferred a worse prognosis in spite of a higher than expected positive hormone receptor status, more anthracycline-based adjuvant chemotherapy and equivalent adjuvant tamoxifen hormonal therapy in younger patients. This negative impact on survival was seen in patients with positive lymph nodes and those with positive hormonal receptors.

El Saghir NS, Otrock ZK, Bleik JH. · Division of Hematology-Oncology, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon. · BMC Cancer. · Pubmed #16332258 links to  free full text

Abstract: BACKGROUND: Zoledronic acid is very widely used in patients with metastatic bone disease and osteoporosis. Only one case of bilateral uveitis was recently reported related to its use. CASE PRESENTATION: We report the first case of severe unilateral anterior uveitis in a patient with breast cancer and an intraocular lens. Following zoledronic acid infusion, the patient developed severe and dramatic right eye pain with decreased visual acuity within 24 hours and was found to have a fibrinous anterior uveitis of moderate severity The patient was treated with topical prednisone and atropine eyedrops and recovered slowly over several months. CONCLUSION: Internists, oncologists, endocrinologists, and ophtalmologists should be aware of uveitis as a possible complication of zoledronic acid therapy. Patients should be instructed to report immediately to their physicians and treatment with topical prednisone and atropine eyedrops should be instituted immediately at the onset of symptoms. This report documents anterior uveitis as a complication of zoledronic acid therapy. This reaction could be an idiosyncratic one but further research may shed more light on the etiology.

Choueiri MB, Otrock ZK, Tawil AN, El-Hajj II, El Saghir NS. · Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon. · N Z Med J. · Pubmed #16027755 No free full text.

Abstract: Male breast cancer is very rare, especially inflammatory breast cancer, which is an aggressive, rapidly proliferating manifestation of primary breast carcinoma. We present a case report of a 56-year-old man in Lebanon who died 8 months after being diagnosed with inflammatory breast cancer.

El Saghir NS, Otrock ZK, Bizri AR, Uwaydah MM, Oghlakian GO. · Division of Hematology-Oncology, Department of Internal Medicine, American University of Beirut Medical Center, P.O. Box 113-6044, Beirut, Lebanon. · Breast. · Pubmed #15990307 No free full text.

Abstract: Cellulitis is a well-known complication of lymphedema of the lower extremities. Erysipelas of the upper extremity complicating breast cancer therapy has never been reported in the English-language literature. We describe seven breast cancer patients with erysipelas of the upper extremity. Five had a predisposing injury to the extremity. All patients responded very well to intravenous antibiotics without any sequelae. They had rapid resolution with typical desquamation. No long-term sequelae were seen except for mild increase of lymphedema. Erysipelas should be listed as a rare complication after locoregional therapy for breast cancer. Intravenous penicillin should be used as the initial therapy. Prevention of arm lymphedema and avoidance of any trauma to the arm are important prophylactic measures. Sentinel lymph node biopsy reduces the rate of axillary lymph node dissection and thus should reduce the incidence of lymphedema and erysipelas.

El Saghir NS, Shamseddine A, Geara F, Bikhaz K, Rahal B, Salem Z, Taher A, Tawil A, Khatib Z, Abbas J, Hourani M, Khalil A, Seoud M. · American University of Beirut Medical Center, Lebanon. · Ethn Dis. · Pubmed #15789463 No free full text.

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El Saghir NS, Otrock ZK. · Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon. · Anticancer Drugs. · Pubmed #15057145 No free full text.

Abstract: We report a new case of central line extravasation of docetaxel into the normal breast of a patient with metastatic left breast cancer. During the infusion of docetaxel, the patient complained of mild discomfort at the site of a subclavian Port-a-Cath, followed by redness, warmth and itchiness of the entire skin of the right breast beneath the port of entry, and it involved the entire right breast by the next day. Over the following few days, she developed blistering, desquamation and oozing of serous fluid through skin fissures. Anti-histamines and hydrocortisonebased ointment induced partial relief of symptoms. Warm soaks induced skin relief. Reaction resolved over few weeks leaving a brownish pigmentation of the skin of the breast, with clearly demarcated lines, as the only sequlae.

El Saghir NS, Shamseddine AI, Geara F, Bikhazi K, Rahal B, Salem ZM, Taher A, Tawil A, El Khatib Z, Abbas J, Hourani M, Seoud M. · Department of Internal Medicine, American University of Beirut, Beirut, Lebanon. · J Med Liban. · Pubmed #12841305 No free full text.

Abstract: BACKGROUND: Breast cancer is the most common cancer in Lebanese women. Lebanon has no national cancer registry and the American University of Beirut Medical Center (AUBMC) is one of the largest hospitals in Lebanon and has a fully operational cancer registry. Earlier studies showed that it sees about one third of all cancer cases in Lebanon. METHODS: All female breast cancer patients recorded at AUBMC between 1983 and 2000 were evaluated. We used the sex-specific age distribution of 1995 Lebanese Population and Housing Survey to estimate the age-specific incidence of breast cancer in Lebanon. The results were calculated as number and proportion of cases, 10-year age-specific incidence rates, crude rates and age standardized rates (ASR) per 100,000 population. The ASR per 100,000 population was estimated by the direct method with the use of the World Standard Population. RESULTS: Between 1983 and 2000, there were a total of 16421 cancers of which 8007 were in women. There were 2673 female breast cancers, averaging 148 cases per year (Range:94-202). Almost half of cases (49.1%) were in women below the age of fifty. The mean age was:49.8 years +/- 13.9 years. Ten-year age groups distribution showed that 4.7% were below 30 years of age, 16.1% were 30-39 years, 28.3% were 40-49 years, 26.3% were 50-59 years, 16.9 % were 60-69 years, 6.1% were 70-79 years and 1.6% were 80 years of age or older. Twenty-two patients (0.9 %) had their age missing in the records. Overall ASR was 30.6, for a crude rate of 27.7. Age adjusted incidence rate had its peak in women aged 50-59, followed by women 40-49 then 60-69 with values of 96.3, 79.9 and 77.4 per 100,000 respectively. We also noted 19 male breast cancer cases corresponding to 0.7% of the 2692 combined total. CONCLUSIONS: The percentage of women with breast cancer in Lebanon seen at AUBMC in pre-menopausal and younger-aged groups is higher than those reported from western countries. Our results emphasize the need to search for possible environmental, lifestyle and/or genetic risk factors in Lebanon. Our study also shows the importance of implementing early detection and screening programs which, along with high quality mammography and medical care, can have a positive impact on survival, especially in younger-aged women.