Rapid growth rate in breast cancer: a confounding variable in adjuvant-chemotherapy trials

In randomised trials of adjuvant chemotherapy for node-positive breast cancer, significant benefits has been seen in premenopausal but not postmenopausal patients. A possible explanation for this distinction is that premenopausal groups contain a greater proportion of patients with rapidly growing tumours that respond well to chemotherapy. The purpose of this study was to assess the plausibility of this explanation, using a clinical index to estimate rate of growth. From a cohort of women with primary breast cancer, none of whom had received adjuvant chemotherapy, an adjuvant-treated population was simulated by means of a study of the 164 patients who would have been eligible for entry into an adjuvant trial. The prognosis for each patient was categorised according to premenopausal or postmenopausal status, nodal status (1-3 or greater than or equal to 4), and growth rate of the cancer (non-rapid or rapid). Patients with rapid growth rates comprised a greater proportion of the premenopausal group (32%) than of the postmenopausal group (20%). On the assumption that adjuvant chemotherapy would preferentially benefit the rapid-growth stratum, the potential impact of the disproportionate distribution of the rapid-growth-rate stratum on the results of adjuvant trials was calculated. The results showed that a disparity in distribution of the rapid-growth-rate stratum could account for the apparently greater benefit in premenopausal patients.