Despite the successes of adjuvant chemotherapy and hormonal therapy, many patients that receive such treatments have recurrences and die. To optimize results, when choosing treatment, tumor and patient biology must be taken into account. This is most apparent in the use of hormonal therapy. Although there is a small but real response rate with tamoxifen in metastatic hormone receptor-negative breast cancer, the 1995 meta-analysis found no significant benefit to adjuvant tamoxifen in women with receptor-poor tumors.31 It is, therefore, critical that hormone receptor be measured in any patient with newly diagnosed breast cancer.4 Although there was some controversy in the past as to whether hormone receptor status is also of value in predicting response to chemotherapy, it is now known that no such relationship exists.19 On the other hand, there is preliminary data that suggest the presence of an overexpressed c-erbB-2 oncogene in breast cancers may have predictive value in the choice of chemother-apy.53 54 The NSABP trial found that melphalan with fluorouracil + doxorubicin was more effective adjuvant therapy than melphalan with fluo-rouracil alone. However, when the data were reanalyzed, the benefit was only seen in patients whose tumors overexpressed c-erbB-2.53 The CALGB trial randomized women to three different dose-intense CAF regimens. The two higher-dose regimens (both within the range of standard dosage) were superior to the low-dose regimen; however, an analysis of the data by c-erbB-2 status found the difference to be present only in the subset of oncogene overexpres-sor.54 These data suggest that if adjuvant chemotherapy is to be given in the presence of c-erbB-2 overexpression, it should contain dox-orubicin at full dose. What is not clear is whether lack of c-erbB-2 overexpression predicts the effectiveness of nondoxorubucin-con-taining regimens. While there are suggestions that c-erbB-2 overexpression may predict unre-sponsiveness to adjuvant tamoxifen,55,56 recent studies are not supportive.57,58
Though the biology of the tumor is important, so too is the biology of the patient in the choice of adjuvant systemic therapy. Age is the most important factor. There is little data on the efficacy of chemotherapy in patients over the age of 70 years; of the 19,000 reviewed in the EBCTCG chemotherapy overview, there were only 600 women over 70 years. They could draw no conclusion as to the value of chemotherapy in that age group.19 Chemotherapy should be reserved for women over 70 years with poor prognostic tumors containing no hormone receptor, with a reasonable life expectancy, and that are physiologically in excellent health. It is important to emphasize, however, that being over 70 years should not a priori exclude a woman from consideration of chemotherapy. In the younger postmenopausal groups, chemotherapy is clearly beneficial alone or when added to tamoxifen. Nevertheless, it should not be universally given. The EBCTCG trial analyzed the same randomized trials where they found a survival benefit to chemotherapy plus tamoxifen in women 50 to 69 years but found no increase in "quality (of life)-adjusted survival" compared with tamox-ifen alone.59 The implication is not that chemotherapy should not be given to women age 50 to 69 years but rather that its use in addition to tamoxifen should be limited to high-risk, poor-prognosis patients, despite calls to the contrary. The administration of adjuvant systemic therapy cannot be considered a standardized process. It must always be individualized.
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