Adjuvant Therapies

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Breast Cancer Survivors

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Over the past several years, the role of adjuvant therapies have become well defined for breast cancer patients, contributing to the declining mortality rates for this cancer. Generally accepted prognostic factors after surgery for breast cancer include patient age, tumor size, lymph node status, grade, mitotic rate and hormonal receptor status. As summarized by a recent NIH Consensus Statement, adjuvant hormonal therapy should be offered to all women whose tumors stain positive for expression of the estrogen receptor.39 A 5-year treatment course with tamoxifen is considered standard for adjuvant therapy for this group of women, although ovarian ablation can be considered for selected premenopausal patients. Adjuvant multiagent chemotherapy is also recommended for the majority of women with localized breast cancer independent of nodal, menopausal or hormone receptor status, since it has also been shown to improve survival in this setting. Recent data suggest that incorporation of the anthracyclines enhances outcomes with adjuvant chemotherapy for this malignancy; an analogous role for the taxanes has not been determined. Finally, there is also fairly strong evidence that women with a high risk of locoregional recurrence after mastectomy may benefit from adjuvant radiotherapy. This high-risk group includes women with four or more positive lymph nodes or a locally advanced primary cancer. The role of adjuvant radiation therapy for women with 1-3 positive lymph nodes has not yet been defined. Overall, the role of adjuvant therapies for women with breast cancer is now well defined, with a beneficial effect now demonstrated in several subpopulations that in total represent a substantial majority of women with the disease.39

Adjuvant treatments for prostate cancer are much more controversial, reflecting a lack of randomized prospective data, and again indicative of the contrast between the two malignancies, with prostate cancer unfortunately lagging behind in many respects. Adjuvant radiotherapy for men with high-risk features, such as positive margins, remains highly controversial, with many centers opting for observation rather than active treatment. A substantial proportion of such patients may remain disease-free even without adjuvant treatment, and our ability to salvage a significant number of men who exhibit a rising prostate specific antigen (PSA) level after surgery through the timely administration of salvage radiation therapy have encouraged this more conservative approach.40 Still, there are several studies suggesting an advantage to radiation therapy in an adjuvant setting for high-risk patients and this more proactive approach should be considered in younger patients with good functional status after surgery. Similarly, a role for early administration of chemotherapy for patients at high risk for systemic recurrence (patients with a high Gleason score, seminal vesical involvement, etc.) remains uncertain, and is now being tested in several randomized prospective studies.

Finally, the role of adjuvant hormonal blockade also remains controversial, although the recent Eastern Cooperative Oncology Group (ECOG) study from Messing and colleagues did show a survival benefit for early androgen deprivation therapy for men with positive lymph nodes after radical prostatectomy.41 One interesting trend has been the recent use of anti-androgen monotherapy as an adjuvant treatment in patients with a wide variety of disease stage and treatment status, analogous to the use of tamoxifen for breast cancer patients. Early results suggest a delay in clinical progression, but current studies are not yet mature enough to evaluate the effect on survival.42'43 As with tamoxifen, anti-androgen monotherapy is not without potential morbidity, with breast tenderness and/or enlargement reported in over

50% of the patients enrolled in the bicalutamide study (150 mg per day).

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