1-Phenylalanine mustard (L-PAM) in the management of premenopausal patients with primary breast cancer.Lack of association of disease-free survival with depression of ovarian function

Abstract

Breast cancer patients participating in a prospective randomized clinical trial who were ≤49 years of age, had positive axillary nodes, and who received prolonged l‐phenylalanine mustard (L‐PAM) as an adjuvant to mastectomy continue (after 4 years) to demonstrate a significantly greater disease‐free survival (p = 0.007) than do patients who received placebo. Benefit was achieved in patients who were ≤39 years as well as those who were 40–49 years of age. Those in the younger age group showed a greater improvement in disease‐free survival at 4 years relative to their controls (32% vs. 69%; p = 0.01) than did those in the older age group (48% vs. 61%; p = 0.09). When patients were examined relative to their nodal status, a highly favorable effect was found to have been achieved with L‐PAM in those with 1–3 positive nodes (54% vs. 86%; p = 0.006). Results indicate that both age groups were benefited. When considered over time, they demonstrate that a relatively greater effect was achieved in the younger women. While L‐PAM failed to significantly alter the disease‐free survival of those with ≥4 positive nodes a slightly better effect was achieved in the group ≤39 years. Since adjuvant chemotherapy has been found to be more effective in premenopausal than postmenopausal women, it has been presumed that decreased ovarian function, as a result of the chemotherapy, is responsible for the findings. To support or repudiate that concept, information regarding serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E₂), as well as menstrual function, has been obtained from women receiving L‐PAM or L‐PAM plus 5‐FU therapy. In contrast to findings relative to disease‐free survival, ovarian function and menses were most affected in patients 40–49 years of age. Amenorrhea occurred in 73% of patients in that age group and in only 22% of those ≤39 years (p < 0.001). Similarly, a significant increase in LH and FSH and a decrease in E₂, all indicative of ovarian suppression, was observed only in the older group of patients. Thus, it is concluded that while ovarian suppression may account for some of the adjuvant chemotherapeutic effect in premenopausal women, the dichotomy of findings in younger and older premenopausal women relative to therapeutic response and ovarian function indicates that other factors could be responsible.