ONCOLOGY Vol 18 No 14

The rapid emergence of gemcitabine (Gemzar) as a viable component inchemotherapy for breast cancer is indeed an encouraging development.Specifically, until relatively recently, the focus of research and treatmentwith gemcitabine was primarily on lung cancer. Growing opinion amongmany experts in breast cancer held that studies of gemcitabine in breast cancer werenoticeably lacking and that such research was warranted. Fortunately, these voiceswere heard, and the manufacturers of gemcitabine responded with an acceleratedinitiative to explore further the role of gemcitabine in breast cancer. Rapid progresswas made.

The authors have presented acomprehensive review of rectalcancer, challenging cliniciansto consider whether some patientsare being overtreated with anymodality including surgical resection,chemotherapy, and/or radiotherapy.Tables 2 and 3 provide an excellentoverview of suggested criteria for decidingbetween polypectomy/observationand radical resection for a cancerconfined to a rectal polyp.

The past several years have seenthe fruition of a new era in cancertherapy-targeted approachesusing biologic modifiers.However, as the clinical experiencewith novel inhibitors grows, some ofthe premises on which the treatmentswere designed are being challenged,and clinical findings are leading to newparadigms. Drs. Song and Raben providea forward-thinking review of thestatus of epidermal growth factor receptor(EGFR)-targeted therapy in headand neck cancer, a paper that serves toboth highlight progress and raise issuesthat continue to challenge the implementationof targeted therapy.

This year alone, more than 215,000 women in the United States will bediagnosed with, and over 40,000 will die from, invasive breast cancer.Recently, mortality from female breast cancer has declined despite anincrease in its incidence. This decline corresponds with improved screeningfor prompt tumor detection, and advances in the treatment of earlydisease. Of these, endocrine therapy has played a prominent role. Forwomen with estrogen receptor (ER)-positive and/or progesterone receptor(PR)-positive breast cancers, endocrine therapy has proven to be amajor component of adjuvant therapy, but it is not effective in womenwhose breast cancers lack ERs and PRs. The selective estrogen-receptormodulator (SERM) tamoxifen has been well established as safe and effectivein the adjuvant care of both pre- and postmenopausal women withhormone-receptor–positive early breast cancer. For premenopausalwomen, ovarian suppression is an important option to be considered.Additionally, the aromatase inhibitors have recently demonstrated utilityin postmenopausal women. The ideal sequencing of treatment withtamoxifen and/or an aromatase inhibitor is the subject of several ongoingstudies. Factors involved in selecting an appropriate endocrine regimenhave grown considerably over the past decade. It is becoming more importantfor those caring for women with breast cancer to fully understandthe available endocrine treatment options and the prognostic and predictivefactors available to help select the most appropriate treatment. Thegoal of this article is to assist clinicians in making decisions regardingadjuvant hormonal therapy and to provide information regarding availableclinical trials. To achieve this, the therapeutic options for hormonaltherapy will be reviewed, as will prognostic and predictive factors used inmaking decisions. Finally, four cases illustrating these difficult decisionswill be discussed, with recommendations for treatment.

Dr. Eneman and colleagues providea thorough and timely reviewof adjuvant endocrinetherapy for hormone-receptor–positiveearly breast cancer. This field is rapidlyshifting, with the accumulation of recentlypresented and published datafrom randomized trials in both pre- andpostmenopausal patients. As with mostnew clinical research data, findingsfrom these recent trials raise as manyquestions as they provide conclusions.A few of the issues discussed in thiswell-written review deserve comment.

