ONCOLOGY Vol 19 No 11

The articles and accompanyingcommentaries in ONCOLOGYprovide important clinical informationbut also an opportunity tocall attention to language projectingattitudes and judgments that are unintended,probably unconscious, andgenerally unchallenged. We note thatrecent articles and reviews refer tothe “patient having failed” treatment;patients are identified with their canceras if they are one, and the descriptionof therapy as “salvage” indirectlycompares the human experience oftreating patients to saving, rescuing,or restoring goods.

The patient is a 74-year-old gentleman who presented with a visual disturbance and right shoulder pain. On routine chest x-ray, he was found to have a right apical lung mass.

In their article entitled “AdjuvantHormonal Therapy in Early BreastCancer,” Kumar and Leonard summarizemuch of the available datafrom trials of hormonal therapy in preandpostmenopausal women. They concludethat the use of aromatase inhibitorshas led to an improvement indisease-free survival in postmenopausalpatients with early-stage breast cancer,but that the optimal timing ofaromatase inhibitor therapy and thelong-term side effects of the drugsremain uncertain. The authors alsohighlight the benefits associated withtamoxifen in premenopausal womenand discuss the unresolved role of ovarianablation in this population.

Breast cancer is a systemic diseasewith 10-year relapse risksafter surgery alone ranging between30% and 50%.[1] About 60%to 75% of breast cancers are hormonereceptor–positive[2] and are potentiallyresponsive to endocrine therapy,which remains a cornerstone in the adjuvanttherapy of such tumors in thisera of targeted therapy and genomics.

For many years, tamoxifen has been the gold standard adjuvanthormonal therapy with the greatest impact in early breast cancer forboth pre- and postmenopausal women. Tamoxifen-based adjuvant endocrinetherapy and chemotherapy have together contributed substantiallyto the reduction in breast cancer mortality that has occurred inrecent years. Over the past few years, the role of aromatase inhibitorshas grown in prominence and they are now on the threshold of supplantingtamoxifen as the new gold standard adjuvant therapy for postmenopausalwomen with estrogen-receptor–positive disease. With extendeduse of oral antihormones such as tamoxifen, the role of ovariansuppression on the other hand has become less clear in the adjuvantsetting. This article reviews the most important data regarding the variousadjuvant hormonal treatments in the management of early breastcancer and will also give a brief overview of the role of these agents inthe neoadjuvant setting.

Drs. Winell and Roth provide agood overview of the commonpsychiatric disorders andcancer-related symptoms in elderly individualswith cancer. Because of thelarge and growing percentage of cancerpatients who are over age 65, theauthors duly highlight the importanceof this topic. The article is highly relevantto the clinical practice of oncologyand detailed information is includedto help guide treatment options formajor depression, anxiety, delirium,and other cancer-related symptoms.

Even now, cancer is a disease ofaging; the average age of a newlydiagnosed cancer patient inthe United States is greater than 65years. Safe and effective medical carefor the elderly will become an increasinglyimportant issue as our populationages over the next severaldecades. By 2025, 20% of the USpopulation will be over the age of 65.It will be essential for physicians tobe well versed in assessing and treatingpatients in this age group in a mannerappropriate to their unique medicalneeds. As the population ages, and bettertreatment for other diseases contributesto longer life expectancy, theassessment and treatment of cancer inthe elderly will be an increasingly commonproblem for oncologists.

The review by Beth Peshkin andClaudine Isaacs in this issue ofONCOLOGY is an excellentoverview of the recognition, evaluation,and clinical management ofwomen with BRCA1 and BRCA2mutations. It is comprehensive andpractical, and emphasizes the approachthat a risk assessment and clinicalgenetics program might take tothe evaluation of an individual concernedabout the possibility thathereditary breast/ovarian cancer predispositionmight be present in herkindred. The authors clearly and conciselypresent the risks of breast, ovarian,and other cancers associated withBRCA1 and BRCA2 mutation carrierstatus, as well as some of the issues thathave arisen in the estimation of thoserisks. They provide a review of factorsthat may modify gene penetrance(cancer risks), and devote the finalsegment of their article to a clear andrational discussion of the surveillanceand preventive options available forthe management of the associatedbreast and ovarian cancer risks.

