ONCOLOGY Vol 20 No 1

The past 2 decades of systemic therapy for breast cancer have beena period of monumental change, in terms of both theory and technology.Adjuvant therapy developed from two strands of research-one insystemic chemotherapy and one in hormonal therapy-both of whichwere aided by the application of higher statistical methodology to clinicaltrials. The agent with the single greatest public health impact inoncology has been tamoxifen, but problems with tamoxifen therapy ledto the development of the aromatase inhibitors, and further researchled to the use of hormonal therapy in a chemopreventive capacity. Theevolution of systemic chemotherapy for breast cancer has been an interplaybetween theory-driven approaches and new agents. By the late1980s, accumulating data revealed that overexpression of HER2 (erbB2)played an important role in a substantial portion of breast cancers,which prompted the development of trastuzumab (Herceptin), an agenttargeting HER2-positive disease. Determining HER2 status proved essentialto assessing patient eligibility for trastuzumab therapy. Decodingof the human genome and application of bioinformatics furtherrevolutionized the possibilities in breast cancer treatment.

Endometrial cancer is the mostcommon gynecologic malignancyaffecting women in theUnited States. In 1988, the InternationalFederation of Gynecology andObstetrics shifted from a clinical stagingprotocol to one based on surgicalfactors, making surgical staging theaccepted treatment approach to endometrialcancers, with excellentsurvival compared to other gynecologicmalignancies. The manuscript byKirby et al brings to light the controversiessurrounding the surgical evaluationof endometrial cancers. Althoughsurgical staging has been shown to haveboth prognostic and therapeutic benefit,major problems in the United Statescontinue to result in suboptimal treatmentof patients with endometrial cancer.These problems include the lack ofan accepted surgical protocol (in termsof adequacy of lymph node sampling)and incomplete surgical staging secondaryto patient factors or the lack ofreferral to specialty-trained gynecologiconcologists.

After peaking in 1990, the absolutenumber of deaths peryear attributed to breast cancerhas fallen steadily.[1] This declineoccurred despite trends thatwould seem to increase breast cancermortality (population growth, aging,increased obesity) and was mirroredeven in countries lacking routine supportfor mammography. Systemictherapy is at least partly responsiblefor this mortality decline, and in supportof this conclusion the predictedbenefits (based on trials and metaanalyses)have been seen in population-based studies.[2] In this issue ofONCOLOGY, Mina and Sledge providea timely and inspiring review of2 decades of progress in systemic therapyfor breast cancer. This leads toseveral questions, including: How didwe get here and what is next?

Traditionally, most hereditarynonpolyposis colorectal cancer(HNPCC) syndrome patientshave been identified and cared for bygastroenterologists, colorectal surgeons,and gastrointestinal medicaloncologists. Hence, the realization thatgynecologic tumors actually play amajor role in HNPCC has come relativelylate. Consequently, much of theclinical and basic science focus ofresearch in HNPCC has concentratedon colorectal cancer.

We are delighted to reviewthe article by Dr. TonyBack on communicationwith cancer patients. We applaud hiseffort to provide recommendations forenhanced communication with patientsand families based on findings fromthe literature. We agree that using thecancer trajectory to identify key communicationtasks provides a useful heuristicmodel because, by matchingcommunication tasks to "high-stakes"clinical encounters, this approach intuitivelyappeals to practicing clinicians.As clearly described by Dr. Back, thevast majority of recommendations forcommunication among oncologist, patient,and family are not derived fromevidence-based research. This underscoresthe importance of conductingadditional research to use as a basis forguiding clinicians in how to handlethese challenging communication tasks.

As noted by Back,[1] the primarygoals of effective patient-physician communicationare to enhance patient understandingof the illness, to improvedecision-making, and to facilitate patientadjustment. These three goalsare sensible and important concernsof the communication dyad. A numberof studies have examined variousaspects of the communication processand the factors that influence communicationoutcomes, and a few evenhave tested interventions to improvephysician communication skills. However,there remains a dearth of studiesthat examine communication effectson the three major goals articulatedabove and that evaluate the effectivenessof communication skill interventionsin influencing patient outcomes.