The treatment of head and neck cancer has been at the forefront ofnovel therapeutic paradigms. The introduction of drugs that interactwith selective biologic pathways in the cancer cell has generated considerableattention recently. A wide variety of new compounds that attemptto target growth-signaling pathways have been introduced intothe clinic. A majority of studies in the clinic have focused on epidermalgrowth factor receptor (EGFR) antagonists, but future studies will likelybuild upon or complement this strategy with agents that target angiogenicor cell-cycle pathways. EGFR activation promotes a multitude ofimportant signaling pathways associated with cancer development andprogression, and importantly, resistance to radiation. Since radiationtherapy plays an integral role in managing head and neck squamouscell cancer (HNSCC), inhibiting the EGFR pathway might improveour efforts at cancer cure. The challenge now is to understand whenthe application of these EGFR inhibitors is relevant to an individualpatient and how or when these drugs should be combined with radiationor chemotherapy. Are there molecular markers available to determinewho will respond to EGFR inhibitors and who should be treatedwith alternative approaches? What are the mechanisms behind intrinsicor acquired resistance to targeted agents, and how do we preventthis problem? We need to formulate integrated laboratory/clinicalresearch programs that address these important issues.

Head and neck squamous cellcarcinoma (HNSCC) is themost common malignant neoplasmarising in the upper aerodigestivetract, accounting for approximately40,000 new cases each yearin the United States. Despite increasingawareness of the importance ofearly cancer detection, the majorityof patients continue to present withadvanced-stage (stage III/IV) disease.Standard therapy has included surgicalresection followed by externalbeamradiation or chemotherapy inconjunction with radiotherapy(chemoradiation). Although no prospectiveclinical trials have comparedsurgical with nonsurgical therapies,only 50% of patients are cured of theirprimary tumors. Even with successfuleradication of the primary tumor,second primary tumors can be expectedto occur at the rate of 4% to 5% peryear and are often fatal. Given the extrememorbidity and mortality ofHNSCC, new and innovative treatmentsbased on the biologic alterations thatcharacterize these tumors are required.

In this issue of ONCOLOGY, Dr.Rothenberger and colleagueshave collated clinicopathologicdata with the theme of local recurrenceand selective use of adjuvanttherapy. They conclude that the datasuggest we continue to overtreat somepatients with rectal cancer. As a generalization,I completely agree withthe authors. However, it is quite difficultto take outcomes data from largenumbers of patients and selectivelyapply the end results to the prospectivemanagement of an individualpatient with rectal cancer in the absenceof highly accurate preoperativestaging.

Adjuvant therapy, almost bydefinition, overtreats patients.It is the holy grail of those ofus involved in adjuvant therapy to definethe patients who are going to failso that we can decrease the incidenceof tumor recurrence and avoid givingadditional therapy to patients who havebeen cured by their primary treatment.

The definition of overtreatment of rectal cancer is controversial,and thus it is difficult to accurately quantitate its prevalence. All componentsof rectal cancer treatment are associated with significant potentialfor morbidity and dysfunction that may have a negative impacton the patient’s quality of life. No one would disagree with the tenetthat overtreatment should be avoided whenever possible. Despite thatconsensus, little attention is given in the literature to the issues ofovertreatment of rectal cancer. This review article presents a varietyof clinical scenarios and summarizes available data demonstratingthat overtreatment of some patients with rectal cancer is occurring ona regular basis. It is hoped that this will stimulate clinicians to criticallyreview their own practices to eliminate such overtreatment. Developmentof new clinical trials to determine whether current practiceguidelines are promoting overtreatment of selected rectal cancer patientsis proposed.

Our understanding of the biologyof breast cancer has undoubtedlyimproved in the pastdecade, and remarkable progress hasbeen achieved in its treatment. Thosecaring for these patients have longrealized that breast cancer is a diseasewith an extremely diverse natural history,and much remains to be learnedabout the interaction among knownpredictive and prognostic factors. Notlong ago, the “more is better” strategyexemplified by high-dose chemotherapy(often resulting in high-dose toxicity)dominated the research agendaand clinical practices of many institutions.Although a minimum chemotherapydose intensity is required[1]and increasing the frequency of specificregimens is advantageous,[2] furtherdose intensification with[3] orwithout stem cell rescue[4-6] offersno meaningful benefit in the adjuvantsetting.