A vision for the future?

Systemic adjuvant therapy is recommended immediately following surgical removal of the primary tumour in the majority of patients with early breast cancer, to prevent the recurrence of distant metastases. Significant progress has been made in the development and evaluation of endocrine therapies for systemic adjuvant therapy. In pre- and perimenopausal women, ovarian ablation has proven to be a valuable treatment option, though not always desirable for young patients. Thus, reversible medical ovarian suppression with a luteinizing hormone releasing hormone agonist, such as goserelin (Zoladex), may provide an attractive alternative for such patients. International trials have indicated that goserelin provides an important addition to the choice of adjuvant therapies now available to pre- and perimenopausal patients. For postmenopausal patients, it is hoped that the ATAC (Arimidex, tamoxifen, alone or in combination) trial will reveal whether or not the benefits of anastrozole (Arimidex) observed in advanced disease, where it has proven to be well tolerated and at least as effective as tamoxifen in recent trials, will translate to the early setting to provide further management options for these patients. On the horizon is yet another exciting endocrine agent, ICI 182,780 (Fulvestrant), which has also been shown to be as effective as anastrozole in advanced disease. In terms of the future, these agents are likely to provide additional valuable treatment choices for early breast cancer across the patient spectrum.     

Plastic surgery for breast conservation therapy: How to define the volume of the tumor bed for the boost?

Purpose

To describe the procedure of definition of the boost volume using pre- and post-operative computed tomography (CT) and surgical clips in the tumor bed after oncoplastic surgical procedure.

Patients and methods

Thirty-one consecutive breast cancer patients who underwent simple lumpectomy or oncoplastic surgery were studied. All of them underwent pre- and post-operative CT scan in treatment position to evaluate the planning target volume (PTV) boost volume and define the primary tumor (gross tumor volume (GTV)) and tumor bed zones (CTV), with an overall margin of 5 mm in lateral and 10 mm in craniocaudal directions, corresponding to localization and setup uncertainties.

Results

Thirteem patients underwent simple lumpectomy and 18 oncoplastic surgery. The volumetric analysis showed that the intersection between GTV and CTV clips was significantly higher in patients with three and more clips (28.4% vs 3.14%; p < 0.001). In the case of patients with oncoplastic surgery, more than three clips were needed to define the tumor bed volume with accuracy. The number of clips was directly related to the exact definition of the boost volume.

Conclusions

The use of more than three clips allows better definition of the PTV boost volume after oncoplastic surgical procedure.     

Does the reservoir for self-renewal stem from the ends?

Stem cell research is a burgeoning field with an alluring potential for therapeutic intervention, and thus begs a critical understanding of the long-term consequences of stem cell replacement. Operationally, a stem cell may be defined as a rarely dividing cell with the capacity for self-renewal throughout the lifetime of the organism, and an ability to reconstitute its appropriate lineages via proliferation and differentiation. In many differentiated normal and cancer cell types, the maintenance of telomeres plays a pivotal role in their continued division potential. Taken together with the presence of the enzymatic activity responsible for telomere addition, telomerase, in several progenitor cell lineages, it is presumed that telomere maintenance will be critical for the replenishment of stem cells or their successors. The purpose of this review is to discuss the role of telomere length maintenance in self-renewal, and the consequent challenges and potential pitfalls to the manipulation of normal and cancer-derived stem cells.     

What and Where for Publications by Cancer Registries in the Asian Pacific? - Roles for the APJCP in the Future

The absolute necessity of cancer registration for cancer control planning is well accepted. The registry at thenational or local level can provide not only essential data for cancer incidence, mortality and survival but mayalso point to risk and protective factors and efficacy of interventions by conducting epidemiological research.Timely publication of research findings in PubMed indexed journals is of the essence, especially in examplesthat allow free access so that the widest dissemination of information can be achieved. The present commentarycovers the scope of research in Asia or using Asian data the period 2008-2013, nearly 40% of a total of over 300papers being published in the APJCP. In order to reach its full potential the registry should incorporate manyskills. Cooperation for this purpose, whether it be national, regional, Asia-wide or international, is a high priorityand the International Agency for Research on Cancer, together with the National Cancer Institute in Thailandand the APOCP/APJCP are staging an Asian Cancer Network Forum in Bangkok in February of 2014 to allowdiscussion of ways forward. It is hoped that representatives from all regions of Asia will decide to attend anda l so contribute country reports for publication in a special supplement of the APJCP.     

Can the stroma provide the clue to the cellular basis for mammographic density?

Mammographic density is recognised as a useful phenotypic biomarker of breast cancer risk. Deeper understanding is needed of the cellular basis, but evidence is limited because of difficulty in designing studies to validate hypotheses. The ductal epithelial components do not adequately explain the physical and dynamic features observed. The stroma is thought to interact with ductal structures in cancer initiation. Stromal tissues might account for the mammographic features, and this interplay can be hypothesised to relate risk to density. In a paper in this issue of Breast Cancer Research, Alowami has shown a relationship between density and stromal proteins, which might provide useful insight into mammographic density.     

Coordinated Research and the Question of an 'IARC' for the Asian-Pacific?

