A. Goldhirsch et al., NEW TREATMENTS FOR BREAST-CANCER - BREAKTHROUGHS FOR PATIENT-CARE OR JUST STEPS IN THE RIGHT DIRECTION, Annals of oncology, 9(9), 1998, pp. 973-976
Three areas of clinical research in breast cancer treatment led to new
s breaking presentations at the American Society of Clinical Oncology
(ASCO) meeting, 1998. in Los Angeles. All three subjects represent imp
ortant advances in cancer medicine. Prevention: Two related drugs, tam
oxifen and raloxifene, were found in placebo controlled trials to sign
ificantly reduce the incidence of breast cancer for women at increased
risk of developing the disease. Patterns of relapse showed that the r
educed rate of breast cancer was exclusively observed for tumors expre
ssing estrogen receptors, while the rate of tumors classified as estro
gen-receptor negative was similar for the treatment and the control gr
oups. This may indicate that the observed reduction in breast cancer i
ncidence is due to a treatment effect on occult disease rather than it
s prevention. We certainly have no adequate information on mortality p
revention. Adjuvant therapies: Taxol given every three weeks for four
courses following an adjuvant treatment with four courses of doxorubic
in and cyclophosphamide (AC) combination was found to be superior to n
ot adding treatment after the four courses of AC in a trial involving
3170 patients. At 22 months of median follow-up, the quoted P-values w
ere P = 0.0077 for disease-free survival and P = 0.039 for overall sur
vival, but these did not cross the prospectively defined interim analy
sis boundaries for statistical significance at the 0.05 level. The dif
ference was observed early during follow-up, and was exclusively seen
in the 40% of patients who had ER-negative primaries and, therefore, d
id not receive tamoxifen following chemotherapy. One may thus argue th
at the early difference observed was primarily due to differences in t
he duration of the treatment regimens in the two groups and the early
entry into the trial of patients with particularly aggressive neoplasi
a (e.g., ER-negative primaries) who would have benefited from a longer
duration treatment. Treatment of advanced disease: The use of monoclo
nal anti bodies to c-erb-B2 was found to induce responses in metastati
c breast cancer. Patients with tumors expressing c-erb-B2 responded to
weekly infusions of this biological agent. It was particularly impres
sive that the response rate for patients receiving infusion of the mon
oclonal antibodies together with the cytotoxics was superior to that w
ith chemotherapy alone in a randomized trial. It is important to note
that only patients with tumors overexpressing c-erbB-2 (the overall in
cidence is about 20%) were tested. It must still be demonstrated that
the effect of these monoclonal antibodies is indeed confined to cells
overexpressing c-erbB-2. Treatment related cardiac toxicity remains a
problem, and the effects of treatment in various subsets of patients n
eed to be defined before starting investigations in the adjuvant setti
ng, which is a clear further objective of this specific research. The
significant findings from clinical research opened several new questio
ns, which must be answered before allowing them to be employed in rout
ine patient care.