Following the discovery of theBRCA1 and BRCA2 genes justa decade ago, many felt it prematureto introduce these predictivemolecular markers into clinical practice.At the time, there were concernsregarding perceived limitations ofcancer genetic tests, including the limitedaccuracy of risk estimates associatedwith mutations of BRCA (andother susceptibility genes), the complextechnology needed for sequenceanalysis of large genes, the unprovenoptions for cancer prevention and earlydetection for mutation carriers, thelimited number of cancer genetic specialists,and the potential for adversesequelae following cancer genetic testing.The review by Peshkin and Isaacsprovides an excellent summary of theprogress over the past decade in addressingthese concerns. Nonetheless,as will be summarized here, importantchallenges remain in each of theseareas.

The use of adjuvant endocrinetherapy in early-stage breastcancer is thought to eradicatemicrometastatic disease that may leadto systemic recurrences. Until relativelyrecently, the standard adjuvantendocrine therapy option was tamoxifen.Data from the Early Breast CancerTrialists’ Collaborative Group(EBCTCG) overview analysis reporteda 50% reduction in the risk of relapseand a 28% reduction in the riskof death in estrogen receptor (ER)-positive patients treated with 5 yearsof tamoxifen.[1] This benefit was observedregardless of menopausal orlymph node status and whether or notpatients were receiving chemotherapy.There was no such benefit documentedin ER-negative cancersreceiving tamoxifen. Tamoxifen hasalso been associated with a 47% reductionin the risk of developing contralateralbreast cancer.[1]

More than a decade has passedsince the cancer predispositiongenes BRCA1 andBRCA2 were cloned. Collectively,these genes are responsible for virtuallyall hereditary breast/ovarian cancerfamilies as well as a smaller subsetof hereditary site-specific breast cancerfamilies.[1] Their discovery helped usherin a new age of predictive and preventivemedicine for those at risk ofbreast and ovarian cancer, two of themost common forms of cancer in womenin the United States.[2] Peshkin andIsaacs provide an excellent summaryof cancer susceptibility due to inheritedmutations in BRCA1 and BRCA2,including approaches to assessing personaland family history for the likelihoodof finding these mutations, theirassociated cancer risks, and options forclinical management.

Genetic counseling and testing for susceptibility to breast and ovariancancer is often an integral component of management for womenwith a personal and/or family history of these malignancies. In thisarticle, we will briefly review the function and genetic epidemiology ofthe two major susceptibility genes, BRCA1 and BRCA2. We will thenaddress approaches to risk assessment for women at high risk with respectto the probability that they harbor a deleterious mutation in oneof these genes, and the likelihood that they will develop cancer if sucha mutation is identified. The process of genetic counseling and testingis discussed, including a summary of the potential benefits, limitations,and risks of testing as well as a summary of test result interpretation.We conclude with a review and appraisal of the various options forbreast and ovarian cancer risk reduction and screening options forwomen with a BRCA1 or BRCA2 mutation.

The number of older adults in the general population continues togrow. As their numbers rise, the elderly and the management of theirmedical problems must be of increasing concern for health-care professionals.Within this older population, cancer is a leading cause ofmorbidity and mortality. Although many studies have looked at the psychiatricimplications of cancer in the general population, few studiestackle the issues that may face the older adult with cancer. This articlefocuses on the detection and treatment of depression, anxiety, fatigue,pain, delirium, and dementia in the elderly cancer patient.

In this issue of ONCOLOGY,Winell and Roth review the veryimportant topic of assessment andtreatment of psychiatric symptoms inelderly cancer patients. Their reviewis comprehensive and practical. Thiscommentary further develops a numberof themes raised in their article.