Research needs in breast cancer.

New research questions emerge as medical needs continue to evolve and as we improve our understanding of cancer biology and treatment of malignancies. Although significant advances have been made in some areas of breast cancer research resulting in improvements in therapies and outcomes over the last few decades, other areas have not benefited to the same degree and we continue to have many gaps in our knowledge. This article summarizes the 12 short and medium-term clinical research needs in breast cancer deemed as priorities in 2016 by a panel of experts, in an attempt to focus and accelerate future research in the most needed areas: (i) de-escalate breast cancer therapies in early breast cancer without sacrificing outcomes; (ii) explore optimal adjuvant treatment durations; (iii) develop better tools and strategies to identify patients with genetic predisposition; (iv) improve care in young patients with breast cancer; (v) develop tools to speed up drug development in biomarker-defined populations; (vi) identify and validate targets that mediate resistance to chemotherapy, endocrine therapy and anti-HER2 therapies; (vii) evaluate the efficacy of local-regional treatments for metastatic disease; (viii) better define the optimal sequence of treatments in the metastatic setting; (ix) evaluate the clinical impact of intra-patient heterogeneity (intra-tumor, inter-tumor and inter-lesion heterogeneity); (x) better understand the biology and identify new targets in triple-negative breast cancer; (xi) better understand immune surveillance in breast cancer and further develop immunotherapies; and (xii) increase survivorship research efforts including supportive care and quality of life.

Current landscape of ESMO/ASCO Global Curriculum adoption and medical oncology recognition: a global survey.

BACKGROUND: With the implementation of multidisciplinary treatment and development of multiple novel anticancer drugs in parallel with expanding knowledge of supportive and palliative care, a need for separate training and specialisation in medical oncology emerged. A Global Curriculum (GC) in medical oncology, developed and updated by a joint European Society for Medical Oncology/American Society of Clinical Oncology (ESMO/ASCO) GC Task Force/Working Group (GC WG), greatly contributed to the recognition of medical oncology worldwide. MATERIAL AND METHODS: ESMO/ASCO GC WG carried out a global survey on medical oncology recognition and GC adoption in 2019. RESULTS: Based on our survey, medical oncology is recognised as a separate specialty or sub-specialty in 47/62 (75%) countries participating in the survey; with a great majority of them (39/47, 83%) recognising medical oncology as a standalone specialty. Additionally, in 9 of 62 (15%) countries, medical oncology is trained together with haematology as a specialty in haemato-oncology or together with radiotherapy as a specialty in clinical oncology. As many as two-thirds of the responding countries reported that the ESMO/ASCO GC has been either fully or partially adopted or adapted in their curriculum. It has been adopted in a vast majority of countries with established training in medical oncology (28/41; 68%) and adapted in 12 countries with mixed training in haemato-oncology, clinical oncology or other specialty responsible for training on systemic anticancer treatment. CONCLUSIONS: With 75% of participating countries reporting medical oncology as a separate specialty or sub-specialty and as high as 68% of them reporting on GC adoption, the results of our survey on global landscape are reassuring. Despite a lack of data for some regions, this survey represents the most comprehensive and up-to-date information about recognition of medical oncology and GC adoption worldwide and will allow both societies to further improve the dissemination of the GC and global recognition of medical oncology, thus contributing to better cancer care worldwide.

Effects of CYP2B6 genetic polymorphisms in patients receiving cyclophosphamide combination chemotherapy for breast cancer.

PURPOSE: The purpose of this study was to measure the frequency of three CYP2B6 [CYP2B6*4 (rs2279343), CYP2B6*5 (rs3211371) and CYP2B6*9 (rs3745274)] alleles in patients with breast cancer receiving cyclophosphamide (CP) therapy and test whether these variants are predictors of CP-associated toxicity and efficacy. METHODS: A total of 145 female breast cancer patients admitted to the American University of Beirut Medical Center for breast cancer-related therapy were included. Chart review was performed for collection of toxicity data. A time-to-event analysis was performed with a subset of 38 patients. RESULTS: The minor allele frequencies of CYP2B6*9, CYP2B6*4 and CYP2B6*5 were 0.27, 0.29 and 0.07, respectively. CYP2B6 *5/*6, *6/*9 or *6/*6 haplotypes were associated with a significantly shorter time to recurrence of the disease. There were no significant associations with myelo-toxicity. CONCLUSIONS: This is the first report on the pharmacogenetic profile of patients with breast cancer and the therapeutic and myelo-toxic behavior of CP in women from an Arab Middle Eastern country. Our results show that genotyping for these CYP2B6 alleles does not help in personalizing therapy from a toxicity perspective, and the association of shorter survival in these subjects with homozygous variants is interesting yet insufficient to justify routine genotyping prior to therapy, or to consider using a higher CP dose. Larger future studies or meta-analyses will be needed to further clarify the potential implication of these genetic polymorphisms.