Effective communication between patients and oncologists is an areaof active and growing research interest. Evidence-based recommendationscan be drawn from studies examining (1) the patient-physicianrelationship; (2) how physicians handle medical information; (3) howphysicians deal with patient emotions; (4) system-level communicationinterventions; (5) physician self-management, and (6) educational interventionsdesigned to improve communication. Existing research providesa great deal of descriptive data about patient-oncologist communication,although intervention studies that link communication to patientoutcomes are much less common.

Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomaldominant cancer susceptibility syndrome associated with inheriteddefects in the DNA mismatch repair system. HNPCC family membersare at high risk for developing colorectal, endometrial, and ovariancancers. Studies of HNPCC families have helped define the importantrole that mismatch repair genes play in the molecular pathogenesis ofendometrial and ovarian cancers. This review will describe some of theimportant clinical and molecular features of HNPCC-related endometrialand ovarian cancer and describe how genetic susceptibility can beidentified in patients with sporadic endometrial and ovarian cancers. Itis important to identify patients with HNPCC, as families of mutationcarriers may benefit from genetic counseling, testing, and intensifiedcancer surveillance.

Over a 30-year period in the20th century, human flightevolved from the propeller tothe jet engine and then managed tosend us to the moon and back. Thechanges over the past 30 years in ourunderstanding of the biology of breastcancer and its application to treatmentare no less startling. Since 1975, wehave witnessed an astounding evolutionin our strategies to prevent,[1]diagnose,[2] and manage[3] a diseasethat affects the lives of so many in theUnited States[4] and around theworld.[5] These efforts have generatedmany headlines and an occasionalstumble. Nonetheless, they have hada dramatic impact on the lives of millionsof people, and it is hoped thatthe rate of improvement will furtheraccelerate in years to come.

Kirby et al are correct in theirstatement that continued controversysurrounds the comprehensivesurgical staging of all patientswith clinical stage I endometrialadenocarcinoma. Such is the case becauselymph node metastasis is foundin only 10% of these patients. Theproportion of patients found to havelymph node metastasis is even loweramong those with grade 1 and 2 tumorswith minimal or no invasion. Ahigh proportion of patients with endometrialadenocarcinoma fall intothis group.

Early presentation of endometrial cancer permits effective managementwith excellent clinical outcome. The addition of hysteroscopy todilatation and curettage (D&C) in the evaluation of postmenopausalbleeding adds little to the detection of malignancy. Imaging studies suchas computed tomography, magnetic resonance imaging, and positronemissiontomography may be of use in determining the presence ofextrauterine disease in patients medically unfit for surgical staging.However, these studies are not sufficiently sensitive to replace surgicalstaging and have little role in routine preoperative evaluation. Clinicalstaging alone is clearly inadequate, as 23% of preoperative clinicalstage I/II patients are upstaged with comprehensive surgical staging.Preoperative tumor grade from D&C or office biopsy may be inaccurateand lead to an underestimate of tumor progression if used to determinewhich patients should be surgically staged. Clinical estimationof depth of invasion, with or without frozen section, is inaccurate andmay lead to underestimation of disease status when surgical staging isnot performed. The practice of resecting only clinically suspicious nodesshould be discouraged as it is no substitute for comprehensive surgicalstaging. Comprehensive surgical staging provides proper guidance forpostoperative adjuvant therapy, avoiding needless radiation in 85% ofclinical stage I/II patients. Finally, resection of occult metastasis withsurgical staging may improve survival.

In their article, Taylor and Mutchbring attention to the gynecologiccancer risks associated with hereditarynonpolyposis colorectal cancer(HNPCC).[1] The identificationof individuals and families at risk forHNPCC has often focused on the coloncancer phenotype, but the diagnosisof endometrial or ovarian cancershould also be considered.