The stated goal of the APOCP/APJCP is to promote an increased awareness in all areas of cancer prevention ‍and stimulate practical intervention approaches. Whether this should be targeted solely through the publication ‍of the APJCP or also through activities in institutions independently capable of research has yet to be decided by ‍the membership. This will in fact be debated at the forthcoming First General Assembly Conference but we ‍have already argued earlier for an APOCP Training Centre/Practical Prevention Program Pilot Centre and ‍indeed made a practical start. Since the International Agency for Research on Cancer (IARC) and the Union ‍International Contra Cancrum (UICC) are already active in the Asian Pacific the question arises as to what ‍relationship the APOCP should aim for with these international bodies. If they had local offices sited conveniently ‍for efforts specific to this region of the world, coordination and the search for financial support would be greatly ‍facilitated. In particular, one could then envisage an expanded Asian country base for the IARC which would ‍allow greatly enhanced promotion of collaborative projects in our region, with a balanced mix of primary and ‍secondary prevention activities appropriate to the prevailing socioeconomic environments. Possibly under the ‍auspices of the Asian Pacific Federation of Organizations for Cancer Control and Research (APFOCC) through ‍the UICC, the APOCP could act as a local partner to an ‘IARC’ institute for the Asian Pacific. If this idea is ever ‍to be realised we must promote debate and establish concensus so that our voices can be heard. The question we ‍ask now is whether it should indeed be official policy of the APOCP?     

Trastuzumab therapy for the metastatic patient: does the primary match?

"They were a well-matched couple as both of them were madlyin love—she with herself, and he with himself." This issue of Annals of Oncology contains a critically importantarticle [1] comparing HER-2 status between primary breast cancerand corresponding distant metastatic sites. Since trastuzumabis indicated for HER-2-overexpressing breast cancer patientswith metastatic disease, and since one relies almost exclusivelyon pathological testing in the primary breast sample, the perfectmatching of primary with metastatic HER-2 testing becomes crucial.The seminal work of Fidler, Folkman (and others referenced inthe Gancberg article) have not only demonstrated critical biologicaldifferences between primary and metastatic tumours, but usedthese differences as the basis for novel antimetastatic approachesto therapy.     

Gastric cancer: Where is the place for the surgeon,the oncologist and the endoscopist today?

Gastric cancer remains a major health issue and a leading cause of death worldwide.While the incidence is decreasing in western countries,there has been a shift to more proximal cancers of the diffuse type,which are usually more aggressive and associated with a worse prognosis.Radical surgery still offers the only chance of long term survival,but surgery has reached a plateau of effectiveness and more aggressive approaches like"ultraradical" lymphadenectomy have not improved prognosis.There are three options to improve the situation:Earlier detection,neoadjuvant chemotherapy and adjuvant therapy.Whilst systematic gastroscopic screening makes sense in countries with a high incidence of gastric cancer,in other regions targeted investigation of risk groups including first-degree relatives of cancer patients,patients with a chronic corpusdominant gastritis or with defined genetic abnormalities may help to detect cancer at an earlier stage.Neoadjuvant chemotherapy has meanwhile proved to significantly improve the prognosis not only in patients with a locally advanced cancer who cannot be resected for cure but but also in those who are potentially amenable to curative resection.In the largest randomised study so far reported,perioperative chemotherapy raised overall survival after 5 years from 23%to 36%.The role of adjuvant chemotherapy has been discussed for over 30 years.Meta-analyses demonstrate a small but significant effect which,however,seems to be restricted to Asian patients.In a large USstudy,adjuvant radiochemotherapy appeared to significantly improve outcomes.However,less than 50%of the study patients underwent a systematic lymphadenectomy and so the results of the therapy group were not better to those of"only resected"patients in two large European studies.Thus,the indication of adjuvant(radio-)chemotherapy in gastric cancer currently remains uncertain.Endoscopists have found a therapeutic role through endoscopic resection of early cancers,introduced mainly by Japanese authors.With the development of high resolution endoscopy,endosonography and adequate equipment,the endoscopic curative resection of T1a-tumors(restricted to the mucosal layer) has been established.     

Searching for leukemia stem cells--not yet the end of the road?

Defining the characteristics of leukemia stem cells is critical in order to better understand both the genesis of leukemic disease and strategies by which such cells may be eradicated. In this issue of Cancer Cell, Somervaille and Cleary describe studies in which the properties of malignant stem cells are elucidated in a mouse model of leukemia induced by expression of the MLL-AF9 translocation. Biological features of leukemia stem cells in this system challenge previous thinking in several ways and suggest an unexpected degree of heterogeneity among stem cells in various forms of leukemia.     

Has the time arrived for gene expression use at the bedside?

The microarray technology has enabled scientists to simultaneously investigate the expression of thousands of genes. Regarding breast cancer, this technology has provided a molecular classification into clinically relevant subtypes, new tools to predict disease outcome and response to treatment and new insights into carcinogenesis and metastatic progression pathways. Here we describe the state of the art of gene expression profiling for breast cancer, and we discuss the potential impact on breast cancer patient management considering its limits and promises.