Some possible explanations are considered for the better response to surgical adjuvant chemotherapy in premenopausal than in postmenopausal breast cancer patients. Mean estrogen receptor (ER) concentration is lower in premenopausal women. It is proposed that ER-negative women tend to respond more favorably to chemotherapy for breast cancer because higher estrogen levels in this group may induce hydrolytic enzymes which break down the stromal barrier to the tumor, resulting in a less viscous, less fibrous stroma, and an increased vascular supply. These conditions may facilitate the diffusion of chemotherapeutic agents to the interior of a tumor. This hypothesis can be investigated utilizing existing data gathered in clinical trials of adjuvant chemotherapy.