BACKGROUND: The concomitant occurrence of breast cancer and pregnancy remains a challenging clinical situation combining ethical and medical problems. There are few prospective data on pregnancy-associated breast cancer (PABC) whose incidence continuously increases. PATIENTS AND METHODS: Forty patients with PABC were compared with 61 non-pregnant, age-matched patients with infiltrative breast carcinomas (BC) diagnosed and followed since 1982. RESULTS: Although PABC and BC tumor size, grade and type, and lymphovascular and lymphnode invasion were similar, the BC cases showed better overall--(p=0.0001) and disease-free (p-0.015) survival. Moreover, the outcome of pregnant patients was worse than post-partum patients (p=0.017). Importantly, the number of PABC patients receiving hormonotherapy was lower than the BC patients (p<0.0004), due to lower estrogen receptor (ER) (p=0.038) and progesterone receptor (PR) (p=0.008) immunohisto-chemical (IH) levels. Retrospective estrogen-regulated pS2/trefoil factor 1 (pS2/TFF1) immunohistochemitry showed no difference between PABC and BC. All the children delivered were healthy. CONCLUSION: Pregnancy and the post-partum period increase breast cancer aggressiveness, pregnancy being the most detrimental. PABC hormone-dependence is under-estimated using ER and PR, and pS2/TFF1 might help in its determination. Appropriate treatment does not impair child outcome.