Patterns of relapse in breast cancer: changes over time.

Adjuvant systemic treatment for breast cancer has evolved resulting in improved outcomes. A relevant question is whether these advances have changed the pattern of distant relapse. Women diagnosed with stage I-III breast cancer were divided into three time cohorts according to changes in adjuvant therapy; A: 1989-1991-CMF chemotherapy in premenopausal and tamoxifen for postmenopausal women; B: 1992-1997-anthracycline chemotherapy and tamoxifen for pre/postmenopausal women; C: 1998-2001-broader use of anthracyclines. The primary endpoint was 5-year cumulative incidence of bone metastasis (BM) as first site of metastasis (FSOM) versus non-bone metastasis (NBM). The ratios NBM/BM in each period were calculated. The eligibility criteria were met by 21,415 cases; Cohorts A: 1989-1991 (n = 3,915), B: 1992-1997 (n = 9,229) and C: 1998-2001 (n = 8,271). Between 1989 and 2001, the percentage of patients receiving adjuvant chemotherapy increased from 23.1 to 34.4%. A decline in cumulative 5-year incidence rates for BM and NBM as FSOM was seen comparing cohort A to C, P < 0.0001. The ratio NBM/BM was significantly increased from 1.53 in the early cohort to 2.00 in the later one, P = 0.0083. The most prominent increase (84%) was in the ER-negative group, chemotherapy treated, P = 0.0272. A significant decline in 5-year cumulative incidence of metastases and an increase in the proportion of NBM as first site of metastasis were observed between earlier and later cohorts. This may reflect the need for more successful adjuvant treatment options for aggressive breast cancer subtypes which are more likely to present with early spread to visceral organs. Understanding patterns of relapse may help design new adjuvant strategies.