Treatment of acquired amegakaryocytic thrombocytopenic purpura with cyclophosphamide.

A patient with severe amegakaryocytic thrombocytopenic purpura was treated with cyclophosphamide and had an excellent response after four weeks. His condition remained in complete remission for at least five months. Acquired amegakaryocytic thrombocytopenic purpura is a rare disorder with several possible causes. An intrinsic defect at the level of the megakaryocyte colony-forming units, or a circulating autoantibody directed against these colony-forming units has been suggested. This patient's response to cyclophosphamide supports the hypothesis of an immune mechanism in some of these cases, and it is recommended that immunosuppressive therapy be further evaluated.

Cancer in Lebanon: an epidemiological review of the American University of Beirut Medical Center Tumor Registry (1983-1994).

PURPOSE: Cancers recorded in the Tumor Registry at the American University of Beirut Medical Center (AUBMC), the largest tertiary care center, in Lebanon were reviewed. METHODS: Results were compared with those from the same center 30 years ago and current data from western Asia. RESULTS: Between 1983 and 1994, 9364 cases were recorded, averaging 780 cases per year, representing more than one-third of the national case-load. Cases were almost equally distributed between males and females. Average age of females was significantly younger (48.7 years) than that of males (52.2 years). Among males, the five most frequently reported cancers were of the lung, bladder, larynx, lymphoma, and leukemia. Among females, the four most frequently reported cancers were of the breast, cervix uteri, lymphoma, and brain, with leukemia and corpus uteri ranking equally as fifth. Over the past 30 years, the frequency of colorectal cancer decreased and that of lung cancer increased in both sexes. Oral cancer decreased dramatically among males. Digestive system cancers in this series were less frequent than in cumulative data from western Asia area. CONCLUSIONS: Cancer dynamics changed little since the 1950s, except regard to cancers related to smoking and diet. Diet differences may explain the lower frequencies of digestive cancers in Lebanon as compared with elsewhere in western Asia. The potential impact of cancer prevention and early detection on highly prevalent cancer types such as lung, larynx, breast, and cervix was highlighted.

Infectious complications during therapy of acute leukaemia in Saudi Arabia.

In 40 febrile neutropenic episodes during the induction and consolidation chemotherapy of acute leukaemia in Riyadh, 51% of organisms causing septicaemia were gram-negative, 26% gram-positive, 8% anaerobes and 15% fungi. In 21 (52%) febrile episodes there were pulmonary infiltrates; of the 12 where aetiology was known, six were due to fungi. Pulmonary infiltrates progressed to adult respiratory distress syndrome and death in nine instances. There was no significant occurrence of parasitic and tropical infections. The results show that the pattern of infection, during therapy of acute leukaemia in developing countries, may have important differences when compared with western centres. Empiric amphotericin B may need to be introduced at an earlier stage in patients with persistent fever or progressive pulmonary infiltrates.

Cavitating pneumonia due to Trichosporon beigelii in a patient with acute myeloid leukaemia.

A 21-year-old man with acute myeloid leukaemia developed cavitating pneumonia while neutropenic and on broad spectrum antibiotics following induction chemotherapy. Trichosporon beigelii was isolated from several samples of sputum. He was successfully treated with amphotericin B. Previous reports of lung infection with this organism are reviewed.

Pressure ulcer accelerated healing with local injections of granulocyte macrophage-colony stimulating factor.

This is the first report of granulocyte macrophage-colony stimulating factor (GM-CSF) inducing accelerated healing of a sacral pressure ulcer in a bedridden patient with bilateral hemiplegia. GM-CSF was diluted and injected locally around and into the ulcer bed every 2-3 days for 2 weeks, then weekly for 4 weeks until complete healing occurred. A new firm granulation tissue was noted within a few days. The ulcer showed 85% healing within 2 weeks and 100% by 2 months. Healing started from the periphery and from within the ulcer bed at sites of GM-CSF injections. It was slower at areas where there was complete necrosis and detachment of skin from underlying tissue. The ulcer remained closed until the patient's sudden death 9 months later. A biopsy of granulation tissue showed inflammatory cells and reactive fibroblasts. The potential role of GM-CSF and growth factors in pressure ulcer therapy and wound healing are discussed.

Combination cisplatin-vinorelbine for relapsed and chemotherapy-pretreated metastatic breast cancer.

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.

Tamoxifen and ovarian cysts: a prospective study.

PURPOSE: To prospectively follow a group of women with breast cancer on tamoxifen for the development of ovarian cysts. METHODS: 72 women were followed every 6 months with pelvic examination and vaginal ultrasound. Chi square and Student's t-test were used for statistical analysis. RESULTS: The duration of treatment was 31.5+/-20 months. The mean age was 51.2+/-9.8 years. 55.6% were post-menopausal. Out of 72 women, 18 (25%) developed ovarian cysts. The mean age of women who developed ovarian cysts was significantly lower than in those who did not (47.0+/-7.0 and 52.5+/-10.2 years, respectively, P=0.03), however, the mean duration of treatment was not significantly different (33.3+/-17.4 and 29.3+/-20 months, respectively, P=0.45). Out of 32, 14 (43.8%) pre-menopausal and out of 40, 4 (10%) post-menopausal women developed ovarian cysts (P=0.003). They developed the cysts after an average duration of 33.3+/-18 and 50.7+/-6.2 months, respectively (P=0.7). The average diameter of the cysts was 2.8+/-1.2 cm. All cysts were simple except for one pre-menopausal women. All the cysts in post-menopausal women resolved spontaneously. One pre-menopausal patient had a multi-loculated cyst, was operated and had a serious cystadenoma. In nine patients, the cysts resolved spontaneously and in three after discontinuation of tamoxifen, and one patient was lost to follow-up. All cysts were asymptomatic. CONCLUSION: Ovarian cysts frequently develop in women with breast cancer on tamoxifen. The majority of the cysts resolve spontaneously, therefore an expectant management with follow-up ultrasonography is recommended.

Cancer in Lebanon: analysis of 10,220 cases from the American University of Beirut Medical Center.

Cancers seen and recorded between 1983 and 1995 in the Hospital Tumor Registry at the American University of Beirut Medical Center (AUBMC), one of the largest primary and tertiary care hospitals in Lebanon, were retrospectively reviewed and analyzed. There was a total of 10,220 cases, excluding 916 skin cancers other than skin melanoma, averaging 786 cases per year. There were 5086 cancer cases in males with the five most common cancers being: lung cancer (915 cases: 17.9%) followed by bladder cancer (503 cases: 9.8%), larynx (438 cases: 8.6%), lymphoma (393 cases: 7.7%) and leukemia (336 cases: 6.6%). As for female cancer cases, a total of 5134 cases were observed with the five most common cancers being: breast cancer (1821 cases), followed by cervical cancer (535 cases), colo-rectal cancer (256 cases: 4.9%), lymphoma (232 cases: 4.5%), and brain cancer (213 cases: 4.1%). The average age for all cancer cases was 50.5 years with a standard deviation (SD) of 18.8 years. The average age of females (48.8 yrs; SD 17.4) was relatively lower than that of males (52.2 yrs; SD 19.9) and the difference was statistically significant. 40.6% of the patients were under the age of 50 years. 49% of breast cancer patients were below 50 years of age. In children less than 15 years of age, there were 555 cases, with leukemia being the commonest (185 cases: 33.3% of childhood cases) followed by brain cancer (112 cases: 20.1%), lymphoma (63 cases: 11.3%), bone cancer (41 cases: 7.3%), soft tissue sarcoma (35 cases: 6.3%) and kidney cancer (28 cases: 5.0%). Lung cancer in males and breast cancer in females are the most common cancers in Lebanon. These cancers are amenable to prevention (cigarette cessation and anti-smoking campaigns for lung cancer) and early detection (screening, regular breast examination and mammography for breast cancer). Our paper emphasizes the importance of addressing those and other issues including bladder cancer and age at diagnosis of breast cancer. It also presents important epidemiological and historical reference data on cancer in Lebanon during the civil war and immediately after it.

1st International consensus guidelines for advanced breast cancer (ABC 1).

The 1st international Consensus Conference for Advanced Breast Cancer (ABC 1) took place on November 2011, in Lisbon. Consensus guidelines for the management of this disease were developed. This manuscript summarizes these international consensus guidelines.